bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency Issues among Statistical Methods for Demonstrating Efficacy of Caries Prevention
Authors: Mancl L.A. , Hujoel P.P. , Derouen T.A.
Published: January 2009

Although repeated tooth-surface-specific information is commonly collected during a longitudinal caries clinical trial, traditional methods often make limited use of the repeated measures. Newer methods of analysis, such as methods based on time-to-event and methods for longitudinal or clustered data, have the potential to increase the efficiency of the statistical analysis. We compare a range of analytical methods from the traditional analysis based only on the number of caries onsets to newer methods that incorporate time at risk and surface-specific information, such as Poisson regression methods for clustered data, with respect to the efficiency of treatment comparisons. Under most circumstances, the greatest gain in efficiency associated with time-to-event methods will be due to the ability of subjects to contribute caries onsets to the analysis until they are lost from the study. Incorporating the number of surfaces at risk, the surface time at risk, and surface-specific characteristics will typically produce only a modest gain in efficiency.
Using Survival Methodologies in Demonstrating Caries Efficacy
Authors: Hannigan A.
Published: January 2009

Exploiting recent advances in statistical methods, particularly for correlated intra-subject data, could increase the efficiency of caries clinical trials. Methods of analysis using the tooth surface as the unit should be investigated. Whole-mouth measures such as the DMFS increment ignore the variation in the number of surfaces at risk between subjects and within a subject over time. The use of “survival time” for each surface as the outcome measure— i.e., the time from the start of the trial to when a surface is recorded as decayed or filled—is proposed. Data from caries clinical trials could be described as clustered survival data, where clustering of tooth surfaces exists such that survival times within the same cluster or subject are correlated. Advances in the analysis of clustered survival data, such as the use of marginal models with robust variance estimators, have recently been exploited in the analysis of caries clinical trials. The analysis produced results similar to those achieved by conventional DMFS-based analysis. The results using survival analysis are easily interpreted—for example, the median survival time of tooth surfaces in female subjects using a toothpaste with a higher level of fluoride (1500 ppm F) is 1.07 times the median survival time of surfaces in female subjects using toothpaste with less fluoride (1000 ppm F). Further research is required to investigate if survival analysis is a more sensitive method of analysis, i.e., whether causative factors can be identified with fewer subjects than with the conventional method of analysis.
Analysis of Clinical Trials Involving Non-cavitated Caries Lesions
Authors: Imrey P.B. , Kingman A.
Published: January 2009

Treatments to halt or reverse the progression of noncavitated caries lesions are of increasing interest. Diagnostic technologies under development offer potential for the assessment of gradual progression and regression of such lesions. Many therapies directed at correcting demineralization-remineralization imbalance should, in principle, protect enamel similarly across lesion severities from initiation to near cavitation. If this is so, and if acceptable reproducibility and predictive validity can be demonstrated for a diagnostic of acceptable cost, then clinical trials of agents to prevent cavitation can become more efficient by the use of outcome indices that reflect, in addition to cavitation, the expansion and regression of non-cavitated lesions. However, to achieve such a benefit will require data analyses that fully exploit ordinal or continuous-scale outcome measures. We consider comparison of such measures of lesion status between treatment groups, with most attention to ordinal categorical data. Interim data from a clinical trial in Lithuanian children are used for illustration.
The Role of Risk Factors in the Identification of Appropriate Subjects for Caries Clinical Trials: Design Considerations
Authors: Johnson M.F.
Published: January 2009

