recent journal articles: dentistry, oral surgery & medicine


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Recent Articles in Journal of Dental Research

Adachi T, Nakanishi T, Yumoto H, Hirao K, Takahashi K, Mukai K, Nakae H, Matsuo T
Caries-related Bacteria and Cytokines Induce CXCL10 in Dental Pulp.
J Dent Res. 2007 Dec;86(12):1217-22.
Marked infiltration of inflammatory cells, such as activated T-cells, is observed in the progression of pulpitis; however, little is known about the mechanism of their recruitment into pulpal lesions. It has been recently demonstrated that CXC chemokine ligand 10 (CXCL10) chemoattracts CXC chemokine receptor 3 (CXCR3)-positive activated T-cells. We therefore examined whether CXCL10 is involved in the pathogenesis of pulpitis. CXCL10 mRNA expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Immunostaining results revealed that CXCL10 was detected in macrophages, endothelial cells, and fibroblasts in inflamed dental pulp, and that CXCR3 expression was observed mainly on T-cells. Moreover, cultured dental pulp fibroblasts produced CXCL10 after stimulation with live caries-related bacteria, peptidoglycans, and pro-inflammatory cytokines. In contrast, heat-killed bacteria did not induce CXCL10 secretion. These findings suggest that CXCL10-CXCR3 may play an important role in the pulpal immune response to caries-related bacterial invasion. Abbreviations: CXCL10, CXC chemokine ligand 10; CXCR3, CXC chemokine receptor 3; IFN, interferon; FBS, fetal bovine serum; LTA, lipoteichoic acid; PGN, peptidoglycan; IL, interleukin; TNF, tumor necrosis factor; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay; CCL, C-C chemokine ligand; TLR, Toll-like receptor; NOD, nucleotide oligomerization domain; HDPF, human dental pulp fibroblasts. [Abstract]

Wescott DC, Pinkerton MN, Gaffey BJ, Beggs KT, Milne TJ, Meikle MC
Osteogenic Gene Expression by Human Periodontal Ligament Cells under Cyclic Tension.
J Dent Res. 2007 Dec;86(12):1212-6.
The forces that orthodontic appliances apply to the teeth are transmitted through the periodontal ligament (PDL) to the supporting alveolar bone, leading to the deposition or resorption of bone, depending upon whether the tissues are exposed to a tensile or compressive mechanical strain. To evaluate the osteogenic potential of PDL cells, we applied a 12% uni-axial cyclic tensile strain to cultured human PDL cells and analyzed the differential expression of 78 genes implicated in osteoblast differentiation and bone metabolism by real-time RT-PCR array technology. Sixteen genes showed statistically significant changes in expression in response to alterations in their mechanical environment, including cell adhesion molecules and collagen fiber types. Genes linked to the osteoblast phenotype that were up-regulated included BMP2, BMP6, ALP, SOX9, MSX1, and VEGFA; those down-regulated included BMP4 and EGF. This study has expanded our knowledge of the transcriptional profile of PDL cells and identified several new mechanoresponsive genes. [Abstract]

Zhao Z, Wang Z, Ge C, Krebsbach P, Franceschi RT
Healing Cranial Defects with AdRunx2-transduced Marrow Stromal Cells.
J Dent Res. 2007 Dec;86(12):1207-11.
Marrow stromal cells (MSCs) include stem cells capable of forming all mesenchymal tissues, including bone. However, before MSCs can be successfully used in regeneration procedures, methods must be developed to stimulate their differentiation selectively to osteoblasts. Runx2, a bone-specific transcription factor, is known to stimulate osteoblast differentiation. In the present study, we tested the hypothesis that Runx2 gene therapy can be used to heal a critical-sized defect in mouse calvaria. Runx2-engineered MSCs displayed enhanced osteogenic potential and osteoblast-specific gene expression in vitro and in vivo. Runx2-expressing cells also dramatically enhanced the healing of critical-sized calvarial defects and increased both bone volume fraction and bone mineral density. These studies provide a novel route for enhancing osteogenesis that may have future therapeutic applications for craniofacial bone regeneration. [Abstract]

Oh J, Wang CJ, Poole M, Kim E, Davis RC, Nishimura I, Pae EK
A genome segment on mouse chromosome 12 determines maxillary growth.
J Dent Res. 2007 Dec;86(12):1203-6.
The primary and modifier genes that regulate normal maxillofacial development are unknown. Previous quantitative trait locus (QTL) analyses using the F2 progeny of 2 mouse strains, DBA/2J (short snout/wide face) and C57BL/6J (long snout/narrow face), revealed a significant logarithm-of-odds (LOD) score for snout length on mouse chromosome 12 at 44 centimorgan (cM). We further sought to validate this locus contributing to anterior-posterior dimensions of the upper mid-face at the D12Mit7 marker in a 44-centimorgan portion of chromosome 12. Congenic mice carrying introgressed DNA from DBA/2J on a C57BL/6J background were selected for submental vertex cephalometric imaging. Results confirmed QTLs, determining that short snout length (P < 0.05) and face width relative to snout length (P < 0.01) were present in the 44-cM region of chromosome 12. We conclude that one or more genes contributing to the shape of the maxillary complex are located near 44 cM of mouse chromosome 12. [Abstract]

Koolstra JH, van Eijden TM
Consequences of viscoelastic behavior in the human temporomandibular joint disc.
J Dent Res. 2007 Dec;86(12):1198-202.
The consequences of the viscoelastic behavior of the temporomandibular joint disc were analyzed in simulated jaw open-close cycles. It was hypothesized that viscoelasticity helps protect the underlying bone, while augmenting the smoothness of articular movements. Simulations were performed with a dynamic model of the masticatory system, incorporating the joints' cartilaginous structures as Finite Element Models. A non-linear viscoelastic material model was applied for the disc. The apparent stiffness of the disc to principal stress was largest when the jaw was closed, whereas, with the Von Mises' stress, it appeared largest when the jaw was open. The apparent stiffnesses appeared to be dependent on both the speed of the movements and the presence of a resistance between the teeth. It was concluded that the disc becomes stiffer when load concentrations can be expected. During continued cyclic motion, it softens, which favors smoothness of joint movement at the cost of damage prevention. [Abstract]

Tam LE, Noroozi A
Effects of direct and indirect bleach on dentin fracture toughness.
J Dent Res. 2007 Dec;86(12):1193-7.
There are concerns that tooth-whitening procedures irreversibly damage tooth structure. We investigated the hypothesis that dental bleaches significantly affect dentin structural integrity. The objective was to evaluate the effects of peroxide bleaches on dentin fracture toughness. Compact test specimens, composed of human dentin, were used (n = 10/group). Bleach (16% or 10% carbamide peroxide or 3% hydrogen peroxide) or control material, containing 0.1% sodium fluoride, was applied directly or indirectly to dentin through enamel (6 hrs/day) for 2 or 8 weeks. Fracture toughness results were analyzed by ANOVA and Fisher's LSD test (p < 0.05). There were significant decreases in mean fracture toughness after two- and eight-week direct (19-34% and 61-68%, respectively) and indirect (up to 17% and 37%, respectively) bleach application. The in vitro reduction in dentin fracture toughness caused by the application of peroxide bleaches was greater for the direct application method, longer application time, and higher bleach concentration. [Abstract]

Ayesh EE, Jensen TS, Svensson P
Hypersensitivity to Mechanical and Intra-articular Electrical Stimuli in Persons with Painful Temporomandibular Joints.
J Dent Res. 2007 Dec;86(12):1187-92.
This study tested whether persons with TMJ arthralgia have a modality-specific and site-specific hypersensitivity to somatosensory stimuli assessed by quantitative sensory tests (QST). Forty-three healthy persons and 20 with TMJ arthralgia participated. The QST consisted of: sensory and pain detection thresholds and summation threshold to intra-articular electrical stimulation, tactile and pin-prick sensitivity in the TMJ area, pressure-pain threshold and tolerance on the lateral side of the TMJ and on the finger. Persons with TMJ arthralgia had lower pain detection and summation thresholds (P < 0.001), higher ratings of tactile and pin-prick stimuli (P < 0.05), and markedly lower pressure thresholds on the TMJ and finger (P <0.001) than did healthy individuals. Correlation analysis revealed associations between several QST and clinical pain measures. This study provides new evidence of sensitization of the TMJs as well as central nociceptive pathways. QST may facilitate a mechanism-based classification of temporomandibular disorders. [Abstract]

Hoekema A, Doff MH, de Bont LG, van der Hoeven JH, Wijkstra PJ, Pasma HR, Stegenga B
Predictors of obstructive sleep apnea-hypopnea treatment outcome.
J Dent Res. 2007 Dec;86(12):1181-6.
Oral appliance therapy is an alternative to continuous positive airway pressure (CPAP) for treating the obstructive sleep apnea-hypopnea syndrome. However, the ability to pre-select suitable candidates for either treatment is limited. The aim of this study was to assess the value of relevant variables that can predict the outcome of oral appliance and CPAP therapy. Fifty-one patients treated with oral appliance therapy and 52 patients treated with CPAP were included. Relevant clinical, polysomnographic, and cephalometric variables were determined at baseline. The predictive value of variables for treatment outcome was evaluated in univariate and multivariate analyses. The outcome of oral appliance therapy was favorable, especially in less obese patients with milder sleep apnea and with certain craniofacial characteristics (mandibular retrognathism in particular). Neither univariate nor multivariate analyses yielded variables that reliably predicted the outcome of CPAP. We conclude that the variables found in this study are valuable for pre-selecting suitable candidates for oral-appliance therapy. [Abstract]

Zakhary GM, Clark RM, Bidichandani SI, Owen WL, Slayton RL, Levine M
Acidic Proline-rich Protein Db and Caries in Young Children.
J Dent Res. 2007 Dec;86(12):1176-80.
Polymorphic, acidic proline-rich proteins (PRPs) in saliva influence the attachment of bacteria associated with caries. Our aims were to detect one of three acidic PRP alleles of the PRH1 locus (Db) using polymerase chain-reaction (PCR) on genomic DNA, and to determine its association with caries. DNA was obtained from buccal swabs from Caucasian and African-American children, and their caries experience was recorded. PCR primers designed around exon 3 of the PRH1 locus gave a 416-base product representing Db and a 353-base product representing the other two alleles (Pa or Pif). In Caucasians, Db gene frequency was 14%, similar to Db protein from parotid saliva. In African-Americans, however, it was 37%, 18% lower than Db from parotid saliva (reported previously). Compared with African-Americans, all Caucasians had significantly greater Streptococcus mutans colonization, but only Db-negative Caucasians had significantly more caries. Alleles linked to Db may explain racial differences in caries experience. [Abstract]

Nowjack-Raymer RE, Sheiham A
Numbers of Natural Teeth, Diet, and Nutritional Status in US Adults.
J Dent Res. 2007 Dec;86(12):1171-5.
Evidence that dental status affects diet is equivocal. The hypothesis of this study was that diet was affected by dental status. The objective was to assess the relationship between numbers of teeth and diet and nutritional status in US adult civilians without prostheses. We examined 6985 NHANES (1988-1994) participants. Data included socio-economics, demographics, dental status, and diet and nutritional status. Dietary data were obtained from food frequency questionnaires and 24-hour dietary recall. Serum levels of beta carotene, folate, and vitamin C were measured with isocratic high-performance liquid chromatography. The population was classified by numbers of teeth. Covariance and Satterthwaite F-adjusted statistical comparisons were made between tooth groupings and the fully dentate population. Multilinear regression models adjusted for covariates. People with fewer than 28 teeth had significantly lower intakes of carrots, tossed salads, and dietary fiber than did fully dentate people, and lower serum levels for beta carotene, folate, and vitamin C. Dental status significantly affects diet and nutrition. [Abstract]

Sanders AE, Slade GD, Turrell G, Spencer AJ, Marcenes W
Does psychological stress mediate social deprivation in tooth loss?
J Dent Res. 2007 Dec;86(12):1166-70.
It is unclear which theoretical dimension of psychological stress affects health status. We hypothesized that both distress and coping mediate the relationship between socio-economic position and tooth loss. Cross-sectional data from 2915 middle-aged adults evaluated retention of < 20 teeth, behaviors, psychological stress, and sociodemographic characteristics. Principal components analysis of the Perceived Stress Scale (PSS) extracted 'distress' (a = 0.85) and 'coping' (a =0.83) factors, consistent with theory. Hierarchical entry of explanatory variables into age- and sex-adjusted logistic regression models estimated odds ratios (OR) and 95% confidence intervals [95% CI] for retention of < 20 teeth. Analysis of the separate contributions of distress and coping revealed a significant main effect of coping (OR = 0.7 [95% CI = 0.7-0.8]), but no effect for distress (OR = 1.0 [95% CI = 0.9-1.1]) or for the interaction of coping and distress. Behavior and psychological stress only modestly attenuated socio-economic inequality in retention of < 20 teeth, providing evidence to support a mediating role of coping. [Abstract]

Hughes TE, Bockmann MR, Seow K, Gotjamanos T, Gully N, Richards LC, Townsend GC
Strong genetic control of emergence of human primary incisors.
J Dent Res. 2007 Dec;86(12):1160-5.
Our understanding of tooth eruption in humans remains incomplete. We hypothesized that genetic factors contribute significantly to phenotypic variation in the emergence of primary incisors. We applied model-fitting to data from Australian twins to quantify contributions of genetic and environmental factors to variation in timing of the emergence of human primary incisors. There were no significant differences in incisor emergence times between zygosity groups or sexes. Emergence times of maxillary central incisors and mandibular lateral incisors were less variable than those of maxillary lateral incisors and mandibular central incisors. Maxillary lateral incisors displayed significant directional asymmetry, the left side emerging earlier than the right. Variation in timing of the emergence of the primary incisors was under strong genetic control, with a small but significant contribution from the external environment. Estimates of narrow-sense heritability ranged from 82 to 94% in males and 71 to 96% in females. [Abstract]

Carmona IT, Diz Dios P, Scully C
Efficacy of antibiotic prophylactic regimens for the prevention of bacterial endocarditis of oral origin.
J Dent Res. 2007 Dec;86(12):1142-59.
Despite the controversy about the risk of individuals developing bacterial endocarditis of oral origin, numerous Expert Committees in different countries continue to publish prophylactic regimens for the prevention of bacterial endocarditis secondary to dental procedures. In this paper, we analyze the efficacy of antibiotic prophylaxis in the prevention of bacteremia following dental manipulations and in the prevention of bacterial endocarditis (in both animal models and human studies). Antibiotic prophylaxis guidelines remain consensus-based, and there is scientific evidence of the efficacy of amoxicillin in the prevention of bacteremia following dental procedures, although the results reported do not confirm the efficacy of other recommended antibiotics. The majority of studies on experimental models of bacterial endocarditis have verified the efficacy of antibiotics administered after the induction of bacteremia, confirming the efficacy of antibiotic prophylaxis in later stages in the development of bacterial endocarditis. There is no scientific evidence that prophylaxis with penicillin is effective in reducing bacterial endocarditis secondary to dental procedures in patients considered to be "at risk". It has been suggested that there is a high risk of severe allergic reactions secondary to prophylactically administered penicillins, but, in reality, very few cases have been reported in the literature. It has been demonstrated that antibiotic prophylaxis could contribute to the development of bacterial resistance, but only after the administration of several consecutive doses. Future research on bacterial endocarditis prophylactic protocols should involve the re-evaluation of the time and route of administration of antibiotic prophylaxis, and a search for alternative antimicrobials. [Abstract]

Qin C, D'Souza R, Feng JQ
Dentin Matrix Protein 1 (DMP1): New and Important Roles for Biomineralization and Phosphate Homeostasis.
J Dent Res. 2007 Dec;86(12):1134-41.
Previously, non-collagenous matrix proteins, such as DMP1, were viewed with little biological interest. The last decade of research has increased our understanding of DMP1, as it is now widely recognized that this protein is expressed in non-mineralized tissues, as well as in cancerous lesions. Protein chemistry studies have shown that the full length of DMP1, as a precursor, is cleaved into two distinct forms: the C-terminal and N-terminal fragments. Functional studies have demonstrated that DMP1 is essential in the maturation of odontoblasts and osteoblasts, as well as in mineralization via local and systemic mechanisms. The identification of DMP1 mutations in humans has led to the discovery of a novel disease: autosomal-recessive hypophosphatemic rickets. Furthermore, the regulation of phosphate homeostasis by DMP1 through FGF23, a newly identified hormone that is released from bone and targeted in the kidneys, sets a new direction for research that associates biomineralization with phosphate regulation. [Abstract]

Slade GD, Diatchenko L, Bhalang K, Sigurdsson A, Fillingim RB, Belfer I, Max MB, Goldman D, Maixner W
Influence of psychological factors on risk of temporomandibular disorders.
J Dent Res. 2007 Nov;86(11):1120-5.
Psychological characteristics potentially may be a cause or consequence of temporomandibular disorder (TMD). We hypothesized that psychological characteristics associated with pain sensitivity would influence risk of first-onset TMD, but the effect could be attributed to variation in the gene encoding catechol-O-methyltransferase (COMT). We undertook a prospective cohort study of healthy female volunteers aged 18-34 yrs. At baseline, participants were genotyped, they completed psychological questionnaires, and underwent quantitative sensory testing to determine pain sensitivity. We followed 171 participants for up to three years, and 8.8% of them were diagnosed with first-onset TMD. Depression, perceived stress, and mood were associated with pain sensitivity and were predictive of 2- to 3-fold increases in risk of TMD (P < 0.05). However, the magnitude of increased TMD risk due to psychological factors remained unchanged after adjustment for the COMT haplotype. Psychological factors linked to pain sensitivity influenced TMD risk independently of the effects of the COMT haplotype on TMD risk. [Abstract]

Yoshihara A, Takano N, Hirotomi T, Ogawa H, Hanada N, Miyazaki H
Longitudinal relationship between root caries and serum albumin.
J Dent Res. 2007 Nov;86(11):1115-9.
Serum albumin levels are a practical marker of general health status in the elderly and have been used to determine the severity of an underlying disease and the risk for death. This longitudinal study evaluated the relationship between serum albumin levels and root caries. A total of 266 persons with at least 1 tooth at baseline underwent a baseline examination and then annual investigations for 6 years. Multiple linear regression analysis was used to assess the relationship between changes in serum albumin levels and the number of root caries lesions over 6 years, after adjustment for confounding factors. Change in the number of root caries lesions was significantly associated with change in serum albumin concentrations. The standardized coefficient was -0.148 (p = 0.024). We can confirm that serum albumin concentration correlates with root caries events. From these data, we conclude that persons with hypoalbuminemia are at high risk for root caries. [Abstract]

Phipps KR, Chan BK, Madden TE, Geurs NC, Reddy MS, Lewis CE, Orwoll ES
Longitudinal study of bone density and periodontal disease in men.
J Dent Res. 2007 Nov;86(11):1110-4.
Bone loss is a feature of both periodontitis and osteoporosis, and periodontal destruction may be influenced by systemic bone loss. This study evaluated the association between periodontal disease and bone mineral density (BMD) in a cohort of 1347 (137 edentulous) older men followed for an average of 2.7 years. Participants were recruited from the Osteoporotic Fractures in Men Study. Random half-mouth dental measures included clinical attachment loss (CAL), pocket depth (PD), calculus, plaque, and bleeding. BMD was measured at the hip, spine, and whole-body, by dual-energy x-ray absorptiometry, and at the heel by ultrasound. After adjustment for age, smoking, race, education, body mass index, and calculus, there was no association between number of teeth, periodontitis, periodontal disease progression, and either BMD or annualized rate of BMD change. We found little evidence of an association between periodontitis and skeletal BMD among older men. [Abstract]

López R, Baelum V
Oral health impact of periodontal diseases in adolescents.
J Dent Res. 2007 Nov;86(11):1105-9.
The need for treatment of destructive periodontal diseases is based on observations made by oral health professionals, who, prompted by clinical findings, recommend treatment. We hypothesized that clinical signs of periodontal destruction have an impact on the oral-health-related quality of life of adolescents. We conducted a cross-sectional study among 9203 Chilean high school students sampled by a multistage random cluster procedure. We recorded clinical attachment levels and the presence of necrotizing ulcerative gingivitis. The students answered the Spanish version of the Oral Health Impact Profile and provided information on several socio-economic indicators. The results of multivariable logistic regression analyses (adjusted for age, gender, and tooth loss) showed that both attachment loss [OR = 2.0] and necrotizing ulcerative gingivitis [OR = 1.6] were significantly associated with higher impact on the Oral Health Related Quality of Life of adolescents. Individuals in lower socioeconomic positions systematically reported a higher impact on their oral-health-related quality of life. [Abstract]

Lu HK, Chou HP, Li CL, Wang MY, Wang LF
Stimulation of cells derived from nifedipine-induced gingival overgrowth with Porphyromonas gingivalis, lipopolysaccharide, and interleukin-1beta.
J Dent Res. 2007 Nov;86(11):1100-4.
The purpose of this study was to clarify the main contributory factor of nifedipine-induced gingival overgrowth either by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or interleukin-1beta (IL-1beta). Human gingival fibroblasts from healthy tissues and nifedipine-induced gingival overgrowth tissues were stimulated with nifedipine, IL-1beta, Escherichia coli lipopolysaccharide (Ec-LPS), and Pg-LPS, and the gene expressions were analyzed by RT-PCR. Analysis of the data showed no strong evidence of a synergistic effect of nifedipine and Pg-LPS on IL-6, connective tissue growth factor (CTGF), and type 1 collagen gene expression of either healthy cells or nifedipine-induced gingival overgrowth cells. Among the three stimulants--IL-1beta, Pg-LPS, and Ec-LPS--androgen receptor and IL-6 gene expressions in both the healthy and nifedipine-induced gingival overgrowth groups were strongly up-regulated by the presence of IL-1beta only. Furthermore, the responses to IL-1beta in the nifedipine-induced gingival overgrowth group were stronger than those of the healthy group. It can be concluded that IL-1beta is an important mediator responsible for the higher IL-6 and androgen receptor expression of nifedipine-induced gingival overgrowth cells. [Abstract]

Le TQ, Zhang Y, Li W, Denbesten PK
The effect of LRAP on enamel organ epithelial cell differentiation.
J Dent Res. 2007 Nov;86(11):1095-9.
Leucine-rich amelogenin peptide (LRAP) is an alternatively spliced amelogenin found in the developing enamel organ. LRAP functions to regulate the development of mesenchymal-derived cells; however, its effect on cells of the enamel organ remains unclear. The hypothesis tested in this study is that LRAP also regulates human enamel organ epithelial cells. Recombinant human LRAP (rH58) was synthesized in E. coli, purified, and exogenously added to cultures of human primary enamel epithelial cells, which were analyzed for changes in cell proliferation and differentiation. rH58 had no effect on cell proliferation, but altered enamel epithelial cell morphology, resulting in larger, more rounded cells. Immunofluorescence showed that rH58 treatment increased amelogenin synthesis, but down-regulated Notch1 expression in enamel epithelial cells. LAMP-1, a membrane receptor for LRAP in mesenchymal cells, was identified and was up-regulated in the presence of rH58. These results suggest that rH58 promotes differentiation of human enamel organ epithelial cells. [Abstract]

Andrade I, Silva TA, Silva GA, Teixeira AL, Teixeira MM
The role of tumor necrosis factor receptor type 1 in orthodontic tooth movement.
J Dent Res. 2007 Nov;86(11):1089-94.
Orthodontic tooth movement is dependent on osteoclast activity. Tumor necrosis factor (TNF)-alpha plays an important role, directly or via chemokine release, in osteoclast recruitment and activation. This study aimed to investigate whether the TNF receptor type 1 (p55) influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and p55-deficient mice (p55(-/-)). Levels of TNF-alpha and 2 chemokines (MCP-1/CCL2, RANTES/CCL5) were evaluated in periodontal tissues. A significant increase in CCL2 and TNF-alpha was observed in both groups after 12 hrs of mechanical loading. However, CCL5 levels remained unchanged in p55(-/-) mice at this time-point. The number of TRAP-positive osteoclasts in p55(-/-) mice was significantly lower than that in WT mice. Also, there was a significantly smaller rate of tooth movement in p55(-/-) mice. Analysis of our data suggests that the TNFR-1 plays a significant role in orthodontic tooth movement that might be associated with changes in CCL5 levels. [Abstract]

Minami T, Kuroishi T, Ozawa A, Shimauchi H, Endo Y, Sugawara S
Histamine amplifies immune response of gingival fibroblasts.
J Dent Res. 2007 Nov;86(11):1083-8.
Histamine is an important mediator in immune responses, but it is unclear whether periodontal tissues express histamine receptors and are able to respond to histamine. We hypothesized that histamine, inflammatory cytokines, and bacterial components released in inflamed periodontal tissues may be synergistically involved in periodontitis. The present study showed that human gingival fibroblasts mainly express histamine receptor H1R, and responded to histamine to produce interleukin (IL)-8. Stimulation of gingival fibroblasts with tumor necrosis factor-alpha, IL-1alpha, and lipopolysaccharide markedly induced IL-8 production, and the IL-8 production was synergistically augmented in the presence of or pre-treatment with histamine. Selective inhibitors of mitogen-activated protein kinases (MAPKs), nuclear factor (NF)-kappaB, and phospholipase C (PLC) significantly inhibited the synergistic effect. These results indicate that histamine induces IL-8 production from gingival fibroblasts through H1R, and synergistically augments the inflammatory stimuli by amplification of the MAPK and NF-kappaB through H1R-linked PLC.Abbreviations used: HDC, histidine decarboxylase; LPS, lipopolysaccharide; IL, interleukin; TNF, tumor necrosis factor; HR, histamine receptor; PLC, phospholipase C; MAPK, mitogen-activated protein kinase; NF, nuclear factor; ERK, extracellular signal-related kinase; JNK, c-Jun N-terminal kinase; R, receptor; TLR, Toll-like receptor; alpha-MEM, alpha-minimum essential medium; FCS, fetal calf serum; RT-PCR, reverse-transcriptase polymerase chain-reaction; ELISA, enzyme-linked immunosorbent assay; SD, standard deviation; LDH, lactate dehydrogenase. [Abstract]

Teughels W, Newman MG, Coucke W, Haffajee AD, Van Der Mei HC, Haake SK, Schepers E, Cassiman JJ, Van Eldere J, van Steenberghe D, Quirynen M
Guiding periodontal pocket recolonization: a proof of concept.
J Dent Res. 2007 Nov;86(11):1078-82.
The complexity of the periodontal microbiota resembles that of the gastro-intestinal tract, where infectious diseases are treatable via probiotics. In the oropharyngeal region, probiotic or replacement therapies have shown some benefit in the prevention of dental caries, otitis media, and pharyngitis, but their effectiveness in the treatment of periodontitis is unknown. Therefore, this study addressed the hypothesis that the application of selected beneficial bacteria, as an adjunct to scaling and root planing, would inhibit the periodontopathogen recolonization of periodontal pockets. Analysis of the data showed, in a beagle dog model, that when beneficial bacteria were applied in periodontal pockets adjunctively after root planing, subgingival recolonization of periodontopathogens was delayed and reduced, as was the degree of inflammation, at a clinically significant level. The study confirmed the hypothesis and provides a proof of concept for a guided pocket recolonization (GPR) approach in the treatment of periodontitis. [Abstract]

Koizumi H, Nomura K, Ishihama K, Yamanishi T, Enomoto A, Kogo M
Inhibition of trigeminal respiratory activity by suckling.
J Dent Res. 2007 Nov;86(11):1073-7.
The trigeminal motor system is involved in many rhythmic oral-motor behaviors, such as suckling, mastication, swallowing, and breathing. Despite the obvious importance of functional coordination among these rhythmic activities, the system is not well-understood. In the present study, we examined the hypothesis that an interaction between suckling and breathing exists in the brainstem, by studying the respiratory activity in trigeminal motoneurons (TMNs) during fictive suckling using a neonatal rat in vitro brainstem preparation. The results showed that fictive suckling, which was neurochemically induced by bath application of N-methyl-D,L-aspartate and bicuculline-methiodide, or by local micro-injection of the same drugs to the trigeminal motor nucleus, inhibited the inspiratory activities in both respiration TMNs and respiratory rhythm-generating neurons. Under patch-clamp recording, fictive suckling caused membrane potential hyperpolarization of respiration TMNs. We conclude that the brainstem preparation contains an inhibitory circuit for respiratory activity in the trigeminal motor system via the rhythm-generating network for suckling. Abbreviations: BIC, bicuculline methiodide; GABA, gamma aminobutyric acid; NMA, N-methyl-D,L-aspartate; NMDA, N-methyl-D-aspartate; and TMN, trigeminal motoneuron. [Abstract]

Vecchione L, Byron C, Cooper GM, Barbano T, Hamrick MW, Sciote JJ, Mooney MP
Craniofacial morphology in myostatin-deficient mice.
J Dent Res. 2007 Nov;86(11):1068-72.
GDF-8 (myostatin) is a negative growth regulator of skeletal muscle, and myostatin-deficient mice are hypermuscular. Muscle size and force production are thought to influence growth of the craniofacial skeleton. To test this relationship, we compared masticatory muscle size and craniofacial dimensions in myostatin-deficient and wild-type CD-1 control mice. Myostatin-deficient mice had significantly (p < 0.01) greater body (by 18%) and masseter muscle weight (by 83%), compared with wild-type controls. Significant differences (p < 0.05) were noted for cranial vault length, maxillary length, mandibular body length, and mandibular shape index. Significant correlations were noted between masseter muscle weight and mandibular body length (r = 0.68; p < 0.01), cranial vault length (r = -0.57; p < 0.05), and the mandibular shape index (r = -0.56; p < 0.05). Masticatory hypermuscularity resulted in significantly altered craniofacial morphology, probably through altered biomechanical stress. These findings emphasize the important role that masticatory muscle function plays in the ontogeny of the cranial vault, the maxilla, and, most notably, the mandible. [Abstract]

Tummers M, Yamashiro T, Thesleff I
Modulation of epithelial cell fate of the root in vitro.
J Dent Res. 2007 Nov;86(11):1063-7.
Mouse molars are normally not capable of continuous growth. We hypothesized that the mouse molar has intrinsic potential to maintain the epithelial stem cell niche and assessed this potential by growth in vitro. Although the tooth germs flattened considerably, they developed a mineralized crown and a root. However, histologically, the root surface was composed of 3 structurally different regions affecting the fate of the dental epithelium. The anterior and posterior aspects maintained the morphological and molecular characteristics of the cervical loop of a continuously growing incisor, with a continuous layer of ameloblasts. The epithelium making contact with the supporting filter resembled Hertwig's epithelial root sheath. The top of the cultured molar exposed to air lacked epithelium altogether. We conclude that the fate of the epithelium is regulated by external cues influenced by culture conditions, and that the molar has the intrinsic capacity to grow continuously. [Abstract]

Tohnak S, Mehnert AJ, Mahoney M, Crozier S
Synthesizing dental radiographs for human identification.
J Dent Res. 2007 Nov;86(11):1057-62.
The task of identifying human remains based on dental comparisons of post mortem (PM) and ante mortem (AM) radiographs is labor-intensive, subjective, and has several drawbacks, including: inherently poor image quality, difficulty matching the viewing angles in PM radiographs to those taken AM, and the fact that the state of the dental remains may entirely preclude the possibility of obtaining certain types of radiographs PM. The aim of the present study was to investigate the feasibility of using radiograph-like images reconstructed from PM x-ray computed tomography (CT) data to overcome the shortcomings of conventional radiographic comparison. Algorithms for computer synthesis of panoramic, periapical, and bitewing images are presented. The algorithms were evaluated with data from clinical examinations of two persons. The results demonstrate the efficacy of the CT-based approach and that, in comparison with conventional radiographs, the synthesized images exhibit minimal geometric distortion, reduced blurring, and reduced superimposition of oral structures. [Abstract]

Savignat M, De-Doncker L, Vodouhe C, Garza JM, Lavalle P, Libersa P
Rat nerve regeneration with the use of a polymeric membrane loaded with NGF.
J Dent Res. 2007 Nov;86(11):1051-6.
Exogenous neurotrophic factors, delivered by various systems, are used to improve nerve regeneration. This study tested the effectiveness of a polymeric membrane loaded with Nerve Growth Factor (NGF) on mental nerve regeneration after a crush injury in rats. We tested NGF application, known to play a role in afferent fiber repair in dental neurobiology, to see if it could improve the regeneration. Afferent neurogram recordings and histological analyses of the trigeminal ganglion neurons were performed. One month after the crush injury, early regeneration was observed independently of exogenous NGF. However, as compared with the activity level recorded before the injury, the afferent activity was reduced by 28.5% without NGF, and the mean number of labeled neurons decreased. With NGF, activity was increased by 30.8%, with no significant histological difference compared with animals without lesions. NGF application through a polymeric membrane can influence degenerative and/or regenerative processes after a crush injury. [Abstract]

Kim JW, Kim JH, Thompson VP, Zhang Y
Sliding contact fatigue damage in layered ceramic structures.
J Dent Res. 2007 Nov;86(11):1046-50.
Porcelain-veneered restorations often chip and fracture from repeated occlusal loading, making fatigue studies relevant. Most fatigue studies are limited to uni-axial loading without sliding motion. We hypothesized that bi-axial loading (contact-load-slide-liftoff, simulating a masticatory cycle), as compared with uni-axial loading, accelerates the fatigue of layered ceramics. Monolithic glass plates were epoxy-joined to polycarbonate substrates as a transparent model for an all-ceramic crown on dentin. Uni-and bi-axial cyclic contact was applied through a hard sphere in water, by means of a mouth-motion simulator apparatus. The uni-axial (contact-load-hold-liftoff) and traditional R-ratio fatigue (indenter never leaves the specimen surface) produced similar lifespans, while bi-axial fatigue was more severe. The accelerated crack growth rate in bi-axial fatigue is attributed to enhanced tensile stresses at the trailing edges of a moving indenter. Fracture mechanics descriptions for damage evolution in brittle materials loaded repeatedly with a sliding sphere are provided. Clinical relevance is addressed. [Abstract]

Jiang T, Ma X, Wang Y, Zhu Z, Tong H, Hu J
Effects of hydrogen peroxide on human dentin structure.
J Dent Res. 2007 Nov;86(11):1040-5.
It has been hypothesized that hydrogen peroxide (H(2)O(2)) bleaching may cause destruction of dentin by a mechanism of protein oxidation. However, to our knowledge, there has been no direct chemical evidence to validate this viewpoint. To investigate the effects of H(2)O(2) on the structure of human dentin, we used Fourier transform infrared spectroscopy (FTIR) and attenuated total reflection (ATR) spectroscopy. Human intact dentin specimens were treated either with 30% H(2)O(2) or Hanks' balanced salt solution (HBSS). Significant differences were observed in ATR spectra parameters. Additionally, demineralized dentin specimens were also tested. They were completely dissolved in the H(2)O(2), but remained intact in the 0.1 N HCl and HBSS. The results suggested that H(2)O(2) attacked both the organic and mineral components of dentin. Destruction of the organic components was mainly because of the oxidizing ability of H(2)O(2), while changes in the mineral components were probably due to its acidity. [Abstract]


Recent Articles in Critical Reviews in Oral Biology and Medicine: An Official Publication of the American Association of Oral Biologists

Meurman JH, Sanz M, Janket SJ
Oral health, atherosclerosis, and cardiovascular disease.
Crit Rev Oral Biol Med. 2004;15(6):403-13.
During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). The advent of the inflammation paradigm in coronary pathogenesis stimulated research in chronic infections caused by a variety of micro-organisms-such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus-as well as dental pathogens, since these chronic infections are thought to be involved in the etiopathogenesis of CVD by releasing cytokines and other pro-inflammatory mediators (e.g., C-reactive protein [CRP], tumor necrosis factor [TNF-alpha]) that may initiate a cascade of biochemical reactions and cause endothelial damage and facilitate cholesterol plaque attachment. Yet, due to the multi-factorial nature of dental infection and CVD, confirming a causal association is difficult, and the published results are conflicting. The main deficit in the majority of these studies has been the inadequate control of numerous confounding factors, leading to an overestimation and the imprecise measurement of the predictor or overadjustment of the confounding variables, resulting in underestimation of the risks. A meta-analysis of prospective and retrospective follow-up studies has shown that periodontal disease may increase the risk of CVD by approximately 20% (95% confidence interval [CI], 1.08-1.32). Similarly, the reported risk ratio between periodontal disease and stroke is even stronger, varying from 2.85 (CI 1.78-4.56) to 1.74 (CI 1.08-2.81). The association between peripheral vascular disease and oral health parameters has been explored in only two studies, and the resultant relative risks among individuals with periodontitis were 1.41 (CI 1.12-1.77) and 2.27 (CI 1.32-3.90), respectively. Overall, it appears that periodontal disease may indeed contribute to the pathogenesis of cardiovascular disease, although the statistical effect size is small. [Abstract]

Venezia E, Goldstein M, Boyan BD, Schwartz Z
The use of enamel matrix derivative in the treatment of periodontal defects: a literature review and meta-analysis.
Crit Rev Oral Biol Med. 2004;15(6):382-402.
BACKGROUND: Periodontal disease results in the loss of the attachment apparatus. In the last three decades, an increasing effort has been placed on seeking procedures and materials to promote the regeneration of this tissue. The aim of this paper is to evaluate the effect of enamel matrix derivative (EMD) during regenerative procedures. In addition, a meta-analysis is presented regarding the clinical results during regeneration with EMD, to gain evidence as to what can be accomplished following treatment of intrabony defects with EMD in terms of probing depth reduction, clinical attachment level gain, defect fill (using re-entry studies), and radiographic parameters. METHODS: The review includes in vitro and in vivo studies as well as human case reports, clinical comparative trials, and histologic findings. In addition, a meta-analysis is presented regarding the regenerative clinical results. For this purpose, we used 28 studies-including 955 intrabony defects treated with EMD that presented baseline and final data on probing depth, clinical attachment level (CAL) gain, or bone gain-to calculate weighted mean changes in the different parameters. The selected studies were pooled from the MEDLINE database at the end of May, 2003. RESULTS: The meta-analysis of intrabony defects treated with EMD resulted in a mean initial probing depth of 7.94 +/- 0.05 mm that was reduced to 3.63 +/- 0.04 mm (p = 0.000). The mean clinical attachment level changed from 9.4 +/- 0.06 mm to 5.82 +/- 0.07 mm (p = 0.000). These results were significantly better than the results obtained for either open-flap debridement (OFD) or guided tissue regeneration (GTR). In contrast, histologically, GTR is more predictable than EMD in terms of bone and cementum formation. No advantage was found for combining EMD and GTR. Xenograft, or EMD and xenograft, yielded inferior results compared with EMD alone, but a limited number of studies evaluated this issue. Promising results were noted for the combination of allograft materials and EMD. CONCLUSIONS: EMD seems to be safe, was able to regenerate lost periodontal tissues in previously diseased sites based on clinical parameters, and was better than OFD or GTR. Its combination with allograft materials may be of additional benefit but still needs to be further investigated. [Abstract]

Nair PN
Pathogenesis of apical periodontitis and the causes of endodontic failures.
Crit Rev Oral Biol Med. 2004;15(6):348-81.
Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. The treatment of apical periodontitis, as a disease of root canal infection, consists of eradicating microbes or substantially reducing the microbial load from the root canal and preventing re-infection by orthograde root filling. The treatment has a remarkably high degree of success. Nevertheless, endodontic treatment can fail. Most failures occur when treatment procedures, mostly of a technical nature, have not reached a satisfactory standard for the control and elimination of infection. Even when the highest standards and the most careful procedures are followed, failures still occur. This is because there are root canal regions that cannot be cleaned and obturated with existing equipments, materials, and techniques, and thus, infection can persist. In very rare cases, there are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The data on the biological causes of endodontic failures are recent and scattered in various journals. This communication is meant to provide a comprehensive overview of the etio-pathogenesis of apical periodontitis and the causes of failed endodontic treatments that can be visualized in radiographs as asymptomatic post-treatment periapical radiolucencies. [Abstract]

Prime SS, Davies M, Pring M, Paterson IC
The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II).
Crit Rev Oral Biol Med. 2004;15(6):337-47.
The role of transforming growth factor-beta (TGF-beta) in epithelial malignancy is complex, but it is becoming clear that, in the early stages of carcinogenesis, the protein acts as a potent tumor suppressor, while later, TGF-beta can function to advance tumor progression. We review the evidence to show that the pro-oncogenic functions of TGF-beta are associated with (1) a partial loss of response to the ligand, (2) defects of components of the TGF-beta signal transduction pathway, (3) over-expression and/or activation of the latent complex, (4) epithelial-mesenchymal transition, and (5) recruitment of signaling pathways which act in concert with TGF-beta to facilitate the metastatic phenotype. These changes are viewed in the context of what is known about the pathogenesis of oral cancer and whether this knowledge can be translated into the development of new therapeutic modalities. [Abstract]

Prime SS, Pring M, Davies M, Paterson IC
TGF-beta signal transduction in oro-facial health and non-malignant disease (part I).
Crit Rev Oral Biol Med. 2004;15(6):324-36.
The transforming growth factor-beta (TGF-beta) family of cytokines consists of multi-functional polypeptides that regulate a variety of cell processes, including proliferation, differentiation, apoptosis, extracellular matrix elaboration, angiogenesis, and immune suppression, among others. In so doing, TGF-beta plays a key role in the control of cell behavior in both health and disease. In this report, we review what is known about the mechanisms of activation of the peptide, together with details of TGF-beta signal transduction pathways. This review summarizes the evidence implicating TGF-beta in normal physiological processes of the craniofacial complex-such as palatogenesis, tooth formation, wound healing, and scarring-and then evaluates its role in non-malignant disease processes such as scleroderma, submucous fibrosis, periodontal disease, and lichen planus. [Abstract]

Alvares O
It is time to move on.....
Crit Rev Oral Biol Med. 2004;15(6):321. [Abstract]

Kayaoglu G, Řrstavik D
Virulence factors of Enterococcus faecalis: relationship to endodontic disease.
Crit Rev Oral Biol Med. 2004;15(5):308-20.
Enterococcus faecalis is a micro-organism that can survive extreme challenges. Its pathogenicity ranges from life-threatening diseases in compromised individuals to less severe conditions, such as infection of obturated root canals with chronic apical periodontitis. In the latter situation, the infecting organisms are partly shielded from the defense mechanisms of the body. In this article, we review the virulence factors of E. faecalis that may be related to endodontic infection and the periradicular inflammatory response. The most-cited virulence factors are aggregation substance, surface adhesins, sex pheromones, lipoteichoic acid, extracellular superoxide production, the lytic enzymes gelatinase and hyaluronidase, and the toxin cytolysin. Each of them may be associated with various stages of an endodontic infection as well as with periapical inflammation. While some products of the bacterium may be directly linked to damage of the periradicular tissues, a large part of the tissue damage is probably mediated by the host response to the bacterium and its products. [Abstract]

Siavash H, Nikitakis NG, Sauk JJ
Signal transducers and activators of transcription: insights into the molecular basis of oral cancer.
Crit Rev Oral Biol Med. 2004;15(5):298-307.
Recent efforts on developing more direct and effective targets for cancer therapy have revolved around a family of transcription factors known as STATs (signal transducers and activators of transcription). STAT proteins are latent cytoplasmic transcription factors that become activated in response to extracellular signaling proteins. STAT proteins have been convincingly reported to possess oncogenic properties in a plethora of human cancers, including oral and oropharyngeal cancer. Signal transduction pathways mediated by these oncogenic transcription factors and their regulation in oral cancer are the focus of this review. [Abstract]

Ganss B, Jheon A
Zinc finger transcription factors in skeletal development.
Crit Rev Oral Biol Med. 2004;15(5):282-97.
Cellular and molecular processes that regulate the development of skeletal tissues resemble those required for regeneration. Given the prevalence of degenerative skeletal disorders in an increasingly aging population, the molecular mechanisms of skeletal development must be understood in detail if novel strategies are to be developed in regenerative medicine. Research in this area over the past decade has revealed that cell differentiation is largely controlled at the level of gene transcription, which in turn is regulated by transcription factors. Transcription factors usually recognize and bind to specific DNA sequences in the promoter of target genes via characteristic DNA-binding domains. Although the gene family containing C2H2 zinc fingers as DNA-binding motifs is the largest family of transciptional regulators, with several hundred individual members in mammals, only a small but increasing number of zinc finger genes have been implicated in bone, cartilage, or tooth development. These zinc finger proteins (ZFPs) contain multiple structural motifs that require zinc to maintain their structural integrity and function. Interestingly, zinc deficiency is known to result in skeletal growth retardation and has been identified as a risk factor in the pathogenesis of osteoporosis. This review attempts to summarize our current state of knowledge regarding the role of ZFPs in the molecular regulation of skeletogenesis. [Abstract]

