bluuebunny/crossref_metadata_2025 huggingface dataset:
αvβ3 Integrin Expression in Human Odontoblasts and Co-localization with Osteoadherin
Authors: Lucchini M. , Couble M.-L. , Romeas A. , Staquet M.-J. , Bleicher F. , Magloire H. , Farges J.-C.
Published: January 2009

Integrins are heterodimeric transmembrane receptors which promote cell adhesion, thus contributing to the maintenance of tissue organization in both normal and pathological conditions. To characterize the way odontoblasts may interact with other cells and the extracellular matrix in human teeth, we studied expression of αvβ3 integrin, a putative receptor for osteoadherin. We showed that αvβ3 integrin expression was restricted to odontoblasts, blood vessels, and small rounded cells in sound and carious pulp. Odontoblast staining intensity increased from the apical to the cusp region. Osteoadherin staining was strong in the whole odontoblast layer (with a slight decrease in the cusp region) and in predentin. Odontoblasts differentiating in vitro were stained with the anti-αvβ3 integrin antibody, first at the level of intercellular contacts, then throughout the cell membrane. These results suggest that the αvβ3 integrin could play a role in interodontoblast adhesion and odontoblast binding to the surrounding predentin/dentin/pulp matrix, possibly through osteoadherin.
Dentin Regeneration by Dental Pulp Stem Cell Therapy with Recombinant Human Bone Morphogenetic Protein 2
Authors: Iohara K. , Nakashima M. , Ito M. , Ishikawa M. , Nakasima A. , Akamine A.
Published: January 2009

Regenerative medicine is based on stem cells, signals, and scaffolds. Dental pulp tissue has the potential to regenerate dentin in response to noxious stimuli, such as caries. The progenitor/stem cells are responsible for this regeneration. Thus, stem cell therapy has considerable promise in dentin regeneration. Culture of porcine pulp cells, as a three-dimensional pellet, promoted odontoblast differentiation compared with monolayers. The expression of dentin sialophosphoprotein (Dspp) and enamelysin/matrix metalloproteinase 20 (MMP20) mRNA confirmed the differentiation of pulp cells into odontoblasts and was stimulated by the morphogenetic signal, bone morphogenetic protein 2 (BMP2). Based on the in vitro experiments, an in vivo evaluation of pulp progenitor/stem cells in the dog was performed. The autogenous transplantation of the BMP2-treated pellet culture onto the amputated pulp stimulated reparative dentin formation. In conclusion, BMP2 can direct pulp progenitor/stem cell differentiation into odontoblasts and result in dentin formation.
Mechanical Strain Delivers Anti-apoptotic and Proliferative Signals to Gingival Fibroblasts
Authors: Danciu T.E. , Gagari E. , Adam R.M. , Damoulis P.D. , Freeman M.R.
Published: January 2009

Physical forces play a critical role in the survival and proliferation of many cell types, including fibroblasts. Gingival fibroblasts are exposed to mechanical stress during mastication, orthodontic tooth movement, and wound healing following periodontal surgery. The aim of this study was to examine the effect of mechanical strain on human gingival fibroblasts (hGF). Cells were subjected to short-term (up to 60 min) and long-term (up to 48 hrs) 20% average elongation at 0.1 Hz. We monitored survival signaling by evaluating the phosphorylation status and localization of Forkhead box (FoxO) family members, which are mediators of apoptosis. We also examined strain-induced proliferation by measuring the level of proliferating cell nuclear antigen (PCNA). We observed that cyclic strain caused the phosphorylation and retention in the cytoplasm of FoxO family members. Moreover, mechanical strain resulted in increased ERK kinase phosphorylation and PCNA expression. In conclusion, cyclic strain delivers anti-apoptotic and proliferative stimuli to hGF.
Cementoblast Gene Expression is Regulated by Porphyromonas gingivalis Lipopolysaccharide Partially via Toll-like Receptor-4/MD-2
Authors: Nociti F.H. , Foster B.L. , Barros S.P. , Darveau R.P. , Somerman M.J.
Published: January 2009

Lipopolysaccharides are potent inflammatory mediators considered to contribute to destruction of periodontal tissues. Here, we hypothesized that Porphyromonas gingivalis lipopolysaccharide (P-LPS) treatment would regulate gene expression in murine cementoblasts through Toll-like receptor 4. Real-time (RT)-PCR and Northern blot analysis indicated that P-LPS decreased expression of transcripts for osteocalcin (OCN) and receptor activator of nuclear factor κB ligand (RANKL). In contrast, a dose-dependent up-regulation in mRNA levels for osteopontin (OPN) and osteoprotegerin (OPG) was observed. Similarly, ELISA demonstrated decreased RANKL and increased OPG levels. A monoclonal antibody specific for mouse TLR-4/MD-2 partially neutralized the P-LPS effect on cementoblasts. These results indicate that exposure of cementoblasts to P-LPS can alter cell function by regulating markers of osteoclastic activity ( e.g., RANKL/OPG), thereby potentially affecting the inflammation-associated resorption of mineralized tissues.
Oxidative Stress-induced DNA Damage in the Synovial Cells of the Temporomandibular Joint in the Rat
Authors: Yamaza T. , Masuda K.F. , Atsuta I. , Nishijima K. , Kido M.A. , Tanaka T.
Published: January 2009