In seeking new and more effective therapies to delay or prevent caries development, investigators must design clinical trials focused on high-risk populations with a predictable incidence of caries over a limited period of time. In children and adolescents, the strongest predictors of caries incidence appear to be baseline levels of caries activity (present caries, e.g., dmfs, DMFT, caries lesions in first molars). Other predictors of caries risk typically include oral hygiene level, counts of cariogenic micro-organisms in plaque and saliva, fluoride history, sucrose intake, and parent's socio-economic level. This paper will briefly review existing literature to address the most useful and relevant prognostic factors for predicting future caries onset. The relative merits of identifying high-risk subjects based on these factors, either singly or in combination, will be explored in terms of statistical efficiency. Particular attention will focus on the advantages of covariate adjustment in the context of survival-based methods for the analysis of caries data. Further, with the advent of more sophisticated diagnostic procedures ( e.g., quantitative light fluorescence) to screen and monitor study subjects for caries activity, there is the potential for earlier states of lesion initiation and progression (or regression) to be detected, with, therefore, improved experimental sensitivity to treatment effects. The validity of risk assessment and outcome measurement on the basis of these new diagnostic tools vs. more conventional methods will be examined.
Methods for Pooling Results from Multi-center Studies
Authors: Worthington H.
Published: January 2009

A multi-center study is one conducted simultaneously in several participating centers following an agreed protocol, where the randomization has been carried out independently within each center. The main consideration for pooling the data from the individual centers is the choice between a weighted analysis, which weights centers relative to the number of patients in them, or an unweighted analysis as the primary statistical method. The unweighted analysis is used to investigate whether there was an interaction between the centers and study groups. Another issue is whether a fixed- or random-effects model should be used. There is unresolved controversy among statisticians about whether to use a weighted (type II) or unweighted analysis (type III), since there are advantages and disadvantages to the use of either method. The weighted analysis provides the most powerful test of the treatment contrast if there is no interaction between treatment and center. If there is an interaction, the unweighted analysis leads to unbiased estimates. Although, from an estimation and hypothesis testing standpoint, there is no need to balance the number of patients between the sites, it is sensible to avoid major imbalances among the study sites. There is agreement among statisticians that a fixed-effects model should be used.
Potential Modern Alternative Designs for Caries Clinical Trials (CCTs) and How These can be Validated against the Conventional Model
Authors: Chesters R.K. , Ellwood R.P. , Biesbrock A.R. , Smith S.R.
Published: January 2009

The main reasons that industry runs caries clinical trials (CCTs) are to provide proof of efficacy and to collect in vivo safety data on new products. In recent years, predominantly due to declining caries levels and the use of positive controls, the cost of performing these CCTs has escalated. It is now reaching the stage where it is becoming commercially prohibitive to conduct new studies. This is likely to stifle innovation of new anticaries products, and we now need new, more discriminatory, faster, and less expensive study designs. There are many ways in which the design of CCTs may be changed, such as improving diagnostic efficiency, improving data handling/statistical modeling, and using high-risk populations. However, it is paramount that the overriding principle behind CCT design validation must be that the results/conclusions from any new design are in line with those shown previously by ‘conventional’ CCTs, to ensure the maintenance of standards for both efficacy and safety. It is suggested that the validation of any new trial design must involve comparisons with regimens previously shown in conventional CCTs to have different anticaries efficacies. For example, since several clinical trials have shown convincing evidence for a monotonic dose response for fluoride at least up to levels of 2500 ppm F, one could choose two products, differing solely in their fluoride level. One aim for this workshop is to identify and agree on validation principles for new clinical trial designs. This will facilitate general international acceptance of novel smaller/faster CCTs designs both now and in the future. We recognize that any new design must not compromise the standard of proof of either efficacy or safety. In addition, any principles will need to take account of current understanding of the caries process, while recognizing the need for change to match future developments in cariology. Finally, the mechanism of action of the test product must be considered, in assessments of the acceptability of novel designs, if this differs markedly from the regimens used to validate the design.
Proteins in Whole Saliva during the First Year of Infancy
Authors: Ruhl S. , Rayment S.A. , Schmalz G. , Hiller K.-A. , Troxler R.F.
Published: January 2009