Rowe PS
The wrickkened pathways of FGF23, MEPE and PHEX.
Crit Rev Oral Biol Med. 2004;15(5):264-81.
The last 350 years since the publication of the first medical monograph on rickets (old English term wrickken) (Glisson et al., 1651) have seen spectacular advances in our understanding of mineral-homeostasis. Seminal and exciting discoveries have revealed the roles of PTH, vitamin D, and calcitonin in regulating calcium and phosphate, and maintaining healthy teeth and skeleton. However, it is clear that the PTH/Vitamin D axis does not account for the entire picture, and a new bone-renal metabolic milieu has emerged, implicating a novel set of matrix proteins, hormones, and Zn-metallopeptidases. The primary defects in X-linked hypophosphatemic rickets (HYP) and autosomal-dominant hypophosphatemic rickets (ADHR) are now identified as inactivating mutations in a Zn-metalloendopeptidase (PHEX) and activating mutations in fibroblast-growth-factor-23 (FGF23), respectively. In oncogenic hypophosphatemic osteomalacia (OHO), several tumor-expressed proteins (MEPE, FGF23, and FRP-4) have emerged as candidate mediators of the bone-renal pathophysiology. This has stimulated the proposal of a global model that takes into account the remarkable similarities between the inherited diseases (HYP and ADHR) and the tumor-acquired disease OHO. In HYP, loss of PHEX function is proposed to result in an increase in uncleaved full-length FGF23 and/or inappropriate processing of MEPE. In ADHR, a mutation in FGF23 results in resistance to proteolysis by PHEX or other proteases and an increase in half-life of full-length phosphaturic FGF23. In OHO, over-expression of FGF23 and/or MEPE is proposed to result in abnormal renal-phosphate handling and mineralization. Although this model is attractive, many questions remain unanswered, suggesting a more complex picture. The following review will present a global hypothesis that attempts to explain the experimental and clinical observations in HYP, ADHR, and OHO, plus diverse mouse models that include the MEPE null mutant, HYP-PHEX transgenic mouse, and MEPE-PHEX double-null-mutant. [Abstract]

Rodu B, Jansson C
Smokeless tobacco and oral cancer: a review of the risks and determinants.
Crit Rev Oral Biol Med. 2004;15(5):252-63.
Smokeless tobacco has been associated with oral cancer for many decades. The purpose of this article is to review research relevant to this association, including epidemiologic studies, studies of putative carcinogens such as tobacco-specific nitrosamines (TSNAs) and other contaminants, and possible cancer inhibitors. Epidemiologic studies addressing this issue primarily consist of case-control studies. They show that the use of chewing tobacco and moist snuff is associated with very low risks for cancers of the oral cavity and related structures (relative risks [RR] from 0.6 to 1.7). The use of dry snuff is associated with higher RRs, ranging from 4 to 13, while the RRs from smokeless tobacco, unspecified as to type, are intermediate (RR = 1.5 to 2.8). With regard to TSNAs, historical levels in American moist snuff products were higher than those in their Swedish counterparts, but levels in contemporary products are uniformly low. TSNA levels in chewing tobacco have always been low, but levels in dry snuff have been higher, including some very high levels in current products. In general, smokeless tobacco users are not exposed to significant levels of cadmium, lead, benzo(a)pyrene, polonium-210, and formaldehyde, when compared with concentrations of these compounds in foods. Finally, low oral cancer risk from smokeless tobacco use may be influenced by the presence of cancer inhibitors, mainly anti-oxidants, in smokeless tobacco products. [Abstract]

Stellingsma C, Vissink A, Meijer HJ, Kuiper C, Raghoebar GM
Implantology and the severely resorbed edentulous mandible.
Crit Rev Oral Biol Med. 2004;15(4):240-8.
Patients with a severely resorbed edentulous mandible often suffer from problems with the lower denture. These problems include: insufficient retention of the lower denture, intolerance to loading by the mucosa, pain, difficulties with eating and speech, loss of soft-tissue support, and altered facial appearance. These problems are a challenge for the prosthodontist and surgeon. Dental implants have been shown to provide a reliable basis for fixed and removable prostheses. This has resulted in a drastic change in the treatment concepts for management of the severely resorbed edentulous mandible. Reconstructive, pre-prosthetic surgery has changed from surgery aimed to provide a sufficient osseous and mucosal support for a conventional denture into surgery aimed to provide a sufficient bone volume enabling implants to be placed at the most optimal positions from a prosthetic point of view. The aim of this paper is to review critically the literature on procedures related to the severely resorbed edentulous mandible and dental implant treatment. The study includes the transmandibular implant, (short) endosseous implants, and reconstructive procedures such as distraction osteogenesis, augmentation of the mandibular ridge with autogenous bone, and bone substitutes followed by the placement of implants. The number of patients participating in a study, the follow-up period, the design of the study, the degree of mandibular resorption, and the survival rate of the dental implants all are considered evaluation parameters. Although numerous studies have described the outcome results of dental implants in the edentulous mandible, there have been few prospective studies designed as randomized clinical trials that compare different treatment modalities to restore the severely resorbed mandible. Therefore, it is not yet possible to select an evidence-based treatment modality. Future research has to be focused on long-term, detailed follow-up clinical trials before scientifically based decisions in treating these patients can be made. This will contribute to a higher level of care in this field. [Abstract]

Scully C, Bagan JV
Adverse drug reactions in the orofacial region.
Crit Rev Oral Biol Med. 2004;15(4):221-39.
A wide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed. [Abstract]

Lux R, Shi W
Chemotaxis-guided movements in bacteria.
Crit Rev Oral Biol Med. 2004;15(4):207-20.
Motile bacteria often use sophisticated chemotaxis signaling systems to direct their movements. In general, bacterial chemotactic signal transduction pathways have three basic elements: (1) signal reception by bacterial chemoreceptors located on the membrane; (2) signal transduction to relay the signals from membrane receptors to the motor; and (3) signal adaptation to desensitize the initial signal input. The chemotaxis proteins involved in these signal transduction pathways have been identified and extensively studied, especially in the enterobacteria Escherichia coli and Salmonella enterica serovar typhimurium. Chemotaxis-guided bacterial movements enable bacteria to adapt better to their natural habitats via moving toward favorable conditions and away from hostile surroundings. A variety of oral microbes exhibits motility and chemotaxis, behaviors that may play important roles in bacterial survival and pathogenesis in the oral cavity. [Abstract]

Levin M
The embryonic origins of left-right asymmetry.
Crit Rev Oral Biol Med. 2004;15(4):197-206.
The bilaterally symmetric body plan of vertebrates features several consistent asymmetries in the placement, structure, and function of organs such as the heart, intestine, and brain. Deviations from the normal pattern result in situs inversus, isomerisms, or heterotaxia (independent randomization), which have significant clinical implications. The invariance of the left-right (LR) asymmetry of normal morphology, neuronal function, and phenotype of several syndromes raises fascinating and fundamental questions in cell, developmental, evolutionary, and neurobiology. While a pathway of asymmetrically expressed signaling factors has been well-characterized in several model systems, very early steps in the establishment of LR asymmetry remain poorly understood. In particular, the origin of consistently oriented asymmetry is unknown. Recently, a candidate for the origins of asymmetry has been suggested: bulk transport of extracellular morphogens by rotating primary cilia during gastrulation. This model is appealing because it 'bootstraps' morphological asymmetry of the embryo from the intrinsic structural (molecular) chirality of motile cilia. However, conceptual and practical problems remain with this hypothesis. Indeed, the genetic data are also consistent with a different mechanism: cytoplasmic transport roles of motor proteins. This review outlines the progress and remaining questions in the field of left-right asymmetry, and focuses on an alternative model for 'Step 1' of asymmetry. More specifically, based on wide-ranging data on ion fluxes and motor protein function in several species, it is suggested that laterality is driven by pH/voltage gradients across the midline, which are established by chiral movement of motor proteins with respect to the cytoskeleton. [Abstract]

Ha PK, Califano JA
The role of human papillomavirus in oral carcinogenesis.
Crit Rev Oral Biol Med. 2004;15(4):188-96.
Human papillomavirus (HPV) infection with high-risk types 16 and 18 has widely been reported as one of the prominent mechanisms behind the development of cervical squamous cell carcinoma. Links between HPV and oral cavity cancer have been suggested as well, based on epidemiologic and molecular means, though the association is less well-established. It is likely that HPV plays a role in oral cavity carcinogenesis, though only in a small subset of cases. The difficulty in providing true causal evidence of HPV's role in oral cancer lies in our lack of understanding of the significance of mechanisms by which HPV leads to oral carcinogenesis, as well as limitations in the molecular analysis of HPV. Further studies are necessary for the contribution of HPV in oral cavity malignancy to be better demonstrated. [Abstract]

Braga RR, Ferracane JL
Alternatives in polymerization contraction stress management.
Crit Rev Oral Biol Med. 2004;15(3):176-84.
Polymerization contraction stress of dental composites is often associated with marginal and interfacial failures of bonded restorations. The magnitude of stress depends on composite composition (filler content and matrix composition) and its ability to flow before gelation, which is related to the cavity configuration and curing characteristics of the composite. This article reviews variations among studies regarding contraction-stress-testing methods and contraction stress values of current composites, and discusses the validity of contraction stress studies in relation to results from microleakage tests. The effects of lower curing rates and alternative curing routines on contraction stress values are also discussed, as well as the use of low-elastic-modulus liners. Moreover, studies with experimental dimethacrylate-based composites and recent developments in low-shrinkage monomers are described. [Abstract]

Trackman PC, Kantarci A
Connective tissue metabolism and gingival overgrowth.
Crit Rev Oral Biol Med. 2004;15(3):165-75.
Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth. [Abstract]

Rosen A, Casciola-Rosen L
Altered autoantigen structure in Sjögren's syndrome: implications for the pathogenesis of autoimmune tissue damage.
Crit Rev Oral Biol Med. 2004;15(3):156-64.
The etiology and pathogenic mechanisms underlying Sjögren's syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet. [Abstract]

Hoekema A, Stegenga B, De Bont LG
Efficacy and co-morbidity of oral appliances in the treatment of obstructive sleep apnea-hypopnea: a systematic review.
Crit Rev Oral Biol Med. 2004;15(3):137-55.
The Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a common sleep-related breathing disorder characterized by repetitive obstructions of the upper airway during sleep. Modification of pharyngeal patency by Oral Appliance (OA) therapy has been suggested as an alternative to various treatment modalities for OSAHS. To determine the evidence base with respect to the efficacy and co-morbidity of OA therapy in OSAHS, we conducted a systematic review of the available literature. Primary outcome measures were the reduction in number of upper-airway obstructions and co-morbidity related to the craniomandibular or craniofacial complex, respectively. Eligible studies regarding efficacy were independently assessed by two assessors using a quality assessment scale. Effect sizes of methodologically sound studies were calculated. In identical interventions, effect sizes were pooled with the use of a random-effects model. Given the scarcity of controlled studies related to co-morbidity, appraisal was confined to a description of eligible studies. Sixteen controlled trials related to efficacy were identified. With respect to the primary outcome measure, OA therapy was clearly more effective than control therapy (pooled effect size, -0.96; 95% confidence interval [CI], -1.49 to -0.42) and possibly more effective than uvulopalatopharyngoplasty. Although patients generally preferred OA therapy, improvement of respiratory variables, such as the number of upper-airway obstructions, was usually better in Continuous Positive Airway Pressure (CPAP) therapy (pooled effect size, 0.83; 95% CI, 0.59 to 1.06). Moreover, specific aspects related to OA design may influence patient-perceived efficacy and preference. Twelve patient-series and one controlled trial related to co-morbidity were identified. Analysis of the data suggests that OA therapy may have adverse effects on the craniomandibular and craniofacial complex. Although CPAP is apparently more effective and adverse effects of OA treatment have been described, it can be concluded that OA therapy is a viable treatment for, especially, mild to moderate OSAHS. Controlled studies addressing the specific indication and co-morbidity of OA therapy are warranted. [Abstract]

Qin C, Baba O, Butler WT
Post-translational modifications of sibling proteins and their roles in osteogenesis and dentinogenesis.
Crit Rev Oral Biol Med. 2004;15(3):126-36.
The extracellular matrix (ECM) of bone and dentin contains several non-collagenous proteins. One category of non-collagenous protein is termed the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family, that includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE). These polyanionic SIBLING proteins are believed to play key biological roles in the mineralization of bone and dentin. Although the specific mechanisms involved in controlling bone and dentin formation are still unknown, it is clear that some functions of the SIBLING family members are dependent on the nature and extent of post-translational modifications (PTMs), such as phosphorylation, glycosylation, and proteolytic processing, since these PTMs would have significant effects on their structure. OPN and BSP are present in the ECM of bone and dentin as full-length forms, whereas amino acid sequencing indicates that DMP1 and DSPP exist as proteolytically processed fragments that result from scission of X-Asp bonds. We hypothesized that the processing of DMP1 and DSPP is catalyzed by the PHEX enzyme, since this protein, an endopeptidase that is predominantly expressed in bone and tooth, has a strong preference for cleavage at the NH2-terminus of aspartyl residue. We envision that the proteolytic processing of DMP1 and DSPP may be an activation process that plays a significant, crucial role in osteogenesis and dentinogenesis, and that a failure in this processing would cause defective mineralization in bone and dentin, as observed in X-linked hypophosphatemic rickets. [Abstract]

Hartsfield JK, Everett ET, Al-Qawasmi RA
GENETIC FACTORS IN EXTERNAL APICAL ROOT RESORPTION AND ORTHODONTIC TREATMENT.
Crit Rev Oral Biol Med. 2004;15(2):115-122.
External apical root resorption (EARR) is a common sequela of orthodontic treatment, although it may also occur in the absence of orthodontic treatment. The degree and severity of EARR associated with orthodontic treatment are multifactorial, involving host and environmental factors. Genetic factors account for at least 50% of the variation in EARR. Variation in the Interleukin 1 beta gene in orthodontically treated individuals accounts for 15% of the variation in EARR. Historical and contemporary evidence implicates injury to the periodontal ligament and supporting structures at the site of root compression following the application of orthodontic force as the earliest event leading to EARR. Decreased IL-1beta production in the case of IL-1B (+3953) allele 1 may result in relatively less catabolic bone modeling (resorption) at the cortical bone interface with the PDL, which may result in prolonged stress concentrated in the root of the tooth, triggering a cascade of fatigue-related events leading to root resorption. One mechanism of action for EARR may be mediated through impairment of alveolar resorption, resulting in prolonged stress and strain of the adjacent tooth root due to dynamic functional loads. Future estimation of susceptibility to EARR will likely require the analysis of a suite of genes, root morphology, skeleto-dental values, and the treatment method to be used-or essentially the amount of tooth movement planned for treatment. [Abstract]

Bergenholtz G, Spĺngberg L
CONTROVERSIES IN ENDODONTICS.
Crit Rev Oral Biol Med. 2004;15(2):99-114.
Diseases of the dental pulp often have an infectious origin, and treatments are aimed to control infections of the root canal system. Endodontic treatment principles originally evolved on the basis of trial and error, and only in recent decades have scientific methods been adopted to support clinical strategies. Yet, relevant research on the disease processes, their diagnoses, and efficient treatment are rare in the endodontic literature. Hence, the advancement of biologically based knowledge significant to clinical endodontics has been slow. Therefore, many differences of opinion still prevail in this field of dentistry. This review highlights and analyzes the background of some of the more heavily debated issues in recent years. Specifically, it deals with disagreements regarding the clinical management of pulpal exposures by caries in the adult dentition, definitions of success and failure of endodontic therapy, and causes of and measures to control infections of the root canal system. Clearly, a most apparent gap in the published endodontic literature is the lack of randomized clinical trials that address the more significant controversial matters relating to the management of pulpal wounds, medication, and the number of appointments required for the treatment of infected root canals. However, trials in endodontics require extremely long follow-up periods if valid conclusions are to be generated. Therefore, it is not to be expected that there will be rapid solutions to these issues in the foreseeable future. [Abstract]

Lundy FT, Linden GJ
NEUROPEPTIDES AND NEUROGENIC MECHANISMS IN ORAL AND PERIODONTAL INFLAMMATION.
Crit Rev Oral Biol Med. 2004;15(2):82-98.
It is generally accepted that the nervous system contributes to the pathophysiology of peripheral inflammation, and a neurogenic component has been implicated in many inflammatory diseases, including periodontitis. Neurogenic inflammation should be regarded as a protective mechanism, which forms the first line of defense and protects tissue integrity. However, severe or prolonged noxious stimulation may result in the inflammatory response mediating injury rather than facilitating repair. This review focuses on the accumulating evidence suggesting that neuropeptides have a pivotal role in the complex cascade of chemical activity associated with periodontal inflammation. An overview of neuropeptide synthesis and release introduces the role of neuropeptides and their interactions with other inflammatory factors, which ultimately lead to neurogenic inflammation. The biological effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) are summarized, and evidence for their involvement in the localized inflammatory lesions which characterize periodontitis is presented. In this context, the role of CGRP in bone metabolism is described in more detail. Recent research highlighting the role of the nervous system in suppressing pain and inflammation is also discussed. [Abstract]

Lerner UH
NEW MOLECULES IN THE TUMOR NECROSIS FACTOR LIGAND AND RECEPTOR SUPERFAMILIES WITH IMPORTANCE FOR PHYSIOLOGICAL AND PATHOLOGICAL BONE RESORPTION.
Crit Rev Oral Biol Med. 2004;15(2):64-81.
Osteoclasts are tissue-specific polykaryon bone-resorbing cells derived from the monocyte/macrophage hematopoietic lineage with specialized functions required for the adhesion of the cells to bone and the subsequent polarization of the cell membrane, secretion of acid to dissolve mineral crystals, and release of proteolytic enzymes to degrade the extracellular matrix proteins. Most pathological conditions in the skeleton lead to loss of bone due to excess osteoclastic bone resorption, including periodontal disease, rheumatoid arthritis, and osteoporosis. In rare cases, most of them genetic, patients with osteopetrosis exhibit sclerotic bone due either to a lack of osteoclasts or to non-functional osteoclasts. Mainly because of phenotypic findings in genetically manipulated mice or due to spontaneous mutations in humans, mice, and rats, several genes have been discovered as being crucial for osteoclast formation and activation. Recent breakthroughs in our understanding of osteoclast biology have revealed the critical roles in osteoclast differentiation played by RANKL, RANK, and OPG, three novel members of the tumor necrosis factor ligand and receptor superfamilies. The further study of these molecules and downstream signaling events are likely to provide a molecular basis for the development of new drugs for the treatment of diseases with excess or deficient osteoclastic bone resorption. [Abstract]

Bouillaguet S
BIOLOGICAL RISKS OF RESIN-BASED MATERIALS TO THE DENTIN-PULP COMPLEX.
Crit Rev Oral Biol Med. 2004;15(1):47-60.
Over the past 30 years, restorative dentistry has seen a revolution in materials, restorative techniques, and patient priorities. This revolution has been made possible with the development of new resin-based materials which can be bonded to the tooth structure. Not all of these changes have been without controversy or concern, and some have raised questions about the biological safety of these new materials and techniques. It is the purpose of this review to present recent and relevant information about the biological risks and consequences of resin-tooth bonding and how these risks are affected by the material, its clinical properties, and its manipulation by the practitioner. These biological risks are complex and interactive, and are still incompletely defined. In broad terms, these risks can be divided into those stemming from the toxicological properties of the materials themselves (direct biological risks) and those stemming from microbiological leakage (indirect biological risks). [Abstract]

Torpet LA, Kragelund C, Reibel J, Nauntofte B
ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.
Crit Rev Oral Biol Med. 2004;15(1):28-46.
A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive drug metabolite; S, substrate for CYP isoform; SJS, Stevens-Johnson syndrome; SLE, systemic lupus erythematosus; and TEN, toxic epidermal necrolysis. [Abstract]

Goldberg M, Smith AJ
CELLS AND EXTRACELLULAR MATRICES OF DENTIN AND PULP: A BIOLOGICAL BASIS FOR REPAIR AND TISSUE ENGINEERING.
Crit Rev Oral Biol Med. 2004;15(1):13-27.
Odontoblasts produce most of the extracellular matrix (ECM) components found in dentin and implicated in dentin mineralization. Major differences in the pulp ECM explain why pulp is normally a non-mineralized tissue. In vitro or in vivo, some dentin ECM molecules act as crystal nucleators and contribute to crystal growth, whereas others are mineralization inhibitors. After treatment of caries lesions of moderate progression, odontoblasts and cells from the sub-odontoblastic Höhl's layer are implicated in the formation of reactionary dentin. Healing of deeper lesions in contact with the pulp results in the formation of reparative dentin by pulp cells. The response to direct pulp-capping with materials such as calcium hydroxide is the formation of a dentinal bridge, resulting from the recruitment and proliferation of undifferentiated cells, which may be either stem cells or dedifferentiated and transdifferentiated mature cells. Once differentiated, the cells synthesize a matrix that undergoes mineralization. Animal models have been used to test the capacity of potentially bioactive molecules to promote pulp repair following their implantation into the pulp. ECM molecules induce either the formation of dentinal bridges or large areas of mineralization in the coronal pulp. They may also stimulate the total closure of the pulp in the root canal. In conclusion, some molecules found in dentin extracellular matrix may have potential in dental therapy as bioactive agents for pulp repair or tissue engineering. [Abstract]

Scheie AA, Petersen FC
THE BIOFILM CONCEPT: CONSEQUENCES FOR FUTURE PROPHYLAXIS OF ORAL DISEASES?
Crit Rev Oral Biol Med. 2004;15(1):4-12.
Biofilm control is fundamental to oral health. Existing oral prophylactic measures, however, are insufficient. The main reason is probably because the micro-organisms involved organize into complex biofilm communities with features that differ from those of planktonic cells. Micro-organisms have traditionally been studied in the planktonic state. Conclusions drawn from many of these studies, therefore, need to be revalidated. Recent global approaches to the study of microbial gene expression and regulation in non-oral micro-organisms have shed light on two-component and quorum-sensing systems for the transduction of stimuli that allow for coordinated gene expression. We suggest interference with two-component and quorum-sensing systems as potential novel strategies for the prevention of oral diseases through control of oral biofilms. Information is still lacking, however, on the genetic regulation of oral biofilm formation. A better understanding of these processes is of considerable importance. [Abstract]

Kinane DF, Hart TC
Genes and gene polymorphisms associated with periodontal disease.
Crit Rev Oral Biol Med. 2003;14(6):430-49.
The scientific literature during the last ten years has seen an exponential increase in the number of reports claiming links for genetic polymorphisms with a variety of medical diseases, particularly chronic immune and inflammatory conditions. Recently, periodontal research has contributed to this growth area. This new research has coincided with an increased understanding of the genome which, in turn, has permitted the functional interrelationships of gene products with each other and with environmental agents to be understood. As a result of this knowledge explosion, it is evident that there is a genetic basis for most diseases, including periodontitis. This realization has fostered the idea that if we can understand the genetic basis of diseases, genetic tests to assess disease risk and to develop etiology-based treatments will soon be reality. Consequently, there has been great interest in identifying allelic variants of genes that can be used to assess disease risk for periodontal diseases. Reports of genetic polymorphisms associated with periodontal disease are increasing, but the limitations of such studies are not widely appreciated. While there have been dramatic successes in the identification of mutations responsible for rare genetic conditions, few genetic polymorphisms reported for complex genetic diseases have been demonstrated to be clinically valid, and fewer have been shown to have clinical utility. Although geneticists warn clinicians on the over-enthusiastic use and interpretation of their studies, there continues to be a disparity between the geneticists and the clinicians in the emphasis placed on genes and genetic polymorphism associations. This review critically reviews genetic associations claimed for periodontal disease. It reveals that, despite major advances in the awareness of genetic risk factors for periodontal disease (with the exception of periodontitis associated with certain monogenetic conditions), we are still some way from determining the genetic basis of both aggressive and chronic periodontitis. We have, however, gained considerable insight into the hereditary pattern for aggressive periodontitis. Related to our understanding that it is autosomal-dominant with reduced penetrance comes a major clinically relevant insight into the risk assessment and screening for this disease, in that we appreciate that parents, offspring, and siblings of patients affected with aggressive periodontitis have a 50% risk of this disease also. Nevertheless, we must exercise caution and proper scientific method in the pursuit of clinically valid and useful genetic diagnostic tests for chronic and aggressive periodontitis. We must plan our research using plausible biological arguments and carefully avoid the numerous bias and misinterpretation pitfalls inherent in researching genetic associations with disease. [Abstract]


Recent Articles in Dental Materials : Official Publication of the Academy of Dental Materials

Vichi A, Vano M, Ferrari M
The effect of different storage conditions and duration on the fracture strength of three types of translucent fiber posts.
Dent Mater. 2007 Nov 29; .
OBJECTIVES: (a) To evaluate the effects of storage duration, storage condition and type of fiber post on post fracture strength. (b) To morphologically evaluate the post structure before and after storage. METHODS: Three types of fiber posts were divided in different groups (n=14) according to the storage duration (1, 6, 12 months), and storage condition (dry at 37 degrees C; saline water at 37 degrees C; mineral oil at 37 degrees C and storage inside the roots of extracted human teeth immersed in saline water at 37 degrees C). Specimens were loaded in a universal testing machine with a compressive load until fracture. A 3-way ANOVA and Tukey's test (alpha=.05) were used to compare the effect of the experimental factors on the fracture strength. Two posts of each group were observed before and after the storage using a scanning electron microscope. RESULTS: Storage conditions and post type, had a significant effect on post fracture strength (p<0.05). The interaction between these factors was significant (p<0.05). Water storage significantly decreased the fracture strength, regardless of the post type and the storage duration. Storage inside roots, in oil, and at dry conditions did not significantly affect post fracture strength. SEM micrographs revealed voids between fibers and resin matrix for posts stored in water. Posts stored under the other conditions showed a compact matrix without porosities. SIGNIFICANCE: Fiber posts placed inside human root canals immersed in water are not affected by the detrimental effect of water. [Abstract]

Srimaneepong V, Yoneyama T, Kobayashi E, Doi H, Hanawa T
Comparative study on torsional strength, ductility and fracture characteristics of laser-welded alpha+beta Ti-6Al-7Nb alloy, CP Titanium and Co-Cr alloy dental castings.
Dent Mater. 2007 Dec 1;
OBJECTIVES: The purpose of this study was to compare torsional strength, ductility and fracture behaviors of Ti-6Al-7Nb, CP Ti and Co-Cr alloy castings after laser welding. METHODS: Dumbbell-shaped castings of three metal alloys (Ti-6Al-7Nb alloy, CP Ti, Co-Cr alloy) were cut in half and laser welded with a Nd:YAG pulse laser-welding machine at either 220V or 260V of laser voltage. After being laser welded, all cast specimens were tested with a multi-axial hydraulic testing machine (MTS 858 Mini Bionix((R))) using a torsional test. The fracture surfaces were investigated with a scanning electron microscope. RESULTS: None of the laser-welded Ti-6Al-7Nb alloy and CP Ti castings was broken within the welded joint, showing torsional strength as high as the unwelded castings. Unlike the other groups, the laser-welded Co-Cr alloy castings exhibited brittle fracture appearance and provided substantially less torsional strength. SIGNIFICANCE: The torsional strength of the laser-welded Ti-6Al-7Nb alloy and CP Ti castings was as high as that of the unwelded castings while this finding could not apply to the Co-Cr alloy castings. This indicates that the mechanical strength of the laser-welded Ti-6Al-7Nb alloy dental casting is sufficient for clinical applications. [Abstract]

Moszner N, Gianasmidis A, Klapdohr S, Fischer UK, Rheinberger V
Sol-gel materials 2. Light-curing dental composites based on ormocers of cross-linking alkoxysilane methacrylates and further nano-components.
Dent Mater. 2007 Nov 26;
OBJECTIVES: The objective of this study was to investigate the use of ormocers, which were synthesized from amine or amide dimethacrylate trialkoxysilanes. Ormocers showed improved biocompatibility in dimethacrylate-diluent-free composite restoratives. Selected mechanical properties, such as flexural strength and flexural modulus of experimental composites containing ormocers were investigated. In addition, the influence of methacrylate-substituted ZrO(2) clusters and SiO(2) organosols on the mechanical properties of composites was studied. METHODS: The flexural strength and flexural modulus of elasticity were determined according to ISO 4049: 2000. For this purpose, test specimens (2mmx2mmx25mm) of the composites investigated were prepared in stainless steel moulds and light-cured (150mW/cm(2), 2x180s). The flexural strength and flexural modulus of elasticity were measured after the samples had been stored in water for 24h at 37 degrees C. RESULTS: While visible light-cured dimethacrylate-diluent-free composite restoratives based on the investigated ormocers showed a similar flexural strength and flexural modulus of elasticity compared to composites that contain only dimethacrylates, their double bond conversion was considerable lower. The simultaneous addition of methacrylate-substituted ZrO(2) clusters and SiO(2) organosols to the ormocer composite improved the mechanical properties of the composites. SIGNIFICANCE: Ormocers of amine or amide dimethacrylate trialkoxysilanes enabled the preparation of dimethacrylate-diluent-free composite restoratives. Based on the lower cytotoxicity of the ormocers, the prepared restorative composites should show improved biocompatibility. With the addition of nanoparticles, such as methacrylate-substituted ZrO(2) clusters or SiO(2) organosols, the mechanical properties of composites can be improved. [Abstract]

Guo X, Wang Y, Spencer P, Ye Q, Yao X
Effects of water content and initiator composition on photopolymerization of a model BisGMA/HEMA resin.
Dent Mater. 2007 Nov 26;
AIMS: The purpose of this study was to evaluate the effects of photoinitiator type and water content on the polymerization rate (R(p)) and degree of conversion (DC) of a model BisGMA/HEMA-based resin. MATERIALS AND METHODS: The comonomer mixture consisted of BisGMA/HEMA (60/40 by weight). Different two- or three-component photoinitiator systems were incorporated. Two-component systems were 0.5% CQ (camphorquinone) and 0.5% DMAEMA (2-(dimethylamino) ethyl methacrylate) or 0.5% CQ and 0.5% 4E (ethyl 4-dimethylaminobenzoate). The three-component systems were added 1% DPIHP (diphenyliodonium hexafluorophosphate) to the above systems. Each system was tested as made, or after addition of 5, 10, 15wt% water. When cured under a conventional dental light, the R(p) and DC of each formulation was determined using time-resolved attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy. RESULTS: For mixtures containing two-component initiator systems, when the hydrophobic initiator CQ was used in combination with hydrophilic DMAEMA, R(p)s and DCs were dramatically decreased as a function of water content. The R(p)s and DCs of the hydrophobic CQ/4E system were higher than those of the CQ/DMAEMA system in the presence of water. For three-component initiator systems, incorporation of DPIHP enhanced the polymerization of all mixtures in the presence of water compared to their counterpart two-component initiators. Interestingly, the CQ/DMAEMA caused greater DC and R(p) when DPIHP was used. SIGNIFICANCE: The hydrophobicity/hydrophilicity of photoinitiator components significantly affects both the DC as well as R(p) when in the presence of water. The results indicate that formulation of photoinitiator components should be based on the effectiveness of the bonding systems under both dry and wet conditions. [Abstract]

Wood JD, Sobolewski P, Thakur V, Arola D, Nazari A, Tay FR, Pashley DH
Measurement of microstrains across loaded resin-dentin interfaces using microscopic moiré interferometry.
Dent Mater. 2007 Nov 26;
Little is known about the mechanical behavior of resin-dentin interfaces during loading. The presence of relatively compliant hybrid and adhesive layers between stiffer dentin and resin composite should deform more during compressive loading. OBJECTIVE: The objective of this study was to measure changes in microstrain across bonded dentin interfaces in real time using a recently developed microscope moiré interferometer. METHOD: This system used a miniature moiré interferometer, using two CCD cameras for simultaneous recording of longitudinal and transverse deformation fields, a piezotransducer for fringe shifting and use of a microscope objective with magnification up to 600x. Small beams (1mmx2mmx6mm) of moist resin-bonded dentin covered with cross-lined diffraction grating replica were placed in a miniature compression tester to allow controlled loading from 2 to 37N while imaging the interference fringe patterns. RESULTS: Resin-dentin interfaces created by bonding dentin with Single Bond/Z100, under compressive loading, exhibited comparatively large strains across the adhesive-hybrid interface. When the wrapped phase maps were unwrapped to permit conversion of fringe order to displacements, the 2-D profiles of strain fields revealed non-uniform strains across the adhesive interface. In the adhesive/hybrid layer zone, the negative strain was larger (i.e. -6000muvarepsilon) than that seen in the adjacent resin composite or underlying mineralized dentin. The changes were elastic because they disappeared when the load was removed. SIGNIFICANCE: Microscopic moiré interferometry can be very useful in revealing real-time strain across bonded interfaces under load. [Abstract]

Brandt WC, de Moraes RR, Correr-Sobrinho L, Sinhoreti MA, Consani S
Effect of different photo-activation methods on push out force, hardness and cross-link density of resin composite restorations.
Dent Mater. 2007 Nov 26;
OBJECTIVES: To evaluate push out force, hardness and cross-link density (CLD) of composite restorations photo-activated by different methods. METHODS: Z250 (3M ESPE) and XL2500 halogen unit (3M ESPE) were used. For push out force and hardness tests, conical restorations were made in bovine incisors. For CLD evaluation, cylindrical specimens were prepared. Different activation methods were tested: high-intensity continuous (HIC), low-intensity continuous (LIC), soft-start (SS) or pulse-delay (PD), with constant radiant exposure. Knoop readings were performed on bottom and top surfaces. Data were submitted to two-way ANOVA and Tukey's test (alpha=0.05). Push out force data were submitted to ANOVA and Tukey's test (alpha=0.05). Failure modes were classified under magnification (40x). CLD was estimated by hardness readings before and after storage in ethanol. Data were submitted to RM-ANOVA and Tukey's test (alpha=0.05). RESULTS: No significant differences in top hardness (KHN, N/mm(2)) were observed for HIC (598), LIC (564), SS (585) and PD (573). LIC presented significantly lower bottom hardness (520) than HIC (574), SS (562) and PD (572). Push out force (N) for SS (246) and PD (238) were similar, but significantly higher compared to LIC (198) and HIC (193). For HIC and LIC, only adhesive and mixed failures were observed. For SS and PD, cohesive failures also occurred. After storage, HIC and LIC presented significantly lower softening than PD. HIC also presented lower softening than SS, and similar results were observed for SS and PD. SIGNIFICANCE: Different activation methods can interfere with push out force, hardness and CLD of composite restorations. [Abstract]

Erhardt MC, Toledano M, Osorio R, Pimenta LA
Histomorphologic characterization and bond strength evaluation of caries-affected dentin/resin interfaces: Effects of long-term water exposure.
Dent Mater. 2007 Nov 14;
OBJECTIVES: To evaluate the longevity of sound (SD) and caries-affected dentin (CAD) bonds made with etch-and-rinse and self-etching adhesives after a 6-month water-storage period, using bond strength and morphological evaluations. METHODS: Extracted human molars with coronal carious lesions were selected. Flat surfaces of CAD surrounded by SD were bonded with etch-and-rinse (Adper Scotchbond 1) or with self-etching (Clearfil Protect Bond and AdheSE) adhesives. Trimmed resin-dentin bonded interfaces (1mm(2)) were stored in distilled water for 24h or 6 months and subjected to microtensile bond strength (muTBS) evaluation. The quality of the dentin beneath fractured specimens was measured by Knoop microhardness (KHN). ANOVA and multiple comparisons tests were used (P<0.05). Fractographic analysis and interfacial nanoleakage evaluation were performed by scanning electron microscopy (SEM). Resin-dentin bonded sections (10mum thick) were stained with Masson's trichrome and examined using light microscopy. Collagen exposure and adhesive penetration were examined qualitatively. RESULTS: muTBS to SD was significantly higher than that to CAD for all bonding agents. Bonds made with AdheSE were weaker than the other adhesives after 6-months storage regardless of the dentin substrate. CAD bonded specimens presented a significant muTBS decrease over time. Lower KHN was recorded in CAD compared to SD. An increase in the exposed collagen zone and a decrease in the quality of the adhesive infiltration were observed in CAD interfaces. SIGNIFICANCE: CAD bonded interfaces are more prone to hydrolytic degradation than SD bonds. Additionally, as compared to SD, there were remarkable differences in depth of demineralization, adhesive infiltration and interfacial bond strength with CAD. [Abstract]

Issa Y, Brunton P, Waters CM, Watts DC
Cytotoxicity of metal ions to human oligodendroglial cells and human gingival fibroblasts assessed by mitochondrial dehydrogenase activity.
Dent Mater. 2007 Nov 14;
OBJECTIVES: To assess the variable concentrations of several metal salts on human oligodendrocyte MO3.13 and human gingival fibroblasts HGF and to enable any difference in cell type sensitivity to be examined. METHODS: Cytotoxicity was measured as mitochondrial dehydrogenase activity assessed by MTT assay. The mean of the 50% response (TC50) was calculated by using equation-fitting software (TableCurve 2D). RESULTS: The results of the MTT assay showed that metal ions induce reproducible cytotoxic effects in MO3.13 oligodendroglia and human gingival fibroblasts, that is dose dependent on the tested agent. Cadmium relatively showed the highest cytotoxic effects on MO3.13 cells (TC50 9.8muM) whereas mercury showed the highest cytotoxic effects on HGF (TC50 74muM) comparing with other tested metals. The two cell types responded differently. MO3.13 cells were more sensitive than the HGF to most of the metals. CONCLUSION: Metals have a wide range of toxicity to human oligodendroglial cells (MO3.13) and human gingival fibroblasts. Fortunately, however, in vivo the normal levels of these metals are much lower than those determined as toxic in vitro. [Abstract]

Guess PC, Stappert CF
Midterm results of a 5-year prospective clinical investigation of extended ceramic veneers.
Dent Mater. 2007 Nov 13;
OBJECTIVES: Midterm-evaluation of a prospective 5-year clinical study on long-term performance and success rate of pressed-ceramic veneers with two extended preparation designs. METHODS: Anterior teeth of 25 patients were restored with 66 extended veneers. Forty-two overlap veneers (OV) (incisal-edge-reduction 0.5-1.5mm, butt-joint) and 24 full veneers (FV) were inserted. Both veneer designs were similar in buccal (0.5mm) and proximal (0.5-0.7mm) chamfer preparation, but differed in palatal extension. Ceramic veneers were fabricated with IPS Empress* and adhesively luted with dual-polymerizing composite Variolink II* (*Ivoclar Vivadent). Clinical reevaluations were performed 6, 12, 25, 39, 45, and 62 months after insertion of the veneers according to the modified USPHS-criteria. Absolute failures were recorded as survival-rate, relative failures demonstrated by Kaplan-Meier success-rate. RESULTS: After an observation time up to 5 years, survival-rate of full veneers was 100%, of overlap veneers 97.5% due to one severe fracture. Kaplan-Meier-analysis of relative failures resulted in a success-rate of 85% for FV and 72% for OV. Reasons for relative failures were cracks, ceramic-cohesive-fractures, and loss-of-adhesion. No significant differences were found between the two veneer groups. Secondary caries and endodontic complications did not occur. Increased clinical service time resulted in enhanced marginal discoloration and decrease of marginal adaptation. SIGNIFICANCE: Extended pressed-ceramic veneers (both OV and FV) proved to be reliable procedures to restore larger deficits in anterior teeth. Pronounced palatal extension of full veneers was not linked to a higher failure probability. Reliable adhesive bonding, as well as ceramic fatigue and fracture resistance are considered key factors for long-term success of extended-veneer restorations. [Abstract]

Pinto MM, Cesar PF, Rosa V, Yoshimura HN
Influence of pH on slow crack growth of dental porcelains.
Dent Mater. 2007 Nov 13;
OBJECTIVES: To evaluate the effect of pH of storage medium on slow crack growth (SCG) parameters of dental porcelains. METHODS: Two porcelains were selected: with (UD) and without (VM7) leucite particles, in order to assess if the microstructure would affect the response of the material to the pH variation. Disc specimens were produced following manufacturers' instructions. Specimens were stored in artificial saliva in pHs 3.5, 7.0 or 10.0 for 10 days and after that the fatigue parameters (n: SCG susceptibility coefficient and sigma(0): scaling parameter) were obtained by the dynamic fatigue test using the same pH of storage. Microstructural analysis of the materials was also performed. RESULTS: For VM7, the values of n obtained in the different pHs were similar and varied from 29.9 to 31.2. The sigma(0) value obtained in pH 7.0 for VM7 was higher than that obtained in the other pHs, which were similar. For porcelain UD, n values obtained in pHs 7.0 and 10.0 were similar (40.8 and 39.6, respectively), and higher than that obtained in pH 3.5 (26.5). With respect to sigma(0), the value obtained for porcelain UD in pH 10.0 was lower than those obtained in pHs 3.5 and 7.0, which were similar. SIGNIFICANCE: The effect of pH on the stress corrosion susceptibility (n) depended on the porcelain studied. While the n value of VM7 was not affected by the pH, UD presented lower n value in acid pH. For both porcelains, storage in acid or basic pH resulted in strength degradation. [Abstract]

Staninec M, Kim P, Marshall GW, Ritchie RO, Marshall SJ
Fatigue of dentin-composite interfaces with four-point bend.
Dent Mater. 2007 Nov 8;
OBJECTIVES: The objective was to determine the fracture and cyclic fatigue properties of composite-dentin beams bonded with a self-etching adhesive in four-point bend. METHODS: Beams of rectangular cross-section were shaped to a size of approximately 0.87mmx0.87mmx10mm and placed in a four-point bending apparatus, with the loading points 1.8 and 7.2mm apart, with the interface centered between the inner rollers. Cyclical loading was performed in Hanks' Balanced Salt Solution at 25 degrees C, with forces between 54% and 99% of the bending strength of the bonded beams. RESULTS: Solid dentin and solid composite beams [n=6] had bending strengths of 164.4 and 164.6MPa, respectively, under monotonically increasing loads. Bonded beams [n=6] had strengths of 90.6MPa. No significant difference was found between solid composite and solid dentin beams, the bonded beams were different (ANOVA, p<0.0001) With long-term cycling, stresses below 49MPa were tolerated for 10(6) cycles, but with increasing stress up to 90MPa, beams failed earlier, demonstrating that subcritical fatigue cycling will eventually cause failure. SIGNIFICANCE: Fatigue may be a significant mechanism of dentin-composite bond degradation. [Abstract]

Cheung GS, Darvell BW
Low-cycle fatigue of rotary NiTi endodontic instruments in hypochlorite solution.
Dent Mater. 2007 Nov 7;
OBJECTIVE: To examine the low-cycle fatigue (LCF) behaviour of NiTi rotary endodontic instruments in aqueous sodium hypochlorite solution. METHODS: Four brands of NiTi rotary instrument (n=179) were subjected to a rotational-bending fatigue test at a rate of 250rpm until fracture, the instrument being immersed in 1.2% sodium hypochlorite solution. The surface strain amplitude, calculated from the curvature (from a pre-test photograph) and diameter of the fracture cross-section (from SEM photomicrograph) was plotted against the total number of revolutions to failure. An apparent fatigue-ductility exponent was determined from a regression line fitted to the LCF lives for each brand of instrument. All detached fragments were examined fractographically for crack initiation and the extent of crack extension into the cross-section. The values were compared using one-way analysis of variance (ANOVA) or chi(2), where appropriate, at alpha=0.05. RESULTS: A linear strain-life relationship was obtained for all groups; the apparent fatigue-ductility exponent was similar between various brands (ANOVA, P>0.05), but not for the number of crack origins (chi(2), P<0.05). There was an inverse, linear relationship between the square root of the extension of the fatigue-crack and the strain amplitude. SIGNIFICANCE: NiTi rotary instruments fatigued in hypochlorite shows a strain-life relationship with low-cycle and high-cycle fatigue regions. The LCF behaviour is not affected by the cross-sectional shape of the instrument. There appears to be a critical extent of crack propagation for various surface strain amplitudes leading to final, catastrophic fracture of the instrument. [Abstract]