Synovial hyperplasia is a feature of degenerative temporomandibular joint (TMJ) disease. However, the mechanism by which hyperplasia progresses in the TMJ is unknown. Based on the hypothesis that the oxidative stress generated by mechanical loading causes degenerative changes in the TMJ synovium, we investigated the generation of the highly reactive species, peroxynitrite, and the occurrence of DNA damage in the synovium. After condylar hypermobility of rat TMJs, a marker of peroxynitrite, nitrotyrosine, was localized to the nuclei and cytoplasm of the synovial lining cells and fibroblasts in synovitis-induced TMJ. DNA single-strand breaks were found in the nuclei of the synovial cells only after enzyme treatment, whereas DNA double-strand breaks were not detected. These findings indicate that condylar hypermovement induces the proliferation of synovial cells, and suggest that oxidative stress leads to the progression of synovial hyperplasia via DNA damage of the synovial cells in TMJs after mechanical loading.
Estimating Rates of New Root Caries in Older Adults
Authors: Griffin S.O. , Griffin P.M. , Swann J.L. , Zlobin N.
Published: January 2009

Although older adults are keeping their teeth longer, no national data are available on new caries in this age group. To characterize the extent of caries among older adults, we systematically reviewed studies on root caries incidence, increment, attack rate, and annual total (root + coronal) caries increment. We used a random-effects model to estimate annual summary measures and their 95% confidence intervals (CI) and tested for heterogeneity. For the 9 studies reporting root caries incidence, the summary measure equaled 23.7% (CI = 17.1–30.2%). For the 9 studies reporting root caries increment, the summary measure was 0.47 surfaces (CI = 0.34–0.61). For the 7 studies reporting total caries increment, the summary measure equaled 1.31 surfaces (95% CI = 1.01–1.61 surfaces). Because of heterogeneity, summary measures should be interpreted with caution. This research suggests, however, that older adults experience high rates of new caries and could benefit from caries-prevention programs.
Laboratory Stresses and Tractional Forces on the TMJ Disc Surface
Authors: Nickel J.C. , Iwasaki L.R. , Beatty M.W. , Marx D.B.
Published: January 2009

The etiology of degenerative disease of the TMJ may involve fatigue produced by surface tractional forces and compressive stresses. This study tested the time-dependent effects of compressive loading and stress-field translation on TMJ disc-surface tractional forces and stresses. In laboratory experiments with 50 porcine discs, an acrylic indenter imposed 10 N static loads for 10 and 60 sec, followed by translation of the loaded indenter along the mediolateral axis of the disc. Maximum tractional forces were found to occur following 60 sec of static loading (p < 0.001), and increased with translation velocity (R2 = 0.73); whereas maximum compressive stresses occurred after 10 sec of static loading (p < 0.001). Overall, the results were consistent with current mechanical theories of the time-dependent effects of compressive loading of cartilage.
Expression of SIBLINGs and Their Partner MMPs in Salivary Glands
Authors: Ogbureke K.U.E. , Fisher L.W.
Published: January 2009

Three members of the SIBLING family of integrin-binding phosphoglycoproteins (bone sialoprotein, BSP; osteopontin, OPN; and dentin matrix protein-1, DMP1) were recently shown to bind with high affinity (nM) and to activate 3 different matrix metalloproteinases (MMP-2, MMP-3, and MMP-9, respectively) in vitro. The current study was designed to document the possible biological relevance of the SIBLING-MMP activation pathway in vivo by showing that these 3 SIBLINGs and their known MMP partners are co-expressed in normal adult tissue. BSP, OPN, and DMP1 were invariably co-expressed with their partner MMPs in salivary glands of humans and mice. The 2 SIBLING proteins without known MMP partners, dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE), were also expressed in salivary glands. Expression of all SIBLINGs in this normal, non-mineralizing epithelial tissue suggests that they serve at least one function in vivo other than directly promoting matrix mineralization—a function we hypothesize involves local activation of MMPs.
Influence of Temporomandibular Joint Pain on Sleep Patterns: Role of Nitric Oxide
Authors: Schütz T.C.B. , Andersen M.L. , Tufik S.
Published: January 2009

Since nitric oxide is related to nociception and the sleep-wake cycle, this study sought to determine its involvement in the altered sleep pattern in a temporomandibular joint pain model by investigating the effect of the inhibitor of nitric oxide synthase (L-NAME) and that of its precursor (L-arginine). The temporomandibular joints of test animals were injected with Freund’s adjuvant or saline, and their sleep was recorded. The procedure was repeated after the administration of L-NAME and L-arginine. L-NAME increased rapid eye movement (REM) sleep in the control group. The orofacial pain group showed a reduction in total sleep time and an increase in sleep latency compared with the SHAM group. L-NAME increased sleep time, non-rapid eye movement (NREM), and REM sleep and reduced sleep latency in the orofacial pain group. L-arginine did not alter sleep parameters. Thus, L-NAME improved sleep efficiency, whereas L-arginine did not modify it, suggesting the involvement of nitric oxide in painful temporomandibular joint conditions.
Amelogenin-guided Crystal Growth on Fluoroapatite Glass-ceramics
Authors: Habelitz S. , Kullar A. , Marshall S.J. , DenBesten P.K. , Balooch M. , Marshall G.W. , Li W.
Published: January 2009