During the first year of an infant’s life, the oral environment is subject to drastic changes that coincide with the eruption of teeth. Proteins in saliva are important for protecting oral surfaces and provide receptors for bacterial adhesins. The objective of this longitudinal study was to monitor the general composition and expression of proteins in whole saliva of infants, to prove the hypothesis that expression of certain proteins changes during infant development, and might be associated with tooth eruption. The results showed a remarkable constancy in the overall pattern of salivary proteins and glycoproteins during infancy. Exceptions were the mucins and albumin. The mucins are expressed differentially, with first MUC7 and later MUC5B being predominant. Albumin, a marker of serum leakage, started to rise in whole saliva preceding tooth eruption. Thus, the expression of only few proteins appears to be changed during infant development.
Cyclic Motion of the Soft Palate in Feeding
Authors: Matsuo K. , Hiiemae K.M. , Palmer J.B.
Published: January 2009

The soft palate moves rhythmically during feeding, but the timing and frequency of this motion are not known. We tested the hypothesis that cyclic soft palate motion is temporally linked to cyclic jaw movement. Nine healthy, asymptomatic human subjects with normal dentition ate solid food coated with barium. Videofluorographic recordings showed that rhythmic motions of the soft palate during mastication were linked temporally to jaw motion. Soft palate motion occurred in every recording but not in every jaw cycle. The soft palate moved upward as the jaw opened, but the nasopharynx was not sealed. During swallowing, however, the soft palate invariably elevated during the intercuspal phase of jaw motion, sealing the nasopharynx. The frequency of soft palate cycles was lowest early in a feeding sequence and gradually increased as the sequence progressed from ingestion to swallowing. We conclude that cyclic movement of the soft palate in feeding is temporally linked to jaw motion.
Novel Mutation of the Initiation Codon of PAX9 Causes Oligodontia
Authors: Klein M.L. , Nieminen P. , Lammi L. , Niebuhr E. , Kreiborg S.
Published: January 2009

Tooth development is under strict genetic control. Oligodontia is defined as the congenital absence of 6 or more permanent teeth, excluding the third molar. The occurrence of non-syndromic oligodontia is poorly understood, but in recent years several cases have been described where a single gene mutation is associated with oligodontia. Several studies have shown that MSX1 and PAX9 play a role in early tooth development. We screened one family with non-syndromic oligodontia for mutations in MSX1 and PAX9. The pedigree showed an autosomal-dominant pattern of inheritance. Direct sequencing and restriction enzyme analysis revealed a novel heterozygous A to G transition mutation in the AUG initiation codon of PAX9 in exon 1 in the affected members of the family. This is the first mutation found in the initiation codon of PAX9, and we suggest that it causes haploinsufficiency.
Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis are Components of a Polymicrobial Intracellular Flora within Human Buccal Cells
Authors: Rudney J.D. , Chen R. , Sedgewick G.J.
Published: January 2009

Previously, we used in situ hybridization and confocal microscopy to detect the periodontal pathogens Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis within buccal epithelial cells taken directly from the mouth. This study tested the hypothesis that the intracellular flora of buccal cells is polymicrobial. Mixtures containing a red fluorescent universal probe paired with green fluorescent versions of either A. actinomycetemcomitans-, P. gingivalis-, or T. forsythensis-specific probes were hybridized with buccal cells collected from each of 38 healthy humans. We verified co-localization of probe pairs within cells by generating three-dimensional reconstructions. Intracellular bacteria were detected in every subject. Each cell that was labeled with a species-specific probe also contained bacteria recognized only by the universal probe. Bacteria labeled with specific probes often occupied smaller regions within larger masses of bacteria. Those findings suggest that future studies of invasion by oral bacteria may need to include microbial consortia.
Cyclic Mechanical Strain Regulates the PTHrP Expression in Cultured Chondrocytes via Activation of the Ca2+ Channel
Authors: Tanaka N. , Ohno S. , Honda K. , Tanimoto K. , Doi T. , Ohno-Nakahara M. , Tafolla E. , Kapila S. , Tanne K.
Published: January 2009