López-Suevos F, Dickens SH
Degree of cure and fracture properties of experimental acid-resin modified composites under wet and dry conditions.
Dent Mater. 2007 Oct 31;
OBJECTIVE: Evaluate the effects of core structure and storage conditions on the mechanical properties of acid-resin modified composites and a control material by three point bending and conversion measurements 15min and 24h after curing. METHODS: The monomers pyromellitic dimethacrylate (PMDM), biphenyldicarboxylic-acid dimethacrylate (BPDM), (isopropylidene-diphenoxy)bis(phthalic-acid) dimethacrylate (IPDM), oxydiphthalic-acid dimethacrylate (ODPDM), and Bis-GMA were mixed with triethyleneglycol dimethacrylate (TEGDMA) in a 40/60 molar ratio, and photo-activated. Composite bars (Barium-oxide-glass/resin=3/1 mass ratio, (2mmx2mmx25mm), n=5) were light-cured for 1min per side. Flexural strength (FS), elastic modulus (E), and work-of-fracture (WoF) were determined in three-point bending after 15min (stored dry); and after 24h under dry and wet storage conditions at 37 degrees C. Corresponding degrees of conversion (DC) were evaluated by Fourier transform infrared spectroscopy. Data was statistically analyzed (2-way analysis of variance, ANOVA, Holm-Sidak, p<0.05). RESULTS: Post-curing significantly increased FS, E and DC in nearly all cases. WoF did not change, or even decreased with time. For all properties ANOVA found significant differences and interactions of time and material. Wet storage reduced the moduli and the other properties measured with the exception of FS and WoF of ODPDM; DC only decreased in BPDM and IPDM composites. SIGNIFICANCE: Differences in core structure resulted in significantly different physical properties of the composites studied with two phenyl rings connected by one ether linkage as in ODPDM having superior FS, WoF and DC especially after 24h under wet conditions. As expected, post-curing significantly contributed to the final mechanical properties of the composites, while wet storage generally reduced the mechanical properties. [Abstract]

Parkinson CR, Sasov A
High-resolution non-destructive 3D interrogation of dentin using X-ray nanotomography.
Dent Mater. 2007 Oct 25;
OBJECTIVES: Dentin, a calcareous material sandwiched between the pulp and the enamel in the tooth structure contains highly orientated tubules. As a result of enamel erosion, gum recession, physical trauma or caries the dentin tubules can become patent to the oral cavity. It has been demonstrated in vivo that dentinal fluid flows out of the tubule lumen into the oral cavity and it has been postulated that alterations in fluid flow form the basis of dentin hypersensitivity. In order to better understand the mode of action of desensitising occlusion-based agents the ability to interrogate dentin non-destructively is paramount. Destructive analysis of the tooth structure may yield subtle artifacts leading to erroneous conclusions or inhibit the accurate assessment of the relationship between an occluding agent and the internal dentin morphology. This paper describes the use of a novel and accessible, non-invasive, high-focused X-ray computer tomographic technique for analysis of the dentin substructure. METHODS: Dentin slices, ca. 300mum(3) in size, were taken from the coronal section of unerupted human third molars and etched in citric acid to reveal the open tubule structure. Samples were analyzed, in their dry state, using the Skyscan 2011 nanoCT system. RESULTS: Numerous, homogeneously dispersed elliptical features, distinguished by their contrast and hence low-mineral density, were observed. These features are observed to be approximately 2-5mum in diameter at a density equivalent to 10(6)cm(-2). 2D CT re-slices demonstrate that these circular features form highly orientated cylindrical manifestations extending throughout the sample. SIGNIFICANCE: Ultra-high-resolution X-ray computed tomography has been shown to be a powerful new technique for interrogating the submicron tubular structure of dentin non-destructively. [Abstract]

Nihei T, Dabanoglu A, Teranaka T, Kurata S, Ohashi K, Kondo Y, Yoshino N, Hickel R, Kunzelmann KH
Three-body-wear resistance of the experimental composites containing filler treated with hydrophobic silane coupling agents.
Dent Mater. 2007 Oct 25;
This paper evaluated the wear resistance of resin composite materials with fillers which were modified with a novel hydrophobic silane coupling agent. The novel silane coupling agent containing hydrophobic phenyl group 3-(3-methoxy-4-methacryloyloxyphenyl)propyltrimethoxysilane (p-MBS) was synthesized. The experimental light-cure hybrid composites containing 85wt% of filler modified with this silane were formulated. Twelve specimens were prepared for the three-body-wear test with the ACTA machine and the collected data were analyzed statistically using a one-way ANOVA and Tukey's multiple comparison test as the post hoc test. The wear of the composites containing fillers treated with p-MBS was significantly lower compared with the composite materials containing fillers pretreated with 3-methacryloyloxypropyltrimethoxysilane or the commercially composites (AP-X and ELS extra low shrinkage) after a wear test for 200,000 cycles (p<0.05). It is suggested that the resin composites containing fillers modified with the novel hydrophobic silane has high wear resistant, because of the coupling layers treated with this silane had an excellent affinity with the base resin and formed a highly hydrophobic layer on the filler surface. [Abstract]

Wataha JC, Lewis JB, McCloud VV, Shaw M, Omata Y, Lockwood PE, Messer RL, Hansen JM
Effect of mercury(II) on Nrf2, thioredoxin reductase-1 and thioredoxin-1 in human monocytes.
Dent Mater. 2007 Oct 22;
OBJECTIVES: Human blood levels of mercury are commonly 10nM, but may transiently reach 50-75nM after dental amalgam placement or removal. Controversy persists about the use of mercury because the effects of these 'trace' levels of mercury are not clear. Concentrations of mercury >/=5000nM unequivocally alter redox balance in blood cells including monocytes. In the current study, we tested a hypothesis that concentrations of mercury <100nM altered levels and activities of key proteins that maintain monocytic redox balance. METHODS: Human THP1 monocytes were exposed to 10-75nM of Hg(II) for 6-72h, with or without activation by lipopolysaccharide (LPS). The redox management proteins Nrf2 and thioredoxin-1 (Trx1) were separated by electrophoresis, then quantified by immunoblotting. The activity of the seleno-enzyme thioredoxin reductase (TrxR1), important in maintaining Trx1 redox balance, was measured by cell-free and cell-dependent assays. RESULTS: Concentrations of Hg(II) between 10-75nM increased Nrf2 levels (3.5-4.5 fold) and decreased Trx1 levels (2-3 fold), but these changes persisted <24h. Hg(II) potently inhibited (at concentrations of 5-50nM) TrxR1 activity in both cell-free and intracellular assays. Furthermore, Hg(II) transiently amplified LPS-induced Nrf2 levels by 2-3 fold and limited LPS-induced decreases in Trx1. All effects of Hg(II) were mitigated by pre-adding N-acetyl-cysteine (NAC) or sodium selenide (Na(2)SeO(3)), supplements of cellular thiols and selenols, respectively. SIGNIFICANCE: Our results suggest that nanomolar concentrations of Hg(II) transiently alter cellular redox balance in monocytes that trigger changes in Nrf2 and Trx1 levels. These changes indicate that monocytes have a capacity to adapt to trace concentrations of Hg(II) that are introduced into the bloodstream after dental amalgam procedures or fish consumption. The ability of monocytes to adapt suggests that low levels of mercury exposure from dental amalgam may not overtly compromise monocyte function. [Abstract]

Dehoff PH, Barrett AA, Lee RB, Anusavice KJ
Thermal compatibility of dental ceramic systems using cylindrical and spherical geometries.
Dent Mater. 2007 Oct 17;
OBJECTIVE: To test the hypothesis that bilayer ceramic cylinders and spheres can provide valid confirmation of thermal incompatibility stresses predicted by finite element analyses. METHODS: A commercial core ceramic and an experimental core ceramic were used to fabricate open-ended cylinders and core ceramic spheres. The core cylinders and spheres were veneered with one of four commercial dental ceramics representing four thermally compatible groups and four thermally incompatible groups. Axisymmetric thermal and viscoelastic elements in the ANSYS finite element program were used to calculate temperatures and stresses for each geometry and ceramic combination. This process required a transient heat transfer analysis for each combination to determine input temperatures for the structural model. RESULTS: After fabrication, each specimen was examined visually using fiberoptic transillumination for evidence of cracking. There were 100% failures of the thermally incompatible cylinders while none of the thermally compatible combinations failed. Among the spheres, 100% of the thermally incompatible systems failed, 16% of one of the thermally compatible systems failed, and none of the remaining compatible combinations failed. The calculated stress values were in general agreement with the experimental observations, i.e., low residual stresses for the specimens that did not fail and high residual stresses for the specimens that did fail. SIGNIFICANCE: Simple screening geometries can be used to identify highly incompatible ceramic combinations, but they do not identify marginally incompatible systems. [Abstract]

Nomoto R, Mishima A, Kobayashi K, McCabe JF, Darvell BW, Watts DC, Momoi Y, Hirano S
Quantitative determination of radio-opacity: Equivalence of digital and film X-ray systems.
Dent Mater. 2007 Oct 6;
OBJECTIVES: To evaluate the equivalence of a digital X-ray system (DenOptix) to conventional X-ray film in terms of the measured radio-opacity of known filled-resin materials and the suitability of attenuation coefficient for radio-opacity determination. METHODS: Discs of five thicknesses (0.5-2.5mm) and step-wedges of each of three composite materials of nominal aluminum-equivalence of 50%, 200% and 450% were used. X-ray images of a set of discs (or step-wedge), an aluminum step-wedge, and a lead block were taken at 65kV and 10mA at a focus-film distance of 400mm for 0.15s and 1.6s using an X-ray film or imaging plate. Radio-opacity was determined as equivalent aluminum thickness and attenuation coefficient. The logarithm of the individual optical density or gray scale value, corrected for background, was plotted against thickness, and the attenuation coefficient determined from the slope. The method of ISO 4049 was used for equivalent aluminum thickness. RESULTS: The equivalent aluminum thickness method is not suitable for materials of low radio-opacity, while the attenuation coefficient method could be used for all without difficulty. The digital system gave attenuation coefficients of greater precision than did film, but the use of automatic gain control (AGC) distorted the outcome unusably. CONCLUSION: Attenuation coefficient is a more precise and generally applicable approach to the determination of radio-opacity. The digital system was equivalent to film but with less noise. The use of AGC is inappropriate for such determinations. [Abstract]

Watts DC, Satterthwaite JD
Axial shrinkage-stress depends upon both C-factor and composite mass.
Dent Mater. 2007 Oct 4;
OBJECTIVES: To measure and then mathematically model polymerization stress-dependence upon systematic variations of C-factor (bonded/unbonded area ratio) for the Bioman instrument [1], recording stress by free cantilever-beam deflection; compliance 1.5mum/MPa. METHODS: A light-cured resin-composite (RZD103; Ivoclar) with 57% (v/v) 450nm filler was studied. Facing surfaces: glass slab and steel rod-end, constituting the Bioman test chamber, being perpendicular to the measured axial stress-direction, were varied: (a) with rod-diameters (varphi), from 1 to 10mm in 1mm increments (with 0.8mm gap height); and then (b) with gap heights (h) in 16 steps from 0.05 to 1.50mm (with varphi=10mm). For each h and varphi combination, giving C-factors ranging from 0.6 to 100, shrinkage-stress was recorded for 1h from start of 40s irradiation at 600mWcm(-2) for photo-polymerization at 23 degrees C (n=3). Shrinkage-stress (S(sigma)) was plotted directly as functions of h, varphi, and C and also per unit composite mass, (S(sigma)g(-1)). ANOVA and Tukey's statistics were applied. RESULTS: Series A-diameter variation; with C-factor increasing from 0.6 to 6, gave an exact exponential decrease in S(sigma) from 45 to 8MPa. Series B-height variation; with C-factor increasing from 3 to 100, gave increasing S(sigma) from 1 to 8MPa. Since composite mass played an equally dominant role, plots of stress-variations per unit composite mass, (S(sigma)g(-1)) separated these effects, confirming progressive off-axial stress-relief with increasing h. SIGNIFICANCE: (i) Values of h=0.8 and varphi=10mm, recommended [1] for Bioman use, were confirmed as appropriate. Every lab instrument for measuring S(sigma) necessarily embodies specific C-factors and compliance values in the instrument design. (ii) Configuration (C) factor is recognized as an important parameter affecting manifestation of shrinkage-stress within restorative cavities and luting gaps. However, the restorative mass must equally be considered when translating shrinkage-science into specific clinical recommendations. [Abstract]

Samuelsen JT, Holme JA, Becher R, Karlsson S, Morisbak E, Dahl JE
HEMA reduces cell proliferation and induces apoptosis in vitro.
Dent Mater. 2007 Oct 4;
OBJECTIVES: Methacrylate monomers have been identified in aqueous extracts of freshly cured compomers. Both cells in the pulpal cavity and various cells of the oral mucosa can potentially be exposed to these leachables. Short-term exposure to dental monomers at relatively high concentrations induces adverse biological effects in vitro. The mechanisms involved have not been fully elucidated although involvement of various signaling pathways including ROS formation, activation of MAP-kinases and caspases has been suggested. The aim of this study was to investigate potential cellular responses following long-term exposure to relatively low and potentially more clinical relevant HEMA concentrations. METHODS: A submandibular gland cell line was exposed to HEMA (20-600muM) for up to 72h. The impact on cell proliferation, apoptosis, and possible underlying mechanisms was assessed by flow cytometry, microscopy and western blotting. RESULTS: Exposure to HEMA (600muM) resulted in reduced cell proliferation after 24h and increased apoptosis after 60h. Further, we observed ATM dependent phosphorylation of p53, advocating an initial DNA damage in the HEMA exposed cells. SIGNIFICANCE: In conclusion, we show that exposure to relatively low concentration of HEMA for a prolonged time result in cell death, possibly as a consequence of DNA damage. [Abstract]

Beyth N, Bahir R, Matalon S, Domb AJ, Weiss EI
Streptococcus mutans biofilm changes surface-topography of resin composites.
Dent Mater. 2007 Sep 24;
OBJECTIVES: Polymerized resin composites and nonpolymerized monomers are reported to accelerate bacterial growth. Furthermore, in vivo, resin composite restorations accumulate more plaque than other restorative materials. The purpose of this study was to test the hypothesis that bacteria-composite surface interaction causes changes in surface-topography. METHODS: Resin composite disks were polymerized between two glass slides. Streptococcus mutans cells were brought in contact with and grown on the disks for 1 day, 1 week or 1 month. The disks were analyzed using atomic force microscopy. One-month-aged composite specimens were assayed for changes in micro-hardness and bacterial outgrowth. RESULTS: Atomic force microscopy analysis revealed a time-dependent increase in root mean square (RMS) roughness (p<0.0001). S. mutans outgrowth was accelerated following direct contact with the surface of aged composites, with no changes in micro-hardness. SIGNIFICANCE: Our results show that S. mutans growth on resin composite increases surface roughness without affecting micro-hardness. The change in surface integrity may further accelerate biofilm accumulation. [Abstract]

Michelsen VB, Moe G, Strřm MB, Jensen E, Lygre H
Quantitative analysis of TEGDMA and HEMA eluted into saliva from two dental composites by use of GC/MS and tailor-made internal standards.
Dent Mater. 2007 Sep 20;
OBJECTIVES: The use of resin-based dental restorative materials is rapidly increasing, concurrently the biocompatibility of the materials is under investigation. Attention has been placed on studies addressing the cytotoxic, genotoxic and estrogenic potential of these materials. Therefore, the degree of exposure to eluted compounds from the dental materials is of high interest. The aim of this study was to assess the amounts of 2-hydroxyethyl methacrylate (HEMA) and triethyleneglycol dimethacrylate (TEGDMA), released from two composites, eluting into human saliva. To improve the method of quantification, three tailor-made internal standards were synthesized. METHODS: Specimens made from two composites (Tetric EvoCeram and Filtek Z250) were polymerized and immersed in human saliva for 24h. Eluted TEGDMA and HEMA were identified and quantified. The quantitative analyses were performed by use of combined gas chromatography-mass spectrometry (GC/MS) with tailor-made internal standards synthesized by dissolving HEMA or TEGDMA in methanol and reducing the double bond of the methacrylate group by hydrogenation with (1)H(2) and (2)H(2) (D(2)) gas. RESULTS: HEMA was released from both materials, whereas TEGDMA eluted from Filtek Z250 only. Full scan GC-MS analysis of each tailor-made internal standard demonstrated one peak only, which was well separated from the corresponding analyte's peak and with no traces of HEMA or TEGDMA. SIGNIFICANCE: The quantification method seems well suited for in vivo analysis, and the three standards synthesized represent an improved tool for quantification of the eluted monomers. The synthesis may be applied to other methacrylate monomers to produce tailor-made standards for quantification. [Abstract]

Sideridou ID, Karabela MM, Vouvoudi EC
Dynamic thermomechanical properties and sorption characteristics of two commercial light cured dental resin composites.
Dent Mater. 2007 Sep 20;
OBJECTIVES: The first objective of this work is the study by DMTA of viscoelastic properties (E', E'', tandelta, T(g)) of two current dental resin composites Tetric EvoCeram (nanohybrid) and Heliomolar (microfilled) in dry condition and in water for up to 30 days. The second objective is to determine the sorption characteristics of these composites in water and ethanol/water solution 75vol.%. METHODS: For DMTA the bar-shaped specimens divided into five groups of three samples each. The first group consisted of dry samples measured 1h after curing. The second and third group consisted of samples, which had been heated in air at 80+/-1 degrees C for 1 day or had been stored in distilled water at 80+/-1 degrees C for 1 day. The fourth and fifth group consisted of samples, which had been stored in distilled water at 37+/-1 degrees C for periods 1 and 7 days correspondingly. Also specimen discs (15mm in diameter and 1mm in thickness) were immersed in water or a 75vol.% ethanol/water solution at 37+/-1 degrees C. At fixed time intervals they were removed, blotted dry to remove excess liquid, weighted and returned to the liquid. This process continued for 30 days. RESULTS: The viscoelastic properties (E', E'', tandelta, T(g)) of the two composites treated under different conditions were recorded and compared. Also the mass uptake, diffusion coefficient, solubility and volumetric changes for immersion of composites in water and ethanol/water solution 75vol.% at 37+/-1 degrees C were determined. SIGNIFICANCE: Tetric EvoCeram a nanohybrid composite with similar about resin matrix with Heliomolar which is a microfilled showed better dynamic thermomechanical properties and sorption characteristics than Heliomolar. [Abstract]

Vuorinen AM, Dyer SR, Lassila LV, Vallittu PK
Effect of rigid rod polymer filler on mechanical properties of poly-methyl methacrylate denture base material.
Dent Mater. 2007 Sep 19;
OBJECTIVES: The aim of this study was to evaluate the mechanical properties of denture base material with rigid rod polymer (RRP) particulate fillers. METHODS: Specimens were fabricated from autopolymerized polymethylmethacrylate denture base resin (Palapress Heraus-Kulzer) and RRP particles were used as fillers (Parmax Mississippi Polymer Technologies, Inc.). Five groups were tested: 0wt% RRP, 10wt% RRP, 20wt% RRP, 30wt% RRP, and 100wt% RRP. Specimens were stored dry at room temperature for 2 days or in water at 37 degrees C for 44 days before testing until failure at a three point bending test (ISO 1567) for measuring flexural properties. The surface microhardness, water sorption, and solubility were also measured. Existence of interpenetrating polymer network (IPN) between filler and denture resin was examined using solvent treatment and scanning electron microscopy (SEM). RESULTS: Specimens with RRP filler revealed higher flexural modulus, but the flexural strength decreased. Specimens with 30% RRP filler showed flexural strength of 67.4MPa, whereas specimens without fillers gave strength of 93.9MPa. The 100% RRP group revealed the highest flexural strength (305MPa). Flexural strength of water-stored test specimens decreased in most groups when compared to dry specimens. Microhardness increased as a function of RRP filler. SEM micrographs revealed no IPN-network on the surface of RRP fillers. Addition of RRP fillers decreased the water sorption, whereas solubility was not affected. SIGNIFICANCE: This study revealed that although RRP polymer has good mechanical properties, addition of RRP to denture base resin as fillers did not increase mechanical properties. This was explained by lack of IPN-formation between RRP fillers and polymer matrix. [Abstract]

Star?uková J, Star?uk Z, Hubálková H, Linetskiy I
Magnetic susceptibility and electrical conductivity of metallic dental materials and their impact on MR imaging artifacts.
Dent Mater. 2007 Sep 18;
OBJECTIVES: The aim of this study was to test the hypothesis that dental materials vary significantly in MR-relevant material parameters-magnetic susceptibility and electrical conductivity, and that knowledge of these parameters may be used to estimate the quality of MR imaging in the presence of devices made of such materials. METHODS: Magnetic susceptibility, electrical conductivity and artifacts were evaluated for 45 standardized cylindrical samples of dental alloys and amalgams. Magnetic susceptibility was determined by fitting the phase of gradient-echo MR images to numerically modeled data. Electrical conductivity was determined by standard electrotechnical measurements. Artifact sizes were measured in spin-echo (SE) and gradient-echo (GE) images at 1.5T according to the standards of the American Society for Testing and Materials. RESULTS: It has been confirmed that dental materials differ considerably in their magnetic susceptibility, electrical conductivity and artifacts. For typical dental devices, magnetic susceptibility differences were found of little clinical importance for diagnostic SE/GE imaging of the neck and brain, but significant for orofacial imaging. Short-TE GE imaging has been found possible even in very close distances from dental devices made of amalgams, precious alloys and titanium alloys. Nickel-chromium and cobalt-chromium artifacts were found still acceptable, but large restorations of aluminum bronzes may preclude imaging of the orofacial region. The influence of electrical conductivity on the artifact size was found negligible. SIGNIFICANCE: MR imaging is possible even close to dental devices if they are made of dental materials with low magnetic susceptibility. Not all materials in current use meet this requirement. [Abstract]

Taskonak B, Griggs JA, Mecholsky JJ, Yan JH
Analysis of subcritical crack growth in dental ceramics using fracture mechanics and fractography.
Dent Mater. 2007 Sep 8;
OBJECTIVES: The aim of this study was to test the hypothesis that the flexural strengths and critical flaw sizes of dental ceramic specimens will be affected by the testing environment and stressing rate even though their fracture toughness values will remain the same. METHODS: Ceramic specimens were prepared from an aluminous porcelain (Vitadur Alpha; VITA Zahnfabrik, Bad Säckingen, Germany) and an alumina-zirconia-glass composite (In-Ceram((R)) Zirconia; VITA Zahnfabrik). Three hundred uniaxial flexure specimens (150 of each material) were fabricated to dimensions of 25mmx4mmx1.2mm according to the ISO 6872 standard. Each group of 30 specimens was fractured in water using one of four different target stressing rates ranging on a logarithmic scale from 0.1 to 100MPa/s for Vitadur Alpha and from 0.01 to 10MPa/s for In-Ceram((R)) Zirconia. The fifth group was tested in inert environment (oil) with a target stressing rate of 100MPa/s for Vitadur Alpha and 1000MPa/s for In-Ceram((R)) Zirconia. The effects of stressing rate and environment on flexural strength, critical flaw size, and fracture toughness were analyzed statistically by Kruskal-Wallis one-way ANOVA on ranks followed by post hoc comparisons using Dunn's test (alpha=0.05). In addition, 20 Vitadur Alpha specimens were fabricated with controlled flaws to simplify fractography. Half of these specimens were fracture tested in water and half in oil at a target stressing rate of 100MPa/s, and the results were compared using Mann-Whitney rank sum tests (alpha=0.05). A logarithmic regression model was used to determine the fatigue parameters for each material. RESULTS: For each ceramic composition, specimens tested in oil had significantly higher strength (P</=0.05) and smaller critical flaw size (significant for Vitadur Alpha, P</=0.05) than those tested in water but did not have significantly different fracture toughness (P>0.05). Specimens tested at faster stressing rates had significantly higher strength (P</=0.05) but did not have significantly different fracture toughness (P>0.05). Regarding critical flaw size, stressing rate had a significant effect for In-Ceram((R)) Zirconia specimens (P</=0.05) but not for Vitadur Alpha specimens (P>0.05). Fatigue parameters, n and lnB, were 38.4 and -12.7 for Vitadur Alpha and were 13.1 and 10.4 for In-Ceram((R)) Zirconia. SIGNIFICANCE: Moisture assisted subcritical crack growth had a more deleterious effect on In-Ceram((R)) Zirconia core ceramic than on Vitadur Alpha porcelain. Fracture surface analysis identified fracture surface features that can potentially mislead investigators into misidentifying the critical flaw. [Abstract]

Mesquita RV, Geis-Gerstorfer J
Influence of temperature on the visco-elastic properties of direct and indirect dental composite resins.
Dent Mater. 2007 Sep 7;
OBJECTIVES: The first aim of this study was to determine the visco-elastic properties of two direct (DiamondLite and Grandio) and two indirect (Artglass and Vita Zeta LC) dental composites over a wide range of temperatures, in order to avoid choosing a composite that would undergo sudden changes in its mechanical properties during service. METHODS: Within this objective the composites were tested immediately after fabrication or after storage at 37 degrees C, either in air or distilled water for 1 day, 7 or 90 days. During dynamic testing, the elastic modulus (E'), viscous modulus (E'') and loss tangent (tandelta) were determined using a dynamic mechanical analyzer (DMA) over a temperature range from 0 to 200 degrees C, at an approximate masticatory frequency of 1Hz. RESULTS: Based on their high glass transition temperatures (T(g)) and on the fact that materials are basically equilibrated at 37 degrees C in the mouth and are not thermal conductors, temperature changes from 37 degrees C are expected to be small and should lead to only modest changes in both moduli. However, composites might improve their initial degree of conversion when exposed to normal mouth temperature and higher temperatures due to the ingestion of hot food and beverages. This event can have positive and negative effects on the restoration, such as greater rigidity and additional micro-leakage, respectively. SIGNIFICANCE: According to these results it could be said that monitoring the visco-elastic properties of dental composites under conditions that simulate the oral environment seems to be a useful tool to predict their clinical performance as restorative materials. [Abstract]

Vichi A, Fraioli A, Davidson CL, Ferrari M
Influence of thickness on color in multi-layering technique.
Dent Mater. 2007 Dec;23(12):
OBJECTIVES: The aim of the study was to evaluate the influence of layer thickness on the final color for different shade and opacity composite combinations in a laboratory set-up simulating a 2-layer stratification technique. METHODS: Resin disks of different thicknesses were made. From one composite system (Point4, Kerr Co.), four dentin shades were selected (A1, A2, A3, A4). For each shade, disks were produced of 0.5-3.0mm thickness, with increasing thickness steps of 0.5mm. Moreover, from the three translucent shades of the same system (T1, T2, T3) disks were made of 0.5-2.0mm thickness, again with increasing thickness steps of 0.5mm. For all 288 combinations of base+translucent material color was determined with a spectrophotometer. RESULTS: For a mounting layer thickness from 0.5 to 3.0mm of the base material, differences till to DeltaE=5.1 were recorded. These differences increased when the layer thickness of the translucent material decreased. The translucent shade also influence the final aspect of the samples, whereas each translucent shade acted differently dependent on their shade and their thickness. Their layer thickness played a significant role in color perception. SIGNIFICANCE: Layer thickness and the proportion of thicknesses of the dentin and translucent shade greatly influence the final aspect of a multi-layer composite restoration. Good understanding of the optical behavior of each composite system is essential in order to obtain high quality in aesthetic dentistry. [Abstract]

Jia H, Hou W, Wei L, Xu B, Liu X
The structures and antibacterial properties of nano-SiO(2) supported silver/zinc-silver materials.
Dent Mater. 2007 Sep 4;
OBJECTIVES: The aims of this study were to investigate the structures and antibacterial properties of two kinds of sterilizing nano-SiO(2) specimens. METHODS: The specimens were synthesized by adsorption methodology. One of them was synthesized by adsorbing silver cation onto nano-SiO(2) carrier (silver-loading nano-SiO(2) specimen (SLS)), and the other one by co-adsorbing zinc and silver cations onto the same kind of carrier (zinc-silver-loading nano-SiO(2) specimen (SLZS)). Chemical compositions of these specimens were estimated. The structure and morphology of the specimens were determined by X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Also, the antibacterial properties of the specimens were examined. RESULTS: The amount of silver loaded in SLZS was approximate to that of SLS. Consequently, it can be proved that the amount of nano-SiO(2) adsorbed silver cation did not change with the addition of zinc cation. The obvious differences were not observed among the XRD patterns for each specimen. So it was possible to confirm no formation of new phase(s) after Ag(+)/Zn(2+) absorption. The loaded silver and zinc existed as nano-particles, as observed by HRTEM. Antibacterial properties of SLS and SLZS were excellent against Escherichia coli and S. faecalis. The antibacterial effect of the same antibacterial agent against E. coli or S. faecalis was different. In addition, the antibacterial effect of SLZS was better than that of SLS. SIGNIFICANCE: These results suggested SLS and SLZS can be effectively incorporated in dental resin-based materials to provide antibacterial activity against bacteria. [Abstract]

Schroeder WF, Cook WD, Vallo CI
Photopolymerization of N,N-dimethylaminobenzyl alcohol as amine co-initiator for light-cured dental resins.
Dent Mater. 2007 Sep 3;
OBJECTIVE: The present study was carried out in order to assess the suitability of N,N-dimethylaminobenzyl alcohol (DMOH) as co-initiator of camphorquinone (CQ) and 1-phenyl-1,2-propanedione (PPD) in light-cured dental resins. METHODS: DMOH was synthesized and used as co-initiator for the photopolymerization of a model resin based on {2,2-bis[4-(2-hydroxy-3-methacryloxyprop-1-oxy)phenyl]propane} (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA). Experimental formulations containing CQ or PPD in combination with DMOH at different concentrations were studied. The photopolymerization was carried out by means of a commercial light-emitting diode (LED) curing unit. The evolution of double bonds consumption versus irradiation time was followed by near-infrared spectroscopy (NIR). The photon absorption efficiency (PAE) of the photopolymerization process was calculated from the spectral distribution of the LED unit and the molar absorption coefficient distributions of PPD and CQ. RESULTS: DMOH is an efficient photoreducer of CQ and PPD resulting in higher polymerization rate and higher double bond conversion compared with dimethylaminoethylmethacrylate. The PAE for PPD was higher than that for CQ. However, the polymerization initiated by PPD progressed at a lower rate and exhibited lower values of final conversion compared with the resins containing CQ. This observation indicates that the lower polymerization rate of the PPD/amine system should be explained in terms of the mechanism of generating primary radicals by PPD, which is less efficient compared with CQ. SIGNIFICANCE: The DMOH/benzoyl peroxide redox system, has recently been proposed as a more biocompatible accelerator for the polymerization of bone cements based on poly(methyl methacrylate), because cytotoxity tests have demonstrated that DMOH possesses better biocompatibility properties compared with traditional tertiary amines. The results obtained in the present study reveal the suitability of the CQ/DMOH initiator system for the polymerization of light-cured dental composites. [Abstract]


Recent Articles in Oral Oncology

Vairaktaris E, Spyridonidou S, Papakosta V, Vylliotis A, Lazaris A, Perrea D, Yapijakis C, Patsouris E
The hamster model of sequential oral oncogenesis.
Oral Oncol. 2007 Nov 29; .
Oral squamous cell carcinoma (OSCC) is a common cancer characterised by low survival rate and poor prognosis. The multistep process of oral carcinogenesis is affected by multiple genetic events such as alterations of oncogenes and tumour suppressor genes. The use of appropriate experimental animal models that accurately represent the cellular and molecular changes which are associated with the initiation and progression of human oral cancer is of crucial importance. The Syrian golden hamster cheek pouch oral carcinogenesis model is the best known animal system that closely correlates events involved in the development of premalignant and malignant human oral cancers. Therefore, we established an experimental system of chemically induced oral carcinogenesis in hamsters, in order to study different stages of tumour formation: normal mucosa, hyperkeratosis, hyperplasia, dysplasia, early invasion, well differentiated OSCC and moderately differentiated OSCC. We investigated the expression of oncogenes EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun, apoptosis markers Bax and Bcl-2, tumour suppressor genes p53 and p16, and cell proliferation marker Ki-67 in the sequential stages of hamster oral oncogenesis. Here, we describe the findings of the experimental model in regard to the involvement of signal transduction pathways in every stage of cancer development. Increased apoptosis and cell proliferation were observed in early stages of oral oncogenesis. Furthermore, the increased expression of transmembrane receptors (EGFR, erbB2, FGFR-2 and FGFR-3) as well as the increased expression of nuclear transcriptional factors in early stages of oral cancer indicates that these molecules may be used as early prognostic factors for the progression of OSCC. Since the expression of both H-ras and N-ras do not seem to affect signal transduction during oral oncogenesis, it can be assumed that a different signalling pathway, such as the PI3K and/or PLCgamma pathway, may be implicated in the pathogenesis of OSCC. [Abstract]

Pimenta FJ, Cordeiro GT, Pimenta LG, Viana MB, Lopes J, Gomez MV, Aldaz CM, De Marco L, Gomez RS
Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias.
Oral Oncol. 2007 Nov 29;
Oral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3-24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis. [Abstract]

Acay RR, Santos ED, Machado de Sousa SO
Correlation between c-Jun and human papillomavirus in oral premalignant and malignant lesions.
Oral Oncol. 2007 Nov 29;
c-Jun, one of the components of the transcription factor activating protein-1 (AP-1), is suggested as a factor in malignant progression of oral lesions. c-Jun and other AP-1 components relationships with human papillomavirus (HPV) infection have been investigated, but not yet focusing on oral carcinogenesis. The aim of this study was to verify whether c-Jun immunohistochemical expression is related to HPV DNA detection in oral premalignant and malignant lesions. Fifty cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas (OSCC) were submitted to immunohistochemistry to detect c-Jun and to in situ hybridization with signal amplification to assess HPV DNA. It was verified that c-Jun nuclear expression increased according to the degree of dysplasia within the lesion, with the greatest expression in OSCC. The same did not happen concerning HPV infection - a discrete proportional relation was observed in indexes found in leukoplakia with no dysplasia, leukoplakia with dysplasia and OSCC, but statistically insignificant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. Nevertheless, the overall prevalence of HPV infection was 24% and the high-risk HPV types were the most frequently identified, which does not allow excluding HPV as a risk factor in oral carcinogenesis. When relating c-Jun expression and HPV infection, no statistically significant relationship is observed. Results suggest then that malignant progression mediated by c-Jun is independent of the presence of HPV in oral carcinogenesis. [Abstract]

Lu JJ, Kong L, Shakespeare TP, Loh KS, Zhang Q, Luke Tan KS, Lee KM
Prospective phase II trial of concomitant boost radiotherapy for stage II nasopharyngeal carcinoma.
Oral Oncol. 2007 Nov 29;
Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in suboptimal outcome. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C-Boost) schedule. Forty-seven 1997 AJCC Stage II NPC patients were enrolled and analyzed in this prospective phase II clinical trial. The primary tumor and clinically involved nodes received a total dose of 72Gy in 42 fractions. C-Boost for gross disease consisted of 18Gy in 12 fractions commencing on day 19, and delivered at least 6h after the first dose. Patients were assessed for response, survival and toxicity. With a median follow-up of 30months, 4 patients developed local recurrence only, 2 had persistent neck nodal disease or recurrence, and 1 with both locoregional recurrences. Distant metastases were seen in 5 patients, with or without locoregional recurrence. A total of 5 patients succumbed from nasopharyngeal cancer: four from effects of distant metastases and 1 from progressive local disease. The 3-year local, regional, and overall survival rates were 87.1%, 92%, and 85.9%, respectively. All patients experienced some degree of acute and/or late toxicity. Moderate to severe late toxicities (grade 3 and 4) were observed in 17% of cases. This C-Boost radiotherapy regimen administers a higher biologically effective dose compared with conventional radiation schedules. The local control after C-Boost radiation seems high for patients with stage II nasopharyngeal carcinoma, thus justifies further investigation to confirm its efficacy. [Abstract]

Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R
Metastatic tumours to the oral cavity - Pathogenesis and analysis of 673 cases.
Oral Oncol. 2007 Nov 29;
The oral region is an uncommon site for metastatic tumour cell colonization and is usually evidence of a wide spread disease. In 25% of cases, oral metastases were found to be the first sign of the metastatic spread and in 23% it was the first indication of an undiscovered malignancy at a distant site. The jawbones, particularly the mandible, were more frequently affected than the oral soft tissues (2:1). In the oral soft tissues, the attached gingiva was the most commonly affected site (54%). The major primary sites presenting oral metastases were the lung, kidney, liver, and prostate for men, breast, female genital organs (FGO), kidney, and colo-rectum for women. The primary site differs according to oral site colonization, in men the lung was the most common primary site affecting both the jawbones and oral mucosa (22% and 31.3%, respectively) followed by the prostate gland in the jawbones (11%) and kidney in the oral soft tissues (14%). In women, the breast was the most common primary tumour affecting the jawbones and soft tissues (41% and 24.3%, respectively), followed by the adrenal and female genital organs (FGO) in the jawbones (7.7%) and FGO in the soft tissues (14.8%). The clinical presentation of the metastatic lesions differ between the various sites in the oral region. In the jawbones most patients complain of swelling, pain and paresthesia which developed in a relative short period. Early manifestation of the gingival metastases resembled a hyperplastic or reactive lesion, such as pyogenic granuloma, peripheral giant cell granuloma, or fibrous epulis. Because of its rarity, the diagnosis of a metastatic lesion in the oral region is challenging, both to the clinician and to the pathologist, in recognizing that a lesion is metastatic and in determining the site of origin. The clinical presentation of a metastatic lesion in the oral cavity can be deceiving leading to a misdiagnosis of a benign process, therefor, in any case where the clinical presentation is unusual especially in patients with a known malignant disease a biopsy is mandatory. [Abstract]

Sathyan KM, Nalinakumari KR, Abraham T, Kannan S
CCND1 polymorphisms (A870G and C1722G) modulate its protein expression and survival in oral carcinoma.
Oral Oncol. 2007 Nov 29;
Cyclin D1 is an essential regulator of the G1 phase of the cell cycle progression and plays an important role in the transition of the cell from the G1 phase to the S phase of the cell cycle. Overexpression of cyclin D1 is a frequently observed feature of human cancers of diverse histological origin. Recently, we have reported overexpression of cyclin D1 in oral carcinoma. However, the underlying mechanism leading to this aberrant expression remains poorly understood. In this study, we have investigated the role of CCND1 A870G and C1722G polymorphisms on cyclin D1 expression and prognosis in a relatively homogenous population of 178 oral squamous cell carcinoma patients by PCR-SSCP, RFLP, RT-PCR and immunohistochemical methods. Genotype frequencies of both the polymorphisms were conformed to Hardy-Weinberg equilibrium. CCND1 A870G (p=0.004) and C1722G (p=0.012) polymorphisms were significantly associated with cyclin D1 expression. Kaplan-Meier estimates revealed that CCND1 genotypes A870G 'GG' (p=0.012) and C1722G 'CC' (p=0.021) could predict the poor survival of the patients. In multivariate analysis, CCND1 A870G genotype combination (p=0.024, HR - 1.74 (1.08-2.81)) and cyclin D1 expression (p=0.025, HR - 1.72 (1.07-2.77)) were independent predictors of survival in this patient cohort. Our results thus demonstrate, CCND1 polymorphisms stand-in as cis-acting regulatory elements modulating its expression and cyclin D1 genotype and phenotype could provide valuable additional information regarding prognosis of oral cancer patients. [Abstract]

Tsai TC, Yu CH, Cheng SJ, Liu BY, Chen HM, Chiang CP
Expression of RCAS1 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan.
Oral Oncol. 2007 Nov 29;
This study used an immunohistochemical technique to examine the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in 84 specimens of oral squamous cell carcinoma (OSCC), 106 specimens of oral epithelial dysplasia (OED, 32 mild, 44 moderate, and 30 severe OED cases), and 20 specimens of normal oral mucosa (NOM). We found that the mean RCAS1 labeling indices (LIs) increased significantly from NOM (12+/-5%) through mild OED (31+/-13%), moderate OED (44+/-17%), and severe OED (56+/-18%) to OSCC samples (68+/-20%, p<0.001). A significant correlation was found between the higher mean RCAS1 LI and OSCCs with larger tumor size (p=0.001), positive lymph node metastasis (p<0.001), or more advanced clinical stages (p<0.001). Positive lymph node metastasis (p=0.0073) and RCAS1 LI>==60% (p=0.048) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a RCAS1 LI>==60% had a significantly poorer cumulative survival than those with a RCAS1 LI<60% (log-rank test, p=0.0113). We conclude that the expression of RCAS1 is an early event in oral carcinogenesis. The RCAS1 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients. [Abstract]

Fendri A, Khabir A, Hadhri-Guiga B, Sellami-Boudawara T, Ghorbel A, Daoud J, Frikha M, Jlidi R, Gargouri A, Mokdad-Gargouri R
Overexpression of COX-2 and LMP1 are correlated with lymph node in Tunisian NPC patients.
Oral Oncol. 2007 Nov 29;
Cyclooxygenase 2 (COX-2) an inducible form of COX is frequently up-regulated in many human tumours. The expression of COX-2 in nasopharyngeal carcinoma (NPC) and its relationship to clinicopathological features were studied in Tunisian patients. COX-2 mRNA was detected in 91% of tumour tissues. Immunohistochemical analysis showed that COX-2 protein was strongly detected in tumour cells and the staining was mainly cytoplasmic. In contrast, COX-2 mRNA and protein were very low or undetectable in normal nasopharyngeal mucosa. Our result showed a significant association of COX-2 overexpression with the lymph node involvement, however, no correlation was observed with age, tumour stage, histological type and distant metastasis. Moreover, we showed that all tumour specimens co-overexpressed COX-2 and the EBV oncoprotein LMP1 corroborating the fact that LPM1 is known to induce COX-2. Altogether, our data suggests that the COX-2 is overexpressed in NPC biopsies and that is linked to the lymph node involvement. [Abstract]

Haddad R, Crum C, Chen Z, Krane J, Posner M, Li Y, Burk R
HPV16 transmission between a couple with HPV-related head and neck cancer.
Oral Oncol. 2007 Nov 29;
Although squamous cell carcinoma of the head and neck (SCCHN) is closely linked to tobacco and alcohol use, there is an increasing incidence HPV16-related SCCHN arising in the oropharynx. The mechanisms of viral transmission, carcinogenesis and natural history are not well understood. Here, we report a couple-husband and wife diagnosed synchronously with squamous cell carcinoma of the head and neck wherein the tumors were positive for HPV16 by PCR diagnosis. Both viral genomes were genetically identical and closely related to the revised European prototype, HPV16R. An uncommon signal variant nucleotide was identified in both genomes that is not present in the HPV16R. These tumors likely represent transmission between the couple. [Abstract]

Zimmermann BG, Wong DT
Salivary mRNA targets for cancer diagnostics.
Oral Oncol. 2007 Nov 29;
Head and neck squamous cell carcinoma (HNSCC) affects almost 1 million people worldwide per year. Despite therapeutic advances the overall survival rate remains low because diagnosis often occurs only at advanced stages with poor prognosis. Like in most cancers, the implementation of an early detection scheme would have a positive impact on this disease. Similarly, as oral cancer has a very high recurrence rate, the early identification of recurrence or second primary tumors is an important challenge. HNSCC detection is currently based on expert clinical examination of the upper aerodigestive tract and histologic analysis of suspicious areas, but it may be undetectable in hidden sites, and unfortunately visual screening for oral lesions is an often neglected part of dental healthcare. Our group is actively pursuing the assembly of a toolbox for the molecular analysis of oral fluid. Here we present our current status utilizing the salivary transcriptome for oral cancer diagnostics. [Abstract]