The formation of aligned fibrous apatite crystals in enamel is predominantly attributed to the involvement of amelogenin proteins. We developed a model to study interactions of matrix proteins with apatite mineral in vitro and tested the hypothesis that amelogenin solubility affects the ability to induce protein-guided mineralization. Crystal growth experiments were performed on fluoroapatite (FAP) glass-ceramics in mineralizing solutions containing recombinant full-length amelogenin (rH174) at different concentrations. Using atomic force microscopy, we observed that mineral precipitated randomly on the substrate, but also formed thin layers (height, 10 nm) on FAP within 24 hrs. This growth pattern was unaffected when 0.4 mg/mL of rH174 was added. In contrast, crystals grew on FAP at a rate up to 20 times higher, at 1.6 mg/mL protein. Furthermore, nanospheres and mineral bound specifically to FAP and aligned in strings approximately parallel to the c-axis of FAP, leading us to the conclusion that amelogenin proteins indeed control direction and rate of growth of apatite in enamel.
Inhibition of Phosphatidylinositol 3-Kinase Amplifies TEGDMA-induced Apoptosis in Primary Human Pulp Cells
Authors: Spagnuolo G. , Galler K. , Schmalz G. , Cosentino C. , Rengo S. , Schweikl H.
Published: January 2009

Cytotoxicity of triethylene glycol dimethacrylate (TEGDMA), a co-monomer of dental resinous restorative materials, is firmly established in vitro, but the molecular mechanisms are unknown. Here we examined apoptosis and necrosis induced by TEGDMA in human primary pulp cells. The levels of apoptotic and necrotic cell populations differentially increased after exposure to increasing concentrations of TEGDMA. A two-fold increase in the percentage of apoptotic cells was induced by 1 mmol/L TEGDMA. However, a population shift among cells in apoptosis and necrosis was detected when cell cultures were exposed to 2 mmol/L TEGDMA. Inhibition of the MAP Kinase/ERK pathway had no influence on cell survival, but inhibition of phosphatidylinositol 3 kinase (PI3-Kinase; Akt/protein kinase B) by LY294002 amplified TEGDMA-induced apoptosis. Moreover, Akt phosphorylation was inhibited in the presence of TEGDMA. These results suggest that depression of PI3K signaling may be a primary target in TEGDMA-induced apoptosis.
Predictors of Outcome for Orofacial Pain in the General Population: a Four-year Follow-up Study
Authors: Macfarlane T.V. , Blinkhorn A.S. , Davies R.M. , Kincey J. , Worthington H.V.
Published: January 2009

Orofacial pain is often persistent, but it is not clear why it lasts in some patients but not in others. We aimed to describe the natural course of orofacial pain in a general population sample over a four-year period and to identify factors that would predict the persistence of pain. A cross-sectional population-based survey was conducted in the United Kingdom, involving 2504 participants (participation rate 74%), of whom 646 (26%) reported orofacial pain. Overall, 424 (79% adjusted participation rate) of these individuals participated at the four-year follow-up, of whom 229 (54%) reported orofacial pain and 195 (46%) did not report such pain. Persistent orofacial pain was associated with females, older age, psychological distress, widespread body pain, and taking medication for orofacial pain at baseline. These findings may have implications for the identification and treatment of patients with orofacial pain.
Mouth-opening Increases Upper-airway Collapsibility without Changing Resistance during Midazolam Sedation
Authors: Ayuse T. , Inazawa T. , Kurata S. , Okayasu I. , Sakamoto E. , Oi K. , Schneider H. , Schwartz A.R.
Published: January 2009

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to −3.6 ± 2.9 cm H2O compared with −8.7 ± 2.8 (p = 0.002) for closed mouths and −7.2 ± 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 ± 6.6 vs. 17.7 ± 7.6 vs. 21.5 ± 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 ± 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.
MSX1, PAX9, and TGFA Contribute to Tooth Agenesis in Humans
Authors: Vieira A.R. , Meira R. , Modesto A. , Murray J.C.
Published: January 2009

In this study, we sought to determine the association between tooth agenesis and DNA sequence variation in the genes MSX1 and PAX9 in an ethnically diverse human population. Since cleft lip/palate is also associated with both tooth agenesis and the gene TGFA, we included TGFA in the analysis as well. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed by single-strand conformational polymorphism or kinetic polymerase chain-reaction assays. Transmission distortion of the marker alleles and DNA sequence analysis was performed. Results showed that tooth agenesis is associated with markers of the genes MSX1 and TGFA. No mutations were found in MSX1 or PAX9 coding regions. There were statistically significant data suggesting that MSX1 interacts with PAX9. These findings suggest that MSX1, PAX9, and TGFA play a role in isolated dental agenesis.
Tissue-engineered Rabbit Cranial Suture from Autologous Fibroblasts and BMP2
Authors: Hong L. , Mao J.J.
Published: January 2009