The association between mechanical stimulation and chondrocyte homeostasis has been reported. However, the participation of PTHrP (parathyroid-hormone-related protein) in the mechano-regulation of chondrocyte metabolism remains unclear. We determined whether mechanical stimulation of chondrocytes induces the expression of PTHrP and, further, whether the mechano-modulation of PTHrP is dependent on the maturational status of chondrocytes. Cyclic mechanical strain was applied to rat growth plate chondrocytes at the proliferating, matrix-forming, and hypertrophic stages at 30 cycles/min. Cyclic mechanical strain significantly increased PTHrP mRNA levels in chondrocytes at the proliferating and matrix-forming stages only. The induction of PTHrP was dependent on loading magnitude at the proliferating stage. Using specific ion channel blockers, we determined that mechano-induction of PTHrP was inhibited by nifedipine, a Ca2+ channel blocker. These results suggest that mechanical induction of PTHrP possibly provides the environment for greater chondrocyte replication and matrix formation that would subsequently affect cartilage formation.
Chromosomal Instability in Oral Cancer Cells
Authors: Reshmi S.C. , Gollin S.M.
Published: January 2009

Chromosomal instability is a common feature of human tumors, including oral cancer. Although a tumor karyotype may remain quite stable over time, chromosomal instability can lead to ‘variations on a theme’ of a clonal cell population, often with each cell within a tumor possessing a different karyotype. Thus, chromosomal instability appears to be an important acquired feature of tumor cells, since propagation of such a diverse cell population may facilitate evasion of standard therapies. There are several sources of chromosomal instability, although the primary causes appear to be defects in chromosomal segregation, telomere stability, cell-cycle checkpoint regulation, and the repair of DNA damage. Our understanding of the biological basis of chromosomal instability in cancer cells is increasing rapidly, and we are finding that the seemingly unrelated origins of this phenomenon may actually be related through the complex network of cellular signaling pathways. Here, we review the general causes of chromosomal instability in human tumors. Specifically, we address the state of our knowledge regarding chromosomal instability in oral cancer, and discuss various mechanisms that enhance the ability of cancer cells within a tumor to express heterogeneous karyotypes. In addition, we discuss the clinical relevance of factors associated with chromosomal instability as they relate to tumor prognosis and therapy.
A Critical Review of the Durability of Adhesion to Tooth Tissue: Methods and Results
Authors: De Munck J. , Van Landuyt K. , Peumans M. , Poitevin A. , Lambrechts P. , Braem M. , Van Meerbeek B.
Published: January 2009

The immediate bonding effectiveness of contemporary adhesives is quite favorable, regardless of the approach used. In the long term, the bonding effectiveness of some adhesives drops dramatically, whereas the bond strengths of other adhesives are more stable. This review examines the fundamental processes that cause the adhesion of biomaterials to enamel and dentin to degrade with time. Non-carious class V clinical trials remain the ultimate test method for the assessment of bonding effectiveness, but in addition to being high-cost, they are time- and labor-consuming, and they provide little information on the true cause of clinical failure. Therefore, several laboratory protocols were developed to predict bond durability. This paper critically appraises methodologies that focus on chemical degradation patterns of hydrolysis and elution of interface components, as well as mechanically oriented test set-ups, such as fatigue and fracture toughness measurements. A correlation of in vitro and in vivo data revealed that, currently, the most validated method to assess adhesion durability involves aging of micro-specimens of biomaterials bonded to either enamel or dentin. After about 3 months, all classes of adhesives exhibited mechanical and morphological evidence of degradation that resembles in vivo aging effects. A comparison of contemporary adhesives revealed that the three-step etch-and-rinse adhesives remain the ‘gold standard’ in terms of durability. Any kind of simplification in the clinical application procedure results in loss of bonding effectiveness. Only the two-step self-etch adhesives approach the gold standard and do have some additional clinical benefits.
Occlusal Force and Condylar Motion in Patients with Anterior Open Bite
Authors: Miyawaki S. , Araki Y. , Tanimoto Y. , Katayama A. , Fujii A. , Imai M. , Takano-Yamamoto T.
Published: January 2009