Laaksonen M, Suojanen J, Nurmenniemi S, Läärä E, Sorsa T, Salo T
The enamel matrix derivative (Emdogain((R))) enhances human tongue carcinoma cells gelatinase production, migration and metastasis formation.
Oral Oncol. 2007 Nov 29;
Enamel matrix derivative Emdogain((R)) (EMD) is widely used in periodontal treatment to regenerate lost connective tissue and to improve the attachment of the teeth. Gelatinases (MMP-2 and -9) have an essential role in the promotion and progression of oral cancer growth and metastasis formation. We studied the effects of EMD on human tongue squamous cell carcinoma (HSC-3) cells in vitro and in vivo. In vitro, EMD (100mug/ml and 200mug/ml) remarkably induced the MMP-2 and -9 production from HSC-3 cells analysed by zymography and enzyme-linked immunosorbent assay. EMD also slightly induced the MMP-2 and -9 production from benign human mucosal keratinocytes (HMK). Furthermore, EMD clearly induced the transmigration of HSC-3 cells but had no effect on the HMK migration in transwell assays. The in vitro wound closure of HSC-3 cells was notably accelerated by EMD, whereas it had only minor effect on the wound closure of HMKs. The migration of both cell lines was inhibited by a selective cyclic anti-gelatinolytic peptide CTT-2. EMD had no effect on HSC-3 cell proliferation or apoptosis and only a limited effect on cell attachment to various extracellular matrix components. The in vivo mice experiment revealed that EMD substantially induced HSC-3 xenograft metastasis formation. Our results suggest that the use of EMD for patients with oral mucosal carcinomas or premalignant lesions should be carefully considered, possibly avoided. [Abstract]

van der Waal I, Reichart PA
Oral proliferative verrucous leukoplakia revisited.
Oral Oncol. 2007 Nov 29; [Abstract]

Ponzanelli A, Vigo V, Marcenaro M, Bacigalupo A, Gatteschi B, Ravetti JL, Corvň R, Benasso M
Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: Optimal compliance and promising 4-year results.
Oral Oncol. 2007 Nov 29;
Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90mg/m(2), day 1 and cisplatin, 40mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial. [Abstract]

Agulnik M, Epstein JB
Nasopharyngeal carcinoma: Current management, future directions and dental implications.
Oral Oncol. 2007 Nov 29;
Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck. Approximately 70% of patients with NPC present with locally advanced disease. Phase III clinical trials support combined chemotherapy and radiotherapy for the initial treatment of these patients. Current treatment approaches for metastatic disease are variable. Oral complications of therapy for NPC are very common. In order to support cancer therapy the dental provider must be aware of the diagnosis, prognosis and approach to treatment. Dental care requires that radiation fields be understood as well as the permanent changes that occur with high dose radiation therapy. Radiation causes changes in bone and soft tissue that may result in acute and chronic oral complications. The most common acute complications are mucositis, infection, xerostomia and taste changes. Mucositis is of increased severity and duration when chemotherapy is combined with radiation therapy. Chronic complications are due to late effects of radiation therapy including hyposalivation, infection, taste change, dysphagia and trismus. Treatment innovations with molecularly targeted therapies and immunotherapy are being assessed to improve treatment outcomes in NPC and will impact oral complications and oral care. [Abstract]

Chambers MS, Fleming TJ, Toth BB, Lemon JC, Craven TE, Bouwsma OJ, Garden AS, Espeland MA, Keene HJ, Martin JW, Sipos T
Erratum to "Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 2: Phase I study".
Oral Oncol. 2007 Jan;43(1):
Radiation-induced xerostomia can result in the rapid onset and progression of dental caries in head and neck cancer patients. Topically applied fluorides have been successfully used to inhibit the formation of dental caries in this population. However, because intensive daily self-application is required, compliance is an issue. The intraoral fluoride-releasing system (IFRS) containing a sodium fluoride core is a newly developed, sustained-release, passive drug delivery system that does not require patient involvement except for periodic replacement, thus reducing the effect of patient compliance on its effectiveness in dental caries prevention. Twenty-two head and neck cancer patients from U. T. M. D. Anderson Cancer Center, with radiation-induced xerostomia, were entered into a pilot study to contrast the daily home use of a 0.4% stannous fluoride-gel-containing tray (control group) to IFRS (study group) with respect to tolerability and adherence, and to obtain information on relative caries preventive efficacy. Participants were stratified on the basis of radiation exposure and randomly assigned to treatment with either IFRS or stannous fluoride gel. Patients in both groups were fitted with two IFRS retainers and also were instructed to use a 1100-ppm fluoride conventional sodium fluoride dentifrice twice daily. The study was conducted as a single-blinded, parallel-cell trial. Pre-existing carious lesions were restored prior to the beginning of the study. The efficacy variable was determined by the mean number of new or recurrent decayed surfaces. Patients were examined for caries 4, 8, 12, 24, 36, and 48 weeks after initiation of treatment. Reports of adverse reactions were based on information volunteered by patients and that were elicited during interviews. At baseline, the resting and stimulated salivary flow rates (g/5min) were significantly greater in the control group than in the study group (p<0.05). Patients in the control group had received significantly more radiation than those in the test group (68Gy vs. 60Gy; p=0.047). No marked differences in follow-up new and recurrent caries were found between the stannous fluoride gel control and IFRS groups during the study period. The rate of new or recurrent carious lesions in the group treated with the fluoride gel was slightly lower than in the IFRS group, based on carious lesions at the baseline examination (Poisson mean number of new or recurrent carious lesions for the control group=0.55 per year vs. 0.83 per year for the study group, p=0.705; odds ratio of the occurrence of any new or recurrent caries during follow-up for control group vs. the study group=0.80; p=0.781). This pilot study revealed that the IFRS was well-tolerated and safe in this study population associated with minimal complications during the duration of this study and was comparable in efficacy to a SnF(2) gel in preventing caries development. The IFRS provided similar rates of control for caries formation to a fluoride-gel-containing tray. The IFRS is designed to release a daily dose of 0.12mg of sodium fluoride, which can be evenly distributed throughout the oral cavity for a single application of 4 months. It would be more convenient than the daily home application of a tray of 0.4% stannous fluoride or 1.1% sodium fluoride gel, and avoids the problem of variable patient compliance. [Abstract]

Chambers MS, Mellberg JR, Keene HJ, Bouwsma OJ, Garden AS, Sipos T, Fleming TJ
Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 2: Phase I study.
Oral Oncol. 2006 Oct;42(9):
Radiation-induced xerostomia can result in the rapid onset and progression of dental caries in head and neck cancer patients. Topically applied fluorides have been successfully used to inhibit the formation of dental caries in this population. However, because intensive daily self-application is required, compliance is an issue. The intraoral fluoride-releasing system (IFRS) containing a sodium fluoride core is a newly developed, sustained-release, passive drug delivery system that does not require patient involvement except for periodic replacement, thus reducing the effect of patient compliance on its effectiveness in dental caries prevention. Twenty-two head and neck cancer patients from U. T. M. D. Anderson Cancer Center, with radiation-induced xerostomia, were entered into a pilot study to contrast the daily home use of a 0.4% stannous fluoride-gel-containing tray (control group) to IFRS (study group) with respect to tolerability and adherence, and to obtain information on relative caries preventive efficacy. Participants were stratified on the basis of radiation exposure and randomly assigned to treatment with either IFRS or stannous fluoride gel. Patients in both groups were fitted with two IFRS retainers and also were instructed to use a 1100-ppm fluoride conventional sodium fluoride dentifrice twice daily. The study was conducted as a single-blinded, parallel-cell trial. Pre-existing carious lesions were restored prior to the beginning of the study. The efficacy variable was determined by the mean number of new or recurrent decayed surfaces. Patients were examined for caries 4, 8, 12, 24, 36, and 48 weeks after initiation of treatment. Reports of adverse reactions were based on information volunteered by patients and that were elicited during interviews. At baseline, the resting and stimulated salivary flow rates (g/5min) were significantly greater in the control group than in the study group (p<0.05). Patients in the control group had received significantly more radiation than those in the test group (68Gy vs. 60Gy; p=0.047). No marked differences in follow-up new and recurrent caries were found between the stannous fluoride gel control and IFRS groups during the study period. The rate of new or recurrent carious lesions in the group treated with the fluoride gel was slightly lower than in the IFRS group, based on carious lesions at the baseline examination (Poisson mean number of new or recurrent carious lesions for the control group=0.55 per year vs. 0.83 per year for the study group, p=0.705; odds ratio of the occurrence of any new or recurrent caries during follow-up for control group vs. the study group=0.80; p=0.781). This pilot study revealed that the IFRS was well-tolerated and safe in this study population associated with minimal complications during the duration of this study and was comparable in efficacy to a SnF(2) gel in preventing caries development. The IFRS provided similar rates of control for caries formation to a fluoride-gel-containing tray. The IFRS is designed to release a daily dose of 0.12mg of sodium fluoride, which can be evenly distributed throughout the oral cavity for a single application of 4 months. It would be more convenient than the daily home application of a tray of 0.4% stannous fluoride or 1.1% sodium fluoride gel, and avoids the problem of variable patient compliance. [Abstract]

Kassouf N, Thornhill MH
Oral cancer cell lines can use multiple ligands, including Fas-L, TRAIL and TNF-alpha, to induce apoptosis in Jurkat T cells: Possible mechanisms for immune escape by head and neck cancers.
Oral Oncol. 2007 Nov 7;
Some cancer cells can induce apoptosis in tumour infiltrating cytotoxic T cells as a means of escaping immune destruction. This study examined the expression of the apoptosis-inducing ligands, Fas-L, TRAIL and TNF-alpha, on three representative oral squamous cell carcinoma (OSCC) cell lines, TR146, SCC25 and CAL27 and investigates the contribution of these ligands to tumour cell killing of Jurkat T cells in vitro. All three cell lines were able to induce apoptosis in Jurkat T cells to varying degrees. The TR146 cell line predominantly killed Jurkats via the well known Fas-L/Fas mediated pathway. Although TR146 also expressed low levels of TRAIL and TNF-alpha, these did not contribute significantly to TR146 killing of Jurkats. In contrast, the CAL27 cell line expressed little if any Fas-L but was still able to kill Jurkats effectively via an almost exclusively TRAIL mediated mechanism. The SCC25 cell line expressed significant levels of all three ligands but we were unable to significantly inhibit killing of Jurkats by blocking any one pathway with antibodies. SCC25 may use a combination of mechanisms to kill Jurkats and switch between them to compensate when one mechanism is blocked. We found that stimulation with interferon-gamma (IFN-gamma) induced or increased the expression of apoptosis-inducing ligands on OSCC as well as the killing of Jurkat T cells. Not only did IFN-gamma increase killing of Jurkats, but it changed the contribution of the Fas-L, TRAIL and TNF-alpha mediated mechanisms to the killing of Jurkat T cells by the different cell lines. These mechanisms if reproduced in vivo, could confer survival advantage on OSCC by enabling them to kill tumour invading cytotoxic lymphocytes and evade immune destruction. [Abstract]

Pan C, Yan M, Yao J, Xu J, Long Z, Huang H, Liu Q
Aurora kinase small molecule inhibitor destroys mitotic spindle, suppresses cell growth, and induces apoptosis in oral squamous cancer cells.
Oral Oncol. 2007 Nov 7;
Mitotic Aurora kinases are required for accurate chromosome segregation during cell division. Ectopic expression of Aurora-A (Aur-A) kinase results in centrosome amplification, aberrant spindles, and consequent aneuploidy. In the present study, we showed that Aurora kinase inhibitory small molecule VX-680 inhibited histone H3 phosphorylation at Ser10, a known in vivo substrate residue of Aurora kinase, in oral squamous cell carcinoma (OSCC) KB cells. In addition, monopolar spindle structures, typical abnormalities induced by inhibition of Aur-A, were generated in VX-680-treated cells. Inhibition of Aurora kinase led to reduced KB cell growth, as assessed by MTT assay. Western blot analysis revealed that VX-680 caused cleavage of two critical apoptotic associated proteins, PARP and caspase-3. In contrast, expression of cell survival factor Bcl-2 was reduced by VX-680 treatment in a dose-dependent manner. Subsequently, nuclear characteristic of DNA fragmentation, indicative of apoptotic cell death, was clearly observed in these OSCC cells with Aurora kinase inhibitory VX-680. Taken together, we showed that Aurora kinase inhibitory VX-680 led to apoptotic cell death in OSCC cells, suggesting a novel therapeutic target in oral cancer. [Abstract]

Martínez-Mata G, Mosqueda-Taylor A, Carlos-Bregni R, de Almeida OP, Contreras-Vidaurre E, Vargas PA, Cano-Valdéz AM, Domínguez-Malagón H
Odontogenic myxoma: Clinico-pathological, immunohistochemical and ultrastructural findings of a multicentric series.
Oral Oncol. 2007 Nov 7;
The aim of this study was to analyze the clinico-pathological and immunohistochemical features of 62 cases of odontogenic myxoma (OM) diagnosed in three Oral Pathology Diagnostic Services in Latin America, as well as to describe the ultrastructural features of three of these cases. OM showed a wide age range (9-71 years), with a mean of 27.97 yr (SD: 11.01) and a male to female ratio of 1:2.2. Mandible was affected in 37 cases (59.6%) and maxilla in 25 (40.4%), with 61.3% located in the posterior region. Thirty-nine cases (62.9%) were multilocular and 23 (37.1%) unilocular. Size ranged from 1 to 13cm, (mean: 5.2cm). Thirty-seven multilocular (54.8%) and 6 unilocular lesions (26%) were larger than 4cm (p<0.05). Epithelial islands were identified in 5 cases (8%) on H&E stained sections, but AE1/AE3 and CK14 disclosed these structures in 15 cases each (24.2%); CK5 was positive in 8 (12.9%); CK7 in 2 (3.2%) and CK19 in only 3 cases (4.8%). All cases were negative for CKs 8 and 18, S-100 protein, NSE and CD68, and showed a low index of expression of Bcl2 and ki-67 proteins (<1%). Mast cell antibodies showed these cells in 45 cases (72.6%). Myofibroblastic differentiation evidenced by myofilaments and fibronexi was found in one case out of the three studied by TEM and 29 cases (46.7%) were positive by immunohistochemistry for alpha actin. In conclusion, only a minority of OM had epithelial islands, and only 3 cases expressed CK 19, indicating an odontogenic epithelium origin. Immunohistochemical and ultrastructural findings suggest that OM is a mesenchymal neoplasm in which several factors may contribute to its pathogenesis, including myofibroblastic differentiation and the participation of mast cell products. However, further investigations are needed to better understand the participation of these elements in this particular neoplasm. [Abstract]

Epstein JB, Silverman S, Epstein JD, Lonky SA, Bride MA
Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue.
Oral Oncol. 2007 Nov 8;
Conventional visual examination and palpation remains the gold-standard for the identification of oral mucosal lesions. The purpose of this study was to investigate the adjunctive value of a chemiluminescent light source (ViziLite((R)), Zila Pharmaceuticals, Phoenix, Arizona) and application of pharmaceutical grade toluidine blue (TBlue(630trade mark), Zila Pharmaceuticals, Phoenix, Arizona) to further assess lesions identified during the conventional oral soft tissue examination. Lesions deemed clinically suspicious by visual examination under incandescent light were further assessed under chemiluminescence and then application of toluidine blue stain. Differences between the conventional visual examination and chemiluminescent examination were noted on four characteristics which may aid in lesion identification. Tissue retention of toluidine blue stain was documented. Each suspicious lesion was biopsied and diagnosed based upon routine histopathology. Both adjunctive exams were evaluated by comparing the histologic diagnosis. The additive value of toluidine blue stain retention was assessed in lesions diagnosed as "serious pathology" defined as severe dysplasia, carcinoma in situ and squamous cell carcinoma. Ninety-seven clinically suspicious lesions in 84 patients were identified. The chemiluminescent exam improved the brightness and/or sharpness of margin in 61.8% of identified lesions. Biopsied lesions with toluidine blue stain retention reduced the false positive rate by 55.26% while maintaining a 100% negative predictive value (NPV). Chemiluminescence was shown to increase the brightness and margins of mucosal lesions in a majority of cases and therefore may assist in identification of mucosal lesions not considered under traditional visual examination. Toluidine blue stain retention was associated with a large reduction in biopsies showing benign histology (false positive biopsy results), while maintaining a 100% NPV for the presence of severe dysplasia or cancer. Practitioners may consider use of these adjuncts in practice, however the results presented are based upon experienced providers in referral centers for mucosal disease or cancer centers and therefore positive findings may be an indication for referral to experienced providers. [Abstract]

Lai SY, Ziober AF, Lee MN, Cohen NA, Falls EM, Ziober BL
Activated Vav2 modulates cellular invasion through Rac1 and Cdc42 in oral squamous cell carcinoma.
Oral Oncol. 2007 Nov 8;
The Rho family of GTPases regulates cellular adhesion and motility. Guanine nucleotide exchange factors (GEFs) in turn regulate GTPases by promoting nucleotide exchange from GDP to GTP. We have determined that GTP-bound Rac1 is elevated in invasive oral squamous cell carcinoma (OSCC) cell lines. Because of the critical role of invasion in the progression and metastasis of OSCC, we investigated if the GEF Vav2 modulated Rac1 and Cdc42 activation and thus influenced OSCC invasion. Expression levels of Vav2 did not correlate with invasion but phosphorylated or activated Vav2 was associated with the more invasive cell lines. Transfection of activated Vav2 into the immortalized keratinocyte cell line HaCat and a low-level expressing Vav2 invasive OSCC cell line resulted in increased GTP-bound Rac1 and Cdc42 and increased invasion. Thus, activation of Vav2 appears to modulate cellular invasion through specific regulation of Rac1 and Cdc42 activity in OSCC. [Abstract]

Copelli C, Bianchi B, Ferrari S, Ferri A, Sesenna E
Malignant tumors of intraoral minor salivary glands.
Oral Oncol. 2007 Nov 8;
Between 1995 and 2004, 43 patients with intraoral minor salivary gland carcinomas were diagnosed and treated at the Department of Maxillofacial Surgery, University of Parma, Italy. The palate was the most common site of involvement and comprised 53.5% of the cases. Adenoid cystic carcinoma was the most common histological type (60.6%), followed by mucoepidermoid carcinoma (27.9%). All patients were treated with surgery as the primary modality. Neck dissection was performed in 20.9% of patients, and more than half (72.1%) were treated with adjuvant radiation therapy. The range of the follow-up was 24-132 months (mean: 66 months). Of the 43 patients examined in this study, 12 died due to the tumor. Treatment failure was documented in 18 of the 43 patients (41.9%). Disease-free intervals ranged from 1month to 9 years and 13.9% of the patients had local failure, whereas 25,6% had distant metastases. The survival rates at 2, 5, and 10 years were 90.7%, 71.8%, and 68%, respectively. The local control rates were 93.1% at 2 years and 83.1% at 5 and 10 years. The 2-, 5-, and 10-year rates for freedom from distant relapse were 95.2%, 83.4%, and 57.5%, respectively. The T stage, cervical lymph node metastasis, surgical margin status and perineural invasion were statistically significant to the outcome. [Abstract]

Daly AJ, McIlreavey L, Irwin CR
Regulation of HGF and SDF-1 expression by oral fibroblasts - Implications for invasion of oral cancer.
Oral Oncol. 2007 Nov 8;
Invasion and metastasis of oral squamous cell carcinoma (OSCC) is dependent on signals received from stromal fibroblasts present in the surrounding connective tissue. The aim of this study was to investigate the regulation of expression of two important signaling molecules - HGF and SDF-1 - by both stromal fibroblasts and their 'activated' form, myofibroblasts, and to determine the role of these two factors in stimulating OSCC cell invasion in vitro. Fibroblasts and myofibroblasts produced similar levels of HGF and SDF-1. IL-1alpha and OSCC cell conditioned medium both stimulated HGF and SDF-1 expression, while TGF-beta(1) inhibited production of each factor. Myofibroblast-derived conditioned medium stimulated OSCC cell invasion through matrigel. Blocking antibodies to both HGF and SDF-1 reduced the level of invasion. In fibroblast-free organotypic raft cultures, addition of HGF and SDF-1 stimulated OSCC cell invasion into the underlying collagen gel, although the pattern of invasion differed from that induced by fibroblasts. Fibroblast-derived HGF and SDF-1 appear to play central roles in the reciprocal interactions between OSCC cells and underlying stromal fibroblasts leading to the local invasion of oral cancer. [Abstract]

Segawa E, Sakurai K, Kishimoto H, Takaoka K, Noguchi K, Hashitani S, Hirota S, Urade M
Expression of cyclooxygenase-2 and DNA topoisomerase II alpha in precancerous and cancerous lesions of the oral mucosa.
Oral Oncol. 2007 Nov 8;
The involvement of cyclooxygenase (COX)-2 in oral carcinogenesis and outcome of the patients is not fully understood. To determine whether COX-2 expression could serve as an indicator for them, we examined the expression of COX-2 and DNA topoisomerase (DNA-Topo) II alpha as an index of cell proliferating activity in precancerous and cancerous lesions of the oral mucosa. A 164 samples composed of 60 intraepithelial dysplasias (IEDs), 12 carcinomas in situ (CISs), 72 squamous cell carcionomas (SCCs) including 12 early invasive SCCs, 10 undifferentiated carcinomas (UCs), and 10 epithelial hyperplasias (EHPs) in the oral mucosa were examined immunohistochemically for COX-2 and DNA-Topo II alpha. Normal squamous epithelium as the control showed no COX-2 expression, whereas 41% of IEDs, 67% of CISs, 74% of SCCs, and 86% of UCs demonstrated increased COX-2 expression with elevated DNA-Topo II alpha labeling index (LI). High COX-2 expression was also observed in 61% of EHPs, but DNA-Topo II alpha LI was very low. Increased expression of COX-2 protein correlated with elevated DNA-Topo II alpha LI, indicating that COX-2 may contribute to malignant transformation and tumor growth. These two enzyme activities were increased as T, N, and M categories and stages proceeded. The patients with high expression of both COX-2 and DNA-Topo II alpha showed poor prognosis. Our results suggested that COX-2 expression become a possible indicator in oral carcinogenesis and may reflect the outcome of the patients. [Abstract]

Müller-Richter UD, Dowejko A, Zhou W, Reichert TE, Driemel O
Different expression of MAGE-A-antigens in foetal and adult keratinocyte cell lines.
Oral Oncol. 2007 Nov 9;
MAGE-A-antigens are an immunologic marker for many cancers. The goal of this study was to compare the expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in foetal and adult keratinocytes with an oral squamous cell carcinoma (OSCC) cell line. Expression of MAGE-A2, -A3, -A4, -A6 and -A10-antigens were detected with PCR in foetal and adult keratinocyte cell lines and in an OSCC cell line (pT4N1M0). Quantitative expression of the single MAGE-A-antigens was measured with rtq-PCR. The results were compared to the reference value of the adult keratinocyte cell line. MAGE-A-antigens were detected in all cell lines. Expression profiles of adult and foetal keratinocyte cell lines differed significantly. Expression profiles of foetal and carcinoma cell lines differed significantly also. MAGE-A-antigens were detected in foetal keratinocyte cell line and oral squamous cell carcinoma cell line but differ in their expression profiles. Up to now MAGE-A-antigens were not detected in foetal keratinocytes. Their role is still unknown. [Abstract]

Scully C
Journal progress in 2007-2008.
Oral Oncol. 2007 Oct 22; [Abstract]

Smolka K, Kraehenbuehl M, Eggensperger N, Hallermann W, Thoren H, Iizuka T, Smolka W
Fibula free flap reconstruction of the mandible in cancer patients: Evaluation of a combined surgical and prosthodontic treatment concept.
Oral Oncol. 2007 Oct 13;
The final goal of mandibular reconstruction following ablative surgery for oral cancer is often considered to be dental implant-supported oral rehabilitation, for which bone grafts should ideally be placed in a suitable position taking subsequent prosthetic restoration into account. The aim of this study was to evaluate the efficacy of a standardized treatment strategy for mandibular reconstruction according to the size of the bony defect and planned subsequent dental prosthetic rehabilitation. Data of 56 patients, who had undergone such a systematic mandibular fibula free flap reconstruction, were retrospectively analyzed. Early complications were observed in 41.5% of the patients but only in those who had been irradiated. Late complications were found in 38.2%. Dental implant survival rate was 92%, and dental prosthetic treatment has been completed in all classes of bony defects with an overall success rate of 42.9%. The main reasons for failure of the complete dental reconstruction were patients' poor cooperation (30.4%) and tumour recurrence (14.3%) followed by surgery-related factors (10.8%) such as implant failure and an unfavourable intermaxillary relationship between the maxilla and the mandible. A comparison of our results with the literature findings revealed no marked differences in the complication rates and implant survival rates. However, a systematic concept for the reconstructive treatment like the method presented here, plays an important role in the successful completion of dental reconstruction. The success rate could still be improved by some technical progress in implant and bone graft positioning. [Abstract]

Saran R, Tiwari RK, Reddy PP, Ahuja YR
Risk assessment of oral cancer in patients with pre-cancerous states of the oral cavity using micronucleus test and challenge assay.
Oral Oncol. 2007 Oct 11;
Oral cancer is a common malignancy, ranking first among all cancers in Western and Asian countries. Use of tobacco is regarded as a major risk factor, along with age and gender. Oral cancer is preceded by some benign lesions or conditions, which are termed pre-cancerous. Only one-third of people at the pre-cancerous stage of disease succumb to cancer. No biomarker is available to identify people with pre-cancerous lesions or conditions at high risk of developing cancer. The focus of this study was to explore such biomarkers. The study included 129 untreated people with cancer, 138 untreated people at the pre-cancerous stage and 176 control participants. For statistical analysis of this data, analysis of variance and t-test were used. Three biomarkers (i.e. micronucleus test [MNT], comet assay and challenge comet assay were used. MNT and comet assay were carried out on buccal epithelial cells. In addition, challenge comet assay was carried out on peripheral blood leucocytes by using mutagen MNNG sensitivity of DNA after DNA repair. A significant stepwise increase in the DNA damage (basal/MNNG-treated/post-repair) was observed in buccal epithelial cells and peripheral blood leucocytes from control to pre-cancer patients and from pre-cancer to cancer patients. Micronucleus frequency also increased in the same way. Considerable inter-individual and inter-cellular variability in DNA damage was observed, which increased from control to pre-cancer patients and from pre-cancer to cancer patients. The outliers among patients with pre-cancerous states were identified on the basis of more than mean +2 SD limits for comet tail length, as well as mean percentage of micronuclei. Hence, those participants whose cells showed high basal DNA damage, extreme sensitivity to MNNG and reduced repair were identified as high-risk individuals. [Abstract]

Kaomongkolgit R, Cheepsunthorn P, Pavasant P, Sanchavanakit N
Iron increases MMP-9 expression through activation of AP-1 via ERK/Akt pathway in human head and neck squamous carcinoma cells.
Oral Oncol. 2007 Oct 11;
Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer that is capable of distant metastasis and is a cause of great morbidity and mortality worldwide. Over-expression of matrix metalloproteinase-9 (MMP-9) is implicated in the invasion and metastasis of HNSCC. There is increasing evidence of an association between iron overload and cancer progression. However, the effect of iron on MMP-9 expression in HNSCC has not been studied. In the present study, we examined the effect of iron on MMP-9 expression in head and neck squamous carcinoma cell lines (OM-2 and HN-22). Ferric ammonium citrate (FAC), a source of iron, at 15mug/ml increased MMP-9 in both cell lines in a dose-dependent manner as shown by reverse transcription polymerase chain reaction and gelatin zymography analyses. Studies using specific inhibitors of extracellular signal-regulated kinase (ERK1/2) and of Akt (SH-5) demonstrated that iron regulated MMP-9 through ERK1/2 and Akt, and that ERK1/2 was an upstream activator of Akt. Analysis of electrophoretic mobility shift assay revealed that iron induces MMP-9 expression by activation of activated protein-1 (AP-1). Application of neutralizing antibody against transferrin receptor could not abolish the stimulated MMP-9 expression, suggesting that iron uptake is non-transferrin dependent. In conclusion, this study is the first to demonstrate that MMP-9 was up-regulated by iron in HNSCC cell lines. We suggest that iron may be one of several factors that cause an increase of MMP-9, which is necessary for the development and progression of HNSCC. [Abstract]

Sun Z, Sood S, Li N, Yang P, Newman RA, Yang CS, Chen X
Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases.
Oral Oncol. 2007 Oct 11;
Oral cancer is a common neoplasm worldwide with tobacco and alcohol being the major etiological factors contributing to its pathogenesis. Epidermal growth factor receptor (EGFR) and ErbB2 are known to be involved in the development of oral cancer with the former up-regulated in up to 90% human cases. The goal of this study was to evaluate the chemopreventive effects of a dual inhibitor of EGFR and ErbB2 tyrosine kinases, GW2974, in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model. A short-term experiment (3-week topical DMBA followed by 1-week topical GW2974) was conducted to examine the effects of GW2974 on aberrant arachidonic acid (AA) metabolism and cell proliferation in the hamster oral epithelium. Topical application of 0.1ml GW2974 (160muM, three times a week) significantly reduced the levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 5-, 12-, 15-hydroxyeicosatetraenoic acid (HETE), and cell proliferation (BrdU-labeling index). In a long-term post-initiation experiment (6-week topical DMBA followed by 18-week topical GW2974), GW2974 (4mM and 8mM) significantly inhibited the incidence, number and size of visible tumors. Under microscope, the numbers of oral lesions (hyperplasia, dysplasia, carcinoma) and the incidence of squamous cell carcinoma (SCC) were also significantly suppressed by GW2974. In summary, our study indicated that dual inhibition of EGFR and ErbB2 tyrosine kinases by GW2974 was effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model. GW2974 exerted its chemopreventive effects in part by suppressing aberrant AA metabolism. [Abstract]


Recent Articles in Journal of Periodontology

Iezzi G, Degidi M, Scarano A, Petrone G, Piattelli A
Anorganic bone matrix retrieved 14 years after a sinus augmentation procedure: a histologic and histomorphometric evaluation.
J Periodontol. 2007 Oct;78(10):2057-61.
BACKGROUND: Anorganic bone matrix (ABM) is reported to have osteoconductive properties. No inflammatory or adverse responses have been reported when this material is used in sinus augmentation procedures. ABM is said to be a bioabsorbable biomaterial, but histologic data seem to suggest that the resorption process is slow. Long-term histologic data in humans are lacking. The aim of this case report was to evaluate the bone response to ABM used in maxillary sinus augmentation and retrieved 14 years after surgery. METHODS: Titanium dental implants were inserted in two sinuses augmented with ABM. The implants were osseointegrated and functioned well for 14 years. After this period of loading, the connecting screw of one of the implants inserted in the left maxilla broke, and it was necessary to remove the implant. A bone core of the augmented area was harvested separately during the implant removal. RESULTS: A very high quantity of mature, compact bone and a small percentage of residual grafted biomaterial were found. About 5% to 7% of the bone was undergoing remodeling. In most cases, residual ABM particles were surrounded by marrow spaces. In other areas, lamellar bone was found in tight contact with the particle surfaces. Histomorphometry showed that the mean amount of mature, compact bone was 71.0% +/- 2.28%, the mean amount of ABM was 22.1% +/- 3.18%, and the mean amount of marrow spaces was 11.2% +/- 5.42%. CONCLUSIONS: ABM seemed to resorb very slowly; after 14 years, only a small quantity of residual grafted particles was present. ABM is an effective graft material for sinus augmentation procedures. Vital, mature bone was formed and maintained over a long period with no chronic inflammatory cell infiltrate, foreign body response, or other adverse effects. [Abstract]

Parashis AO, Tatakis DN
Subepithelial connective tissue graft for root coverage: a case report of an unusual late complication of epithelial origin.
J Periodontol. 2007 Oct;78(10):2051-6.
BACKGROUND: The subepithelial connective tissue graft (SCTG) is one of the most used and predictable periodontal plastic surgery procedures; reports of late complications are very rare. This article presents an SCTG case with a previously unreported late complication of epithelial origin, and we suggest a potential link between the patient's dermatologic condition and this complication. Late SCTG complications also are reviewed. METHODS: A 19-year-old female presented with a 3-mm deep Miller Class I recession defect on the mandibular right central incisor. An SCTG procedure was performed for root coverage, with uneventful initial postoperative healing that resulted in complete root coverage. At 4 months, an asymptomatic solid white discharge was observed at sites along the original graft margin without evidence of inflammation. A month later, the somewhat reduced but still evident discharge was collected and submitted for microscopic examination. RESULTS: Cytologic examination revealed the discharge to be normal epithelial cells, suggesting a proliferative epithelial response. Follow-up indicated that the discharge was self-limiting and was no longer present at 9 months after surgery. This unusual late SCTG complication is consistent with reported epithelial invaginations and projections between graft and overlying flap. The patient had acne, a disease whose pathogenesis includes host predisposition to epithelial hyperproliferation; therefore, a possible association of this SCTG complication with the patient's systemic health is proposed. CONCLUSION: Epithelial cell discharge is a hitherto unreported, self-limiting, late complication of the SCTG procedure, and a potential association between this complication and the patient's dermatologic condition is suggested. [Abstract]

Miliauskaite A, Selimovic D, Hannig M
Successful management of aggressive periodontitis by regenerative therapy: a 3-year follow-up case report.
J Periodontol. 2007 Oct;78(10):2043-50.
BACKGROUND: This case report presents a new treatment for localized aggressive periodontitis using surgery (papilla preservation technique [PPT]) combined with enamel matrix proteins and bioactive glass. METHODS: Eight intrabony defects in a 19-year-old woman with localized aggressive periodontitis were treated by PPT and the application of enamel matrix proteins or enamel matrix proteins in combination with bioactive glass. Probing depth, gingival recession, and clinical attachment level (CAL) were evaluated at baseline, 6 and 12 months, and 2 and 3 years after treatment. The primary outcome variable was CAL. RESULTS: After 3 years, the sites treated with enamel matrix proteins demonstrated a mean CAL change from 8.3 +/- 3.2 mm to 4.0 +/- 3.6 mm (P < 0.39), and the sites treated with enamel matrix proteins combined with bioactive glass showed a mean CAL change from 8.6 +/- 2.4 mm to 3.7 +/- 0.8 mm (P < 0.001). CONCLUSION: In the present case of aggressive periodontitis, application of enamel matrix proteins with or without the addition of bioactive glass resulted in the successful treatment of intrabony defects. [Abstract]

Llambés F, Silvestre FJ, Caffesse R
Vertical guided bone regeneration with bioabsorbable barriers.
J Periodontol. 2007 Oct;78(10):2036-42.
BACKGROUND: Guided bone regeneration (GBR) is a very useful surgical technique to increase limited alveolar bone for implant placement. The use of non-resorbable barriers is well established; however, bioabsorbable collagen membranes may simplify the surgical technique and make it more predictable. METHODS: Vertical ridge augmentation was performed on 11 patients at the time of implant placement. The part of the implant out of bone was covered with autogenous bone/graft, and a slow-resorption collagen membrane was placed on top. Gingival tissues were closed with horizontal mattress and interrupted sutures. Second-stage surgery was performed 4 to 6 months later, and healing abutments were placed. The length of the implant out of bone was determined at stage 1 and stage 2 surgeries on a periapical x-ray 1 year after implant load. Histology was obtained from one of the cases at second-stage surgery. RESULTS: Measurements revealed that the mean implant out of bone was 3.5 mm at stage 1 and 0.5 mm at stage 2. Mean bone gain was 3 mm, which represented 83% of the exposed implant at stage 1. One year after loading, implants showed a mean marginal bone loss of 1.4 mm. Minimal complications were detected, and only one case failed. Histology from one successful case showed new trabecular bone with large cellular marrow spaces in the regenerated area. CONCLUSION: Slow-resorption collagen membranes have the potential to promote vertical ridge augmentation when used with autogenous bone at the time of implant placement. [Abstract]

Kfir E, Kfir V, Eliav E, Kaluski E
Minimally invasive antral membrane balloon elevation: report of 36 procedures.
J Periodontol. 2007 Oct;78(10):2032-5.
BACKGROUND: The posterior maxillary segment frequently has insufficient bone mass to support dental implants. This registry evaluated the feasibility and safety of minimally invasive antral membrane balloon elevation (MIAMBE), followed by bone augmentation and implant fixation. METHODS: Thirty-six consecutive patients referred for posterior maxillary bone augmentation underwent alveolar crest exposure and implant osteotomy followed by MIAMBE (> 10 mm). Fibrin and bone particles were injected beneath the antral membrane, implants were placed into the osteotomies, and primary closure was executed at the same sitting. RESULTS: All 36 patients successfully concluded the procedure with no significant procedural complications or discomfort. Procedure time was 48 +/- 15 minutes. Incremental bone height consistently exceeded 8 mm, and implant survival of 97% was observed at 6 to 8 months. CONCLUSIONS: MIAMBE resulted in high procedural success and satisfactory bone augmentation implant survival and complication rates. Because it is minimally invasive, this procedure may be an alternative to the currently used surgical methods. [Abstract]

Barbosa MD, Gregh SL, Passanezi E
Fibrin adhesive derived from snake venom in periodontal surgery.
J Periodontol. 2007 Oct;78(10):2026-31.
BACKGROUND: A new fibrin adhesive made of buffalo plasma-derived fibrinogen and a thrombin-like enzyme obtained from snake venom was evaluated in this case series with regard to its applicability in periodontal surgery. Free gingival grafts that were sutured (control group) were compared to others immobilized through the use of the adhesive (experimental group). METHODS: The grafts were carried out in contralateral mandibular bicuspids of 15 patients so that each subject received one treatment of each type. The analysis included measurements of probing and vertical dimension of the grafts and photographic follow-up for 90 days. The patients answered a questionnaire concerning postoperative signs and symptoms. RESULTS: The decrease in the vertical dimension of the grafts was significant during the first 30 days and more dramatic for the control group. Probing depth and attachment level presented statistically significant decreases for both groups. The grafts of the experimental group presented better appearance during the first 14 postoperative days. Pain was observed more often in the control group. CONCLUSIONS: Within the limits of the present study, it is suggested that the alternative fibrin adhesive tested may represent an alternative to sutures in periodontal surgery. Nevertheless, randomized clinical trials should be performed to evaluate the clinical advantages and disadvantages of the material. [Abstract]

Rosa DS, Aranha AC, Eduardo Cde P, Aoki A
Esthetic treatment of gingival melanin hyperpigmentation with Er:YAG laser: short-term clinical observations and patient follow-up.
J Periodontol. 2007 Oct;78(10):2018-25.
BACKGROUND: Recently, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser has been applied effectively for periodontal soft tissue management. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a short-term clinical observation. METHODS: Five patients with gingival melanin pigmentation participated in this study. Irradiation was performed at 64.0 mJ/pulse (8.5 J/cm2 per pulse) and 10 Hz under water spray in contact mode. Clinical parameters, such as bleeding, swelling, redness, and healing, were evaluated immediately after the surgery and 24 hours, 1 and 4 weeks, and 3 months later. A visual analog scale was used to evaluate the pain level experienced. RESULTS: The Er:YAG laser effectively ablated the epithelial tissue containing melanin pigmentation. At 1 week, gingiva showed fast epithelization with a healthy appearance in all cases. At 2 weeks, gingiva showed satisfactory healing with significant improvement in color and recovery of the tissue thickness. At 1 month, complete healing was observed; after the 3-month evaluation, no gingival deformity or recession was observed. However, there was a slight recurrence in one case. CONCLUSION: Removal of gingival melanin pigmentation can be performed safely by Er:YAG laser resulting in an esthetically significant improvement of gingival discoloration. [Abstract]

Sant'Ana AC, Marques MM, Barroso TE, Passanezi E, de Rezende ML
Effects of TGF-beta1, PDGF-BB, and IGF-1 on the rate of proliferation and adhesion of a periodontal ligament cell lineage in vitro.
J Periodontol. 2007 Oct;78(10):2007-17.
BACKGROUND: Considering the role of growth factors in periodontal regeneration, the aim of this study was to evaluate the influence of platelet-derived growth factor (PDGF)-BB, insulin-like growth factor (IGF)-1, and transforming growth factor-beta 1 (TGF-beta1), alone or in combination, on the rate of proliferation and adhesion of periodontal ligament (PDL) cells in vitro. METHODS: After establishment and characterization of a primary culture of PDL cells, 72 culture dishes were plated with 10(3) cells distributed among four test groups and a control group. Test groups had PDGF-BB, TGF-beta1, IGF-1, or a combination of all three added to the culture medium, whereas the control group received no growth factor. The samples were counted in triplicate 1, 3, 5, and 7 days after seeding. For the adhesion assay, 14 patients provided 30 root fragments distributed among 10 groups: scaling and root planing (SRP), SRP + growth factors, SRP + citric acid plus tetracycline (CA+T), and SRP + (CA+T) + growth factors. The data were evaluated statistically by analysis of variance complemented by Tukey, Dunnett, and Student-Newman-Keuels methods. RESULTS: Maximum rates of proliferation were observed at day 3 for all groups. TGF-beta1 induced a 344.17% +/- 58.80% increased proliferation rate over control (P < 0.05), followed by the combination (277.5% +/- 29.38%), PDGF-BB (238.79% +/- 5.79%), and IGF-1 (233.16% +/- 19.19%). Groups treated by (CA+T) showed increased numbers of cells attached to root fragments, especially SRP + (CA+T) + combination (13.25 +/- 1.79), with significant differences (P < 0.05) from groups treated only by SRP. CONCLUSION: This combination of growth factors stimulated a mitogenic response and favored the adhesion of PDL cells in vitro, suggesting its possible role in periodontal regeneration. [Abstract]

Rogers JE, Li F, Coatney DD, Otremba J, Kriegl JM, Protter TA, Higgins LS, Medicherla S, Kirkwood KL
A p38 mitogen-activated protein kinase inhibitor arrests active alveolar bone loss in a rat periodontitis model.
J Periodontol. 2007 Oct;78(10):1992-8.
BACKGROUND: Gram-negative bacterial species, such as Actinobacillus actinomycetemcomitans, contain lipopolysaccharide (LPS) that initiates the innate immune system, resulting in inflammatory alveolar bone loss. LPS activates Toll-like receptors on membrane surfaces, stimulating many intracellular signaling cascades, including the p38 mitogen-activated protein kinase (MAPK). Activation of p38 signaling mediates inflammatory cytokine expression, contributing toward osteoclastogenesis and bone loss. The aim of this study was to determine whether the novel, orally active p38 MAPK inhibitor SD282 could arrest progression of LPS-induced alveolar bone destruction in rats. METHODS: Three groups of female Sprague-Dawley rats received LPS injections to the palatal molar gingiva three times per week for 4 weeks to establish periodontitis. From weeks 5 through 8, two groups received the drug SD282 (N = 14) or 1% polyethylene glycol drug vehicle (N = 14) via oral gavage in addition to LPS injections. The third group continued to receive only LPS injections (N = 8). Microcomputed tomography was used to measure volumetric alveolar bone loss, expressed as bone volume fraction (BVF). Expression of interleukin (IL)-1 and -6 and tumor necrosis factor-alpha (TNF-alpha) was assessed by immunohistochemistry, and osteoclasts were enumerated by tartrate-resistant acid phosphatase staining. RESULTS: By 4 weeks, severe alveolar bone resorption was seen in LPS-injected animals. Administration of SD282 significantly blocked additional volumetric bone loss in the LPS-only versus LPS + SD282 groups (0.37 +/- 0.01 BVF versus 0.43 +/- 0.01 BVF; P < 0.01). Significant reductions in IL-1beta (P < 0.01 ), TNF-alpha (P < 0.05), and osteoclast formation (P < 0.01) occurred in the presence of SD282. CONCLUSIONS: An orally active p38 MAPK inhibitor reduced LPS-induced inflammatory cytokine expression, osteoclastogenesis, and alveolar bone loss in rats. Within the limits of the current study, SD282 arrested periodontal disease progression, thus highlighting the therapeutic potential of this novel class of inhibitors. [Abstract]