Craniosynostosis is a congenital disorder of premature ossification of cranial sutures, occurring in one of approximately every 2500 live human births. This work addressed a hypothesis that a cranial suture can be tissue-engineered from autologous cells. Dermal fibroblasts were isolated subcutaneously from growing rabbits, culture-expanded, and seeded in a gelatin scaffold. We fabricated a composite tissue construct by sandwiching the fibroblast-seeded gelatin scaffold between two collagen sponges loaded with recombinant human BMP2. Surgically created, full-thickness parietal defects were filled with the composite tissue construct in the same rabbits from which dermal fibroblasts had been obtained. After four-week in vivo implantation, there was de novo formation of tissue-engineered cranial suture, microscopically reminiscent of the adjacent natural cranial suture. The tissue-engineered cranial suture showed radiolucency on radiographic images, in contrast to radio-opacity of microscopically ossified calvarial defects filled with fibroblast-free, BMP2-loaded constructs. This approach may be refined for tissue engineering of cranial sutures for craniosynostosis patients.
Cortical Activation Resulting from Painless Vibrotactile Dental Stimulation Measured by Functional Magnetic Resonance Imaging (fMRI)
Authors: Ettlin D.A. , Zhang H. , Lutz K. , Järmann T. , Meier D. , Gallo L.M. , Jäncke L. , Palla S.
Published: January 2009

There have been few investigations on hemodynamic responses in the human cortex resulting from dental stimulation. Identification of cortical areas involved in stimulus perception may offer new targets for pain treatment. This initial study aimed at establishing a cortical map of dental representation, based on non-invasive fMRI measurements. Five right-handed subjects were studied. Eight maxillary and 8 mandibular teeth were stimulated after the vibratory perception threshold was determined for each tooth. Suprathreshold stimulation was repeated thrice per session, in a total of three sessions performed on three consecutive days. Statistical inference on cluster level identified increased blood-oxygen-level-dependent signal during vibratory dental stimulation, primarily in the insular cortex bilaterally and in the supplementary motor cortex. No significant brain activation was observed in the somatosensory cortex with this stimulation protocol. These results agree with previous findings obtained from invasive direct electrical cortical stimulation of the human insula.
The Highly Leukotoxic JP2 Clone of Actinobacillus actinomycetemcomitans and Progression of Periodontal Attachment Loss
Authors: Haubek D. , Ennibi O.-K. , Poulsen K. , Benzarti N. , Baelum V.
Published: January 2009

The JP2 clone of Actinobacillus actinomycetemcomitans has been implicated in the etiology of periodontitis in adolescents. The aim of this two-year longitudinal study was to describe clinical attachment loss (CAL) progression and to assess its association with baseline occurrence of the JP2 and non-JP2 types of A. actinomycetemcomitans. Clinical re-examination of 121 adolescents in Morocco was performed. Progression of CAL ≥ 1 mm, ≥ 2 mm, ≥ 3 mm, and ≥ 4 mm on at least one site was found in 58%, 48%, 22%, and 6% of the subjects, respectively. Subjects who, at baseline, harbored the JP2 clone had a significantly higher progression of CAL than did subjects harboring non-JP2 types of A. actinomycetemcomitans. Subjects harboring non-JP2 types displayed a marginally higher CAL progression than did subjects who were culture-negative for A. actinomycetemcomitans.
Root Lengths in 47,XYY Males’ Permanent Teeth
Authors: Lähdesmäki R. , Alvesalo L.
Published: January 2009

Studies on individuals with sex chromosome anomalies have demonstrated the promoting effect of the Y chromosome on tooth crown enamel and dentin growth. The present research investigated permanent tooth root lengths in 47,XYY males. The measurements were made from panoramic radiographs. The results indicate longer tooth roots in 47,XYY males compared with those in control males and females. The promoting effect of the Y chromosome on dental growth thus continues in the form of root dentin after the completion of crown growth. The results, together with those on tooth crown sizes in 47,XYY males, suggest that growth excesses are evident and final, beginning a few months after birth and continuing up to the age of 14 years, at least. The excess root dentin growth in 47,XYY males, as well as sexual dimorphism in the growth of crown and root dentin, might be caused by the same factor on the Y chromosome.
Oral Epithelial Overexpression of IL-1α Causes Periodontal Disease
Authors: Dayan S. , Stashenko P. , Niederman R. , Kupper T.S.
Published: January 2009

Periodontal disease is a bacterial infection that results in inflammatory destruction of tissues that support the teeth, including connective tissue and bone. In this study, we report that transgenic mice that overexpress the 17-kDa form of IL-1α in the basal layer of oral mucosal epithelium develop a syndrome that possesses all of the cardinal features of periodontal disease, including epithelial proliferation and apical migration, loss of attachment, and destruction of cementum and alveolar bone. In this model, bacterial colonization and infection were not required, since levels of periodontal bacteria were equivalent in transgenic and wild-type mice, and continuous treatment with antibiotics from birth did not ameliorate the disease. Our findings therefore indicate that elevated levels of IL-1α in the oral micro-environment can mediate all of the clinical features of periodontal disease.
Hypochlorous Acid and Taurine-N-Monochloramine in Periodontal Diseases
Authors: Mainnemare A. , Mégarbane B. , Soueidan A. , Daniel A. , Chapple I.L.C.
Published: January 2009