Patients with open bite often show a weak occlusal force and temporomandibular disorders (TMDs). If these are the main cause of open bite, it may be hypothesized that both pre-pubertal and adult open-bite patients would show a weak occlusal force and abnormal condylar motion. The purpose of this study was to test this hypothesis. Test group subjects consisted of 13 consecutive pre-pubertal and 13 adult patients with anterior open bite. They were compared with age-matched normal subjects. The adult open-bite group showed a weaker occlusal force and a shorter range of condylar motion compared with the control subjects. In the pre-pubertal subjects, however, there were no significant differences in the occlusal force and range of condylar motion between the open-bite and control groups. Therefore, these results suggest that a weak occlusal force or TMDs may not be the main cause of open bite.
Runx2 (Cbfa1) Inhibits Shh Signaling in the Lower but not Upper Molars of Mouse Embryos and Prevents the Budding of Putative Successional Teeth
Authors: Wang X.-P. , Åberg T. , James M.J. , Levanon D. , Groner Y. , Thesleff I.
Published: January 2009

Heterozygous mutations in the RUNX2 ( CBFA1) gene cause cleidocranial dysplasia, characterized by multiple supernumerary teeth. This suggests that Runx2 inhibits successional tooth formation. However, in Runx2 knockout mice, molar development arrests at the late bud stage, and lower molars are more severely affected than upper ones. We have proposed that compensation by Runx3 may be involved. We compared the molar phenotypes of Runx2/Runx3 double-knockouts with those of Runx2 knockouts, but found no indication of such compensation. Shh and its mediators Ptc1, Ptc2, and Gli1 were down-regulated only in the lower but not the upper molars of Runx2 and Runx2/Runx3 knockouts. Interestingly, in front of the mutant upper molar, a prominent epithelial bud protruded lingually with active Shh signaling. Similar buds were also present in Runx2 heterozygotes, and they may represent the extension of dental lamina for successional teeth. The results suggest that Runx2 prevents the formation of Shh-expressing buds for successional teeth.
Proteinase-activated Receptor-2 (PAR2) Agonist Causes Periodontitis in Rats
Authors: Holzhausen M. , Spolidorio L.C. , Vergnolle N.
Published: January 2009

Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PAR2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR2 activation may participate in periodontal disease in vivo. We investigated the role of PAR2 activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR2 agonist causes periodontitis but also exacerbates existing periodontitis, leading to significant alveolar bone loss and gingival granulocyte infiltration. Inhibition of matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) decreased PAR2 agonist-induced periodontitis. More specifically, the overexpression of COX-1, COX-2, MMP-2, and MMP-9 in gingival tissues suggests that they are involved in PAR2-induced periodontitis. In conclusion, PAR2 agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR2 may represent a novel approach to modulate host response in periodontitis.
Sex-related Differences in Gene Expression in Salivary Glands of BALB/c Mice
Authors: Treister N.S. , Richards S.M. , Lombardi M.J. , Rowley P. , Jensen R.V. , Sullivan D.A.
Published: January 2009

Sex-related differences exist in the structure and function of the major glands in a variety of species. Moreover, many of these variations appear to be unique to each tissue. We hypothesized that this sexual dimorphism is due, at least in part, to gland-specific differences in gene expression between males and females. Glands were collected from male and female BALB/c mice (n = 5/sex/experiment), and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter. Our results demonstrate that significant (P < 0.05) sex-related differences exist in the expression of numerous genes in the major salivary glands, and many of these differences were tissue-specific. These findings support our hypothesis that sex-related differences in the salivary glands are due, at least in part, to tissue-specific variations in gene expression.
Runx2 Regulates Endochondral Ossification in Condyle during Mandibular Advancement
Authors: Tang G.H. , Rabie A.B.M.
Published: January 2009