Uggeri J, Belletti S, Guizzardi S, Poli T, Cantarelli S, Scandroglio R, Gatti R
Dose-dependent effects of platelet gel releasate on activities of human osteoblasts.
J Periodontol. 2007 Oct;78(10):1985-91.
BACKGROUND: Platelet-rich plasma is used in oral and maxillofacial surgery; however, its real efficacy is debated. Also, the in vitro effects on bone-specific functions are contradictory. Understanding the mechanisms of action of platelet-derived factors could be the basis for their proper use in clinical applications. METHODS: The functional parameters of osteoblasts (proliferation, alkaline phosphatase, collagen synthesis, and calcium deposition) were analyzed in vitro for 14 days in the presence of different concentrations (100%, 33%, and 11%) of platelet gel releasate (PGR). RESULTS: Concentrations of 100% PGR and 33% PGR stimulated cells to proliferate more than 10% fetal calf serum. The effect on cell proliferation was dose dependent, and the addition of dexamethasone (dex) and beta-glycerophosphate (beta-GP) reduced the proliferative effects. Alkaline phosphatase activity was stimulated by 33% PGR and 11% PGR after 7 days and was induced further by dex and beta-GP. Also, collagen synthesis, measured on day 11, was stimulated by 33% PGR and 11% PGR. Calcium deposition, evaluated after 7 and 14 days, was greatest in cells treated with PGR supplemented with dex and GP. The mineralization process increased with time; on day 14, calcium aggregates were observed in all cultures treated with PGR (100%, 33%, and 11%). CONCLUSIONS: PGR stimulated osteoblast proliferation in a dose dependent manner and, when used at 33% and 11%, induced maximum levels of alkaline phosphatase and collagen synthesis. Moreover, in the presence of dex and beta-GP, PGR stimulated the end maturative status of cells as expressed by the deposition of calcium nodules. [Abstract]

Emingil G, Berdeli A, Baylas H, Saygan BH, Gürkan A, Köse T, Atilla G
Toll-like receptor 2 and 4 gene polymorphisms in generalized aggressive periodontitis.
J Periodontol. 2007 Oct;78(10):1968-77.
BACKGROUND: Toll-like receptors (TLRs) recognize exogenous ligands such as lipopolysaccharide and bacterial lipoprotein during the immune responses to pathogens. The aim of the present study was to investigate whether TLR2 and TLR4 gene polymorphisms are related to susceptibility to generalized aggressive periodontitis (GAgP). METHODS: A total of 245 subjects were included in the present study. Genomic DNA was obtained from the peripheral blood of 90 patients with GAgP and 155 periodontally healthy subjects. Probing depth, clinical attachment loss, plaque accumulation, and bleeding on probing were recorded. The TLR2 gene Arg753Gln and Arg677Trp polymorphisms and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The data were analyzed by chi2 and Mann-Whitney U tests and logistic regression analysis. RESULTS: There was no significant difference in the distribution of TLR2 and TLR4 genotypes and allele frequencies between GAgP patients and healthy subjects (P > 0.05). The TLR2 753Gln allele was found in 3.9% of the GAgP patients compared to 6.1% in the healthy group. The GAgP patients and healthy subjects did not show homozygosity for the TLR2 mutant alleles. The TLR2 677Trp mutant allele was not found in any of the subjects; 2.2% of the GAgP patients and 2.9% of the periodontally healthy subjects were identified as having the TLR4 299Gly polymorphic allele. With regard to the TLR4 399Ile polymorphic allele, 1.1% of the GAgP patients and 2.3% of the periodontally healthy subjects had this allele. CONCLUSIONS: The present study failed to find any significant association between the TLR polymorphisms and GAgP, potentially because of the small sample size. To the best of our knowledge, this was the first study to examine the prevalence of these polymorphisms in a Turkish population with aggressive periodontitis. [Abstract]

Pradeep AR, Kumar MS, Ramachandraprasad MV, Shikha C
Gingival crevicular fluid levels of neopterin in healthy subjects and in patients with different periodontal diseases.
J Periodontol. 2007 Oct;78(10):1962-7.
BACKGROUND: Neopterin, a metabolite of guanosine, belongs to the class of chemical compounds known as pteridines and is an early and valuable marker of cellular immunity. Recently, it was shown to be associated with the initiation and progression of periodontal disease. The aim of the present study was to assess the relationship between clinical parameters and concentrations of neopterin within gingival crevicular fluid (GCF) from inflamed gingiva and periodontitis sites before and after the treatment of periodontitis. METHODS: Sixty age (35 to 65 years)- and gender-matched (30 males and 30 females) subjects were recruited and divided into the following four groups of 15 subjects each based on gingival index, Ramfjord periodontal disease index, clinical attachment loss (CAL), and radiographic parameters (bone loss): healthy (group 1), gingivitis (group 2), mild periodontitis (group 3), and moderate to severe periodontitis (group 4). A fifth group consisted of the 15 subjects from group 4, 6 to 8 weeks after treatment (scaling and root planing). GCF was collected from each patient, and the neopterin levels were determined by enzyme immunoassay. Results were analyzed statistically. RESULTS: The mean concentration of neopterin in GCF was the highest in group 4 (51 nmol/l) and the lowest in group 1 (1.36 nmol/l). The mean neopterin concentrations in group 2 (9.69 nmol/l) and group 3 (16.58 nmol/l) fell between the highest and lowest values. This suggested a positive correlation between CAL and GCF neopterin concentrations. Neopterin levels in group 4 decreased to 1.77 nmol/l after treatment (group 5). CONCLUSIONS: Neopterin increased in parallel with the severity of inflammatory disease. Its levels in GCF may be potentially useful as an indicator of periodontal inflammation and the host response. [Abstract]

Kurtis B, Tüter G, Serdar M, Pinar S, Demirel I, Toyman U
GCF MMP-8 levels in smokers and non-smokers with chronic periodontitis following scaling and root planing accompanied by systemic use of flurbiprofen.
J Periodontol. 2007 Oct;78(10):1954-61.
BACKGROUND: Cigarette smoking has been identified as an important risk factor for the initiation and progression of chronic periodontitis (CP). The aim of this study was to investigate the effects of phase I periodontal therapy and adjunctive flurbiprofen administration on matrix metalloproteinase (MMP)-8 levels in gingival crevicular fluid (GCF) samples from smoking and non-smoking patients with CP. METHODS: Twenty-nine non-smoking and 29 smoking patients with CP were divided into four groups according to periodontal treatment modalities. Group 1 (non-smokers with CP) and group 3 (smokers with CP) patients received daily 100-mg flurbiprofen tablets in a 2 x 1 regimen for 10 days together with scaling and root planing (SRP). Patients in group 2 (non-smokers with CP) and group 4 (smokers with CP) received placebo tablets in a 2 x 1 regimen for 10 days together with SRP. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) measurements were recorded; GCF samples were collected from each sampling area at baseline and after the 10-day period of drug intake by a single examiner who was unaware of the treatment modality. Assays for GCF MMP-8 were carried out by an enzyme-linked immunosorbent assay. RESULTS: All groups showed statistically significant reductions in PI and GI scores following the phase I periodontal treatment (P < 0.05), but no statistical differences were observed in PD and CAL scores after therapy. In all groups, the reduction of GCF MMP-8 levels after therapy was statistically significant compared to baseline levels (P < 0.001). When groups 1 and 3 and 2 and 4 were compared according to GCF MMP-8 levels after the therapy, no statistically significant differences were observed (P = 0.117 and P = 0.485, respectively). CONCLUSION: Flurbiprofen administration had no additional inhibitory effect over SRP alone on GCF levels of MMP-8 in smokers compared to non-smokers with CP. [Abstract]

Bornstein MM, Bosshardt D, Buser D
Effect of two different bioabsorbable collagen membranes on guided bone regeneration: a comparative histomorphometric study in the dog mandible.
J Periodontol. 2007 Oct;78(10):1943-53.
BACKGROUND: This study compared bone regeneration following guided bone regeneration with two bioabsorbable collagen membranes in saddle-type bone defects in dog mandibles. METHODS: Three standardized defects were created, filled with bone chips and deproteinized bovine bone mineral (DBBM), and covered by three different methods: control = no membrane; test 1 = collagen membrane; and test 2 = cross-linked collagen membrane (CCM). Each side of the mandible was allocated to one of two healing periods (8 or 16 weeks). The histomorphometric analysis assessed the percentage of bone, soft tissue, and DBBM in the regenerate; the absolute area in square millimeters of the bone regenerate; and the distance in millimeters from the bottom of the defect to the highest point of the regenerate. RESULTS: In the 8-week healing group, two dehiscences occurred with CCM. After 8 weeks, all treatment modalities showed no significant differences in the percentage of bone regenerate. After 16 weeks, the percentage of bone had increased for all treatment modalities without significant differences. For all groups, the defect fill height increased between weeks 8 and 16. The CCM group showed a statistically significant (P = 0.0202) increase over time and the highest value of all treatment modalities after 16 weeks of healing, CONCLUSIONS: The CCM showed a limited beneficial effect on bone regeneration in membrane-protected defects in dog mandibles when healing was uneventful. The observed premature membrane exposures resulted in severely compromised amounts of bone regenerate. This increased complication rate with CCM requires a more detailed preclinical and clinical examination before any clinical recommendations can be made. [Abstract]

Fine DH, Markowitz K, Furgang D, Goldsmith D, Ricci-Nittel D, Charles CH, Peng P, Lynch MC
Effect of rinsing with an essential oil-containing mouthrinse on subgingival periodontopathogens.
J Periodontol. 2007 Oct;78(10):1935-42.
BACKGROUND: Studies have shown that the nature and amount of supragingival plaque can influence the composition of the contiguous subgingival flora. The purpose of this study was to investigate the effect of rinsing with an essential oil antimicrobial mouthrinse on levels of representative subgingival bacteria in subjects with mild to moderate periodontitis. METHODS: This controlled study used a randomized, double-masked, 2 x 2 crossover design. After baseline subgingival sampling, 37 qualifying subjects rinsed with the essential oil mouthrinse or a negative control twice daily for 14 days, with a post-treatment sample obtained on day 15. Following a washout period, the procedure was repeated with the alternative rinse. Target organisms enumerated were Porphyromonas gingivalis, Fusobacterium nucleatum, Veillonella sp., and total anaerobes. Intergroup comparisons of post-treatment log-transformed colony forming unit counts were made using analysis of covariance. RESULTS: After 14 days of twice-daily rinsing, the level of each of the target subgingival organisms was significantly lower in the essential oil group than in the control group (P < 0.001), with percent reductions ranging from 66.3% to 79.2%. CONCLUSIONS: Rinsing with the essential oil antiplaque/antigingivitis mouthrinse can have significant antimicrobial activity against subgingival periodontopathogens. Most likely, the antimicrobial effect was mediated primarily by disruption of the contiguous supragingival plaque by the mouthrinse. Because studies have shown that control of supragingival plaque can influence the onset and/or progression of periodontitis, additional studies on non-prescription antimicrobial oral care products may lead to new regimens for decreasing the burden of periodontal diseases in the population. [Abstract]

Cengiz MI, Bal S, Gökçay S, Cengiz K
Does periodontal disease reflect atherosclerosis in continuous ambulatory peritoneal dialysis patients?
J Periodontol. 2007 Oct;78(10):1926-34.
BACKGROUND: Chronic infection and inflammation, including periodontitis, are linked to an increased risk for atherosclerosis. To investigate the possible adverse effects of periodontitis in continuous ambulatory peritoneal dialysis (CAPD) patients, we compared periodontal severity with inflammation and malnutrition, which are associated with poor atherosclerotic outcome in CAPD patients. METHODS: A total of 110 CAPD patients were included in this study to evaluate their clinical periodontal status by using the plaque index, gingival index, and periodontal disease index. Values for nutritional and inflammatory markers and atherosclerotic risk factors were included for analysis with the periodontal index. Analysis of variance, post hoc Tukey's honestly significant difference, univariate and multivariate linear regression analysis, Pearson correlation analysis, and chi2 analysis were used in the evaluation of the data. RESULTS: Poor oral health status was exhibited by 85.5% of our CAPD patients with periodontal disease. We found that age and longer dialysis duration were associated with the severity of periodontitis. Parameters of malnutrition and inflammation and atherosclerotic risk factors also were associated with poor periodontal status. We carried out multiple regression analysis and found that age, albumin level, and duration of dialysis were associated independently with the severity of periodontitis in CAPD patients. A higher percentage of patients in the severe periodontitis group had malnutrition (chi2 = 59.4; P < 0.001), inflammation (chi2 = 60; P < 0.001), and atherosclerosis (chi2 = 65.6; P < 0.001). CONCLUSIONS: Periodontal health is poor in CAPD patients and correlates with markers of malnutrition, inflammation, and atherosclerosis. The diagnosis and treatment of periodontal diseases require better awareness. [Abstract]

Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC, Beck JD
Periodontal disease at the biofilm-gingival interface.
J Periodontol. 2007 Oct;78(10):1911-25.
BACKGROUND: A molecular epidemiologic study provided the opportunity to characterize the biology of the biofilm-gingival interface (BGI) in 6,768 community-dwelling subjects. METHODS: Disease classifications and multivariable models were developed using clinical, microbial, inflammatory, and host-response data. The purpose was to identify new clinical categories that represented distinct biologic phenotypes based upon DNA checkerboard analyses of eight plaque bacteria, serum immunoglobulin G (IgG) titers to 17 bacteria, and the gingival crevicular fluid (GCF) levels of 16 inflammatory mediators. Five BGI clinical conditions were defined using probing depths (PDs) and bleeding on probing (BOP) scores. Subjects with all PDs < or = 3 mm were grouped as BGI-healthy (14.3% of sample) or BGI-gingivitis (BGI-G, 15.1%). Subjects with one or more PDs > or = 4 mm [deep lesion (DL)] were divided into low BOP (18.0%), moderate BOP (BGI-DL/MB, 39.7%), and severe BOP (BGI-DL/SB, 12.9%). RESULTS: Subjects with BGI-G had increased levels of Campylobacter rectus-specific serum IgG levels (P = 0.01), and those with BGI-DL/SB had increased IgG levels to Porphyromonas gingivalis (P < 0.0003) and C. rectus (P < 0.01). BGI-DL/SB subjects had an excessive GCF interleukin (IL)-1beta and prostaglandin E2 response and an enhanced chronic inflammatory response with significant increases in GCF IL-6 and monocyte chemotactic peptide-1. Within BGI-DL/SB subjects, more severe pocketing and BOP were associated with higher levels of GCF IL-1beta, not higher microbial counts or plaque scores. CONCLUSIONS: New BGI classifications create categories with distinct biologic phenotypes. The increased titers of C. rectus IgG among 68.5% of the BGI-G subjects and elevated P. gingivalis titers among BGI-DL/MB and BGI-DL/SB subjects (63.8% and 75.7%, respectively) are strongly supportive of the microbial specificity of pathogenesis for BGI categories. [Abstract]

Rinaggio J, Crossland DM, Zeid MY
A determination of the range of oral conditions submitted for microscopic and direct immunofluorescence analysis.
J Periodontol. 2007 Oct;78(10):1904-10.
BACKGROUND: Direct immunofluorescence (DIF) testing is a useful adjunct for the diagnosis of immune-mediated oral vesiculobullous diseases, helping to identify separate, histologically similar, but prognostically different, conditions. It is unknown how often biopsy of these lesions yields positive DIF results. METHODS: A total of 270 consecutive archival cases submitted to a reference laboratory in Buffalo, New York, over a 2-year span were examined. These specimens were submitted to establish or rule out a diagnosis of a DIF-positive oral vesiculobullous disease. Demographic, clinical, and diagnostic information, based on conventional microscopic and DIF analysis, was tabulated. To assess the contribution of DIF to successful diagnosis, three pathologists examined the hematoxylin and eosin-stained slides of the known DIF-positive specimens without knowledge of the DIF results. RESULTS: Approximately 48% of the specimens demonstrated positive DIF findings and consisted of pemphigus vulgaris, mucous membrane pemphigoid, lichen planus, linear immunoglobulin A disease, and chronic ulcerative stomatitis. The remaining specimens had negative DIF findings and consisted of numerous non-specific inflammatory conditions. Of particular interest were several cases of epithelial dysplasia and squamous cell carcinoma. Of the DIF-positive cases, only pemphigus vulgaris could be diagnosed reliably by conventional microscopy alone. CONCLUSIONS: Approximately half of biopsies of oral conditions that clinically resembled typically DIF-positive vesiculobullous diseases did not yield positive findings on DIF testing. Instead, a wide range of oral diseases can mimic these lesions clinically. With the exception of pemphigus vulgaris, DIF is essential for establishing a definitive diagnosis for known DIF-positive diseases. [Abstract]

Mohammadi M, Shokrgozar MA, Mofid R
Culture of human gingival fibroblasts on a biodegradable scaffold and evaluation of its effect on attached gingiva: a randomized, controlled pilot study.
J Periodontol. 2007 Oct;78(10):1897-903.
BACKGROUND: An adequate width of attached gingiva is necessary to maintain healthy periodontium, especially in orthodontics or restorative treatments in periodontics. The purpose of this study was to evaluate the width of attached gingiva after clinical application of a cultured gingival graft compared to a periosteal fenestration technique. METHODS: This study was conducted on nine patients (18 sites) with insufficient attached gingiva adjacent to at least two teeth in contralateral quadrants of the same jaw. A small portion (approximately 3 x 2 x 1 mm) of attached gingiva (epithelial + connective tissue) was removed with a surgical blade. After culture of gingival fibroblasts, 2 x 10(5) cells in 250 microl nutritional medium were added to 250 microl collagen gel. One tooth in each patient was randomized to receive a periosteal fenestration technique for gingival augmentation (control) or a tissue-engineered mucosal graft (test). Clinical parameters measured at baseline and 3 months included width of keratinized tissue, probing depth, and width of attached gingiva. RESULTS: An increased amount of keratinized tissue was seen at all treated sites after 3 months. The mean increased amount of attached gingiva was 2.8 mm at test sites and 2 mm at control sites; this difference was significant (P < 0.05). CONCLUSION: Based on the results of this investigation, the tissue-engineered mucosal graft is safe and capable of generating keratinized tissue. [Abstract]

DeAngelo SJ, Kumar PS, Beck FM, Tatakis DN, Leblebicioglu B
Early soft tissue healing around one-stage dental implants: clinical and microbiologic parameters.
J Periodontol. 2007 Oct;78(10):1878-86.
BACKGROUND: Despite the potential significance of early soft tissue healing to long-term outcomes, this aspect of one-stage dental implants has not been investigated. The purpose of this prospective study was to characterize clinical and microbiologic parameters of early soft tissue healing around dental implants placed following a one-stage protocol. METHODS: Twenty-one patients (11 females and 10 males, aged 18 to 78 years; two smokers) needing a single implant were included. Clinical parameters included probing depth, buccal flap thickness, papilla height, and bleeding on probing. Subgingival plaque samples were obtained pre- and postoperatively and analyzed using molecular techniques. RESULTS: The newly formed peri-implant sulcus probing depth remained fairly stable from 4 to 12 weeks (P > 0.05). There was no statistically significant association between flap thickness or papillary height and number of implant bleeding sites at 12 weeks (P > 0.05). Detection of known periodontal pathogens was rare. Fusobacterium nucleatum was present in 17 patients prior to surgery, and 71% of them became carriers of this bacterium at the implant site by the second postoperative week. The number of F. nucleatum-positive subjects around the implant was significantly lower than the number of F. nucleatum-positive subjects around teeth (P < 0.05). CONCLUSIONS: Peri-implant soft tissue clinical maturity may be established as early as 4 weeks following implant placement by a one-stage surgical protocol; neither preexisting flap thickness nor papillary height seemed to influence newly forming peri-implant sulcus depth or bleeding on probing prevalence. For the most part, the newly created peri-implant crevices were colonized by specific bacteria within 2 weeks. [Abstract]

Mardinger O, Nissan J, Chaushu G
Sinus floor augmentation with simultaneous implant placement in the severely atrophic maxilla: technical problems and complications.
J Periodontol. 2007 Oct;78(10):1872-7.
BACKGROUND: A one-stage surgical technique has been adopted that allows simultaneous implant placement in as little as 1 to 2 mm of residual bone. The aim of this retrospective study was to describe results and complications in sinus augmentation of severely atrophic edentulous maxillae in patients with 1 to 3 mm residual bone height and compare them to a group of patients treated following the standard protocol with residual bone height > 4 mm. METHODS: The study consisted of a study group (N = 25) and a control group (N = 30). All patients were consecutive admissions treated for one-stage sinus augmentation by one surgeon during the years 2001 to 2005. Patients' medical files were reviewed mainly regarding operative technical problems and complications. RESULTS: Included in the study were 60 sinuses and 164 simultaneous implants placed in grafted maxillary sinuses. Eight implants failed, seven of which were in the study group; three were in heavy smokers with residual bone of 1 to 3 mm. The success rate was 92% for the study group and 98.7% for the control group. A borderline statistically significant difference was found in the success rates between the groups using the Fisher exact test (P = 0.069). CONCLUSION: Sinus augmentation with simultaneous implant placement can be used to treat the atrophic maxilla in patients with 1 to 3 mm of vertical residual bone height when careful case planning and surgical techniques are used. [Abstract]

Gaspirc B, Skaleric U
Clinical evaluation of periodontal surgical treatment with an Er:YAG laser: 5-year results.
J Periodontol. 2007 Oct;78(10):1864-71.
BACKGROUND: The aim of the present study was to evaluate and compare the long-term clinical outcomes of erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser-assisted periodontal flap surgery versus conventional treatment with the modified Widman flap procedure. METHODS: A total of 146 single-rooted periodontally involved teeth from 25 patients were included in this study. In each patient, left or right maxillary single-rooted teeth were assigned randomly to one of two groups: group A (Er:YAG laser) and group B (modified Widman flap surgery). Er:YAG laser was used to debride the bone pockets, scale the root surface, and trim the periodontal flap. Recession, probing depth (PD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), and bleeding on probing (BOP) scores were recorded at baseline and at 3, 6, 12, 24, 36, 48, and 60 months. RESULTS: Both treatments resulted in decreases in PD, PI, GI, and BOP, increases in gingival recession, and gains in CAL. PD reduction in group A versus group B was statistically significant at 6, 12, 24, and 36 months (P < 0.05). Gains in CAL were significantly greater in group A versus group B at 6, 12, 24, and 36 months. BOP scores were significantly lower in group A versus group B at 3 and 6 months (P < 0.05). All other differences between treatment groups were not statistically significant. CONCLUSIONS: Surgical treatment of single-rooted teeth with chronic periodontitis using the Er:YAG laser yields greater PD reduction and gains in CAL for up to 3 years compared to conventional Widman flap surgery. The short-term results obtained with both treatments can be maintained over 5 years. [Abstract]

Matos SM, Guerra FA, Krauser J, Marques F, Ermida JM, Sanz M
Clinical evaluation of the combination of anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (P-15) in particulate and hydrogel form as a bone replacement graft material in human periodontal osseous defects: 6-month reentry controlled clinical study.
J Periodontol. 2007 Oct;78(10):1855-63.
BACKGROUND: This prospective, randomized, controlled clinical trial study compared the clinical outcomes of the biomaterial anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (ABM/P-15) as a biocompatible hydrogel carrier consisting of carboxymethylcellulose and glycerol or in particulate form when used as a bone replacement graft in the treatment of human periodontal infrabony defects. METHODS: Nineteen patients with advanced chronic periodontitis were recruited. All patients had at least two non-adjacent intrabony osseous defects > or = 3 mm after completion of cause-related periodontal therapy. The surgical procedures included access flaps for root instrumentation and filling the defect with ABM/P-15 in hydrogel or particulate form. Reentry access flap surgery was performed at 6 months. Changes in soft and hard tissue outcome measurements between baseline and 6 months were evaluated in all defects. RESULTS: At 6 months, no significant differences between ABM/P-15 hydrogel and ABM/P-15 particulate were demonstrated for the amount of defect fill (3.10 +/- 0.85 mm [75.0%] versus 3.09 +/- 1.11 mm [73.7%], respectively) or defect resolution (85.8% versus 81.9%). Changes in soft tissue clinical outcomes did not show significant differences between the treatments. CONCLUSION: This trial failed to demonstrate superiority of the novel ABM/P-15 hydrogel therapeutic modality over the standard ABM/ P-15 particulate graft in the treatment of intrabony periodontal defects. [Abstract]


Erratum.
J Periodontol. 2007 Dec;78(12):2395. [Abstract]

Stübinger S, Landes C, Seitz O, Sader R
Er:YAG Laser Osteotomy for Intraoral Bone Grafting Procedures: A Case Series With a Fiber-Optic Delivery System.
J Periodontol. 2007 Dec;78(12):2389-94.
Background: With a wavelength of 2.94 mum, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser is suitable for cutting vital osseous tissue. To analyze the benefit of laser osteotomy in implant dentistry, a fiber-guided Er:YAG laser was used for harvesting intraoral bone grafts. Methods: In 10 consecutive patients (six males and four females), 12 block grafts were obtained from the ramus (nine cases), chin (two cases), and tuberosity (one case) region. For the osteotomies, the laser settings included a pulse energy of 500 mJ, a pulse duration of 250 microseconds, and a pulse frequency of 12 Hz. During osteotomy, the laser fiber tip was kept 1 to 2 mm away from the bone surface. Results: Cut efficiency was satisfactory with almost no constraint on the positioning of the laser tip. Laser osteotomy was precise and allowed the blocks to be prepared with minimal waste of bone. The risk for accidentally injuring adjacent soft tissues was minimal. The postoperative wound-healing process was not impaired, and there were no signs of carbonization; however, the surgical procedures were time consuming. Conclusions: Using the Er:YAG laser with the aforementioned settings, successful laser osteotomy was achieved without any complications. However, because laser osteotomy was time-intensive and offered no depth control, it demonstrated only slight advantages for intraoral bone-grafting procedures. If the ablation process could be accelerated, the Er:YAG laser would be a promising alternative to conventional instruments for this surgical technique. [Abstract]

Lin S, Mayer Y
Treatment of a Large Periradicular Lesion of Endodontic Origin Around a Dental Implant With Enamel Matrix Protein Derivative.
J Periodontol. 2007 Dec;78(12):2385-2388.
Background: This case report describes the healing of a large periradicular lesion involving an adjacent implant. Endodontic surgery was performed in combination with placement of an enamel matrix protein derivative. Methods: Endodontic surgery was performed, including root end resection at a 90 degrees angle. Ultrasonic tips were used for retrograde preparation, and the retrograde cavity was sealed with zinc oxide-eugenol. The area was filled carefully with enamel matrix proteins. Sutures were removed after a 2-week healing period. Results: There were no symptoms of pain, inflammation, or discomfort at 18 months post-surgery. Radiographs showed complete healing of the periradicular lesion. Conclusions: Combining an enamel matrix protein derivative with conventional surgery may improve the clinical outcome of large endodontic lesions. Additional research is warranted. [Abstract]

Schulze A, Schönauer M, Busse M
Sudden improvement of insulin sensitivity related to an endodontic treatment.
J Periodontol. 2007 Dec;78(12):2380-4.
Background: Inflammation contributes to the pathogenesis of diabetes. A reciprocal relationship exists between diabetes and chronic periodontitis. This report describes the effects of an acute focal dental inflammation and subsequent endodontic treatment on the required insulin dosage of a 70-year-old man who had moderately controlled diabetes. Methods: Following an exacerbation of a combined endodontic-periodontic (endo-perio) lesion of tooth #3, the patient noticed a sudden increase in his insulin demand. After 3 weeks, the required dosage was approximately 100% greater. In association with hyperglycemic incidents, he reported a prickling sensation in this tooth. The radiograph showed circular bone loss around the tooth. Results: Just 1 day after the root-canal preparation, the insulin need decreased to approximately 50% of that required prior to treatment. Subsequently, an incision and systemic antibiotics were necessary because of the formation of a periodontal abscess. The insulin demand remained low despite this complication. Forty days after endodontic treatment, the insulin dosage was at a level comparable to that taken 4 weeks before the root-canal preparation. Conclusions: This clinical case revealed a highly relevant correlation between insulin resistance and a local dental inflammation. To avoid an increase in insulin resistance, it seems important to attend to radically non-vital teeth as well as any other dental inflammation in diabetic patients. [Abstract]

Heng NH, N'guessan PD, Kleber BM, Bernimoulin JP, Pischon N
Enamel Matrix Derivative Induces Connective Tissue Growth Factor Expression in Human Osteoblastic Cells.
J Periodontol. 2007 Dec;78(12):2369-2379.
Background: Enamel matrix derivative (EMD) stimulates the production of transforming growth factor-beta (TGF-beta), which has been suggested to play a role in mediating the effects of EMD in periodontal tissue regeneration. Connective tissue growth factor (CTGF) is a mediator of TGF-beta and promotes cell development. The interaction between EMD and CTGF is unknown. This study explored the effects of EMD on CTGF expression in human osteoblastic cells and whether the interaction is modulated by the TGF-beta signaling pathway. Also, the roles of CTGF in cell proliferation, cell cycle progression, and mineralized nodule formation of EMD-induced osteoblastic cultures were examined. Methods: Human osteoblastic cells (Saos-2) were treated with 25 to 100 mug/ml EMD with or without the addition of TGF-beta inhibitor. CTGF mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), and CTGF protein levels were assayed by Western blot analysis. In addition, cell cycle progression and DNA synthesis were determined by flow cytometry and 5-bromo-2'-deoxyuridine (BrdU) incorporation following EMD treatment with or without CTGF antibody. Mineralization was examined by alizarin red staining and quantified by elution with cetylpyridinium chloride. Results: Western blot and RT-PCR analysis demonstrated a dose-dependent increase of CTGF expression by EMD. EMD-induced CTGF expression was reduced significantly in the presence of TGF-beta inhibitor. Cell cycle and BrdU analysis revealed an increase in cell proliferation following EMD treatment, which was due to an increase in the percentage of cells in the G2/M phase of the cell cycle. No significant effect was found when anti-CTGF antibody was added. Conversely, mineralization was inhibited significantly in EMD-treated cultures in the presence of anti-CTGF antibody. Conclusions: EMD stimulates CTGF expression, and the interaction is modulated via TGF-beta in osteoblastic cells. Also, CTGF affects EMD-induced osteoblastic mineralization but not cell proliferation. To our knowledge, these results provide novel insight into EMD-CTGF interaction, two biomodifiers that have therapeutic relevance to tissue engineering and regeneration. [Abstract]

Bulut S, Ozdemir BH
Apoptosis and Expression of Caspase-3 in Cyclosporin-Induced Gingival Overgrowth.
J Periodontol. 2007 Dec;78(12):2364-2368.
Background: The pathogenesis of epithelial thickening in gingival overgrowth remains obscure. Apoptosis plays an important role in maintaining tissue hemostasis. The aim of the present study was to investigate apoptosis via immunohistochemical analyses in cyclosporin A-induced gingival overgrowth tissue samples to determine whether these processes play a role in the pathogenesis of gingival overgrowth. Methods: Gingival biopsies (one per person) were harvested from 22 renal transplant recipients (eight men and 14 women; mean age, 36.4 +/- 13.3 years) who had been diagnosed with cyclosporin A-induced gingival enlargement and from 12 systemically healthy persons (seven men and five women; mean age, 27.0 +/- 16.0 years) with plaque-induced gingivitis. Distributions of caspase-3 and apoptosis were determined immunologically. Results: Significant differences were found with regard to caspase-3 levels and the extent of apoptosis between the cyclosporin A group and the control group. Plaque index, gingival index, and probing depths were significantly lower in the control group. Conclusion: The extent of keratinocyte apoptosis and decreased levels of caspase-3 may be an important factor affecting the gingiva of kidney transplant recipients with cyclosporin A-induced gingival overgrowth. [Abstract]

Watkins HR, Lapp CA, Hanes PJ, Dickinson DP, Volkmann KR, Newman CL, Konzelman JL
CCL28 Effects on Periodontal Pathogens.
J Periodontol. 2007 Dec;78(12):2356-2363.
Background: Chemokines are small proteins that signal to and attract cells of the immune system; they are vital components in the modulation of immunity and wound healing. A newly described chemokine was reported to have antibacterial and antifungal activity. This chemokine, chemokine (C-C motif) ligand 28 (CCL28; also called mucosae-associated epithelial chemokine), is secreted by mucosal epithelial cells and is found in saliva and in breast milk. The objective of this study was to test whether CCL28 has antibacterial activity against two anaerobic periodontal pathogens: Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Methods: We used a bacterial viability test, in which two fluorescent dyes are bound differentially to living and killed bacteria. We tested the bacteria at concentrations of 2 x 10(7)/ml, exposing them to CCL28 at concentrations from 0.04 to 10 muM. Results: CCL28 was effective at killing both organisms. After 1 hour of exposure to the chemokine under appropriate oxygen conditions, the percentage of living organisms was reduced significantly for each species. We estimated the 50% effective concentration to be approximately 0.7 muM for P. gingivalis and approximately 2.0 muM for A. actinomycetemcomitans (N = five experiments each). We confirmed these observations using standard bacterial plating methods. Conclusion: Because this chemokine is secreted into the saliva, a reduction in salivary flow (as in xerostomia) may diminish the oral self-defense mechanisms by also reducing the exposure of bacteria to the antibacterial action of CCL28. [Abstract]


Recent Articles in Journal of Periodontal Research

Morimoto Y, Kawahara KI, Tancharoen S, Kikuchi K, Matsuyama T, Hashiguchi T, Izumi Y, Maruyama I
Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1.
J Periodontal Res. 2007 Dec 6;
Background and Objective: High-mobility-group box 1 functions as a late-phase inflammatory mediator. It can be released extracellularly by macrophages and necrotic cells through lipopolysaccharide and tumor necrosis factor-alpha. The objective of this study was to clarify the source of high-mobility-group box 1 in chronic periodontitis tissues and tumor necrosis factor-alpha-stimulated gingival epithelial cells, and subsequently elucidate its inducible inflammatory pathway. Material and Methods: Chronic periodontitis and healthy gingival sections were stained for high-mobility-group box 1 by immunohistochemistry and immunofluorescence. The amounts of high-mobility-group box 1 released into the gingival crevicular fluid and supernatants from gingival epithelial cells stimulated by tumor necrosis factor-alpha were examined by western blot. The phosphorylation of mitogen-activated protein kinases (MAPKs) in gingival epithelial cells was also examined. Results: High-mobility-group box 1 was detected in the cytoplasm and nucleus of gingival epithelial cells with periodontitis. Western blotting revealed a significant increase in high-mobility-group box 1 expression in the gingival crevicular fluid from periodontitis patients. High-mobility-group box 1 production in gingival epithelial cells was increased following stimulation with tumor necrosis factor-alpha. The molecular dialogue between tumor necrosis factor-alpha and gingival epithelial cells involved modulation of the activities of p38MAPK, Jun N-terminal kinase and p44/42. Interestingly, only phosphorylation of p38MAPK contributed to more than half of the signaling initiated by tumor necrosis factor-alpha-elicited high-mobility-group box 1 release. Conclusion: High-mobility-group box 1 is continuously released from the gingival epithelial cells modulated by tumor necrosis factor-alpha. These findings imply that high-mobility-group box 1 expression and possibly p38MAPK constitute important features in periodontitis. [Abstract]

Tang X, Meng H, Han J, Zhang L, Hou J, Zhang F
Up-regulation of estrogen receptor-beta expression during osteogenic differentiation of human periodontal ligament cells.
J Periodontal Res. 2007 Nov 13;
Background and Objective: Estrogen has been shown to up-regulate the expression of osteoblastic phenotypes of human periodontal ligament cells via binding to estrogen receptors and may also help periodontal tissue regeneration. However, which subtype of estrogen receptor (alpha or beta) is predominately expressed in human periodontal ligament cells, and how estrogen receptor expression is regulated during the osteogenic differentiation of human periodontal ligament cells, is still unclear. This study aimed to explore the expression and regulation of estrogen receptor subtypes in human periodontal ligament cells and during their osteogenic differentiation. Material and Methods: Human periodontal ligament cells derived from 10 individual age-matched donors (five male and five female donors) were cultured. Human periodontal ligament cells under osteogenic induction (group M) and the corresponding controls (group C) were harvested on days 7, 14 and 21 for estrogen receptor detection. Results: Both estrogen receptor-alpha and estrogen receptor-beta mRNAs were expressed in human periodontal ligament cells from all of the 10 donors. Protein only of estrogen receptor-beta (not of estrogen receptor-alpha) was detected and was shown to be located in the nuclei of human periodontal ligament cells. The expression levels of estrogen receptor-beta mRNA and protein from both male and female donors in group M were significantly higher compared with group C during the 21-d study period. In comparison, the expression level of estrogen receptor-alpha mRNA of the donors was not significantly different from that of the controls during osteogenic differentiation and no estrogen receptor-alpha protein was detected. Conclusion: The results suggest that estrogen receptor-beta may be the predominant subtype expressed in human periodontal ligament cells and may actively participate in the osteogenic differentiation process of human periodontal ligament cells, both in male and in female subjects. [Abstract]

Laube DM, Dongari-Bagtzoglou A, Kashleva H, Eskdale J, Gallagher G, Diamond G
Differential regulation of innate immune response genes in gingival epithelial cells stimulated with Aggregatibacter actinomycetemcomitans.
J Periodontal Res. 2007 Nov 13;
Background and Objective: The gingival epithelium provides the first line of defense against colonization by periodontal pathogens, both as a physical barrier and by the production of inducible innate immune mediators such as beta-defensins and pro-inflammatory cytokines. The gram-negative bacterium Aggregatibacter actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, although the bacterium is found widely in the healthy population. We hypothesized that gingival epithelial cell-derived innate immune mediators triggered in response to A. actinomycetemcomitans infection may play an important role in increased susceptibility to infection. Material and Methods: Primary cultures of human gingival epithelial cells were cultured in the presence of A. actinomycetemcomitans. Total mRNA was examined for the presence of innate immune markers using RT-PCR. Results: We show here that the mRNA levels of human beta-defensin 2 and interleukin-8 are elevated by live cultures of a clinical isolate of A. actinomycetemcomitans in cultured gingival epithelial cells from healthy individuals, but not by A. actinomycetemcomitans lipopolysaccharide. Cells from a patient with localized aggressive periodontitis, however, did not respond to this bacterial stimulation. In contrast, the pro-inflammatory cytokine interleukin-19 was induced in cells from both localized aggressive periodontitis and healthy subjects. Examination of Toll-like receptors and associated adapter molecules indicated lower levels of Toll-like receptor 2 mRNA in the localized aggressive periodontitis patient-derived cells compared with cells from healthy subjects. Conclusion: These results suggest that a differential expression of innate immune response genes to A. actinomycetemcomitans in the gingival epithelium could be an underlying factor of susceptibility to localized aggressive periodontitis. [Abstract]

Yamanaka A, Kouchi T, Kasai K, Kato T, Ishihara K, Okuda K
Inhibitory effect of cranberry polyphenol on biofilm formation and cysteine proteases of Porphyromonas gingivalis.
J Periodontal Res. 2007 Dec;42(6):589-92.
BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of cranberry polyphenol fraction on biofilm formation and activities of Arg-gingipain and Lys-gingipain in Porphyromonas gingivalis. MATERIAL AND METHODS: The polyphenol fraction was prepared by using a glass column packed with Amberlite XAD 7HP and 70% aqueous ethanol as an elution solvent. RESULTS: Synergistic biofilm formation by P. gingivalis and Fusobacterium nucleatum was significantly inhibited by the polyphenol fraction at a concentration of 250 microg/mL compared with untreated controls (p < 0.01). Arg-gingipain and Lys-gingipain activities in P. gingivalis ATCC 33277 and FDC 381 were inhibited significantly at a polyphenol fraction concentration of > or = 1 microg/mL (p < 0.05). CONCLUSION: These findings indicate that the polyphenol fraction inhibits biofilm formation and the Arg-gingipain and Lys-gingipain activities of P. gingivalis. [Abstract]

Sukkar TZ, Thomason JM, Cawston TE, Lakey R, Jones D, Catterall J, Seymour RA
Gingival fibroblasts grown from cyclosporin-treated patients show a reduced production of matrix metalloproteinase-1 (MMP-1) compared with normal gingival fibroblasts, and cyclosporin down-regulates the production of MMP-1 stimulated by pro-inflammatory cytokines.
J Periodontal Res. 2007 Dec;42(6):580-8.
BACKGROUND AND OBJECTIVE: Cyclosporin-induced gingival overgrowth arises from an alteration in collagen homeostasis and is enhanced by inflammatory changes in the gingival tissues. The aim of this study was to investigate the interaction among interleukin-1, oncostatin M, cyclosporin and nifedipine in promoting the up-regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase by gingival fibroblasts. MATERIAL AND METHODS: Fibroblast cultures (n = 5) were obtained from healthy controls and from patients with cyclosporin-induced gingival overgrowth, and cells were harvested between the fourth and ninth passages. Cells were stimulated with interleukin-1 and oncostatin M, alone or in combination, and with different concentrations of cyclosporin (0-2000 ng/mL) and nifedipine (0-200 ng/mL). MMP-1 and tissue inhibitor of metalloproteinase-1 production was determined using an enzyme-linked immunosorbent assay technique. A CyQuant cell proliferation assay was used to determine the DNA concentration in the sample. RESULTS: Fibroblasts obtained from patients with cyclosporin-induced gingival overgrowth produced significantly lower levels of MMP-1 than control fibroblasts (p < 0.001); tissue inhibitor of metalloproteinase-1 levels were significantly lower (p < 0.05), and the ratio of MMP-1 to tissue inhibitor of metalloproteinase-1 was reduced, in the conditioned medium of patients with cyclosporin-induced gingival overgrowth compared with controls. Interleukin-1 and oncostatin M produced a significant increase in the up-regulation of MMP-1, which was reversed when cyclosporin and nifedipine were added to the cell cultures (p < 0.05). CONCLUSION: Pro-inflammatory cytokines significantly up-regulate MMP-1 in cultured gingival fibroblasts. Up-regulation is attenuated by both cyclosporin and nifedipine. The interaction may account for the synergism between inflammation and cyclosporin-induced gingival overgrowth. [Abstract]

Yoshizawa S, Meguro M, Ohyama H, Takeuchi-Hatanaka K, Matsushita S, Takashiba S, Nishimura F
Focal adhesion kinase mediates human leukocyte histocompatibility antigen class II-induced signaling in gingival fibroblasts.
J Periodontal Res. 2007 Dec;42(6):572-9.
BACKGROUND AND OBJECTIVE: The role of human leukocyte antigen class II molecules on nonantigen-presenting cells has been a matter of controversy. We previously reported that human leukocyte antigen class II molecules on human gingival fibroblasts do not present antigens, but transduce signals into the cells by making a complex with antigenic peptide T-cell receptor or by stimulating cell surface human leukocyte antigen-DR molecules with human leukocyte antigen-DR antibody (L243), which mimics the formation of the human leukocyte antigen class II-antigenic peptide T-cell receptor complex, resulting in the expression of several cytokines. The aim of this study was to detect human leukocyte antigen class II-associated molecules mediating human leukocyte antigen class II-induced signals into the cells. MATERIAL AND METHODS: Antibody-based protein-microarray analysis was performed to detect activated signaling molecules in gingival fibroblasts stimulated via human leukocyte antigen class II molecules. Then, we examined if these molecules structurally associate with human leukocyte antigen class II and actually transduce signals into the cells. RESULTS: Stimulation of human leukocyte antigen class II on gingival fibroblasts by L243 resulted in enhanced phosphorylation of focal adhesion kinase. Focal adhesion kinase was co-immunoprecipitated with human leukocyte antigen-DR by L243. Stimulation of gingival fibroblasts with L243 induced phosphorylation of focal adhesion kinase. Luteolin, a putative focal adhesion kinase inhibitor, suppressed phosphorylation of focal adhesion kinase and dose dependently inhibited human leukocyte antigen class II-induced cytokine production. CONCLUSION: Focal adhesion kinase is structurally associated with human leukocyte antigen-DR and mediates human leukocyte antigen class II-induced signals in gingival fibroblasts. [Abstract]