Chronic periodontitis is a multi-factorial disease involving anaerobic bacteria and the generation of an inflammatory response, including the production of metalloproteinases, pro-inflammatory cytokines, and eicosanoids. Hypochlorous acid (HOCl) and taurine-N-monochloramine (TauCl) are the end-products of the neutrophilic polymorphonuclear leukocyte (PMN) respiratory burst. They act synergistically to modulate the inflammatory response. In the extracellular environment, HOCl and TauCl may directly neutralize interleukin 6 (IL-6) and several metalloproteinases, while HOCl increases the capacity of α2-macroglobulin to bind Tumor Necrosis Factor-alpha, IL-2, and IL-6, and facilitates the release of various growth factors. TauCl inhibits the production of inflammatory mediators, prostaglandins, and nitric oxide. HOCl activates tyrosine kinase signaling cascades, generating an increase in the production of extracellular matrix components, growth factors, and inflammatory mediators. Thus, HOCl and TauCl appear to play a crucial role in the periodontal inflammatory process. Taken together, these findings may offer opportunities for the development of novel host-modulating therapies for the treatment of periodontitis.
NF-κB Protection against Apoptosis Induced by HEMA
Authors: Spagnuolo G. , Mauro C. , Leonardi A. , Santillo M. , Paternò R. , Schweikl H. , Avvedimento E.V. , Rengo S.
Published: January 2009

The cytotoxicity of dental monomers has been widely investigated, but the underlying mechanisms have not been elucidated. We studied the molecular mechanisms involved in cell death induced by HEMA. In human primary fibroblasts, HEMA induced a dose-dependent apoptosis that was confirmed by the activation of caspases-8, -9, and -3. We found an increase of reactive oxygen species (ROS) and NF-κB activation after HEMA exposure. Blocking of ROS production by anti-oxidants had no direct influence on apoptosis caused by HEMA, but inhibition of NF-κB increased the fraction of apoptotic cells. Accordingly, mouse embryonic fibroblasts (MEF) from p65−/− mice were more susceptible to HEMA-induced apoptosis than were wild-type controls. Our results indicate that exposure to HEMA triggers apoptosis and that this mechanism is not directly dependent upon redox signaling. Nevertheless, ROS induction by HEMA activates NF-κB, which exerts a protective role in counteracting apoptosis.
Fluid Movement across the Resin-Dentin Interface during and after Bonding
Authors: Hashimoto M. , Ito S. , Tay F.R. , Svizero N.R. , Sano H. , Kaga M. , Pashley D.H.
Published: January 2009

This study evaluated the extent of water penetration through resin-dentin interfaces before and after being sealed with adhesives. Four adhesive resin systems (2 total-etch adhesives and 2 self-etching primer adhesives) were used in this study. Dentin disks were placed in a split-chamber device, and in situ fluid movement across dentin was measured, with and without physiological pressure, during bonding procedures or 24 hrs after bonding. The fluid movement across dentin occurs via dentin tubules after acid-etching. Large outward or inward fluid shifts across dentin were observed during air-drying and light-curing for resin application. The amount of fluid movement across resin-bonded dentin when total-etch adhesives were used was significantly greater than that with self-etching adhesives. The milder acid-etching effects of self-etching primers may retain hybridized smear plugs within the tubules that reduce outward fluid flow, resulting in superior dentin sealing.
Effect of Dentinal Fluid Composition on Dentin Demineralization in vitro
Authors: Özok A.R. , Wu M.-K. , Ten Cate J.M. , Wesselink P.R.
Published: January 2009

Dentin demineralization is reduced by perfusion with water. We hypothesized that a simulated dentinal fluid (SDF) that contains albumin, in addition to electrolytes, would be more effective in reducing dentin demineralization than water alone, and this effect would increase with increasing flow rate of SDF. Perfusion rate in tooth segments that carried buccal cervical dentin windows was measured in a fluid transport set-up. These windows were then demineralized under perfusion with water, or SDF at 1.47 kPa for 31 days. We analyzed integrated mineral loss and lesion depth with the use of transverse microradiography (TMR), which revealed that 38% more mineral dissolved from dentin lesions perfused with water than from those perfused with SDF. The former were also 18% deeper. Flow rate of dentinal fluid showed no correlation with demineralization. We concluded that composition of dentinal fluid is an important determinant of the rate of lesion formation and progression in dentin.
The Timing of Subsequent Treatment for Teeth Restored with Large Amalgams and Crowns: Factors Related to the Need for Subsequent Treatment
Authors: Kolker J.L. , Damiano P.C. , Jones M.P. , Dawson D.V. , Caplan D.J. , Armstrong S.R. , Flach S.D. , Kuthy R.A. , Warren J.J.
Published: January 2009

