Recent Journal Articles: Dentistry, Oral Surgery and Medicine -- Neurotransmitter.net

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]

L�pez 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, �rstavik 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 Sj�gren'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 Sj�gren'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 s