Noda D, Hamachi T, Inoue K, Maeda K
Relationship between the presence of periodontopathic bacteria and the expression of chemokine receptor mRNA in inflamed gingival tissues.
J Periodontal Res. 2007 Dec;42(6):566-71.
BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic disease characterized by the interaction between periodontopathic bacteria and the host immune response. The aim of this study was to investigate the correlation between periodontopathic bacteria and host immune cell infiltrates. MATERIAL AND METHODS: Twenty-two patients with chronic periodontitis were included in this study. Gingival tissues were taken at the periodontal surgery after completion of initial therapy. Three types of periodontopathic bacteria were detected by polymerase chain reaction, and the prevalence of mRNA expression of chemokine receptors was examined by reverse-transcription-polymerase chain reaction in the gingival tissues. The infiltration of T and B cells was determined by an immunohistochemical method. RESULTS: In the patients, both Porphyromonas gingivalis and Tanerella forsythia were detected, and the mRNA expression of chemokine receptors CXCR1&2, CXCR4, CCR1, CCR2, CCR3 and CCR4 were more prevalent. The mean number of infiltrated B cells was significantly larger than that of T cells in the sites harboring both P. gingivalis and T. forsythia. Similarly, in the sites where P. gingivalis was detected but T. forsythia was not, the mean number of B cells was significantly larger than that of T cells. In the sites with mRNA expression of CCR2 and CCR3, the mean number of B cells was significantly larger. CONCLUSION: These results suggest that a high proportion of T helper 2-associated chemokine receptor-positive T cells may be associated with the predominance of B cells and may play an important role in the formation of chronic periodontitis in sites where both P. gingivalis and T. forsythia are detected. [Abstract]

Borrell LN, Kunzel C, Lamster I, Lalla E
Diabetes in the dental office: using NHANES III to estimate the probability of undiagnosed disease.
J Periodontal Res. 2007 Dec;42(6):559-65.
BACKGROUND AND OBJECTIVE: Recent data have suggested that in the past 15 years there has been a dramatic increase in the incidence of diabetes mellitus in the USA. However, evidence suggests that approximately one-third of diabetes cases remain undiagnosed. Because 60% of Americans see a dentist at least once per year for routine, nonemergent, care, it is reasonable to propose that the dental office can be a healthcare location actively involved in screening for unidentified diabetes. MATERIAL AND METHODS: This study used NHANES III to develop a predictive equation that can form the basis of a tool to help dentists determine the probability of undiagnosed diabetes by using self-reported data and periodontal clinical parameters routinely assessed in the dental office. RESULTS: Our analyses reveal that individuals with a self-reported family history of diabetes, hypertension, high cholesterol levels and clinical evidence of periodontal disease bear a probability of 27-53% of having undiagnosed diabetes, with Mexican-American men exhibiting the highest probability and white women the lowest. CONCLUSION: These findings suggest that the dental office could provide an important opportunity to identify individuals unaware of their diabetic status. [Abstract]

Gnoatto N, Lotufo RF, Matsuda M, Penna V, Marquezini MV
Expression of cell-surface heparan sulfate proteoglycans in human cyclosporin-induced gingival overgrowth.
J Periodontal Res. 2007 Dec;42(6):553-8.
BACKGROUND AND OBJECTIVE: Cyclosporin A-induced gingival overgrowth comprises a variety of signaling pathways (including growth factors and proteoglycans) that are still not completely understood. In the present study, gingival overgrowth was investigated in transplant patients receiving cyclosporin A (cyclosporin A group) and compared with gingival tissues never exposed to the drug (control group) by analyzing the gene expression of the cell-surface heparan sulfate proteoglycans syndecan-2, syndecan-4 and betaglycan. MATERIAL AND METHODS: mRNA analysis was carried out by reverse transcription-polymerase chain reaction amplification of pooled samples from nine patients of the cyclosporin A group and six control subjects. The groups were compared by the Student's t-test. RESULTS: The expression of heparan sulfate proteoglycans was increased in the cyclosporin A group (165% for syndecan-2, 308% for syndecan-4, and 42% for betaglycan) compared with the control group. CONCLUSION: Our findings agree with the current concept of cyclosporin A-induced gingival overgrowth and provide new evidence that its noncollagenous extracellular matrix is overexpressed. [Abstract]

Johannsen A, Rydmark I, Söder B, Asberg M
Gingival inflammation, increased periodontal pocket depth and elevated interleukin-6 in gingival crevicular fluid of depressed women on long-term sick leave.
J Periodontal Res. 2007 Dec;42(6):546-52.
BACKGROUND AND OBJECTIVE: The aim of this work was to investigate periodontal status, in relation to inflammatory markers and cortisol, in the gingival crevicular fluid and saliva of a homogenous group of women on long-term sick leave for job-stress related depression in comparison to nondepressed women. MATERIAL AND METHODS: The participants comprised 20 women with depression (DSM-IV) (mean age 48.5 +/- 6.9 years) and 29 healthy controls (mean age 54.5 +/- 2.9 years). Clinical examination was performed. Gingival crevicular fluid was collected by an intracrevicular washing technique. Interleukin-1 beta, interleukin-6, matrix metalloproteinase (MMP)-8 and MMP-9 were determined with enzyme-linked immunosorbent assay and cortisol was determined by using a radioimmunoassay. One-way analysis of covariance was used as the statistical method. RESULTS: The depressed patients had significantly higher gingival inflammation (p < 0.001), and deeper pockets (p < 0.003), than the healthy controls, after adjusting for age and smoking. The levels of interleukin-6 in the gingival crevicular fluid were significantly higher in the patients than in the controls: 3.84 +/- 1.58 pg per site and 0.79 +/- 1.83 pg per site, respectively, p < 0.003. There were no significant differences in the levels of interleukin-1 beta, MMP-8 and MMP-9. The patients had lower cortisol values in gingival crevicular fluid than the controls, whereas the levels of cortisol in saliva were similar in both groups. CONCLUSION: Women on long-term sick-leave for depression had more severe periodontitis and higher concentrations of interleukin-6 in gingival crevicular fluid than healthy controls. An alteration of the immune system in these patients might be interpreted as reflecting the consequences of long-term stress exposure and might contribute to worse periodontal conditions in these particular patients. [Abstract]

Fukusaki T, Ohara N, Hara Y, Yoshimura A, Yoshiura K
Evidence for association between a Toll-like receptor 4 gene polymorphism and moderate/severe periodontitis in the Japanese population.
J Periodontal Res. 2007 Dec;42(6):541-5.
BACKGROUND AND OBJECTIVE: Chronic periodontitis is an inflammatory disease caused by bacteria in subgingival pockets. Because Toll-like receptor 2 and Toll-like receptor 4 have been shown to play an important role in the recognition of periodontal pathogens, we investigated the relevance of genetic variations in TLR2 and TLR4 to susceptibility to periodontitis. MATERIAL AND METHODS: A total of 97 patients with chronic periodontitis and 100 control subjects were examined for mutations in TLR2 and TLR4. Case-control analysis was performed using individual single nucleotide polymorphisms detected during the mutation search. RESULTS: The missense mutations reported previously in TLR2 (677 Arg>Trp and 753 Arg>Gln) and in TLR4 (299 Asp>Gly and 399 Thr>Ile) were not detected in 97 of the Japanese patients with chronic periodontitis or in 100 of the Japanese control subjects. Nine single nucleotide polymorphisms were identified in exons of TLR2 and TLR4. The case-control analysis revealed that the frequency of the C/C genotype at base-pair position +3725 in TLR4 was significantly higher in both the moderate and the severe periodontitis patient group than in the control group. CONCLUSION: A genetic variation of TLR4 might be associated with moderate and severe periodontitis in the Japanese population. [Abstract]

Gómez-Moreno G, Cutando-Soriano A, Arana C, Galindo P, Bolańos J, Acuńa-Castroviejo D, Wang HL
Melatonin expression in periodontal disease.
J Periodontal Res. 2007 Dec;42(6):536-40.
BACKGROUND AND OBJECTIVE: It was the purpose of this study to examine the relationship between periodontal diseases and melatonin level. Material and METHODS: Forty-six patients with periodontal disease, together with 26 age- and gender-matched healthy controls, were included. Periodontal status was assessed using the Community Periodontal Index. Plasma and salivary melatonin levels were determined using specific commercial radioimmunoassays, whereas lymphocyte subpopulations (e.g. CD3, CD4, CD8, C19 and natural killer cells) were analyzed using flow cytometry. RESULTS: Patients with periodontal disease had significantly (p < 0.001) lower plasma (9.46 +/- 3.18 pg/mL) and saliva (2.55 +/- 0.99 pg/mL) melatonin levels than healthy control patients (14.33 +/- 4.05 and 4.22 +/- 0.87 pg/mL, respectively). A biphasic relationship was observed between plasma melatonin levels and Community Periodontal Indices. The plasma melatonin level was reduced in patients with a lower Community Periodontal Index value (1 or 2) and increased in patients with a higher Community Periodontal Index value (3 or 4). Salivary melatonin parallels the changes of plasma melatonin. The higher the Community Periodontal Index, the older the patient and the higher the total lymphocyte counts. CD4 concentrations also increased as the disease worsened. CONCLUSION: The results obtained from this study suggest that melatonin could act as a protective function in fighting periodontal infection. However, further studies in this area are encouraged. [Abstract]

Leon ER, Iwasaki K, Komaki M, Kojima T, Ishikawa I
Osteogenic effect of interleukin-11 and synergism with ascorbic acid in human periodontal ligament cells.
J Periodontal Res. 2007 Dec;42(6):527-35.
BACKGROUND AND OBJECTIVE: Human periodontal ligament cells are considered to be a key cell type in the regeneration of periodontal tissues because of their unique localization and stem cell-like properties. Interleukin-11 is a multifunctional cytokine known to participate actively in bone metabolism. The purpose of this study was to examine the effect of interleukin-11 on the osteoblastic differentiation of periodontal ligament cells. MATERIAL AND METHODS: Cultured periodontal ligament cells were stimulated with interleukin-11 and/or ascorbic acid, with or without inhibitors for type 1 collagen, janus kinase/signal transducers and activator of transcription, and mitogen-activated protein kinase (MAPK). Osteoblastic differentiation was investigated by examining the alkaline phosphatase activity and gene expression of Runx2, osteocalcin and bone sialoprotein using reverse transcription-polymerase chain reaction. Type 1 collagen and tissue inhibitor of metalloproteinase-1 production were measured using enzyme-linked immunosorbent assays. RESULTS: Interleukin-11 enhanced alkaline phosphatase activity and Runx2, osteocalcin and bone sialoprotein gene expression in the presence of ascorbic acid. Interleukin-11 induced type 1 collagen and tissue inhibitor of metalloproteinase-1 production in periodontal ligament cells. Type 1 collagen inhibitor completely inhibited the alkaline phosphatase activity enhanced by interleukin-11 and ascorbic acid. Furthermore, janus kinase/signal transducers and activator of transcription and MAPK signaling inhibitors reduced interleukin-11/ascorbic acid-induced alkaline phosphatase activity in periodontal ligament cells. CONCLUSION: Interleukin-11/ascorbic acid induced the osteoblastic differentiation of periodontal ligament cells through type 1 collagen production and janus kinase/signal transducers and activator of transcription, and MAPK signaling pathways were involved in this process. These findings suggest that interleukin-11 may function as an osteopromotive cytokine, stimulating the osteoblastic differentiation of periodontal ligament cells mainly through the synthesis of type 1 collagen and possibly by the induction of tissue inhibitor of metalloproteinase-1. [Abstract]

Koshi R, Sugano N, Orii H, Fukuda T, Ito K
Microarray analysis of nicotine-induced changes in gene expression in a macrophage-like human cell line.
J Periodontal Res. 2007 Dec;42(6):518-26.
BACKGROUND AND OBJECTIVE: Cigarette smoking has been suggested as a risk factor for periodontitis. Thousands of components are present in cigarette smoke, including nicotine, which may play an important role in the observed effects of smoking on cell metabolism. However, the mechanisms underlying these effects are unclear. Using DNA microarrays, we monitored differentially expressed genes, responsive to nicotine, in a macrophage-like human cell line. MATERIAL AND METHODS: Human U937 cells were treated for 1 h, with or without 1.0 microg/ml of nicotine. For differentiation, cultures were incubated with 10 nm phorbol myristate acetate for 48 h. Analysis of gene expression was performed using a DNA microarray of 8500 genes. RESULTS: The expression of 4914 genes was detected. Screening was carried out on those genes whose expression in three separate experiments showed an average change of twofold or greater, and 118 up-regulated genes and 97 down-regulated genes were identified. Among these were genes related to inflammation and other immune responses, such as phospholipase A2 and interferon. Consistent with the array findings, we found similar changes in mRNA expression after analysis using the real-time polymerase chain reaction. CONCLUSION: The results suggest that nicotine causes excess inflammation and disturbs host defense mechanisms against pathogens. [Abstract]

Zhao L, Wu YF, Meng S, Yang H, OuYang YL, Zhou XD
Prevalence of fimA genotypes of Porphyromonas gingivalis and periodontal health status in Chinese adults.
J Periodontal Res. 2007 Dec;42(6):511-7.
BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis fimbriae play a key role in colonization of the oral cavity. The fimA gene, which encodes fimbrillin (FimA), can be classified into six types (I-V and Ib) according to nucleotide sequence. In the present study, we investigated the relationship between the prevalence of P. gingivalis-specific fimA genotypes and periodontal health status in Chinese adults. MATERIAL AND METHODS: One-hundred and fifteen patients with chronic periodontitis and 136 periodontally healthy adults were selected. P. gingivalis detection, determination of fimA genotypes, and the co-existence of Actinobacillus actinomycetemcomitans and Tannerella forsythia with various fimA types, were assessed by the polymerase chain reaction. Odds ratios and 95% confidence intervals were calculated for associating the fimA-specific genes with periodontitis. RESULTS: P. gingivalis was detected in 22.1% of healthy subjects and in 81.7% of the patients. A single fimA genotype was detected in most samples. In healthy adults, the most prevalent fimA genotype was type I (66.7%). However, type II was detected most frequently (43.6%) in the patient group, followed by type IV (30.9%). The frequency of co-existing A. actinomycetemcomitans and T. forsythia was highest in type II fimA-positive sites. Statistical analysis revealed that periodontitis was associated with occurrences of type I (odds ratio 0.97), Ib (odds ratio 13.26), II (odds ratio 36.62), III (odds ratio 4.57), IV (odds ratio 22.86) and V (odds ratio 1.19). CONCLUSION: P. gingivalis type II followed by type IV were considered as disease-associated strains that account for the pathogenesis of chronic periodontitis in Chinese adults. [Abstract]

Ji S, Kim Y, Min BM, Han SH, Choi Y
Innate immune responses of gingival epithelial cells to nonperiodontopathic and periodontopathic bacteria.
J Periodontal Res. 2007 Dec;42(6):503-10.
BACKGROUND AND OBJECTIVE: We have previously reported different susceptibilities of periodontopathic and nonperiodontopathic bacteria to antimicrobial peptides and phagocytosis by neutrophils. Differences between the two groups of bacteria may exist also in their ability to induce immune responses from the host. Therefore, we evaluated the effects of various oral bacteria on innate immune responses by gingival epithelial cells. MATERIAL AND METHODS: HOK-16B cells were cocultured with live or lysed nonperiodontopathic (n = 3) and periodontopathic (n = 5) bacterial species. The levels of human beta defensin-1, -2 and -3, and of the cathelicidin, LL-37, were examined by real-time reverse transcription-polymerase chain reaction, and the accumulated interleukin-8 and interleukin-1 alpha were measured by enzyme-linked immunosorbent assay. RESULTS: Nonperiodontopathic bacteria up-regulated some antimicrobial peptides without affecting the levels of cytokines. In the periodontopathic group, the orange-complex bacteria induced antimicrobial peptides and interleukin-8 efficiently, but the red-complex bacteria often demonstrated suppressive effects. In contrast to live bacteria, bacterial lysates had no suppressive effects. In addition, some bacterial lysates demonstrated a reduced ability to induce antimicrobial peptides compared with live bacteria. CONCLUSION: The nonperiodontopathic, the orange-complex, and the red-complex bacteria had different effects on the innate immune responses from gingival epithelial cells, which may affect the outcome of their host-microbial interaction in gingival sulcus. [Abstract]

Rufail ML, Schenkein HA, Koertge TE, Best AM, Barbour SE, Tew JG, van Antwerpen R
Atherogenic lipoprotein parameters in patients with aggressive periodontitis.
J Periodontal Res. 2007 Dec;42(6):495-502.
BACKGROUND AND OBJECTIVE: Certain types of chronic infection increase the plasma level of very-low-density lipoprotein, leading to formation of the particularly atherogenic low-density lipoprotein subclass, small dense low-density lipoprotein. In the present study, we examined whether aggressive forms of periodontitis are associated with these atherogenic lipoprotein parameters. MATERIAL AND METHODS: Twelve healthy control subjects without periodontitis, 12 subjects with localized aggressive periodontitis and 12 subjects with generalized aggressive periodontitis were studied. Lipoprotein subclass levels were determined using nuclear magnetic resonance methodology. RESULTS: Healthy control subjects, localized aggressive periodontitis subjects and generalized aggressive periodontitis subjects had progressively higher plasma levels of very-low-density lipoprotein and progressively smaller average low-density lipoprotein size (p < 0.05, one-way analysis of variance). In pairwise comparisons, differences were only significant between healthy controls and generalized aggressive periodontitis subjects (p < 0.05, Tukey's post test). After adjustment for body mass index, the mean periodontal pocket depth correlated positively with plasma very-low-density lipoprotein levels (p = 0.047). Very-low-density lipoprotein concentrations correlated positively with small dense low-density lipoprotein levels and negatively with average low-density lipoprotein size. Prevalence of the atherogenic lipoprotein pattern-B in healthy controls, localized aggressive periodontitis subjects and generalized aggressive periodontitis subjects was 8.3%, 33.3% and 66.6%, respectively. CONCLUSION: These results indicate that periodontal infection is associated with elevated plasma levels of atherogenic lipoprotein species. This association may account for the increased risk of periodontitis patients for cardiovascular disease. [Abstract]

Pham L, Bezouglaia O, Camargo PM, Nervina JM, Tetradis S
Prostanoids induce egr1 gene expression in cementoblastic OCCM cells.
J Periodontal Res. 2007 Oct;42(5):486-93.
BACKGROUND AND OBJECTIVE: Prostanoids that activate protein kinase C signaling are potent anabolic stimulators of cementoblastic OCCM cells. Using cDNA subtractive hybridization, we identified early growth response gene-1 (egr1) as a prostanoid-induced gene. Egr1, a zinc-finger transcription factor expressed during tooth development, regulates cell growth and differentiation. We hypothesize that Egr1 may mediate part of the prostanoid-induced anabolic effect in cementoblasts. Our objective was to characterize prostanoid-induced egr1 gene expression in OCCM cells. MATERIAL AND METHODS: Total RNA and proteins were assayed by northern blot and western immunoblot assays. RESULTS: Prostaglandin E2-, prostaglandin F2alpha- and fluprostenol-induced egr1 mRNA levels peaked at 0.5 h and returned to baseline by 4 h. Prostaglandin F2alpha and fluprostenol more potently induced egr1 compared with prostaglandin E2. The phorbol ester, phorbol 12-myristate 13-acetate, which activates protein kinase C signaling, induced egr1 mRNA levels 66-fold over the control, whereas forskolin (a cAMP-protein kinase A activator) and ionomycin (a calcium activator) had no effect. Protein kinase C inhibition significantly inhibited prostaglandin E2-, prostaglandin F2alpha- and fluprostenol-induced egr1 mRNA levels. Finally, prostanoids maximally induced Egr1 protein at 1 h. CONCLUSION: egr1 is a primary response gene induced by prostaglandin E2, prostaglandin F2alpha and fluprostenol in OCCM cells through protein kinase C signaling, suggesting that Egr1 may be a key mediator of anabolic responses in cementoblasts. Cementum is vital for periodontal organ maintenance and regeneration. Periodontal ligament fibers (Sharpey's fibers) insert into bone and cementum, thereby supporting the tooth in the alveolus (1). If the periodontal organ is lost, its regeneration requires cementoblast differentiation in order to form new cementum for periodontal ligament fiber insertion. Early attempts to regenerate cementum have proven difficult and rarely generate sufficient tissue (2). A better understanding of the molecular and cellular regulators that promote cementoblast differentiation is critical for developing targeted periodontal regeneration. [Abstract]

Cheng YF, Chen JW, Lin SJ, Lu HK
Is coronally positioned flap procedure adjunct with enamel matrix derivative or root conditioning a relevant predictor for achieving root coverage? A systemic review.
J Periodontal Res. 2007 Oct;42(5):474-85.
BACKGROUND AND OBJECTIVE: This study is a systemic review of coronally positioned flap, coronally positioned flap+chemical root surface conditioning, or coronally positioned flap+enamel matrix derivative (EMD) for the treatment of Miller class I and II gingival recession. MATERIAL AND METHODS: All studies available through the Medline database by the end of October 2005 were used. Each study provided mean clinical attachment level, keratinized tissue, probing pocket depth, gingival recession depth and root coverage percentage before and after treatment with coronally positioned flap alone, coronally positioned flap+chemical root surface conditioning, or coronally positioned flap+EMD. Effectiveness was evaluated by comparing the weighted mean average in gingival recession depth, probing pocket depth, clinical attachment level, keratinized tissue and root coverage percentage achieved with the three treatments. RESULTS: Seven studies for the coronally positioned flap+EMD group, four studies for the coronally positioned flap+chemical root surface conditioning group, and seven studies for the coronally positioned flap group were retrieved for this weighted mean analysis. The results of clinical attachment level, gingival recession depth, and root coverage percentage in the coronally positioned flap+EMD group were statistically significantly better than the changes in the coronally positioned flap and coronally positioned flap+chemical root surface conditioning group at 6 and 12 mo (p<0.001). There was no significant difference at the 6-mo comparison among clinical attachment level, keratinized tissue, probing pocket depth, and gingival recession depth, except in the root coverage percentage for coronally positioned flap and coronally positioned flap+chemical root surface conditioning groups. CONCLUSION: The results suggest that root coverage by the coronally positioned flap and coronally positioned flap+chemical root surface conditioning procedures were unpredictable but became more predictable when the coronally positioned flap procedure was improved by the modification of adding EMD. [Abstract]

Spolidorio LC, Marcantonio E, Spolidorio DM, Nassar CA, Nassar PO, Marcantonio RA, Rossa C
Alendronate therapy in cyclosporine-induced alveolar bone loss in rats.
J Periodontal Res. 2007 Oct;42(5):466-73.
BACKGROUND AND OBJECTIVE: Cyclosporine A is an immunosuppressive drug that is widely used in organ transplant patients as well as to treat a number of autoimmune conditions. Bone loss is reported as a significant side-effect of cyclosporine A use because this can result in serious morbidity of the patients. As we have shown that cyclosporine A-associated bone loss can also affect the alveolar bone, the purpose of this study was to evaluate the effect of the concomitant administration of alendronate on alveolar bone loss in a rat model. MATERIAL AND METHODS: Forty Wistar rats (10 per group) were given cyclosporine A (10 mg/kg, daily), alendronate (0.3 mg/kg, weekly), or both cyclosporine A and alendronate, for 60 d. The control group received daily injections of sterile saline. The expression of proteins associated with bone turnover, including osteocalcin, alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP), and also the calcium levels, were evaluated in the serum. Analysis of the bone volume, alveolar bone surface, the number of osteoblasts per bone surface and the number of osteoclasts per bone surface around the lower first molars was also performed. RESULTS: The results indicate that cyclosporine A treatment was associated with bone resorption, represented by a decrease in the bone volume, alveolar bone surface and the number of osteoblasts per bone surface and by an increase in the number of osteoclasts per bone surface and TRAP-5b. These effects were effectively counteracted by concomitant alendronate administration. CONCLUSION: It is concluded that concomitant administration of alendronate can prevent cyclosporine A-associated alveolar bone loss. [Abstract]

Shimonishi M, Hatakeyama J, Sasano Y, Takahashi N, Uchida T, Kikuchi M, Komatsu M
In vitro differentiation of epithelial cells cultured from human periodontal ligament.
J Periodontal Res. 2007 Oct;42(5):456-65.
BACKGROUND AND OBJECTIVE: Alkaline phosphatase and noncollagenous bone proteins are produced prior to cementum formation. While it has been suggested that epithelial rests of Malassez are involved in cementum formation, little is known about the relationship between epithelial rests of Malassez and cementum formation. The purpose of the present study was to determine whether the epithelial rests of Malassez cells cultured from human periodontal ligament can produce alkaline phosphatase and noncollagenous bone proteins, such as osteopontin, osteocalcin and bone sialoprotein. MATERIAL AND METHODS: An outgrowth of putative epithelial rests of Malassez cells was produced from periodontal ligament explant, and second passage cultures were used in the experiments. Human gingival epithelial cells and periodontal ligament fibroblasts were used as controls. The expression levels of amelogenin were analyzed by immunostaining and in situ hybridization. Furthermore, the expression levels of alkaline phosphatase and noncollagenous bone proteins were assessed by immunostaining and reverse transcription-polymerase chain reaction. RESULTS: Amelogenin, alkaline phosphatase and osteopontin proteins and their corresponding mRNAs were detected at high levels in putative epithelial rests of Malassez cells. Osteocalcin and bone sialoprotein were not expressed in putative epithelial rests of Malassez cells. Alkaline phosphatase and noncollagenous bone proteins were seen in periodontal ligament fibroblasts, but not in gingival epithelial cells. CONCLUSION: Our results suggest that putative epithelial rests of Malassez cells cultured alone do not transform into maturing cells to form the cementum, but may play a potential role in the mineralization process. [Abstract]

Sharma CG, Pradeep AR
Plasma and crevicular fluid osteopontin levels in periodontal health and disease.
J Periodontal Res. 2007 Oct;42(5):450-5.
BACKGROUND AND OBJECTIVE: The level of osteopontin in gingival crevicular fluid has been found to correlate with clinical measures of periodontal disease. The present study was designed to assess the relationship between clinical parameters and osteopontin levels of the gingival crevicular fluid from inflamed gingivae, periodontitis sites and after treatment of periodontitis sites, and to correlate them to the osteopontin levels of the plasma. MATERIAL AND METHODS: Thirty, gender-matched subjects were divided into three groups--healthy, gingivitis and chronic periodontitis--based on modified gingival index scores and clinical attachment loss. The fourth group consisted of 10 subjects in the periodontitis group, 6-8 wk after initial therapy. Plasma and gingival crevicular fluid samples were collected and quantified for osteopontin using an enzyme immunoassay. RESULTS: The highest mean gingival crevicular fluid and plasma osteopontin concentrations were observed in the periodontitis group (1575.01 and 1273.21 ng/mL, respectively) and the lowest in the healthy group (1194.80 and 476.35 ng/mL, respectively). After treatment of the periodontitis group, the level of osteopontin decreased to 1416.15 in gingival crevicular fluid and to 1051.68 ng/mL in plasma. In all groups the gingival crevicular fluid osteopontin levels showed a statistically significant positive correlation with that of plasma and clinical attachment loss. CONCLUSION: Osteopontin levels were highest in the gingival crevicular fluid from sites with periodontal destruction; however, periodontal treatment resulted in the reduction of osteopontin levels. Gingival crevicular fluid and plasma osteopontin levels showed a positive correlation in all of the groups. [Abstract]

Chiang CY, Chen YT, Hung FM, Tu HP, Fu MM, Fu E
Cyclosporin-A inhibits the expression of cyclooxygenase-2 in gingiva.
J Periodontal Res. 2007 Oct;42(5):443-9.
BACKGROUND AND OBJECTIVE: Various inflammatory mediators are involved in the development of cyclosporine A-induced gingival overgrowth. In this study, the gingival expression of cyclooxygenase-2 after cyclosporine A therapy was examined in vivo and in vitro. MATERIAL AND METHODS: After edentulous ridges on maxilla were established, 21 Sprague-Dawley rats received cyclosporine A daily for 4 wk, and a further 21 rats received solvent. After the rats were killed, the expression of cyclooxygenase-2 mRNA, interleukin-1beta mRNA, tumor necrosis factor-alpha mRNA, and interleukin-6 mRNA was examined in the edentulous gingiva. The expression of cyclooxygenase-2 protein and the production of prostaglandin E2 were also evaluated. RESULTS: In cultured human gingival fibroblasts and epithelial cells, the expression of cyclooxygenase-2 mRNA was measured after treatment with cyclosporine A. Significantly lower expression of cyclooxygenase-2 and interleukin-1beta mRNA, but higher interleukin-6 expression, were observed in gingiva from cyclosporine A-treated rats than in those from the control rats. Significantly less prostaglandin E2 production was observed in cyclosporine A-treated rats. Immunohistochemistry revealed that fewer gingival stromal cells were positively stained for cyclooxygenase-2 in cyclosporine A-treated rats. In cultured cells, significantly less cyclooxygenase-2 mRNA was detected after treatment with cyclosporine A. CONCLUSION: The expression of cyclooxygenase-2 was lower in the plaque nonretentive gingivae and the in vitro gingival cells upon treatment with cyclosporine A. Thus, we propose that cyclosporine A inhibits the expression of gingival cyclooxygenase-2. [Abstract]

Oda H, Saiki K, Numabe Y, Konishi K
Effect of gamma-immunoglobulin on the asaccharolytic growth of Porphyromonas gingivalis.
J Periodontal Res. 2007 Oct;42(5):438-42.
BACKGROUND AND OBJECTIVES: A minimal medium is indispensable for examining the growth properties of the asaccharolytic bacterium, Porphyromonas gingivalis. The purpose of the present study was to improve the widely used KGB medium to support good growth of P. gingivalis. MATERIAL AND METHODS: Growth of P. gingivalis (W50, W83, and ATCC33277) in a minimal medium was monitored by measuring the optical density of the culture during incubation. RESULTS: W50, W83, and ATCC33277 grew poorly with bovine serum albumin as the sole carbon and nitrogen source, and alpha-ketoglutarate had little or no effect on this poor growth. In contrast, FeCl3 improved the growth of W83 and ATCC33277; however, the use of a high concentration of FeCl3 elicited black pigmentation of the cells. Bovine gamma-immunoglobulin greatly recovered the growth defect. None of alpha-ketoglutarate, citrate, or trace metal ions, when used to supplement KGB medium, was required for growth. We determined the optimal conditions for growth, and developed a new simple minimal medium for P. gingivalis (GA medium). Growth of ATCC33277 in GA medium was dependent on gingipains; Arg-gingipains and Lys-gingipain contributed comparably to proliferation of the bacterium. CONCLUSION: These data indicate that GA medium is currently the most reliable minimal medium for examining the growth properties of P. gingivalis. [Abstract]

Vardar-Sengul S, Demirci T, Sen BH, Erkizan V, Kurulgan E, Baylas H
Human beta defensin-1 and -2 expression in the gingiva of patients with specific periodontal diseases.
J Periodontal Res. 2007 Oct;42(5):429-37.
BACKGROUND AND OBJECTIVE: beta defensin antimicrobial peptides are important in epithelial innate immunity, and their differential expression is associated with periodontal diseases. The aims of this study were to determine the mRNA expression of human beta defensin-1 and -2 in the gingival tissue of patients with gingivitis, aggressive periodontitis and chronic periodontitis, and to evaluate the relationship between defensin expression and type and/or severity of periodontal destruction. MATERIAL AND METHODS: Fifteen patients in each group with gingivitis, aggressive periodontitis and chronic periodontitis, and 10 healthy subjects, were included in the study (n=55). The periodontal status of the subjects was determined by periodontal clinical measurements and radiographical evaluations. Transcriptional levels of human beta defensin-1 and -2 genes in gingival samples were assessed by using the quantitative real-time polymerase chain reaction technique, and the data were evaluated statistically by the relative expression Software Tool 2 for groupwise comparisons. RESULTS: Expression of the human beta defensin-1 gene was lower in gingivitis and aggressive periodontitis groups, and significantly higher in the chronic periodontitis group, than in the control group (p<0.001). Human beta defensin-2 mRNA expression in the gingivitis group was lower than in the control group; however, the difference was statistically significant only in half of the gingivitis patients (p<0.001). Human beta defensin-2 mRNA levels were higher in some chronic periodontitis patients, but lower in the others when compared with the control group (p<0.001). Expression of the human beta defensin-2 gene increased in the aggressive periodontitis group relative to the control group. CONCLUSION: This study suggests that human beta defensin-1 and -2 genes in the gingival epithelium show differential expression in patients with specific periodontal diseases, and aggressive and chronic periodontitis types demonstrate different gingival beta defensin-1 and -2 expression patterns. [Abstract]

Yuan K, Huang JS, Hsu CW, Hung IJ
A mineralization-associated membrane protein plays a role in the biological functions of the peptide-coated bovine hydroxyapatite.
J Periodontal Res. 2007 Oct;42(5):420-8.
BACKGROUND AND OBJECTIVE: Anorganic bovine mineral coated with a cell-binding peptide (P-15) is superior to anorganic bovine mineral alone in the treatment of periodontal osseous defects. However, the molecular interactions between P-15 and periodontal ligament fibroblasts remain unclear. MATERIAL AND METHODS: We first compared the in vitro osteogenic activities between periodontal ligament fibroblasts cultured with anorganic bovine mineral alone and with the P-15/anorganic bovine mineral combination. We then harvested the periodontal ligament cell lysate, incubated it with various graft materials, and then washed it to remove unbound proteins. The bound proteins were eluted from graft materials and analyzed using electrophoresis, followed by mass spectrometry and then western blotting. Finally, a neutralizing antibody against one bound protein was added to the cell cultures to repeat the osteogenic assays to clarify its role in the in vitro effects of the P-15/anorganic bovine mineral combination. RESULTS: Cells treated with P-15/anorganic bovine mineral were more viable and showed greater osteogenic activities than cells treated with anorganic bovine mineral alone and the no-graft control. Annexin II, a mineralization-associated protein, bound to P-15/anorganic bovine mineral significantly more than to anorganic bovine mineral alone. The addition of neutralizing antibody for annexin II decreased the osteogenic activities of the P-15/anorganic bovine mineral combination. CONCLUSION: Annexin II of periodontal ligament fibroblasts interacted with the peptide of P-15, and was partially responsible for better in vitro osteogenesis in the P-15 graft. [Abstract]

Ji S, Hyun J, Park E, Lee BL, Kim KK, Choi Y
Susceptibility of various oral bacteria to antimicrobial peptides and to phagocytosis by neutrophils.
J Periodontal Res. 2007 Oct;42(5):410-9.
BACKGROUND AND OBJECTIVE: The aim of this study was to compare the susceptibility of nonperiodontopathic and periodontopathic bacteria to major defense mechanisms for bacterial clearance in gingival sulcus. MATERIAL AND METHODS: Twenty strains of 13 oral bacterial species were studied for their susceptibility to phagocytosis by human neutrophils and to the antimicrobial peptides LL-37 and human beta defensin-3. The minimum inhibitory concentrations of LL-37 and human beta defensin-3 were determined by a liquid dilution assay, and susceptibility to phagocytosis was examined by a flow cytometric phagocytosis assay. RESULTS: The minimum inhibitory concentrations of LL-37 and human beta defensin-3 varied greatly, depending on the strain and species. Although a significant difference between the non- and periodontopathic groups was not observed, the red-complex bacteria were more resistant to LL-37 than the others (p=0.004). The susceptibility of oral bacteria to phagocytosis was quite variable, depending on the species but not on the strains. The periodontopathic bacteria, especially Actinobacillus actinomycetemcomitans and the red-complex triad, were more resistant to phagocytosis than were the nonperiodontopathic bacteria (p=0.0003). In addition, bacteria resistant both to antimicrobial peptides and to phagocytosis were more common in the periodontopathic group. CONCLUSION: Our results indicate that immune evasion may contribute to the pathogenicity of some periodontopathic bacteria. [Abstract]

Yoshinaga Y, Ukai T, Abe Y, Hara Y
Expression of receptor activator of nuclear factor kappa B ligand relates to inflammatory bone resorption, with or without occlusal trauma, in rats.
J Periodontal Res. 2007 Oct;42(5):402-9.
BACKGROUND AND OBJECTIVE: Receptor activator of nuclear factor kappa B ligand (RANKL) is an important factor in osteoclast differentiation, activation and survival; however, its involvement in inflammatory bone resorption, with or without occlusal trauma, is unclear. The purpose of the present study was to investigate the distribution of RANKL-expressing cells in rat periodontium during lipopolysaccharide-induced inflammation with or without occlusal trauma. MATERIAL AND METHODS: Lipopolysaccharide was injected into rat gingiva of the lower left first molar to induce inflammation. In addition, the occlusal surface of the upper left first molar of rat was raised by placing a gold inlay to induce occlusal trauma in the lower left first molars. The distribution of RANKL-expressing cells was immunohistochemically observed. RESULTS: In the inflammatory model, many osteoclasts were observed at the apical inter-radicular septum on day 5 and they were reduced by day 10. On the other hand, in the inflammatory model with occlusal trauma, many osteoclasts were still observed on day 10. RANKL expression was similar to the changes in osteoclast number. The expression of RANKL increased in endothelial cells, inflammatory cells and periodontal ligament cells. CONCLUSION: These findings clearly demonstrated that RANKL expression on endothelial cells, inflammatory cells and periodontal ligament cells is involved in inflammatory bone resorption and the expression is enhanced by traumatic occlusion. These results suggest that RANKL expression on these cells is closely involved in the increase of osteoclasts induced by occlusal trauma. [Abstract]

Hung SL, Lin YJ, Chien EJ, Liu WG, Chang HW, Liu TY, Chen YT
Areca nut extracts-activated secretion of leukotriene B4, and phosphorylation of p38 mitogen-activated protein kinase and elevated intracellular calcium concentrations in human polymorphonuclear leukocytes.
J Periodontal Res. 2007 Oct;42(5):393-401.
BACKGROUND AND OBJECTIVE: Polymorphonuclear leukocytes are the major source of leukotriene B4, which is synthesized via the 5-lipoxygenase pathway. Activation of the 5-lipoxygenase pathway is regulated by intracellular calcium and the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The impact of areca nut extracts on the biosynthesis of leukotriene B4 by human polymorphonuclear leukocytes was evaluated, and some of the possible mechanisms underlying the responses were examined. MATERIAL AND METHODS: Polymorphonuclear leukocytes were treated with various concentrations of areca nut extracts. The concentrations of leukotriene B4 released into the supernatants were evaluated using enzyme immunoassay. The phosphorylation of p38 MAPK was monitored using immunoblotting, and the cytosolic calcium kinetics were assessed fluorometrically using Fura-2. RESULTS: Exposure of polymorphonuclear leukocytes to areca nut extracts led to a dose-dependent increase in the production of leukotriene B4, with levels peaking at 30 min and decreasing thereafter. Areca nut extracts enhanced the phosphorylation of p38 MAPK, an enzyme known to activate 5-lipoxygenase. Incubation with areca nut extracts also resulted in a rapid elevation of intracellular calcium concentrations in polymorphonuclear leukocytes. The induction of leukotriene B4 by areca nut extracts was suppressed with the p38 MAPK inhibitor, SB203580, or with the intracellular calcium chelator, BAPTA-AM. CONCLUSION: The interaction of areca nut extracts with polymorphonuclear leukocytes activated the arachidonic acid metabolic cascade. Incubation of polymorphonuclear leukocytes with areca nut extracts resulted in the activation of intracellular events, such as phosphorylation of p38 MAPK and Ca2+ mobilization, involved in the release of pro-inflammatory lipid mediators. The results of this study emphasize the potential importance of polymorphonuclear leukocytes as a source of leukotriene B4, which may modulate the inflammatory response in areca chewers. [Abstract]

Siddhivarn C, Banes A, Champagne C, Riché EL, Weerapradist W, Offenbacher S
Mechanical loading and delta12prostaglandin J2 induce bone morphogenetic protein-2, peroxisome proliferator-activated receptor gamma-1, and bone nodule formation in an osteoblastic cell line.
J Periodontal Res. 2007 Oct;42(5):383-92.
BACKGROUND AND OBJECTIVE: We have previously reported that mechanical strain applied at a 1% level to an osteoblastic cell line induces the transcription of prostaglandin D2 synthase and increases the levels of prostaglandin D2 and its Delta12prostaglandin J2 metabolite. Mechanical strain also induces the expression of peroxisome proliferator-activated receptor gamma-1 and bone nodule formation. We hypothesized that mechanical load induces bone formation via Delta12prostaglandin J2-dependent synthesis of bone morphogenetic proteins. Our goal was to investigate the molecular events involved in osteogenesis induced by mechanical loading and Delta12prostaglandin J2, namely the induction of bone morphogenetic proteins and peroxisome proliferator-activated receptor gamma-1, a nuclear receptor for Delta12prostaglandin J2. MATERIAL AND METHODS: Osteoblast monolayers were stretched for 1 h with a 1-h resting period and stretched for another hour at 1 Hz with 1% elongation. Cells were collected 0, 1, 6 and 16 h after stretching. Cyclooxygenase inhibitors and Delta12prostaglandin J2 were added in some experiments. Relative quantitative reverse transcriptase-polymerase chain reaction was used to examine whether the mRNA of bone morphogenetic protein-2, -4, -6, -7 and peroxisome proliferator-activated receptor gamma-1 was induced. Immunohistochemistry was used to evaluate bone morphogenetic protein expression in cells. RESULTS: Mechanical strain significantly increased the mRNA expression of bone morphogenetic protein-2, -6, -7 and of peroxisome proliferator-activated receptor gamma-1, but not of bone morphogenetic protein-4. In stretched cells, bone morphogenetic protein-2 and peroxisome proliferator-activated receptor gamma-1 expression was blocked by cyclooxygenase inhibitors, but restored by exogenous Delta12prostaglandin J2. Delta12Prostaglandin J2 significantly enhanced bone nodule formation and bone morphogenetic protein-2 expression when added alone to resting osteoblasts. CONCLUSION: These results suggest that the osteoblastic biomechanical pathways that trigger bone formation involve cyclooxygenase and prostaglandin D2 synthase activation, induction of Delta12prostaglandin J2 and its nuclear receptor, peroxisome proliferator-activated receptor gamma-1, and increased expression of bone morphogenetic protein-2. These data suggest that the Delta12prostaglandin J2/peroxisome proliferator-activated receptor gamma-1/bone morphogenetic protein-2 pathway plays an important role in osteogenesis. [Abstract]


Recent Articles in Journal of Clinical Periodontology

Schwarz F, Sager M, Ferrari D, Herten M, Wieland M, Becker J
Bone regeneration in dehiscence-type defects at non-submerged and submerged chemically modified (SLActive((R))) and conventional SLA titanium implants: an immunohistochemical study in dogs.
J Clin Periodontol. 2007 Nov 21;
Objectives: The aim of the present study was to evaluate bone regeneration in dehiscence-type defects at non-submerged and submerged titanium implants with chemically modified (mod) and conventional sandblasted/acid-etched (SLA) surfaces. Material and Methods: Standardized buccal dehiscence defects were surgically created following implant site preparation in both the upper and lower jaws of 12 beagle dogs. Both types of implants were randomly assigned to either a non-submerged or a submerged healing procedure. After 1, 2, 4, and 8 weeks, dissected blocks were processed for histomorphometrical [e.g. new bone height (NBH), per cent linear fill (PLF), percentage of bone to implant contact (BIC-D), area of new bone fill (BF)] and immunohistochemical analysis. Results: At 8 weeks, non-submerged and submerged SLA implants revealed significantly lower mean NBH (1.1+/-0.8-1.9+/-1.2 mm), PLF (27.7+/-20.3-46.0+/-28.5%), BIC-D (26.8+/-10.4-46.2+/-16.2%), and BF (1.3+/-0.9-3.4+/-2.8 mm(2)) values than respective modSLA implants [NBH (2.6+/-0.8-4.3+/-0.1 mm), PLF (64.2+/-19.4-107.2+/-4.7%), BIC-D (67.5+/-18.8-82.1+/-14.8%), BF (2.9+/-1.0-6.7+/-1.1 mm(2))]. Within modSLA groups, significantly highest BF values were observed at submerged implants. Conclusion: It was concluded that (i) modSLA titanium surfaces promoted bone regeneration in acute-type buccal dehiscence defects and (ii) a submerged healing procedure improved the outcome of healing additionally. [Abstract]