Crowns and large amalgams protect structurally compromised teeth to various degrees in different situations. The aim of this investigation was to evaluate the survival of teeth with these two types of restorations and the factors associated with better outcomes. Retrospective administrative and chart data were used. Survival was defined and modeled as: (1) receipt of no treatment and (2) receipt of no catastrophic treatment over five- and 10-year periods. Analyses included: Kaplan-Meier survival curves, Log-Rank tests, and Cox proportional hazards regression modeling. Crowns survived longer with no treatment and with no catastrophic treatment; however, mandibular large amalgams were least likely to have survived with no treatment, and maxillary large amalgams were least likely to have survived with no catastrophic treatment. Having no adjacent teeth also decreased survival. Crowns survived longer than large amalgams, but factors such as arch type and the presence of adjacent teeth contributed to the survival of large amalgams.
Dental Caries in HIV-seropositive Women
Authors: Phelan J.A. , Mulligan R. , Nelson E. , Brunelle J. , Alves M.E.A.F. , Navazesh M. , Greenspan D.
Published: January 2009

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women’s Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.
Synergistic Effects of Streptococcal Glucosyltransferases on Adhesive Biofilm Formation
Authors: Tamesada M. , Kawabata S. , Fujiwara T. , Hamada S.
Published: January 2009

Glucosyltransferases (GTF)-I and GTF-SI of Streptococcus mutans synthesize water-insoluble and both water-soluble and -insoluble glucans, respectively, and play essential roles in the sucrose-dependent adhesion of the organism to tooth surfaces. To examine the interactions of different GTFs on artificial biofilm formed by S. mutans and other oral streptococci, we generated GTF-I- and GTF-SI-hyperproducing isogenic mutant strains. Transformant B42-21, which hyperexpressed GTF-SI, exhibited firm adhesion in the presence of sucrose, whereas transformant B42-10, which hyperexpressed GTF-I, failed to exhibit firm adhesion. Furthermore, co-culture of transformant B42-21 with water-soluble glucan-synthesizing Streptococcus sanguinis yielded firm adhesion, while the addition of dextran T10 to B42-21 growing culture had no effect on adhesion. These findings suggest that GTF-SI has a strong effect on sucrose-dependent adhesion and is essential for biofilm formation on smooth surfaces, in cooperation with water-soluble glucans synthesized de novo by oral streptococci that inherently lack cell adhesion ability.
TEGDMA Modulates Glutathione Transferase P1 Activity in Gingival Fibroblasts
Authors: Lefeuvre M. , Bourd K. , Loriot M.-A. , Goldberg M. , Beaune P. , Périanin A. , Stanislawski L.
Published: January 2009

Dental resinous materials can contain large amounts (from 30 to 50%) of triethylene-glycol-dimethacrylate (TEGDMA). This compound leaches into aqueous media and is toxic to dental pulp, as well as to gingival fibroblasts in vitro. To elucidate the mechanism of TEGDMA toxicity, we investigated the effects on glutathione (GSH) level and glutathione transferase P1 (GSTP1) activity in cultured human gingival fibroblasts. TEGDMA cytotoxic concentrations (from 0.5 to 2 mM) induced a depletion of GSH without formation of oxidized GSH (GSSG). In fibroblasts expressing the wild-type GSTP1, TEGDMA both inhibited and potentiated GSTP1 activity at high (IC50 = 1.1 mM) and low concentrations, respectively. In contrast, cells expressing the GSTP1 *A/*B variant showed a weak inhibition of GST activity only, associated with greater sensitivity to drug toxicity. Biochemical analysis of GSTP1 inhibition revealed that TEGDMA is a non-competitive antagonist with respect to GSH and substrate. Thus, TEGDMA interference with GSH and GSTP1 activity may contribute to dental-resin-induced adverse effects.
Local OPG Gene Transfer to Periodontal Tissue Inhibits Orthodontic Tooth Movement
Authors: Kanzaki H. , Chiba M. , Takahashi I. , Haruyama N. , Nishimura M. , Mitani H.
Published: January 2009

Previously, we discovered that RANKL expression is induced in compressed periodontal ligament cells, and that this promotes osteoclastogenesis on the compression side in orthodontic tooth movement. We hypothesized that local OPG gene transfer to the periodontium would neutralize the RANKL activity induced by mechanical compressive force, thereby inhibiting osteoclastogenesis and diminishing tooth movement. The upper first molars of six-week-old male Wistar rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of functional OPG protein was confirmed in vitro. The inactivated HVJ envelope vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the palatal periodontal tissue of upper first molars. When this local OPG gene transfer was performed, OPG production was induced, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly diminished tooth movement. In this study, we report that OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.
Endurance during Chewing in Whiplash-associated Disorders and TMD
Authors: Häggman-Henrikson B. , Österlund C. , Eriksson P.-O.
Published: January 2009

We have previously shown an association between neck injury and disturbed jaw function. This study tested the hypothesis of a relationship between neck injury and impaired endurance during chewing. Fifty patients with whiplash-associated disorders (WAD) were compared with 50 temporomandibular disorders (TMD) patients and 50 healthy subjects. Endurance was evaluated during unilateral chewing of gum for 5 min when participants reported fatigue and pain. Whereas all healthy subjects completed the task, 1/4 of the TMD and a majority of the WAD patients discontinued the task. A majority of the WAD patients also reported fatigue and pain. These findings suggest an association between neck injury and reduced functional capacity of the jaw motor system. From the results, we propose that routine examination of WAD patients should include jaw function and that an endurance test as described in this study could also be a useful tool for non-dental professionals.
Analysis of Caries Experience Taking Inter-observer Bias and Variability into Account
Authors: Lesaffre E. , Mwalili S.M. , Declerck D.
Published: January 2009