Runx2 is a transcription factor prerequisite for chondrocyte maturation and osteoblast differentiation. We tested the hypothesis that Runx2 is responsible for signaling chondrocyte maturation and endochondral ossification in the condyle during mandibular advancement. Fifty 35-day-old Sprague-Dawley rats were fitted with functional appliances for 3, 7, 14, 21, and 30 days. Experimental animals with 50 matched controls were labeled with bromodeoxyuridine for evaluation of the invasion of chondroclasts and osteoblasts into condylar cartilage. Mandibular advancement elicited Runx2 expression in condylar cartilage, and subsequently led to an expansion of type X collagen domain in the hypertrophic layer. Stronger Runx2 mRNA signals in subchondral bone corresponded with the increase in the recruitment of osteoblasts and chondroclasts, which preceded the increase of new bone formation in the condyle. Thus, Runx2 mediates chondrocyte terminal maturation and endochondral ossification in the mandibular condyle in response to mandibular advancement.
Resin Monomer 2-Hydroxyethyl Methacrylate (HEMA) is a Potent Inducer of Apoptotic Cell Death in Human and Mouse Cells
Authors: Paranjpe A. , Bordador L.C.F. , Wang M.-y. , Hume W.R. , Jewett A.
Published: January 2009

Mechanisms by which the resin monomer 2-hydroxyethyl methacrylate (HEMA) induces hypersensitivity reactions in humans are not well-established, nor have the direct effects of HEMA on cell death been fully characterized. The objective of this study was to establish whether HEMA is capable of inducing apoptotic cell death, and whether differences exist in the levels of apoptotic death induced by HEMA in cells obtained from healthy individuals and from patients with established HEMA hypersensitivity. HEMA induced apoptotic death in Peripheral Blood Mononuclear Cells (PBMCs) obtained from both healthy and HEMA-sensitized patients and in the murine RAW cells in a dose-dependent manner. However, induction of cell death by HEMA was lower in PBMCs obtained from patients in comparison with healthy individuals. Studies reported in this paper demonstrate that HEMA induces apoptotic death, and that decreased susceptibility of lymphocytes to HEMA-mediated death might be an important mechanism for the generation and persistence of hypersensitivity reactions in patients.
Characterization by Electron Spin Resonance Spectroscopy of Reactive Oxygen Species Generated by Titanium Dioxide and Hydrogen Peroxide
Authors: Lee M.-C. , Yoshino F. , Shoji H. , Takahashi S. , Todoki K. , Shimada S. , Kuse-Barouch K.
Published: January 2009

The influence of reactive oxygen species (ROS) on the surface modification of titanium implants and osseointegration is unclear. The aim of this study was to evaluate the ability of titanium dioxide (TiO2) to generate ROS in the presence of H2O2and to determine whether any ROS thus generated play a role in osseointegration, as measured by electron spin resonance (ESR) spin-trapping with 5,5-dimethyl-1-pyrolline- N-oxide (DMPO). We demonstrate that TiO2together with H2O2generated hydroxyl radicals (HO•), as shown by a time-dependent increase in the spin concentration of the ESR signal for the DMPO-OH spin adduct, indicating HO•generation. Interestingly, irradiated TiO2with H2O2generated the superoxide (O2•-), as shown by an increase in the spin concentration of the signal for the DMPO-OOH spin adduct, indicating O2•-generation during the period of irradiation (0–5 min). These results suggest that ROS generated from the TiO2layer may be involved in creating appropriate conditions for the osseointegration of dental implants into alveolar bone tissues.
Monomer-Solvent Phase Separation in One-step Self-etch Adhesives
Authors: Van Landuyt K.L. , De Munck J. , Snauwaert J. , Coutinho E. , Poitevin A. , Yoshida Y. , Inoue S. , Peumans M. , Suzuki K. , Lambrechts P. , Van Meerbeek B.
Published: January 2009