Döri F, Nikolidakis D, Húszár T, Arweiler NB, Gera I, Sculean A
Effect of platelet-rich plasma on the healing of intrabony defects treated with an enamel matrix protein derivative and a natural bone mineral.
J Clin Periodontol. 2007 Nov 21;
Background: Regenerative periodontal surgery utilizing a combination of an enamel matrix protein derivative (EMD) and a natural bone mineral (NBM) and platelet-rich plasma (PRP) has been shown to enhance the outcomes of regenerative surgery significantly. At present, it is unknown whether root conditioning with EMD, followed by defect fill with a combination of NBM+PRP may additionally enhance the clinical results obtained with EMD+NBM. Aim: To compare clinically the treatment of deep intrabony defects with either EMD+NBM+PRP or EMD+NBM. Material and Methods: Twenty-six patients suffering from advanced chronic periodontitis, and each of whom displayed one advanced intrabony defect were randomly treated with either EMD+NBM+PRP (test) or EMD+NBM (control). The following clinical parameters were evaluated at baseline and at 1 year after treatment: plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR) and clinical attachment level (CAL). The primary outcome variable was CAL. Results: Healing was uneventful in all patients. At 1 year after therapy, the test sites showed a reduction in mean PD from 8.8+/-1.9 mm to 3.1+/-0.9 mm ( p<0.001) and a change in mean CAL from 10.8+/-2.0 mm to 6.0+/-1.5 mm ( p<0.001). In the control group the mean PD was reduced from 8.8+/-2.0 mm to 2.8+/-1.6 mm ( p<0.001) and the mean CAL changed from 10.5+/-1.6 mm to 5.5+/-1.4 mm ( p<0.001). CAL gains of >/=4 mm were measured in 77% (i.e. in 10 out of 13 defects) of the cases treated with EMD+NBM+PRP and in 100% (i.e. in all 13 defects) treated with EMD+NBM. No statistically significant differences in any of the investigated parameters were observed between the two groups. Conclusions: Within its limits, the present study has shown that (i) 1 year after regenerative surgery, both treatments resulted in statistically significant PD reductions and CAL gains and (ii) the use of PRP failed to enhance the results obtained with EMD+NBM. [Abstract]

Milanovich N, Wei J, Jenkins W, Hefti AF, de Jager M
Total protein concentration and total bacterial load as measures of residual interproximal plaque in comparative clinical trials.
J Clin Periodontol. 2007 Nov 21;
Aim: Establish total protein concentration and total bacterial load as quantitative measures of residual interproximal plaque (IPP) in a clinical model designed to evaluate oral hygiene interventions. Material and Methods: This clinical model was a randomized, examiner and laboratory technician-blinded, parallel-design study whereby levels of residual IPP were compared for subjects using a manual toothbrush or a toothbrush+floss. Differences between interventions were compared after 7 and 21 days of use. Protein concentration was measured using 3-(4-carboxybenzoyl) quinoline-2-carboxaldehyde in a fluorescence microplate format and bacterial load was assessed by quantitative real-time PCR with universal primers specific for 16S rRNA and detected by SYBR Green. ancova was used to assess the statistical significance of the differences between interventions while clinical relevance was evaluated by a statistical model described by Man-Son-Hing et al. 2002. Results: Ninety-three subjects completed the study. Significant differences between interventions, using both outcome measures, were observed after 7 and 21 days. The difference between interventions by total protein concentration were further determined to be clinically relevant. Conclusions: Only total protein concentration provided both statistically significant and clinically relevant differences between two clinically distinct oral hygiene interventions in this clinical model for evaluating IPP. [Abstract]

Alsaadi G, Quirynen M, Michiles K, Teughels W, Komárek A, van Steenberghe D
Impact of local and systemic factors on the incidence of failures up to abutment connection with modified surface oral implants.
J Clin Periodontol. 2007 Nov 21;
Aim: This study aimed to assess the influence of systemic and local bone and intra-oral factors on the occurrence of early TiUnite(trade mark) implant failures. Material and Methods: A total of 283 consecutive patients (187 females; mean age 56.2), who received a total of 720 TiUnite(trade mark) implants, at the Department of Periodontology of the University Hospital of the Catholic University of Leuven, were prospectively followed. The following aspects were particularly assessed: hypertension, cardiac problems, gastric problems, osteoporosis, hypo- or hyperthyroid, hypercholesterolaemia, asthma, diabetes types I or II, Crohn's disease, rheumatoid arthritis, chemotherapy, hysterectomy and intake of medication (antidepressants, steroids, hormone replacement), radiotherapy of the concerned area, breach of sterility during surgery, implant parameters, bone (quality, quantity, dehiscence or perforation), type of edentulism, antibiotics prescription, fenestration of the implant in the sinus/nasal cavity, immediate implant placement, apical lesion detection and insertion torque. Results and Conclusion: A global failure rate of 1.9% was recorded. Owing to the very few failures, no definitive conclusion concerning statistical significance can be achieved. However, a tendency for more failures was noticed for apical lesions, vicinity with natural dentition, smoking, hormone replacement, gastric problems, Crohn's disease, diabetes I and radical hysterectomy. [Abstract]

Agueda A, Ramón JM, Manau C, Guerrero A, Echeverría JJ
Periodontal disease as a risk factor for adverse pregnancy outcomes: a prospective cohort study.
J Clin Periodontol. 2007 Nov 21;
Aim: The aim of this study was to determine the association between periodontitis and the incidence of preterm birth (PB), low birth weight (LBW) and preterm low birth weight (PLBW) Material and Methods: One thousand and ninty-six women were enrolled. Periodontal data, pregnancy outcome variables and information on other factors that may influence adverse pregnancy outcomes were collected. Data were analysed using a logistic regression model. Results: The incidence of PB and LBW was 6.6% and 6.0%, respectively. The incidence of PLBW was 3.3%. PB was related to mother's age, systemic diseases, onset of prenatal care, previous PBs, complications of pregnancy, type of delivery, the presence of untreated caries and the presence of periodontitis (odds ratio 1.77, 95% confidence interval: 1.08-2.88). LBW was related to mother's smoking habits, ethnicity, systemic diseases, previous LBW babies, complications of pregnancy and type of delivery. PLBW was related to mother's age, onset of prenatal care, systemic diseases, previous LBW babies, complications of pregnancy and type of delivery. Conclusions: The factors involved in many cases of adverse pregnancy outcomes have still not being identified, although systemic infections may play a role. This study found a modest association between periodontitis and PB. Further research is required to establish whether periodontitis is a risk factor for PB and/or LBW. [Abstract]


Periodontal disease increases the risk of severe pre-eclampsia among pregnant women.
J Clin Periodontol. 2007 Dec;34(12):1097. [Abstract]


Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: clinical outcomes.
J Clin Periodontol. 2007 Dec;34(12):1097. [Abstract]

Schiffner U, Bahr M, Effenberger S
Plaque and gingivitis in the elderly: a randomized, single-blind clinical trial on the outcome of intensified mechanical or antibacterial oral hygiene measures.
J Clin Periodontol. 2007 Dec;34(12):1068-73.
Objectives: To study the outcome of intensified mechanical oral hygiene compared with the effect of an adjunctive antibacterial mouth rinse on plaque and gingivitis in elderly people. Material and Methods: In a randomized, single-blind, 6-month controlled clinical study, 106 subjects, 55 years or older, were divided into four groups: (I) Participants were instructed on improved mechanical oral hygiene, including interdental hygiene; (II) subjects used an antibacterial mouth rinse containing amine and stannous fluoride in addition to their usual oral hygiene practices; (III) both intensive mechanical and antibacterial measures were combined; and (IV) a control group with no specific regimen. Gingivitis and plaque were examined. Results: After 6 months, both plaque and gingivitis scores were significantly lower than at baseline in all groups. Reductions in gingivitis differed significantly between the control group and all other groups but not between the three intervention groups. Only groups with improved mechanical oral hygiene showed significant improvements in plaque scores compared with control. Conclusions: Intensive mechanical oral hygiene resulted in greater plaque reduction than the combination of an antibacterial rinse and usual oral hygiene procedures. Gingivitis was reduced by both intensive oral hygiene and use of the amine/stannous fluoride rinse. Combining intensive mechanical oral hygiene with the antibacterial rinse did not result in further gingivitis reduction. [Abstract]

Oettinger-Barak O, Segal E, Machtei EE, Barak S, Baruch Y, Ish-Shalom S
Alveolar bone loss in liver transplantation patients: relationship with prolonged steroid treatment and parathyroid hormone levels.
J Clin Periodontol. 2007 Dec;34(12):1039-45.
Aim: To evaluate the relationship among alveolar bone loss (ABL), bone status and calcium-regulating hormones in liver transplantees. Patients and Methods: Twenty-one liver transplantees underwent a full oral examination. The correlations among bone densitometry, bone metabolic status and drug treatment were examined. Results: Twelve patients had osteopenia, and six were osteoporotic. ABL was 4.33+/-2.32 mm (range 0.67-9.92). Parathyroid hormone (PTH) levels ranged from 14 to 106 (mean 55.2+/-26.4). The mean 25(OH)D(3) was 11.68+/-4.7, range 3.5-21.1 ng/ml. Nine patients were vitamin D deficient (<10 ng/ml); none of the patients had 25(OH)D(3) levels >/=30 ng/ml. No correlation was found between ABL and current or total glucocorticoids dose, although there was an inverse relation with the duration of treatment (r=-0.474, p=0.03). A positive correlation was found between ABL, PTH (r=0.419, p=0.059) and hip bone mineral density (BMD) (r=0.482, p=0.027). ABL correlated closely with age, PTH, glucocorticoid treatment (duration) and hip BMD (r=0.810, p=0.004). Conclusions: The majority of liver transplant patients had insufficient 25(OH)D(3) serum levels. Changes in calcium-regulating hormones and hip BMD were correlated with ABL. Therefore, therapeutic intervention aimed at treating vitamin D deficiency and secondary hyperparathyroidism should be considered in these patients. The benefits of vitamin D treatment in the management of secondary hyperparathyroidism and possible decrease in ABL deserve further evaluation in controlled trials. [Abstract]

Hettne KM, Weeber M, Laine ML, Ten Cate H, Boyer S, Kors JA, Loos BG
Automatic mining of the literature to generate new hypotheses for the possible link between periodontitis and atherosclerosis: lipopolysaccharide as a case study.
J Clin Periodontol. 2007 Dec;34(12):1016-24.
Aim: The aim of the current report was to generate and explore new hypotheses into how, in a pathophysiological sense, atherosclerosis and periodontitis could be linked. Material and Methods: Two different biomedical informatics techniques were used: an association-based technique that generated a ranked list of genes associated with the diseases, and a natural language processing tool that extracted the relationships between the retrieved genes and lipopolysaccharide (LPS). Results: This combined approach of association-based and natural language processing-based literature mining identified a hit list of 16 candidate genes, with PON1 as the primary candidate. Conclusions: Further study of the literature prompted the hypothesis that PON1 might connect periodontitis with atherosclerosis in both an LPS-dependent and a non-LPS-dependent manner. Furthermore, the resulting genes not only confirmed already known associations between the two diseases, but also provided genes or gene products that have only been investigated separately in the two disease states, and genes or gene products previously reported to be involved in atherosclerosis. These findings remain to be investigated through clinical studies. This example of multidisciplinary research illustrates how collaborative efforts of investigators from different fields of expertise can result in the discovery of new hypotheses. [Abstract]

Abu-Ta'a M, Quirynen M, Teughels W, van Steenberghe D
Asepsis during periodontal surgery involving oral implants and the usefulness of peri-operative antibiotics: a prospective, randomized, controlled clinical trial.
J Clin Periodontol. 2007 Nov 15;
Objectives: This randomized clinical trial compares the usefulness of pre- and post-operative antibiotics while strict asepsis was followed during periodontal surgery. Material and Methods: Two groups of 40 consecutive patients each with fully or partially edentulous jaws were enrolled. Antibiotics group (GrAB(+)): 23 men, mean age 60, 128 implants, received oral amoxicillin 1 g, 1 h pre-operatively and 2 g for 2 days post-operatively. Non-antibiotics group (GrAB(-)): 20 men, mean age 57, 119 implants, received no antibiotics. Bacterial samples were taken from the peri-oral skin before and at the end of surgery. In 12 patients in each group, samples were also taken from the nares. A VAS questionnaire evaluated symptoms of infection/inflammation by both the patient and the periodontologist at suture removal. Results: There were no significant differences between both groups, neither for the clinical parameters nor for the microbiota. Staphylococcus aureus was detected in the nares of one patient only. The patients' subjective perception of post-operative discomfort was significantly smaller in the group receiving antibiotics. Three patients lost one or two implants. Conclusions: Antibiotics do not provide significant advantages concerning post-operative infections in case of proper asepsis. It also does not reduce peri-oral microbial contamination. It does on the other hand reduce post-operative discomfort. [Abstract]

Akhter R, Hassan NM, Aida J, Takinami S, Morita M
Relationship between betel quid additives and established periodontitis among Bangladeshi subjects.
J Clin Periodontol. 2007 Nov 15;
Aim: To determine the relationship between betel quid chewing additives and established periodontitis in Bangladeshi subjects. Material and Methods: A total of 864 subjects participated in this study. Among them, 140 pairs of sex- and age-matched case subjects and control subjects were selected. A case was defined as a person who had at least two sites with a clinical attachment level (CAL)>/=6 mm and at least one site with probing depth (PD)>/=5 mm. Subjects who did not fulfill these criteria were considered as controls. Information on sociodemographic variables, psychological stress, dental health behaviour, smoking and betel quid chewing habits was obtained. Results: Multiple logistic regression analysis showed that current betel quid chewers had greater probabilities of having established periodontal disease than did non-chewers (odds ratio=3.97, p<0.05). Mean PD, mean CAL, mean percentage of bleeding on probing and number of missing teeth were significantly higher in chewers of betel quid with tobacco and masala than in chewers of betel quid without such additives adjusting for age, sex, smoking habit, body mass index, dental visit pattern, stress and plaque index. Higher frequency and longer duration of betel quid chewing showed a significant relation to an increase in periodontal parameters. Conclusion: The results indicate that betel quid additives might significantly enhance periodontitis in the population studied. [Abstract]

Raunio T, Nixdorf M, Knuuttila M, Karttunen R, Vainio O, Tervonen T
The extent of periodontal disease and the IL-6(-174) genotype as determinants of serum IL-6 level.
J Clin Periodontol. 2007 Dec;34(12):1025-30.
Aim: To study the extent of periodontal disease and the IL-6(-174) genotype as determinants of serum and mouthwash IL-6 concentration in subjects with moderate to severe periodontal disease. Material and Methods: Fifty-two generally healthy subjects volunteered to participate. Probing pocket depth (PD) and periodontal attachment level (AL) were clinically examined and alveolar bone level (BL) was measured on orthopantomographs. IL-6 concentrations in mouthwash, collected by rinsing with 3 ml saline for 30 s and in serum, obtained by venipuncture, were measured using ELISA. IL-6(-174) polymorphism was studied using a polymerase chain reaction. Results: Eleven subjects carried the GG genotype, and 41 subjects, carried the CG/CC genotype. The mean (+/- SD) concentration of IL-6 in serum was 1.6 (+/- 1.5) pg/ml and, 2.8 (+/- 5.04) pg/ml in mouthwash. The serum concentration of IL-6 was higher in subjects with the GG genotype than with the CG/CC genotype. In regression analyses the percentages of sites with PD>/=6 mm, AL>/=6 mm and BL>/=8 mm, the IL-6(-174) genotype, body mass index and gender associated significantly with serum IL-6 concentration. Conclusions: The extent of moderate to severe periodontal disease and the IL-6(-174) genotype contribute significantly to serum IL-6 concentration. [Abstract]

Cortellini P, Tonetti MS
Minimally invasive surgical technique and enamel matrix derivative in intra-bony defects. I: clinical outcomes and morbidity.
J Clin Periodontol. 2007 Dec;34(12):1082-8.
Aims: This case cohort study was designed to evaluate the clinical performance and the intra-operative and post-operative morbidity of the minimally invasive surgical technique (MIST) associated with the application of an enamel matrix derivative (EMD) in the treatment of isolated deep intra-bony defects. Material and Methods: Forty deep isolated intra-bony defects in 40 patients were surgically accessed with the MIST. This technique was designed to limit the mesio-distal flap extension and the corono-apical flap reflection in order to reduce the surgical trauma and increase flap stability. The incision of the defect-associated papilla was performed according to the principles of the papilla preservation techniques. EMD was applied on the debrided and dried root surfaces. Stable primary closure of the flaps was obtained with modified internal mattress sutures. Surgery was performed with the aid of an operating microscope and microsurgical instruments. Clinical outcomes were collected at baseline and at 1 year. Intra-operative and post-operative morbidity was evaluated with questionnaires. Results: The 1-year clinical attachment gain was 4.9+/-1.7 mm (p<0.0001 compared with baseline). This corresponded to a 77.6+/-21.9% resolution of the defect. Residual probing pocket depths were 3+/-0.6 mm. A minimal increase of 0.4+/-0.7 mm in gingival recession between baseline and 1 year was recorded. No patients experienced intra-operative pain, while only 14 reported a very moderate perception of the hardship of the surgical procedure [7+/-12 visual-analogue scale (VAS) units, on average]. Primary closure was obtained in all treated sites. At the 1-week follow-up visit, 38 sites (95%) were still closed. Only 12 subjects reported moderate post-operative pain (VAS 19+/-10) that lasted for 26+/-17 h. Conclusions: These data indicate that the minimally invasive surgical technique, in combination with EMD, can be successfully applied in the treatment of isolated deep intra-bony defects, resulting in excellent clinical outcomes with very limited intra- and post-operative morbidity. [Abstract]

Scapoli C, Mamolini E, Trombelli L
Role of IL-6, TNF-A and LT-A variants in the modulation of the clinical expression of plaque-induced gingivitis.
J Clin Periodontol. 2007 Dec;34(12):1031-8.
Aim: The purpose of the present study was to assess the association of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-A) and lymphotoxin alpha (LT-A) gene polymorphisms with the clinical parameters of gingivitis in a large experimental gingivitis trial and with each of two subgroups, "high responder" (HR, n=24) and "low responder" (LR, n=24), with distinct susceptibility to gingivitis. Material and Methods: Ninety-six systemically and periodontally healthy non-smokers, 46 males (mean age: 23.9+/-1.7) and 50 females (mean age: 23.3+/-1.6), were included in a randomized split-mouth localized 21-day experimental gingivitis trial. Plaque index, gingival index, gingival crevicular fluid volume and angulated bleeding score were recorded. HR and LR subgroups were characterized by substantially different severities of gingival inflammation despite a similar plaque accumulation rate. All subjects were genetically characterized for IL-6(-174), IL-6(-597), TNF-A(-308) and LT-A(+252) polymorphisms. Results: None of the variants analysed, either as single polymorphisms or as a combined genotype, was associated with the clinical parameters in the overall population. For the polymorphisms studied, genotypic distributions in HR and LR subjects were not significantly different. Conclusions: The present results suggest an absence of association between IL-6, TNF-A and LT-A polymorphisms and subject-based clinical behaviour of the gingiva in response to de novo plaque accumulation. [Abstract]

Merchant AT, Pitiphat W
Researching periodontitis: challenges and opportunities.
J Clin Periodontol. 2007 Dec;34(12):1007-15.
Aim and Methods: The evidence-based approach, voted in January 2007 as one of the 15 most important medical advances in the last 166 years, has increasingly shaped medical practice and education. In this paper, we apply the evidence-based approach to evaluate the aetiology of periodontitis; for comparison, we provide a brief description of the evidence-based method applied to the study of cardiovascular disease aetiology. We then discuss the challenges and opportunities to enhance the evidence base for periodontitis aetiology. Results and Conclusion: While evidence for medical treatments has mostly come from clinical trials, evidence for primary prevention in medicine has largely emerged from cohort studies evaluating disease risk factors. The high cost of conducting large cohort studies makes it challenging to fund these investigations, particularly for primary dental outcomes such as periodontitis. Studies of periodontitis outcomes integrated into larger ongoing cohorts provide one way to overcome this problem. Other potential barriers to the conduct of these studies include outcome definition, prevention of bias, data analysis, and the focus on teeth at risk (rather than people at risk) of the outcome. We analyse these questions and provide possible solutions. As many of these issues are generic to dentistry, possible solutions can improve the quality of future studies and the evidence base for primary prevention in dentistry. [Abstract]

Rajapakse PS, McCracken GI, Gwynnett E, Steen ND, Guentsch A, Heasman PA
Does tooth brushing influence the development and progression of non-inflammatory gingival recession? A systematic review.
J Clin Periodontol. 2007 Dec;34(12):1046-61.
Aim: The aim of this systematic review was to produce the best available evidence and pool appropriate data to evaluate the effect of tooth brushing on the initiation and progression of non-inflammatory gingival recession. Material and Methods: A protocol was developed a priori for the question: "Do factors associated with tooth brushing predict the development and progression of non-inflammatory gingival recession in adults?" The search covered six electronic databases between January 1966 and July 2005. Hand searching included searches of the Journal of Clinical Periodontology, Journal of Periodontal Research and the Journal of Periodontology. Bibliographies of narrative reviews, conference proceedings and relevant texts known to the authors were also searched. Inclusion of titles, abstracts and ultimately full texts was based on consensus between three reviewers. Results: The full texts of 29 papers were read and 18 texts were eligible for inclusion. One abstract from EuroPerio 5 reported a randomized-controlled clinical trial [Level I evidence] in which the authors concluded that the toothbrushes significantly reduced recessions on buccal tooth surfaces over 18 months. Of the remaining 17 observational studies, two concluded that there appeared to be no relationship between tooth brushing frequency and gingival recession. Eight studies reported a positive association between tooth brushing frequency and recession. Other potential risk factors were duration of tooth brushing, brushing force, frequency of changing the toothbrush, brush (bristle) hardness and tooth brushing technique. None of the observational studies satisfied all the specified criteria for quality appraisal and a valid appraisal of the quality of the randomized-controlled trial was not possible. Conclusion: The data to support or refute the association between tooth brushing and gingival recession are inconclusive. [Abstract]

Erdemir EO, Bergstrom J
Effect of smoking on folic acid and vitamin B(12) after nonsurgical periodontal intervention.
J Clin Periodontol. 2007 Dec;34(12):1074-81.
Aim: The main purpose of this study was to investigate the effect of smoking on the serum levels of folic acid and vitamin B(12) in smokers and nonsmokers with chronic periodontal disease after nonsurgical intervention. Material and Methods: The study base consisted of 45 current smokers and 43 nonsmokers. The clinical parameters included plaque index (PI), gingival index (GI), pocket depth (PD), and clinical attachment level (CAL). Folic acid and vitamin B(12) were determined from peripheral blood samples. Clinical measurements and blood samples were collected at baseline and 1, 3, and 6 months after the intervention. Results: Mean PI was significantly greater in smokers compared with non-smokers throughout the observation period (p<0.001). During the first month, GI levels significantly decreased in both groups. From months 1 through 6, a significant return towards an increased GI level was observed in smokers (p<0.001). PD and CAL levels significantly decreased during the first month in both groups. Thereafter, increasing levels of PD and CAL were seen in both groups, although significantly more pronounced in smokers. Throughout the observation period, the mean CAL was significantly greater in smokers relative to nonsmokers (p<0.001). In smokers, the mean folic acid level gradually and significantly decreased and a slight and significant decrease in mean vitamin B(12) levels was observed in both groups over the entire observation period (p<0.001). Conclusion: The clinical response to nonsurgical intervention is impaired by smoking and smoking seems to negatively influence the serum level of folic acid following non-surgical intervention. [Abstract]

Becker J, Ferrari D, Herten M, Kirsch A, Schaer A, Schwarz F
Influence of platform switching on crestal bone changes at non-submerged titanium implants: a histomorphometrical study in dogs.
J Clin Periodontol. 2007 Dec;34(12):1089-96.
Objectives: The aim of the present study was to investigate histomorphometrically the influence of platform switching on crestal bone changes at non-submerged wide-body titanium implants in a dog model. Material and Methods: One-stage insertion of sand-blasted and acid-etched screw-type implants with either matching (CAM) or smaller-diameter healing abutments (CPS) were randomly assigned to the lower jaws of nine beagle dogs. The animals were killed after 7, 14, and 28 days of non-submerged healing. Dissected blocks were processed for histomorphometrical analysis. Measurements were made between the implant shoulder (IS) and: - the apical extension of the long junctional epithelium (aJE), - the most coronal level of bone in contact with the implant (CLB), and - the level of the alveolar bone crest (BC). Results: At 7, 14, and 28 days, the mean IS-aJE values were significantly the lowest at CPS implants. However, after 28 days of healing, both groups revealed significantly increased mean IS-BC values at the buccal aspect of the alveolar bone. The difference in IS-CLB and IS-BC between groups was not significant. Conclusions: Within the limits of the present study, it was concluded that both CAM and CPS implants revealed crestal bone-level changes after 28 days of healing. [Abstract]

Konradsson K, Claesson R, van Dijken JW
Dental biofilm, gingivitis and interleukin-1 adjacent to approximal sites of a bonded ceramic.
J Clin Periodontol. 2007 Dec;34(12):1062-7.
Aim: The aim of this study was to investigate in vivo the influence of aged, resin-bonded, ceramic restorations on approximal dental biofilm formation and gingival inflammatory response, associated with and without customary oral hygiene. Material and Methods: In a cross-sectional and in a 10-day experimental gingivitis study, Quigley-Hein plaque index, gingival index (GI), crevicular fluid and its levels of interleukin (IL)-1alpha, -1beta and receptor antagonist were measured at appoximal surfaces of leucite-reinforced bonded ceramic coverages, resin composite restorations and enamel and compared intra-individually in 17 participants. Results: No differences were found between the ceramic, composite and enamel regarding plaque index, GI, levels of IL-1alpha, -1beta and the receptor antagonist. Throughout, higher crevicular fluid amounts were observed at ceramic sites compared with the enamel (p<0.05). In the experimental gingivitis, plaque index, GI, crevicular fluid and its IL-1alpha levels increased significantly. Conclusion: The need for optimal oral hygiene and professional preventive oral health care does not seem to be reduced with regard to approximal surfaces of aged, resin-bonded, leucite-reinforced ceramic restorations in comparison with those of a hybrid, resin composite and enamel. [Abstract]

Duyck J, Slaets E, Sasaguri K, Vandamme K, Naert I
Effect of intermittent loading and surface roughness on peri-implant bone formation in a bone chamber model.
J Clin Periodontol. 2007 Nov;34(11):998-1006.
Both implant surface characteristics and mechanical loading are known to affect implant osseointegration. Their interaction and the underlying mechanisms by which they affect peri-implant healing processes are still unknown. The aim of this study is therefore to investigate the influence of a turned versus a rough (Plus), Dentsply Friadent) implant surface on peri-implant bone formation in case of unloaded or loaded implant healing. Material and Methods: Bone formation was evaluated around screw-shaped implants under four experimental conditions using a repeated sampling bone chamber methodology: (1) unloaded turned implant (CU), (2) unloaded implant with a rough surface (TU), (3) loaded turned implant (CL), and (4) loaded implant with a rough surface (TL). Peri-implant tissue samples were paraffin embedded after implant removal and examined histologically and histomorphometrically. A mixed model was used for statistical analysis. Results: The surface of bone tissue relative to the total tissue area (bone area fraction) was not affected by the experimental conditions. The areas of bone trabeculae relative to the bone area (bone fraction) were significantly higher for TL compared with CU and TU. The bone fraction in the vicinity (100 microm zone) of the implant (BFZ) was significantly the highest around the loaded roughened implants (TL). Conclusion: Implant loading did not affect bone formation in the absence of surface roughness, and implant surface roughness had no effect in the absence of loading. However, a bone-stimulating effect in the implant's vicinity was assigned to the rough surface when the implant was loaded. [Abstract]

Agbaje JO, Jacobs R, Maes F, Michiels K, van Steenberghe D
Volumetric analysis of extraction sockets using cone beam computed tomography: a pilot study on ex vivo jaw bone.
J Clin Periodontol. 2007 Nov;34(11):985-90.
AIM: The aim of this study was to determine the accuracy of volumetric analysis of extraction sockets using cone beam computed tomography (CBCT). MATERIAL AND METHODS: The volume of 40 dental alveoli in nine dry skull specimens (four mandibles and five maxillae) was determined by measuring the volume of the tooth socket impression using the water displacement technique. This was considered as the gold standard. Then, the tooth socket was scanned with CBCT and data were uploaded in the semi-automated Livewire segmentation software. The software segments the tooth socket in consecutive 1 mm-thick two-dimensional slices. After segmentation, the total volume of the delineated socket was computed. The statistical difference between direct volumetric measurements and those obtained with CBCT imaging was assessed using the Student paired t-test. RESULT: The mean socket volume of the skull specimens was 227+/-91 mm(3) when obtained by direct measurement and 225+/-90 mm(3) when obtained by CBCT imaging. Student paired t-test showed no significant differences between both volume measurements (p>0.1). CONCLUSIONS: CBCT permits imaging of anatomical structures in three planes and allows for reliable volume estimates. The results should be verified in clinical circumstances and might have potential applicability for evaluation of extraction socket healing under different conditions. [Abstract]

Slotte C, Asklöw B, Lundgren D
Surgical guided tissue regeneration treatment of advanced periodontal defects: a 5-year follow-up study.
J Clin Periodontol. 2007 Nov;34(11):977-84.
OBJECTIVES: To study the 5-year outcome of combined use of guided tissue regeneration (GTR) barriers and bovine bone in advanced periodontal defects. MATERIAL AND METHODS: In each of 24 patients, one defect was surgically exposed, debrided, filled with bovine bone, and covered with a bioresorbable barrier. Re-examinations were made after 1, 3, and 5 years. RESULTS: Average full-mouth plaque scores (FMPS) were 14.5% at baseline and 10.7%, 9.8%, and 18.9% after 1, 3, and 5 years, respectively. Mean probing pocket depth (PPD) was 10.0 mm at baseline. Mean PPD reduction was 5.2 mm after 1 year, 5.6 mm after 3 years, and 5.3 mm after 5 years. Mean gingival recession was 1.0 mm after 1 year, 1.6 mm after 3 years, and 1.3 mm after 5 years. Mean gain in clinical attachment level (CAL) was 4.2 mm at the 1-year, 4.1 mm at the 3-year, and 4.3 mm at the 5-year examination. Smoking significantly influenced CAL change at all re-examinations. FMPS were significantly correlated with radiographic defect depth at the 5-year examination and CAL with smoking and FMPS at the 3-year examination. CONCLUSION: Advanced periodontal defects can be successfully treated with the combined use of GTR barriers and bovine bone to substantially reduce PPD and achieve a stable, long-term gain of CAL. [Abstract]

Laudisio A, Marzetti E, Antonica L, Settanni S, Georgakakis I, Bernabei R, Franceschi C, Zuccalŕ G
Masticatory dysfunction is associated with osteoporosis in older men.
J Clin Periodontol. 2007 Nov;34(11):964-8.
AIM: Thirty per cent of hip fractures occur in men. Nevertheless, the determinants of osteoporosis in men are unclear. Masticatory dysfunction is associated with malnutrition, and might represent an emergent cause of osteoporosis. The aim of this study was to assess the association of bone mineral density and self-assessed masticatory dysfunction in a general older population. MATERIAL AND METHODS: We assessed the association of masticatory dysfunction with standard parameters of bone mineral density (T-score, Z-score and the stiffness index) in all 310 subjects aged 75+ living in Tuscania (Italy). RESULTS: Among men, self-assessed masticatory dysfunction was associated with T-score [beta=0.86, confidence intervals (CI)=0.15-1.57; p=0.019], Z-score (beta=0.86, CI=0.16-1.56; p=0.017) and the stiffness index (beta=9.12, CI=0.47-17.77; p=0.039) in linear regression modeling, after adjusting. No significant associations were observed in women. CONCLUSIONS: Masticatory dysfunction is independently associated with osteoporosis in elderly men. Evaluation of masticatory function should enter the routine assessment of older men with osteoporosis. [Abstract]

Gomes-Filho IS, Cruz SS, Rezende EJ, Dos Santos CA, Soledade KR, Magalhăes MA, de Azevedo AC, Trindade SC, Vianna MI, Passos Jde S, Cerqueira EM
Exposure measurement in the association between periodontal disease and prematurity/low birth weight.
J Clin Periodontol. 2007 Nov;34(11):957-63.
AIM: To compare the use of different definitions for exposure measurement in cases of association between periodontal disease (PD) and prematurity and/or low birth weight (PLBW). MATERIAL AND METHODS: A database from a previous case-control study was used to compare four different definitions for periodontitis: at least one site with probing depth > or =4 mm (1); at least one site with clinical attachment loss (CAL)> or =3 mm (2); at least four teeth with one or more sites presenting probing depth > or =4 mm, with CAL> or =3 mm at the same site (3); and at least four teeth with one or more sites with probing depth > or =4 mm, with CAL> or =3 mm at the same site and presence of bleeding on probing (4). The PD frequency, diagnostic values and adjusted association measurements were calculated. RESULTS: PD frequency ranged from 33.1% to 94.7%. Odds ratio(adjusted) varied slightly according to the exposure measurement used. CONCLUSIONS: The association between PD and PLBW weight was consistent, except for exposure measurement 1, i.e. using at least one site with CAL> or =3 mm for periodontitis diagnosis, while the magnitude of this varied according to the definition established. [Abstract]

Lalla E
Periodontal infections and diabetes mellitus: when will the puzzle be complete?
J Clin Periodontol. 2007 Nov;34(11):913-6. [Abstract]

Kerner S, Etienne D, Malet J, Mora F, Monnet-Corti V, Bouchard P
Root coverage assessment: validity and reproducibility of an image analysis system.
J Clin Periodontol. 2007 Nov;34(11):969-76.
AIM: The aim of this methodological study was to validate a new method for root coverage evaluation following periodontal plastic surgery. MATERIAL AND METHODS: Thirty recessions were treated in 21 consecutive patients, using a subepithelial connective tissue graft technique. Clinical measurements and photographs were taken at baseline and 12+/-6 months after treatment. The mean percentage of root coverage for linear and surface area measurements was calculated using conventional clinical evaluation, and compared with ImageJ, a public domain Java image processing program. Bland-Altman plots were used for assessing repeatability and agreement between clinical and ImageJ measurements. The strength of the relationship was calculated using the Pearson product moment correlation coefficient. RESULTS: The repeatability of ImageJ was excellent for both linear and surface area measurements. The agreement between clinical and ImageJ measurements was good for the linear evaluation, showing lower and upper limits of -13.14% and 17.42%, respectively. Significant correlations (p<0.001) were found between clinical and ImageJ measurements, ranging from 0.93 to 0.94 for linear evaluation, and from 0.89 to 0.90 for surface evaluation. CONCLUSIONS: The outcomes of this study show that the ImageJ analysis is a reliable, reproducible method to evaluate the percentage of root coverage after periodontal plastic surgery, when a midfacial linear measurement is used. [Abstract]

Tanner AC, Kent R, Kanasi E, Lu SC, Paster BJ, Sonis ST, Murray LA, Van Dyke TE
Clinical characteristics and microbiota of progressing slight chronic periodontitis in adults.
J Clin Periodontol. 2007 Nov;34(11):917-30.
AIM: This study sought clinical and microbial risk indicators for progressing slight periodontitis. MATERIAL AND METHODS: One hundred and seventeen periodontally healthy or slight periodontitis adults (20-40 years) were monitored clinically at 6-month intervals followed by supragingival cleaning. Inter-proximal sites with >1.5 mm increase in clinical attachment over 18 months were considered disease active. Subgingival plaque was analysed by 78 16S rDNA and 38 whole-genomic DNA probes and by PCR to Porphyromonas gingivalis and Tannerella forsythia. Characteristics were compared between active and inactive subjects. RESULTS: Twenty-two subjects showed disease activity principally at molars. Mean baseline gingival and plaque indices, bleeding on probing, probing depth and clinical attachment level (CAL) were higher in active subjects. DNA probes detected species and not-yet-cultivated phylotypes from chronic periodontitis, although few species were associated with active subjects. By PCR P. gingivalis (p=0.007) and T. forsythia (p=0.075) were detected more frequently during monitoring in active subjects. Stepwise logistic analysis associated baseline levels of gingival index, clinical attachment and bleeding with subsequent clinical attachment loss. CONCLUSIONS: Gingivitis and CAL were significantly associated with progressing slight periodontitis in 20--40-year-old adults. Species associated with moderate and advanced chronic periodontitis were detected in slight periodontitis. [Abstract]

Nibali L, D'Aiuto F, Griffiths G, Patel K, Suvan J, Tonetti MS
Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case-control study.
J Clin Periodontol. 2007 Nov;34(11):931-7.
BACKGROUND AND AIM: A cluster of metabolic factors defines a syndrome that predisposes to diabetes and cardiovascular disease. Chronic infections such as periodontitis might alter these individual metabolic factors and the systemic inflammatory burden. The aim of this study was to investigate the association between severe periodontitis and increase in inflammatory and metabolic risk factors for cardiovascular disease. MATERIALS AND METHODS: We examined 302 patients with severe periodontitis and 183 healthy controls, and we collected a blood sample from each subject in order to investigate differences in inflammatory (leukocyte numbers and differential counts) and metabolic markers (lipids and glucose). RESULTS: After correcting for differences in age, gender, smoking and ethnicity, periodontitis subjects exhibited a low-grade systemic inflammation (increased white cell counts, 1.10+/-1.02 x 10(9)/l, 95%CI 1.05-1.15, p=0.0001), dyslipidemia [lower high-density lipoprotein cholesterol, 1.14+/-1.03 mmol/l, 95%CI 1.08-1.20, p<0.0001 and higher low-density lipoprotein cholesterol, 1.12+/-1.03, 95%CI 1.05-1.19, p<0.0001) and increased non-fasting serum glucose levels (1.04+/-1.01 mmol/l, 95%CI 1.02-1.06, p=0.01) when compared with controls. The associations were confirmed in a subpopulation of Caucasian non-smokers. A trend for a dose dependent effect of the number of periodontal pockets on the tested inflammatory and metabolic markers was observed. Conclusions: These data suggest a possible link between severe generalized periodontitis, systemic inflammation and a dysmetabolic state in otherwise healthy individuals. [Abstract]

Nicu EA, Van der Velden U, Everts V, Van Winkelhoff AJ, Roos D, Loos BG
Hyper-reactive PMNs in FcgammaRIIa 131 H/H genotype periodontitis patients.
J Clin Periodontol. 2007 Nov;34(11):938-45.
BACKGROUND: Receptors for the Fc part of IgG (FcgammaRIIa) on polymorphonuclear leukocytes (PMN) mediate phagocytosis and cell activation. Previous results show that one of the genetic variants of the FcgammaRIIa, the 131 H/H, is associated with more periodontal breakdown than the R/R. This may be due to hyper-reactivity of the H/H-PMNs upon interaction with bacteria. AIM: To study whether the FcgammaRIIa genotype modifies the PMN reactivity in periodontitis patients. MATERIAL AND METHODS: A cohort of 98 periodontitis patients was genotyped. From these, 10 H/H and 10 R/R consented to participate. PMNs were incubated with immune serum-opsonized Actinobacillus actinomycetemcomitans (A.a.). Phagocytosis, degranulation (CD63 and CD66b expression), respiratory burst and elastase release were assessed. Results: Patients of the H/H genotype showed more bone loss than those with the H/R or R/R genotype (p=0.038). H/H-PMNs phagocytosed more opsonized A.a. than did R/R-PMNs (p=0.019). The H/H-PMNs also expressed more CD63 and CD66b than did the R/R-PMNs (p=0.004 and 0.002, respectively) and released more elastase (p=0.001). CONCLUSIONS: The genotyping results confirm previous reports that more periodontal destruction occurs in the H/H genotype than in the H/R or R/R genotype. The functional studies indicate a hyper-reactivity of the H/H-PMN in response to bacteria, which may be one of several pathways leading to more periodontal breakdown. [Abstract]


Recent Articles in Clinical Oral Implants Research

Pjetursson BE, Tan WC, Tan K, Brägger U, Zwahlen M, Lang NP
A systematic review of the survival and complication rates of resin-bonded bridges after an observation period of at least 5 years.
Clin Oral Implants Res. 2007 Dec 7; .
Objectives: The objectives of this systematic review were to assess the 5-year survival of resin-bonded bridges (RBBs) and to describe the incidence of technical and biological complications. Methods: An electronic Medline search complemented by manual searching was conducted to identify prospective and retrospective cohort studies on RBBs with a mean follow-up time of at least 5 years. Patients had to have been examined clinically at the follow-up visit. Assessment of the identified studies and data extraction were performed independently by two reviewers. Failure and complication rates were analyzed using random-effects Poissons regression models to obtain summary estimates of 5-year proportions. Results: The search provided 6110 titles and 214 abstracts. Full-text analysis was performed for 93 articles, resulting in 17 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated survival of RBBs of 87.7% (95% confidence interval (CI): 81.6-91.9%) after 5 years. The most frequent complication was debonding (loss of retention), which occurred in 19.2% (95% CI: 13.8-26.3%) of RBBs over an observation period of 5 years. The annual debonding rate for RBBs placed on posterior teeth (5.03%) tended to be higher than that for anterior-placed RBBs (3.05%). This difference, however, did not reach statistical significance (P=0.157). Biological complications, like caries on abutments and RBBs lost due to periodontitis, occurred in 1.5% of abutments and 2.1% of RBBs, respectively. Conclusion: Despite the high survival rate of RBBs, technical complications like debonding are frequent. This in turn means that a substantial amount of extra chair time may be needed following the incorporation of RBBs. There is thus an urgent need for studies with a follow-up time of 10 years or more, to evaluate the long-term outcomes. [Abstract]

Jung RE, Weber FE, Thoma DS, Ehrbar M, Cochran DL, Hämmerle CH
Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate.
Clin Oral Implants Res. 2007 Dec 7;
Purpose: The aim of the present study was to test whether or not a synthetic matrix consisting of a polyethylene glycol (PEG) hydrogel containing recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with grafting materials enhances bone regeneration compared with grafting alone or empty control sites. Material and methods: In each of 10 rabbits, four titanium cylinders were screwed in perforated slits made in the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: (1) empty control, (2) a combination of a PEG matrix and hydroxyapatite/tricalciumphosphate (HA/TCP) granules and a combination of a PEG matrix containing either 10 mug/ml (3) or 30 mug/ml (4) of BMP-2 and HA/TCP granules. After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis repeated measures ANOVA and subsequent pairwise Student's t-test were applied (P<0.01). Results: Histomorphometric analysis showed an average area fraction of newly formed bone of 13.96+/-5.98% for the empty control, 15.16+/-7.95% for the PEG and HA/TCP group, 26.32+/-8.56% for the group containing 10 mug rhBMP-2/ml, and 30.15+/-7.63% for the group containing 30 mug rhBMP-2/ml. Statistical analysis revealed significantly more newly formed bone in the two rhBMP-2 groups compared with the PEG and HA/TCP group and with the empty control. Regarding the surface fraction of the HA/TCP graft particles covered with newly formed bone the addition of rhBMP-2 revealed a more than two-fold increase compared with cylinders containing HA/TCP granules without rhBMP-2. This difference reached statistical significance. Conclusions: It is concluded that rhBMP-2 significantly enhances bone regeneration in rabbits when delivered by a synthetic matrix containing HA/TCP. This synthetic PEG matrix containing HA/TCP granules apparently fulfills a number of criteria required for an ideal carrier system for rhBMP-2. [Abstract]

Nikolidakis D, van den Dolder J, Wolke JG, Jansen JA
Effect of platelet-rich plasma on the early bone formation around Ca-P-coated and non-coated oral implants in cortical bone.
Clin Oral Implants Res. 2007 Dec 7;
Objectives: The purpose of the present study was to investigate the effect of local application of platelet-rich plasma (PRP) on the early healing of cortical bone around Ti implants with two different surface configurations. Material and methods: Six goats were used in this study. PRP fractions were obtained from a venous blood sample of the goats and administered immediately before implant insertion. PRP was applied via gel preparation and installation of the gel into the implant site, or via dipping of the implants in PRP fraction before insertion. A total of 36 implants (18 non-coated and 18 Ca-P-coated) were placed into the tibial cortical bone. The animals were sacrificed at 6 weeks after implantation and implants with surrounding tissue were prepared for histological examination. Histomorphometrical variables like the percentage of implant surface with direct bone-implant contact and the percentage of new and old bone adjacent to the implant were evaluated. Results: More interfacial bone-to-implant contact was observed for all the three groups of Ca-P-coated implants and the Ti/PRP liquid group. All groups revealed similar percentages of old and new bone adjacent to the implant. Conclusions: It was concluded that the additional use of PRP did not have any effect on the early cortical bone response to the Ca-P-coated implants, while PRP in a liquid form showed a tendency to increase bone apposition to roughened titanium implants. [Abstract]