In larger oral health surveys, clinical measurements are often obtained using several examiners. This raises the issue of inter-observer variability in measurement. Often, the problem is dealt with by reporting kappa values obtained in a calibration exercise. In the present study, the limitations of this statistic are presented, and an alternative, based on a Bayesian approach, is proposed. When the alternative approach was applied to caries experience data obtained in an oral health screening survey in seven-year-old Flemish children (Signal Tandmobiel® study), it could be ruled out that the observed geographic East-West gradient was due to bias induced by variability in scoring of the different dental examiners involved. The proposed method offers an opportunity to refine existing analytical approaches and is relevant to any health outcome study.
New Developments in Medical Clinical Trials
Authors: D'agostino R.B. , Massaro J.M.
Published: January 2009

This paper reviews several new developments and long-standing good practices for conducting clinical trials. Discussion starts with the need for clear statements of study objectives, proceeds to clarify target and sample population, and elaborates on primary vs. secondary variables with the need for alpha adjustment in the presence of multiple outcomes. Here we also review the issue of surrogate endpoints. Study design issues—including blinding, randomization, and multicenter studies—come next. Then we discuss the current trend of the replacement of placebo-controlled trials by active controlled non-inferiority trials, the increasing use of Independent Data Monitoring Committees, the prominence of analysis on Intention-to-Treat samples, and the importance of imputation of missing data. We close with a brief discussion of the unit of analysis, the role of newer statistical analysis methods, safety issues, subset analysis, and, most importantly, clinical significance.
The Continuum of Dental Caries—Evidence for a Dynamic Disease Process
Authors: Featherstone J.D.B.
Published: January 2009

The eventual outcome of dental caries is determined by the dynamic balance between pathological factors that lead to demineralization and protective factors that lead to remineralization. Pathological factors include acidogenic bacteria, inhibition of salivary function, and frequency of ingestion of fermentable carbohydrates. Protective factors include salivary flow, numerous salivary components, antibacterials (both natural and applied), fluoride from extrinsic sources, and selected dietary components. Intervention in the caries process can occur at any stage, either naturally or by the insertion of some procedure or treatment. Dental caries covers the continuum from the first atomic level of demineralization, through the initial enamel or root lesion, through dentinal involvement, to eventual cavitation. The dynamic balance between demineralization and remineralization determines the end result. The disease is reversible, if detected early enough. Since demineralization can be quantified at early stages, before frank cavitation, intervention methods can be tested by short-term clinical trials.
Modern Concepts of Caries Measurement
Authors: Pitts N.B.
Published: January 2009

Following the consideration of several recent systematic and other reviews, there is a growing professional and scientific consensus that caries measurement methodology in caries clinical trials (CCT) should be updated to reflect progress made elsewhere in cariology. In this paper, therefore, “modern” means accepted in contemporary dental research and dental practice on the basis of sound research evidence—not necessarily new or requiring the use of new technology. Caries measurement should be seen in the context of the objectives of modern clinical caries management and the continuum of disease states, ranging from sub-surface carious changes through to more advanced lesions. Measurement concepts can be applied to at least three levels: the tooth surface, the individual, or the group/population. All are relevant to CCTs. Modern clinical caries management can be seen as comprised of seven discrete but linked steps (Steps 2, 3, and 4 are directly concerned with measurement.): (1) ‘Caries detection’ represents a yes/no decision as to whether caries is present; (2) lesion measurement assesses defined stages of the caries process, taking into account the histopatholgical morphology and appearance of different sizes and types of lesion and the diagnostic threshold(s) being used; (3) lesion monitoring by repeated measures at a series of examinations is used when lesions are less advanced than the stage judged to require operative intervention (A comparison of serial measurements permits the efficacy of preventive care aiming either to arrest or to reverse the lesion to be assessed.); (4) caries activity measures would be very valuable, but are relatively poorly developed and tested at present; (5) diagnosis, prognosis, and clinical decision-making are the important human processes in which all the information obtained from steps 1 to 4 is synthesised; (6) interventions/treatments, both preventive and operative, are now routinely used for caries management; and (7) outcome of caries control/management assesses caries management by examining evidence on the long-term outcomes. A challenge for the future is to define a range of optimal caries measurement methods—in use or in development in recent trials, in clinical practice, and/or in caries epidemiology—that will best contribute to more efficient, modern caries clinical trials.
The Challenges of Validating Diagnostic Methods and Selecting Appropriate Gold Standards
Authors: Huysmans M.-C.D.N.J.M. , Longbottom C.
Published: January 2009