One-step adhesives bond less effectively to enamel/dentin than do their multi-step versions. To investigate whether this might be due to phase separation between adhesive ingredients, we characterized the interaction of 5 experimental and 3 commercial self-etch adhesives with dentin using transmission electron microscopy. All adhesives were examined for homogeneity by light microscopy. Bonding effectiveness to dentin was determined with the use of a micro-tensile bond-strength protocol. The lower bond strength of the one-step adhesives was associated with light-microscopic observation of multiple droplets that disappeared slowly. Interfacial analysis confirmed the entrapment of droplets within the adhesive layer. The prompt disappearance of droplets upon application of a small amount of HEMA (2-hydroxyethyl methacrylate) or a HEMA-containing bonding agent, as well as the absence of droplets at the interface of all HEMA-containing adhesives, strongly suggests that the adhesive monomers separate from water upon evaporation of ethanol/acetone. Upon polymerization, the droplets become entrapped within the adhesive, potentially jeopardizing bond durability. This can be avoided by strong air-drying of the adhesive, thereby removing interfacial water and thus improving bonding effectiveness.
In vivo Fluid Movement through Dentin Adhesives in Endodontically Treated Teeth
Authors: Chersoni S. , Acquaviva G.L. , Prati C. , Ferrari M. , Grandini S. , Pashley D.H. , Tay F.R.
Published: January 2009

Fluid transudation through simplified dentin adhesives can occur in bonded vital crown dentin, since these adhesives behave as permeable membranes after polymerization. The effect of adhesive permeability in endodontically treated teeth is unknown. This study examined the hypothesis that in vivo fluid movement through simplified adhesives occurs when they are applied to root canals. Dowel spaces were prepared in endodontically treated teeth with single root canals. Six adhesives were applied to the intra-radicular dentin of canal walls. Impressions were obtained with polyvinyl siloxane, and replicas were fabricated with the use of polyether impression material. Replica hemisections were gold-coated for SEM examination. Fluid transudation was evident on the adhesive surfaces of all simplified total-etch and self-etch adhesives. Conversely, most of the specimens bonded with the control three-step total-etch adhesive were devoid of fluid droplets. Permeability of simplified adhesives results in water movement, even in root-treated dentin. This may adversely affect the coupling of auto-/dual-cured resin cements.
Role of Occlusal Vertical Dimension in Spindle Function
Authors: Yabushita T. , Zeredo J.L. , Toda K. , Soma K.
Published: January 2009

Several studies have suggested the jaw-muscle spindle as the receptor responsible for regulating and maintaining the occlusal vertical dimension (OVD). However, to challenge this assumption, we hypothesized that long-term changes in OVD could affect the sensory inputs from jaw-muscle spindles. In this study, we investigated changes in masseter muscle spindle function under an increased OVD (iOVD) condition. Responses of primary and secondary endings of masseter muscle spindles to cyclic sinusoidal stretches were investigated. Twenty barbiturate-anesthetized female Wistar rats were divided into control and iOVD groups. Rats in the iOVD group received a 2.0-mm composite resin build-up to the maxillary molars. After iOVD, masseter muscle spindle sensitivity gradually decreased. Primary and secondary spindle endings were affected differently. We conclude that iOVD caused reduction in masseter muscle spindle sensitivity. This result suggests that peripheral sensory plasticity may occur following changes in OVD. Such changes may provide a basis for physiological adaptation to clinical occlusal adjustments.
Does Caries in Primary Teeth Predict Enamel Defects in Permanent Teeth? A Longitudinal Study
Authors: Broadbent J.M. , Thomson W.M. , Williams S.M.
Published: January 2009