Verdonck HW, Meijer GJ, Laurin T, Nieman FH, Stoll C, Riediger D, Stoelinga PJ, Baat CD
Implant stability during osseointegration in irradiated and non-irradiated minipig alveolar bone: an experimental study.
Clin Oral Implants Res. 2007 Dec 7;
Objectives: Primary implant stability is related to local bone density. After insertion of an implant, implant stability is subject to changes due to bone remodeling. In patients who have undergone radiotherapy in the head and neck region, implant stability is impaired because irradiation reduces bone vitality. The current study was designed to monitor and test implant stability immediately after implant placement and during osseointegration in irradiated and non-irradiated minipig alveolar bone. Materials and methods: All maxillary and mandibular premolars and molars of six adult Göttingen minipigs were extracted. The maxilla and mandible of three minipigs received three irradiation exposures at a total dose of 24 Gy. After irradiation, five initial implant holes were drilled in the residual alveolar ridge of each edentulous site. In order to assess bone vascularity, laser Doppler flowmetry recordings were carried out in the initial holes. A total of 120 implants were placed in the six minipigs. Subsequently, and at 8, 16, and 24 weeks after implant placement, implant stability was recorded by resonance frequency analysis (RFA). RFA values were expressed as an implant stability quotient (ISQ). Results: ISQ values recorded immediately after implant placement showed no differences between irradiated and non-irradiated minipigs. Repeated measurements at the four recording moments showed a decrease of ISQ values in all minipigs, being more pronounced in irradiated bone, when compared with non-irradiated bone. The results at the third and fourth recording moments showed a stabilization or even a slight increase of ISQ values. Conclusions: The results document the negative effect of irradiation on bone vascularity and hence on implant stability. [Abstract]

Karl M, Graef F, Heckmann S, Krafft T
Parameters of resonance frequency measurement values: a retrospective study of 385 ITI dental implants.
Clin Oral Implants Res. 2007 Dec 7;
Objectives: There is no proven clinical tool to evaluate the amount of osseointegration and stability around dental implants. Therefore, the aim of this retrospective clinical study was to evaluate resonance frequency analysis values of 385 ITI solid screw implants. Material and methods: Both at implant placement and after healing, implant stability quotients (ISQs) were determined. For statistical analysis, Pearson's correlation coefficients, Welch's two-sample t-tests and paired samples t-tests were computed at a level of significance of alpha=0.05. Results: ISQ values ranged from 39 to 86 at implant placement and from 35 to 89 after healing, showing a significant increase. The highest ISQ values at both stages were obtained in the posterior mandible (P</=0.002). After healing, ISQ values in the anterior mandible were significantly higher than in the anterior maxilla (P=0.005). Implant length had a significant influence on ISQ in the anterior mandible (P=0) at insertion and in the anterior (P=0.005) and posterior mandible (P=0.036) after healing. Implant diameter and ISQ at insertion correlated in the anterior mandible (P=0.037). After healing, a significant influence was found for all regions, except the posterior maxilla (P=0.795). With the exception of the anterior maxilla (P=0.542), ISQ at placement had a significant influence on ISQ after healing. In the anterior maxilla (P=0.002) and in the posterior mandible (P=0.007), healing time significantly influenced ISQ after healing. Conclusions: It appears that only repeated ISQ measurements of a specific implant have some diagnostic benefit, although the parameters influencing the absolute values still remain unclear. [Abstract]

Roccuzzo M, Aglietta M, Bunino M, Bonino L
Early loading of sandblasted and acid-etched implants: a randomized-controlled double-blind split-mouth study. Five-year results.
Clin Oral Implants Res. 2007 Dec 7;
Objectives: The aim of the present split-mouth study is to assess the peri-implant conditions around early-loaded sandblasted and acid-etched (SLA) implants, 5 years after abutment connection and to compare, in the same patients, the results obtained with a standard protocol using identical implants with a TPS surface. Material and methods: Surgical procedure was performed by the same operator and was identical at test (SLA) and control (TPS) sites, in 32 healthy patients. Abutment connection was carried out at 35 N cm 6 weeks postsurgery for test sites and 12 weeks for the controls. Patients were seen regularly, for control and professional cleaning. At 60 months, clinical measures and radiographic bone changes were recorded by the same operator, blind to the type of surface of the implant, on 27 patients, as five patients were lost to follow-up. Results: A total number of 106 implants were examined. No implant was lost. No significant differences were found with respect to the presence of plaque [modified plaque index (mPI) 0.27+/-0.56 vs. 0.32+/-0.54], bleeding on probing (29% vs. 32%), mean pocket depth (3.2+/-1 vs. 3.2+/-1 mm) or mean marginal bone loss (0.32+/-1.04 vs. 0.44+/-1.12 mm) between test and control. Four implants that presented 'spinning' at the time of abutment connection presented no significant differences from the rest of the test sites. Conclusion: The results of this prospective study confirm that SLA implants, under defined conditions, are suitable for early loading at 6 weeks in both the mandible and the maxilla. Limited implant spinning, occasionally found at abutment connection, produces no detrimental effect on the clinical outcome when properly handled. [Abstract]

Jung RE, Pjetursson BE, Glauser R, Zembic A, Zwahlen M, Lang NP
A systematic review of the 5-year survival and complication rates of implant-supported single crowns.
Clin Oral Implants Res. 2007 Dec 7;
Objectives: The objective of this systematic review was to assess the 5-year survival of implant-supported single crowns (SCs) and to describe the incidence of biological and technical complications. Methods: An electronic MEDLINE search complemented by manual searching was conducted to identify prospective and retrospective cohort studies on SCs with a mean follow-up time of at least 5 years. Failure and complication rates were analyzed using random-effects Poisson's regression models to obtain summary estimates of 5-year proportions. Results: Twenty-six studies from an initial yield of 3601 titles were finally selected and data were extracted. In a meta-analysis of these studies, survival of implants supporting SCs was 96.8% [95% confidence interval (CI): 95.9-97.6%] after 5 years. The survival rate of SCs supported by implants was 94.5% (95% CI: 92.5-95.9%) after 5 years of function. The survival rate of metal-ceramic crowns, 95.4% (95% CI: 93.6-96.7%), was significantly (P=0.005) higher than the survival rate, 91.2% (95% CI: 86.8-94.2%), of all-ceramic crowns. Peri-implantitis and soft tissue complications occurred adjacent to 9.7% of the SCs and 6.3% of the implants had bone loss exceeding 2 mm over the 5-year observation period. The cumulative incidence of implant fractures after 5 years was 0.14%. After 5 years, the cumulative incidence of screw or abutment loosening was 12.7% and 0.35% for screw or abutment fracture. For supra-structure-related complications, the cumulative incidence of ceramic or veneer fractures was 4.5%. Conclusion: It can be concluded that after an observation period of 5 years, high survival rates for implants and implant-supported SCs can be expected. However, biological and particularly technical complications are frequent. [Abstract]

Qahash M, Susin C, Polimeni G, Hall J, Wikesjö UM
Bone healing dynamics at buccal peri-implant sites.
Clin Oral Implants Res. 2007 Nov 26;
Background: It is common belief that immediate implant placement into extraction sites may act to preserve the alveolar process. The objective of this study was to evaluate healing dynamics at buccal peri-implant sites in relation to the dimensions of the alveolar ridge. Methods: Bilateral, critical-size, supraalveolar, peri-implant defects were created in 12 male Hound Labrador mongrel dogs following surgical horizontal cut-down of the alveolar ridge. Each jaw quadrant received three 10-mm titanium implants placed 5 mm into extraction sites of the third and fourth premolar teeth leaving 5 mm in a supraalveolar position. The mucoperiosteal flaps were advanced, adapted, and sutured for primary intention healing. Bone fluorescent markers were administered at weeks 3 and 4 postsurgery, and pre-euthanasia. Incandescent, polarized, and fluorescent light microscopies were used to assess the width of the buccal wall of the alveolar ridge and local bone remodeling over the 8-week healing interval. Results: There was a significant association between the width of the buccal alveolar ridge and extent of bone resorption evaluated by incandescent and fluorescent light microscopy. A non-linear association was observed between the buccal ridge width and resorption of the alveolar ridge. A 2-mm threshold was established to account for this non-linearity. The strength of this association was two times greater in specimens with a buccal ridge width <2 mm compared with a wider ridge (beta=1.62 vs. 0.80) observed by fluorescent light microscopy. Accordingly, mean buccal resorption was significantly greater when the ridge width was <2 mm. Fluorescent light microscopy consistently showed greater buccal resorption compared with incandescent light microscopy (P<0.05). Agreement between the examination techniques was low (concordance correlation coefficient=0.49), especially for higher values of buccal resorption. Conclusion: When implants are placed into extraction sites, proximity to the buccal alveolar crest appears a major consideration. The observations herein suggest that the width of the buccal alveolar ridge should be at least 2 mm to maintain the alveolar bone level. These observations likely have general implications for implant placement using most surgical protocols. [Abstract]

Alhag M, Renvert S, Polyzois I, Claffey N
Re-osseointegration on rough implant surfaces previously coated with bacterial biofilm: an experimental study in the dog.
Clin Oral Implants Res. 2007 Nov 26;
Objective: The purpose of the study was to investigate whether osseointegration can occur on rough implant surfaces that previously had been coated with bacterial biofilm. Materials and methods: The premolars on both sides of the mandible in four beagle dogs were extracted. Following 3 months healing, three titanium implants Ti-Unite(trade mark), Nobel Biocare((R)) were partially inserted in the left side of each mandible. Some threads protruded from the tissues into the oral cavity. Plaque accumulated on the exposed part of the implant. Following a 5-week healing period, the contaminated parts of each implant were treated using three different techniques: (1) swabbing with citric acid for 30 s followed by rinsing with physiological saline, (2) cleansing with a toothbrush and physiological saline for 1 min, and (3) swabbing with 10% hydrogen peroxide for 1 min followed by rinsing with physiological saline. The treated implants and one pristine implant (control) were installed to the full implant length on the contralateral sides of the mandibles. Following 11 weeks of healing, the dogs were sacrificed and biopsies were obtained. Ground sections were prepared for histomorphometric analysis. Results: All treatment modalities were associated with direct bone-to-implant contact on the portion of implant surface previously exposed to the oral environment. Conclusions: The results demonstrate that rough surfaces, which were plaque contaminated and cleaned by different methods, can re-osseointegrate. [Abstract]

Mesa F, Muńoz R, Noguerol B, Luna JD, Galindo P, O'Valle F
Multivariate study of factors influencing primary dental implant stability.
Clin Oral Implants Res. 2007 Nov 26;
Objectives: The purpose was to determine by multivariate analysis in a large series of dental implants the variables associated with primary endosseous dental implant stability (DIS). Material and methods: A 10-year retrospective study was conducted of 1084 Brĺnemark((R)) implants placed in 316 patients. Clinical variables (age, gender, smoking habit, and periodontal status), implant diameter, implant length, and Periotest((R)) values (PTVs) were analyzed in bivariate and multivariate studies in order to determine their influence on DIS, using a cut-off PTV value of -2. Results: The site of implant insertion showed the strongest association with primary DIS failure among the study variables. Implants in the anterior mandible had a 6.43-fold lower risk of primary DIS risk vs. those at other sites [95% confidence interval (CI) 3.28-12.61], and implants in the maxillary had a 2.70-fold higher risk of primary DIS failure vs. those in the mandible (95% CI 1.82-4). Among other variables, females had a 1.54-fold higher risk of primary DIS failure vs. males (95% CI 1.88-2.22) and implants <15 mm in length had a 1.49-fold higher risk of failure vs. longer implants (95% CI 1.09-2.04). Conclusion: According to these findings, primary DIS failure is more likely in females, at sites other than the anterior mandible, and with dental implants shorter than 15 mm, at least when non-threaded titanium implants are used. These data may be of value in the identification of patients at a high risk of primary DIS failure with immediate implant loading. [Abstract]

Abrahamsson I, Albouy JP, Berglundh T
Healing at fluoride-modified implants placed in wide marginal defects: an experimental study in dogs.
Clin Oral Implants Res. 2007 Nov 26;
Objective: To study the healing at fluoride-modified implants placed in wide circumferential defects. Material and methods: Six mongrel dogs were used. The mandibular premolars and first molars were extracted. Three months later four implants were placed in one side of the mandible of each dog. The control implants (MicroThread(trade mark)) had a TiOblast surface, while the test implants (OsseoSpeed(trade mark)) had a fluoride-modified surface. Two implants of each type were placed. The marginal 50% of the prepared canal was widened using step drills. Following installation a 1 mm wide gap occurred between the implant surface and the bone wall in the defect. All implants were submerged. The installation procedure was repeated in the opposite side of the mandible 4 weeks after the first implant surgery. Two weeks later the animals were euthanized and block biopsies containing the implant and surrounding tissues were prepared for histological analysis. Results: The histological analysis revealed that a significantly larger area of osseointegration was established within the defect at fluoride-modified implants than at implants with a TiOblast surface after 6 weeks of healing. Further, the degree of bone-to-implant contact within the defect area was larger at fluoride-modified implants than at the TiOblast implants. Conclusion: It is suggested that the fluoride-modified implant surface promotes bone formation and osseointegration. [Abstract]

Blanes RJ, Bernard JP, Blanes ZM, Belser UC
A 10-year prospective study of ITI dental implants placed in the posterior region. I: Clinical and radiographic results.
Clin Oral Implants Res. 2007 Dec;18(6):
Objectives: To evaluate the long-term fixture success rate, crestal bone loss and peri-implant soft tissue parameters around ITI dental implants placed in the posterior region of partially edentulous patients. Material and methods: A total of 192 ITI dental implants were consecutively placed in premolars and molars of 83 partially edentulous patients admitted for treatment at Geneva Dental School. All implants were restored by means of ceramic-to-metal fused fixed partial dentures and single crowns. Patients were followed as part of a prospective longitudinal study focusing on implant success. Surgical, radiographic and clinical variables were collected at the 1-year recall after implant placement and at the most recent clinical evaluation. Results: The mean observation time was 6 years (range 5-10 years). Four implants failed, yielding a 10-year cumulative survival rate of 97.9%. The mean annual crestal bone loss was -0.04+/-0.2 mm. Hollow-cylinder implants displayed more crestal bone loss (-0.13+/-0.24 mm) than hollow-screw implants (-0.02+/-0.19 mm; P=0.032). Clinical parameters such as age, gender, implant length and bone quality did not affect crestal bone levels. Increase in recession depth (P=0.025) and attachment level (P=0.011) were significantly associated with crestal bone loss. Conclusions: ITI dental implants placed in the posterior jaw demonstrate excellent long-term clinical success. Hollow-cylinder implants seem to display a higher risk for crestal bone loss. Recession depth and attachment levels appear to be good clinical indicators of peri-implant bone loss. [Abstract]

Lachmann S, Kimmerle-Müller E, Axmann D, Gomez-Roman G, Weber H, Haas R
Reliability of findings around healthy implants in association with oral hygiene measures: a clinical, microbiological, and immunological follow-up in edentulous patients.
Clin Oral Implants Res. 2007 Dec;18(6):
Objectives: To assess the performance of clinical, microbiological, and immunological diagnosis of peri-implant health and the influence of professional hygiene measures on them. Material and methods: Twenty-one edentulous patients with oral implants supporting a lower overdenture were followed up over 3 months beginning 1 week before their annual recall visit. Hygiene scores, probing depth, bleeding on probing (BOP), implant stability, gingival crevicular fluid (GCF) volume, sulcular interleukin-1beta (IL-1beta) and prostaglandin E2 (PGE2) concentrations, and relative concentrations of five bacterial species (polymerase chain reaction) were investigated. Measurement variation was assessed as a function of (a) intra- and (b) inter-examiner reliability, (c) inter-implant variation in each patient, (d) time, and (e) effect of hygiene measures by accuracy, repeatability, reproducibility, and visualization with the Bland and Altman Plot. Results: Measurement means and accuracy (in parentheses) were as follows: GCF volume 1.5 mul (1.5), Interleukin-1beta 8 ng/ml (26), PGE2 63 ng/ml (185), bacteria sum score 0.2 (0.7), plaque score 1 (1), BOP score 0 (1), Periotest value -4 (3), resonance frequency analysis ISQ 66 (11), and pocket probing depth 2.3 mm (0.7). No finding exhibited any statistically significant measurement variation as explained by accuracy, repeatability, or reproducibility. Bland and Altman Plots revealed insufficient agreement for replicated BOP assessments. A short post-treatment reduction in plaque and BOP scores was visually apparent. Still, professional oral hygiene measures exerted no sustained influence on the clinical and biochemical appearance of the peri-implant tissues. Conclusion: All findings except BOP showed statistically acceptable repeatability and moderate vulnerability to influences present 'chairside' in clinical practice. [Abstract]

Ito Y, Sato D, Yoneda S, Ito D, Kondo H, Kasugai S
Relevance of resonance frequency analysis to evaluate dental implant stability: simulation and histomorphometrical animal experiments.
Clin Oral Implants Res. 2007 Nov 6;
Background: Resonance frequency analysis (RFA) is applied to evaluate implant stability, and the clinical relevance of this application is accepted. However, a discrepancy between resonance frequency (RF) and other parameters of implant stability such as implant insertion torque and bone mineral density at the insertion site has been reported. In addition, the relation between RF and histological implant-bone contact has not been well documented. Purpose: To explain this discrepancy and to clarify the relation between RF and histological implant-bone contact, we conducted the present study. Materials and methods: A hydroxyapatite-coated implant, 4 mm diameter and 10 mm length, was used. We placed the implant in a small plastic box vertically and fixed the implant in the box with small screws at different height positions. An 'Osstell' transducer was mounted on the implant and RF was measured with or without loosening the screws. Twenty-four implants were placed in the tibiae of four mini-pigs. The animals were sacrificed 1, 2 and 4 weeks after the placement, and the RF of each implant was measured. Ground sections were prepared and implant-bone contact was histomophometrically measured. Results: Loosening the screw at the neck region of the implant remarkably decreased RF compared with the screws of the other regions. Correlation between RF and implant-bone contact, which was measured all around the implant, was not significant (r=0.221, P=0.299). However, the correlation coefficient increased to '0.361' when implant-bone contact was measured at the neck of the implant (P=0.0835), although these two parameters were not statistically correlated. Conclusions: Although RF did not correlate with histological implant-bone contact, the present results demonstrated that a connection between the implant and bone at the neck region of the implant affects RF the most effectively, further suggesting the superiority of RFA in the process of implant treatment and the follow-up. The present results could explain the discrepancy between RFA and other parameters of implant stability. [Abstract]

Payer M, Kirmeier R, Jakse N, Wimmer G, Wegscheider W, Lorenzoni M
Immediate provisional restoration of XiVE((R)) screw-type implants in the posterior mandible.
Clin Oral Implants Res. 2007 Oct 23;
Objectives: This prospective study evaluated the clinical outcome of immediately restored screw-type implants for the replacement of mandibular (pre)molars. The results were based on survival, clinical stability and on changes of bone levels from implant placement to delivery of the definitive superstructure 6 months after insertion. Material and methods: In this study, 24 patients were treated according to an immediate loading protocol. Forty XiVE((R)) implants were placed in the mandibular (pre)molar regions for single-tooth restoration and the treatment of free-end situations. Radiographic bone levels in relation to implant margins were measured at the time of insertion and recorded. All implants were provided with a transfer coping and restored with provisional crowns within 7 days. After 6 months, the final restorations were fabricated. At this time, survival, Periotest((R)) value and radiographic bone levels were assessed. Results: A total of 40 XiVE((R)) implants were placed with an insertion torque value of at least 45 N cm. The median Periotest((R)) value 6 months post-insertion was -5 (maximum -2, minimum -7). The mean radiographic coronal bone level at prosthetic delivery was 1.4 mm (SD+/-0.57) compared with 0.47 mm (SD+/-0.37) at the time of insertion. No implant failures were observed up to prosthetic restoration 6 months post-insertion. Conclusion: The present data of immediately loaded implants in the posterior mandible are comparable to results with conventional loaded implants. Additional long-term data will be necessary to include this protocol as a standard procedure in our treatment concepts for the edentulous posterior mandible. [Abstract]

Hernández-Alfaro F, Torradeflot MM, Marti C
Prevalence and management of Schneiderian membrane perforations during sinus-lift procedures.
Clin Oral Implants Res. 2007 Oct 23;
This clinical study was undertaken to evaluate the prevalence of surgical complications of the sinus graft procedure and to set a protocol to repair sinus membrane perforations intraoperatively using a variety of techniques and materials. From January 2000 to May 2005, 338 patients were studied, on whom 474 sinus floor augmentation procedures were performed, and a total of 1166 dental implants were simultaneously placed. A total of 104 perforations of the sinus membrane were observed (19 were bilateral). In group number 1, sinus membrane perforations of <5 mm were observed in 56 sinus augmentation procedures (53.85%), 44 were treated using a resorbable collagen membrane and 12 were sutured with a resorbable material. In group number 2, 28 sinus membranes had a perforation size between 5 and 10 mm (26.92%) and were treated using lamellar bone combined with a resorbable membrane. Group number 3 consisted of 20 sinus membrane perforations>10 mm (19.23%), 10 were covered with lamellar bone combined with a buccal fat pad flap, six were treated with a mandibular block graft and four perforations were treated with only a lamellar bone sheet. Two-hundred and seventy-eight implants were placed under repaired membrane perforations and 247 implants survived. Interestingly enough, all the 25 implants that failed to integrate were placed under perforated and reconstructed membranes during the sinus lift procedure. Based on the results of this study, the survival rates of implants placed under reconstructed membranes correlate inversely with the size of the perforations. [Abstract]

Vazquez L, Saulacic N, Belser U, Bernard JP
Efficacy of panoramic radiographs in the preoperative planning of posterior mandibular implants: a prospective clinical study of 1527 consecutively treated patients.
Clin Oral Implants Res. 2007 Oct 23;
Objectives: Various imaging techniques, including conventional radiography and computed tomography, are proposed to localize the mandibular canal prior to implant surgery. The aim of this study is to determine the incidence of altered mental nerve sensation after implant placement in the posterior segment of the mandible when a panoramic radiograph is the only preoperative imaging technique used. Material and methods: The study included 1527 partially and totally edentulous patients who had consecutively received 2584 implants in the posterior segment of the mandible. Preoperative bone height was evaluated from the top of the alveolar crest to the superior border of the mandibular canal on a standard panoramic radiograph. A graduated implant scale from the implant manufacturer was used and 2 mm were subtracted as a safety margin to determine the length of the implant to be inserted. Results: No permanent sensory disturbances of the inferior alveolar nerve were observed. There were two cases of postoperative paresthesia, representing 2/2584 (0.08%) of implants inserted in the posterior segment of the mandible or 2/1527 (0.13%) of patients. These sensory disturbances were minor, lasted for 3 and 6 weeks and resolved spontaneously. Conclusions: Panoramic examination can be considered a safe preoperative evaluation procedure for routine posterior mandibular implant placement. Panoramic radiography is a quick, simple, low-cost and low-dose presurgical diagnostic tool. When a safety margin of at least 2 mm above the mandibular canal is respected, panoramic radiography appears to be sufficient to evaluate available bone height prior to insertion of posterior mandibular implants; cross-sectional imaging techniques may not be necessary. [Abstract]

Hämmerle CH, Jung RE, Yaman D, Lang NP
Ridge augmentation by applying bioresorbable membranes and deproteinized bovine bone mineral: a report of twelve consecutive cases.
Clin Oral Implants Res. 2007 Oct 23;
Objective: Lateral ridge augmentations are traditionally performed using autogenous bone grafts to support membranes for guided bone regeneration (GBR). The bone-harvesting procedure, however, is accompanied by considerable patient morbidity. Aim: The aim of the present study was to test whether or not resorbable membranes and bone substitutes will lead to successful horizontal ridge augmentation allowing implant installation under standard conditions. Material and methods: Twelve patients in need of implant therapy participated in this study. They revealed bone deficits in the areas intended for implant placement. Soft tissue flaps were carefully raised and blocks or particles of deproteinized bovine bone mineral (DBBM) (Bio-Oss((R))) were placed in the defect area. A collagenous membrane (Bio-Gide((R))) was applied to cover the DBBM and was fixed to the surrounding bone using poly-lactic acid pins. The flaps were sutured to allow for healing by primary intention. Results: All sites in the 12 patients healed uneventfully. No flap dehiscences and no exposures of membranes were observed. Nine to 10 months following augmentation surgery, flaps were raised in order to visualize the outcomes of the augmentation. An integration of the DBBM particles into the newly formed bone was consistently observed. Merely on the surface of the new bone, some pieces of the grafting material were only partly integrated into bone. However, these were not encapsulated by connective tissue but rather anchored into the newly regenerated bone. In all of the cases, but one, the bone volume following regeneration was adequate to place implants in a prosthetically ideal position and according to the standard protocol with complete bone coverage of the surface intended for osseointegration. Before the regenerative procedure, the average crestal bone width was 3.2 mm and to 6.9 mm at the time of implant placement. This difference was statistically significant (P<0.05, Wilcoxon's matched pairs signed-rank test). Conclusion: After a healing period of 9-10 months, the combination of DBBM and a collagen membrane is an effective treatment option for horizontal bone augmentation before implant placement. [Abstract]

Park SH, Lee KW, Oh TJ, Misch CE, Shotwell J, Wang HL
Effect of absorbable membranes on sandwich bone augmentation.
Clin Oral Implants Res. 2007 Oct 23;
Objectives: This study was conducted to evaluate the effect of barrier membranes on sandwich bone augmentation (SBA) for the treatment of implant dehiscence defects. Material and methods: Twenty-six implant-associated buccal dehiscence defects in 22 patients were treated according to the SBA concept - mineralized human cancellous allograft (inner layer), mineralized human cortical allograft (outer layer) and coverage with barrier membrane. The defects were randomly assigned to the bovine collagen membrane (BME) group; acellular dermal matrix (ADM) group; and no membrane group. Measurements at baseline and 6 months re-entry included defect height (DH: from smooth-rough junction to the most apical part of the defect), defect width (DW: at the widest part of the defect), and horizontal defect depth (HDD: at three locations - smooth-rough junction, middle, and most apical portion of the defect). All measurements were taken from a reference stent. Statistical analyses were performed for comparison of intra- and inter-group comparisons. Results: All implants placed were successfully osseointegrated. DH at baseline for three groups were not significantly different (P=0.858). Mean % DH reductions for ADM, BME, and control groups at 6 months were 73.9+/-17.6%, 68.1+/-30.1%, and 63.6+/-23.9%, respectively, with no significant difference among the groups (P=0.686). Mean horizontal bone gain, however, was significantly greater for membrane groups (1.7 mm for ADM, 1.6 mm for BME) compared with control group (1 mm) (P=0.044). Implant exposure resulted in significant reduction in total height gain (79.1+/-14.3% vs. 57+/-23.5%, P=0.021). Conclusions: Within the limit of this study, it is concluded that SBA technique achieved predictable clinical outcomes. The addition of absorbable membranes enhanced bone gain in thickness compared with membrane-treated sites. [Abstract]

Evans CD, Chen ST
Esthetic outcomes of immediate implant placements.
Clin Oral Implants Res. 2007 Oct 23;
Background: Single-rooted teeth deemed not restorable via conventional means may be candidates for implant placement at the time of tooth extraction. Immediate implant placements are believed to preserve soft and hard tissue form and contours, reduce the need for augmentation procedures, minimize surgical exposure of the patient, reduce treatment time and improve esthetic outcomes. Method: This retrospective review analyzed the esthetic outcomes of 42 non-adjacent single-unit implant restorations completed using an immediate implant surgical placement protocol. Results: The mean time in function was 18.9 months (range 6-50 months) and the majority of implants placed had a restorative platform diameter of 4.1 and 4.8 mm. A highly significant change in crown height due to marginal tissue recession of 0.9 +/- 0.78 mm (P=0.000) was recorded for all sites, with no difference seen between implant systems (P=0.837). Thin tissue biotype showed slightly greater recession than thick tissue biotype (1 +/- 0.9 vs. 0.7 +/- 0.57 mm, respectively); however, this difference was not statistically significant (P=0.187). Implants with a buccal shoulder position showed three times more recession than implants with a lingual shoulder position (1.8 +/- 0.83 vs. 0.6 +/- 0.55 mm, respectively) with the difference being highly statistically significant (P=0.000). Conclusions: Immediate implant placement requires very careful case selection and high surgical skill levels if esthetic outcomes are to be achieved. Long-term prospective studies on tissue stability and esthetic outcomes are needed. [Abstract]

Chen YH, Chang HH, Chen YJ, Lee D, Chiang HH, Jane Yao CC
Root contact during insertion of miniscrews for orthodontic anchorage increases the failure rate: an animal study.
Clin Oral Implants Res. 2007 Oct 23;
Objectives: Miniscrews and miniplates are increasingly being used for absolute anchorage during orthodontic treatment. However, potential problems of damaging adjacent roots and their consequences during mini-implant placement in the alveolar process have not been clearly described. Materials and methods: Animal experiments were used to evaluate the stability of miniscrews placed with intentional root contact. The root repair was evaluated after screw removal. Seventy-two miniscrews were surgically placed in the mandibular alveolar bone of six adult mongrel dogs with metabolic bone labeling at 3-week intervals. Miniscrews of the experimental group were placed so that they contacted the root of the adjacent teeth, were retained for different time durations, and were then removed. The insertion torque, clinical measurements, removal torque, and histological findings were analyzed. Results: (1) miniscrews contacting the roots showed a significantly higher insertion torque than those without contact; (2) there was a significant difference in the removal torque measurements based on the mobility of miniscrews and the state of root contact; and (3) miniscrews contacting the root were at greater risk of failure. Conclusions: During placement of miniscrews in the aveolar process, increased failure rates were noticed among those contacting adjacent roots. Failed miniscrews appeared to be surrounded with a greater volume of soft tissue. When more inflammation was present, the adjacent roots seemed to experience more resorption. Nevertheless, the created lesion was repaired with a narrow zone of mineralized tissue deposited on the root surface, which was likely cellular cementum, and was mainly filled with alveolar bone, with the periodontal ligament space being maintained. [Abstract]

Beloti MM, Martins W, Xavier SP, Rosa AL
In vitro osteogenesis induced by cells derived from sites submitted to sinus grafting with anorganic bovine bone.
Clin Oral Implants Res. 2007 Oct 23;
Objectives: This study evaluated key parameters of the in vitro osteogenesis induced by osteoblastic cells obtained from sites submitted to sinus grafting with anorganic bovine bone (ABB) in comparison with cells derived from bone sites of the same patients. Materials and methods: In three patients, the augmentation of maxillary sinus was carried out using ABB (Bio-Oss((R))). After at least 6 months, during the surgical intervention for titanium implants placement, biopsies were taken from these areas using trephine burs (grafted group). Bone fragments, of the same patients, from sites that had not received graft were also obtained with trephine burs and used as a control group. Osteoblastic cells were obtained from grafted and control groups by enzymatic digestion and cultured under standard osteogenic condition until subconfluence. First passaged cells were cultured in 24-well culture plates. Cell adhesion was evaluated at 24 h. For proliferation and viability assay, cells were cultured for 1, 3, 7, and 10 days. Total protein content and alkaline phosphatase (ALP) activity were measured at 3, 7, 10, 14, 17, and 21 days. Cultures were stained with Alizarin red S at 21 days, for detection of mineralized matrix. Data were compared by Student's t-test. Results: Cell adhesion and viability were not affected by cell source (P>0.05). Total protein content was greater (P<0.05) for grafted group. Cell proliferation, ALP activity, and bone-like nodule formation were all greater (P<0.05) for the control group. Conclusion: Taken together, these results indicate that the in vivo long-term contact of cells with ABB downregulates the expression of osteoblast phenotype and consequently the in vitro osteogenesis. [Abstract]

Stavropoulos A, Nyengaard JR, Lang NP, Karring T
Immediate loading of single SLA implants: drilling vs. osteotomes for the preparation of the implant site.
Clin Oral Implants Res. 2007 Oct 23;
Objectives: To evaluate whether or not preparation of the implant site with osteotomes instead of drilling may improve peri-implant bone density and/or osseointegration, and whether or not this further improves the predictability of immediate loading of SLA implants. Material and methods: The second, third, and fourth premolars were extracted in both sides of the mandible in six dogs, and after at least 3 months four SLA implants were inserted into each side of the jaw. In three animals, the implant sites were prepared by means of osteotomes, while standard stepwise drilling was used in the remaining animals. In each side of the jaw, two non-adjacent implants were restored with single crowns 4 days after installation, while the remaining two implants were left without crowns to serve as non-loaded controls. After 2, 4, or 12 weeks of loading, specimens including the implants and surrounding tissues were obtained and processed for histologic analysis of undecalcified sections. Results: All implants placed with osteotomes were lost (five before delivery of the crowns and the rest during the first week after loading). None of the conventionally inserted implants, however, was lost, and histomorphometrical analysis revealed similar soft- and hard peri-implant tissue characteristics at immediately loaded and non-loaded implants at all observation times. Average bone-to-implant contact was 59-72% at immediately loaded implants vs. 60-63% at non-loaded ones. Conclusion: Preparation of the implant site by means of osteotomes had a deleterious effect on osseointegration, while immediate loading of single, free-standing, SLA implants following a conventional surgical protocol did not jeopardize their osseointegration. [Abstract]

Van de Velde T, Glor F, De Bruyn H
A model study on flapless implant placement by clinicians with a different experience level in implant surgery.
Clin Oral Implants Res. 2007 Oct 23;
Introduction: Some implant companies advocate that flapless surgery is easy to perform and beneficial for aesthetics and patients morbidity. However, studies objectively analyzing the position in the bone of implants installed with this approach are lacking. This in vitro model study was performed to analyse deviations in position and inclination of implants placed with flapless surgery compared with the ideally planned position and to examine whether the outcome is affected by experience level. Methods: Identical radio-opaque resin models were developed with a silicon lining mimicking the soft tissues and six edentulous single tooth spaces. Eighteen clinicians (six periodontists, six general dentists and six students) drilled four implant sites each (Straumann AG, Basel, Switzerland) with a flapless approach. Corresponding CT-scan images of the models were available. A virtual implant program (Simplant, Materialise NV, Leuven, Belgium) was used to plan the ideal position and to compare this with the implant angulation and position of the test implants. Results: There were no significant differences between the experience groups for all parameters except for global deviations between dentist and students, angle deviations between dentists and students and horizontal deviations between specialists and students. In incisor sites, specialists and students deviated significantly more in global deviation and depth than dentists. In premolar and molar sites, there were no significant differences except for horizontal deviations between specialists and dentists in molar sites. As a consequence of the malpositioning, perforations were seen in 59.7% (43/72) of the implant occasions when the artificial mucosa was removed from the model. Conclusion: The three-dimensional location of implants installed with flapless approach differs significantly from the ideal, although neighbouring teeth were present and maximal radiographical information was available. Within the limitations of this in vitro model study it seems necessary to point out that these deviations would in a clinical situation lead to complications such as loss of implant stability, aesthetical and phonetical consequences. The outcome is not influenced by the level of experience with implant surgery. This points out that more precise measurements of soft tissue in situ or additional use of guiding systems are recommendable. [Abstract]

Celenk C, Celenk P
Evaluation by quantitative magnetic resonance imaging of trabecular bone quality in the dentate and edentulous mandible.
Clin Oral Implants Res. 2007 Oct 23;
Objective: To quantify the differences in mandibular trabecular bone quality between edentulous and dentate patients using quantitative magnetic resonance imaging (QMRI). Methods: The patients in this study had been referred to our clinic for QMRI examination for various reasons. A total of 40 male patients (18 dentate, 22 edentulous), 45-55 years of age, were examined. Mandibular T2(*) axial cross-sections were performed following receipt of consent from each patient. T2(*) relaxation time values (RTVs) were determined in the trabecular area. Results: The mean mandibular T2(*) RTVs of dentate and edentulous patients were 181 and 182, respectively. There were no significant differences between the two groups (P=0.929) (Student's t-test). Conclusions: Mandibular trabecular bone quality may not be influenced by edentulousness according to QMRI. [Abstract]

Molly L, Nackaerts O, Vandewiele K, Manders E, van Steenberghe D, Jacobs R
Speech adaptation after treatment of full edentulism through immediate-loaded implant protocols.
Clin Oral Implants Res. 2007 Oct 18;
Objectives: The objective of the present study was to evaluate the influence of immediate loading of implants on speech adaptation. Material and methods: Ten patients (mean age 54, 6 females) were examined before surgery and 1, 3, 6 and 12 months afterwards. Articulation analysis was done using objective DAT-recoded data evaluated by two groups of speech and language therapists and a computer software program. Besides, patient VAS-scores, myofunctional problems and hearing impairment were recorded and analysed. Results: In the present study only one patient suffered from deteriorated speech after immediate loading. Other patients showed unaffected or improved articulation 3 to 6 months after surgery with a strident and interdental pronunciation mostly becoming addental. Furthermore, myofunctional problems occurred in one patient, other patients adapted to the new situation after three months. Hearing impairment did not influence speech pathology in this study. Conclusion: Immediate loading of oral implants does not seem to compromise the normal 3-6 months speech adaptation period. Whether such procedure presents advantages to the conventional 2-stage rehabilitation remains to be investigated. [Abstract]

Serino G, Rao W, Iezzi G, Piattelli A
Polylactide and polyglycolide sponge used in human extraction sockets: bone formation following 3 months after its application.
Clin Oral Implants Res. 2007 Oct 18;
Objectives: The aim of this study was to evaluate (i) the degree of bone mineralization in the alveolar sockets 3 months following the use of a bio-absorbable graft material and (ii) the degree of resorption of the grafted material. Materials: Twenty patients, undergoing periodontal therapy, participated in this study. All patients were scheduled for extraction of one or more compromised monoradicular teeth and scheduled for replacement of the extracted teeth with dental implants. Methods: Following elevation of full-thickness flaps and extraction of teeth, the alveolar sockets were filled with a bioabsorbable polylactide-polyglycolide acid sponge (Fisiograft((R))) (Test group - T) or natural healing by clot formation was allowed (Control group - C). The flaps were sutured with no attempt to achieve primary closure of the surgical wound. Re-entry for implant surgery was performed 3 months following the extractions. Results: Fifteen biopsies (seven T and nine C) were harvested from the sites where the implants were placed. The biopsies harvested from the T sites revealed that the alveolar sockets healed with newly trabecular bone, highly mineralized and well structured. Particles of the grafted material could not be identified in any of the T biopsies. The bone formed in the C sites was also well structured, with a slightly minor percentage of mineralized bone. In both T and C biopsies, the apical portion presented a higher degree of mineralization compared with the coronal portion. Conclusions: The results of this study indicated that the use of a bio-absorbable synthetic sponge of polylactide-polyglycolide acid did not interfere with the formation of new bone in the alveolar sockets and that the characteristics of the 3-month newly formed bone seemed to be optimal for dental implants' insertion. The biocompatibility, safety and characteristics of Fisiograft((R)) suggest that the material is suitable for filling alveolar sockets following extractions, to prevent volume reduction and collapse of the overlying soft tissue flaps. [Abstract]

Lin CL, Wang JC, Chang WJ
Biomechanical interactions in tooth-implant-supported fixed partial dentures with variations in the number of splinted teeth and connector type: a finite element analysis.
Clin Oral Implants Res. 2007 Oct 18;
Objective: The aim of this study was to investigate the biomechanical interactions in tooth-implant-supported fixed partial dentures (FPDs) under several loading conditions with different numbers of splinted teeth and connector types (rigid and non-rigid) by adopting the three-dimensional (3D) non-linear finite element (FE) approach. Material and methods: A 3D FE FPD model was constructed containing one Frialit-2 implant in the mandibular second-molar region splinted to the first and second premolars. Frictional contact elements were used to simulate realistic interface conditions within the implant system and the non-rigid connector function. The main effects for each level of the three investigated factors (loading condition, number of splinted teeth and connector type) in terms of the stress values and dissimilar mobility of the natural teeth and implant were computed for all models. Results: The results indicated that load condition was the main factor affecting the stress developed in the implant, bone and prosthesis when comparing the type of connector and the number of splinted teeth. The stress values were significantly reduced in centric or lateral contact situations once the occlusal forces on the pontic were decreased. However, the prosthesis stress for the non-rigid connections was increased more than 3.4-fold relative to the rigid connections. Moreover, the average tooth-to-implant displacement ratios (R(TID)) with a non-rigid connection were obviously larger than those for rigid connections under axial loading forces. Adding an extra tooth to support a three-unit tooth-implant FPD only exploited its function when the prosthesis withstood lateral occlusal forces. Conclusions: The load condition is the main factor affecting stress distribution in different components (bone, prosthesis and implant) of tooth-implant-supported FPDs. Minimizing the occlusal loading force on the pontic area through selective grinding procedures could reduce the stress values obviously. A non-rigid connector may more efficiently compensate for the dissimilar mobility between the implant and natural teeth under axial loading forces but with the risk of increasing unfavorable stresses in the prosthesis. [Abstract]

Al-Nawas B, Groetz KA, Goetz H, Duschner H, Wagner W
Comparative histomorphometry and resonance frequency analysis of implants with moderately rough surfaces in a loaded animal model.
Clin Oral Implants Res. 2007 Oct 18;
Objectives: Test of favourable conditions for osseointegration with respect to optimum bone-implant contact (BIC) in a loaded animal model. The varied parameters were surface roughness and surface topography of commercially available dental implants. Method: Thirty-two implants of six types of macro and microstructure were included in the study (total 196). The different types were: minimally rough control: Branemark machined Mk III; oxidized surface: TiUnite MkIII and MkIV; ZL Ticer; blasted and etched surface: Straumann SLA; rough control: titanium plasma sprayed (TPS). Sixteen beagle dogs were implanted with the whole set of the above implants. After a healing period of 8 weeks, implants were loaded for 3 months. For the evaluation of the BIC areas, adequately sectioned biopsies were visualized by subsurface scans with confocal laser scanning microscopy (CLSM). Results: The primary statistical analysis testing BIC of the moderately rough implants (mean 56.1+/-13.0%) vs. the minimally rough and the rough controls (mean 53.9+/-11.2%) does not reveal a significant difference (P=0.57). Mean values of 50-70% BIC were found for all implant types. Moderately rough oxidized implants show a median BIC, which is 8% higher than their minimally rough turned counterpart. The intraindividual difference between the TPS and the blasted and etched counterparts revealed no significant difference. The turned and the oxidized implants show median values of the resonance frequency [implant stability quotients (ISQ)] over 60; the nonself-tapping blasted and etched and TPS implants show median values below 60. Discussion: In conclusion, the benefit of rough surfaces relative to minimally rough ones in this loaded animal model was confirmed histologically. The comparison of different surface treatment modalities revealed no significant differences between the modern moderately rough surfaces. Resonance frequency analysis seems to be influenced in a major part by the transducer used, thus prohibiting the comparison of different implant systems. [Abstract]

Proff P, Bayerlein T, Rottner K, Mai R, Fanghänel J, Gedrange T
Effect of bone conditioning on primary stability of FRIALIT-2((R)) implants.
Clin Oral Implants Res. 2007 Oct 18;
Background: Primary stability is crucial to implants used for orthodontic anchorage. Bone condensing to enhance primary stability is controversial. Material and methods: Fourteen Frialit-2((R))-stepped screw and cylinder implants were placed in the median palatine sutures of 22 cadaveric human heads. In half of both types, the implant bed was prepared using a Frialit((R)) Bone Condenser. Primary implant stability was evaluated using non-invasive resonance frequency analysis. Moreover, the bone-implant contact area was examined histomorphometrically and radiographically. Results: Bone condensing yielded a slightly, yet not significantly increased implant stability quotient compared with a conventional technique. In spongy bone, a significant histomorphometric increase of bone-implant contact (P<0.0001) and a significant increase of radiographic density was revealed for both implant types, while no significant changes were observed within the compact area. Conclusion: The study shows that bone condensing yields an improved histologic implant-bone contact only in spongy bone, which was paralleled by radiographic-densitometric findings. [Abstract]