Caries diagnostic methods are usually methods for caries lesion detection and measurement. Caries lesions occur on a continuous scale of tissue damage, from subclinical surface changes to macroscopic cavities reaching the pulp. Any change of a lesion on this continuous scale offers the opportunity for the diagnosis of disease activity or remission. Research aimed at remineralizing agents may focus on lesions that are amenable to remineralization, and select a method that will measure small changes in early lesions. General caries management strategies depend on detecting all stages of lesion development, and methods covering early to late stages are preferred. This paper addresses some methodological issues in validating caries diagnostic methods. The available gold standards for caries lesions are discussed, with their suitability in different applications, and their “validity” as far as it is known or can be inferred. The gold standards are compared as far as their measurement of lesion parameters and reproducibility is concerned. Tentative conclusions are formulated, and recommendations for future research are given.
Visual and Visuo-tactile Detection of Dental Caries
Authors: Ismail A.I.
Published: January 2009

The objective of this review is to describe and discuss the content validity of a sample of caries detection criteria reported in the literature between January 1, 1966, and May 1, 2000. Using filters to locate randomized or controlled clinical trials on dental caries, fluorides, sealants, and “restorative” care, I identified a total of 171 documents from MEDLINE and the Cochrane Collaboration's Oral Health Group (CC-OHG) special register. These articles met the following inclusion criteria: (1) Data had been collected from samples of patients or populations; and (2) dental caries was assessed clinically, and criteria were either published or described in the paper. From the selected articles, evidence tables were prepared describing each caries detection criterion. Analysis of the content validity of the criteria systems was based on evaluation of the disease process, exclusion of non-caries lesions, subjectivity, use of explorers, and drying of teeth prior to examination. This review included 29 unique criteria systems. Of those, 13 originated from the UK, 3 from the USA, 4 from Denmark, and others from the World Health Organization (WHO), Sweden, Switzerland, Norway, Netherlands, and Canada. Thirteen of the criteria systems either measured active and inactive early and cavitated lesions or defined separate criteria for smooth and occlusal tooth surfaces. Nine systems measured early as well as cavitated stages of the caries process, and 7 measured cavitation only. Eleven of the criteria systems provided explicit descriptions of the disease process measured or information on how to exclude non-caries from caries lesions. The use of explorers and drying and cleaning of teeth varied widely among the criteria. The majority of the newly developed criteria systems originated from Europe. In conclusion, this review of the content validity of the 29 criteria systems found substantial variability in disease processes measured, inclusion and exclusion criteria, and examination conditions.
Improving Clinical Visual Detection—Potential for Caries Clinical Trials
Authors: Ekstrand K.R.
Published: January 2009

It has been the norm in caries clinical trials to measure caries increment by several different caries-recording systems, including the crude DMF-S/T index. However, there is a reserved attitude as to whether to subdivide the non-cavitated lesions and use arrested lesions in clinical trials. This has been due to the belief that it is not possible to achieve reliable data of the early stages of the disease (Radike, 1972). However, recently, Ekstrand et al. (1997, 1998) showed that it was possible: (1) to differentiate between different stages of non-cavitated occlusal lesions, (2) to differentiate between active and inactive occlusal lesions, and (3) to predict the depth of the lesion. In at least 4 other clinical studies, the reproducibility of recording initial active lesions, cavitated active lesions, and arrested lesions was found to be adequate (Carvalho et al., 1989; Nyvad et al, 1999; Ekstrand et al., 2000; Machiulskiene et al., 2001). Since caries today is a more slowly developing disease in many countries in the world, this will result in prolongation of the duration of the clinical trial, which will increase the costs. As indicated above, there is now sufficient evidence that caries can be clinically diagnosed accurately and reliably in earlier stages as well as in an arrested stage. If such stages of caries are used as outcome variables in caries clinical trials, they may have a positive influence on the trials’ duration and costs.
Electrical Measurements for Use in Caries Clinical Trials
Authors: Longbottom C. , Huysmans M.-C.D.N.J.M.
Published: January 2009

This paper reviews the use of electrical measurements of caries, particularly in relation to caries clinical trials. Electrical measurements change as tooth tissue porosity alters in the caries process, but several other variables also have a significant effect on these electrical measurements and hence upon their diagnostic validity. Available electrical-method data, in the context of clinical trials, relate to the use of the Electronic Caries Monitor (ECM), which measures “bulk” resistance. The device is presently limited in scope to occlusal surfaces, and only limited ECM data from clinical trials are available. In the context of clinical trials, more work is needed to determine the potential role of electrical measurements. Such research will need to focus both on an understanding of those electrical parameters which are most valuable in identifying changes and stages in the caries process in individual teeth and also on identifying the extent of the effects of the variables affecting these measurements.
A Review of Potential New Diagnostic Modalities for Caries Lesions
Authors: Hall A. , Girkin J.M.
Published: January 2009

This paper aims to present a simple overview of potential new diagnostic methods for dental caries. There are several novel methods of caries detection (with potential application to diagnosis) which have been proposed in the last few years, in addition to those that are gaining some commercial exposure and clinical acceptance. For the most part, these methods have been demonstrated in laboratories and are generally many years away from routine clinical application. They include multi-photon imaging, infrared thermography and infrared fluorescence, optical coherence tomography, ultrasound, and terahertz imaging.