The notion that caries in primary teeth causes developmental defects of enamel in permanent teeth has been recently revived. The research objective was to test this hypothesis through analysis of data from the Dunedin Multidisciplinary Health and Development Study, a longstanding prospective cohort study. The maxillary incisors of 663 children were assessed for existing restorations and dental caries at age five and for developmental defects of enamel at age nine. Where a primary tooth had been carious, the permanent successor was more likely to have a demarcated opacity after adjustment for gender, family socio-economic status, years of exposure to water fluoridation, trauma to primary teeth, and early loss of primary teeth (unadjusted OR = 2.3, 95% CI 1.3, 4.1; adjusted OR = 2.2, 95% CI 1.1, 4.3). These findings support a time-ordered association between dental caries in primary maxillary incisors and demarcated opacities in their permanent successors.
The Effect of a Bi-annual Professional Application of APF Foam on Dental Caries Increment in Primary Teeth: 24-month Clinical Trial
Authors: Jiang H. , Bian Z. , Tai B.J. , Du M.Q. , Peng B.
Published: January 2009

The purpose of this study was to evaluate the effect of a bi-annual professional application of acidulated phosphate fluoride (APF) foam on caries increment in the primary dentition over a two-year period in the People’s Republic of China. In a double-blind, cluster-randomized, placebo-controlled trial, 392 children aged 3–4 years from 15 classes were randomly assigned to two groups on a school class basis. The experimental group (8 classes) received a bi-annual APF foam application, and the control group (7 classes) received the placebo. The mean increment of dmfs in the experimental group was 24.2% lower than that in the control group (p < 0.05). The significant caries reduction was observed on approximal surfaces in the experimental group compared with the control group (p < 0.01), but there were no differences on occlusal surfaces (p > 0.05). A bi-annual professional application of APF foam was effective in reducing the increment of dental caries in the primary teeth.
Short-term Effects of Intensive Periodontal Therapy on Serum Inflammatory Markers and Cholesterol
Authors: D’Aiuto F. , Nibali L. , Parkar M. , Suvan J. , Tonetti M.S.
Published: January 2009

Severe periodontitis has been associated with increased systemic inflammation. In a three-arm preliminary randomized trial, we investigated the impact of standard (SPT) and intensive periodontal therapy (IPT) on serum inflammatory markers and cholesterol levels. Medical and periodontal parameters, C-reactive protein (CRP), interleukin-6 (IL-6), total cholesterol, and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis. Two months after treatment, both SPT and IPT resulted in significant reductions in serum CRP compared with the untreated control (0.5 ± 0.2 mg/L for SPT, P = 0.030 and 0.8 ± 0.2 mg/L for IPT, P = 0.001). Similar results were observed for IL-6. Changes in inflammation were independent of age, gender, body mass index, and ethnicity, but a significant interaction between cigarette smoking and treatment regimen was found. The IPT group also showed a decrease in total and LDL cholesterol after 2 months. Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects.
Periodontal Disease and Prematurity among Non-smoking Sri Lankan Women
Authors: Rajapakse P.S. , Nagarathne M. , Chandrasekra K.B. , Dasanayake A.P.
Published: January 2009

The hypothesis that periodontal disease is associated with pre-term low birthweight was tested in a prospective follow-up study of rural prima-gravida women (N = 227) who were free of tobacco, alcohol, and drug use. Women with 3rd trimester mean probing pocket depths, plaque, and bleeding scores that were greater than the median value in the cohort were defined as ‘exposed’. There were 17 (7.5%) preterm low birthweight singleton deliveries in the cohort (among ‘exposed’ = 12%; among ‘unexposed’ = 5.6%; Odds Ratio = 2.3; 95% CI = 0.9−6.3). After adjustment for the independent variables, the OR for preterm low birthweight in relation to ‘exposure’ was 1.9 (95% CI = 0.7−5.4). Our results are only suggestive of an association between periodontal disease and preterm low birthweight, perhaps indicating that previously reported associations may have been subjected to residual confounding due to tobacco, alcohol, and drug use.
ENAM Mutations in Autosomal-dominant Amelogenesis Imperfecta
Authors: Kim J.-W. , Seymen F. , Lin B.P.-J. , Kiziltan B. , Gencay K. , Simmer J.P. , Hu J.C.-C.
Published: January 2009

To date, 4 unique enamelin gene (ENAM) defects have been identified in kindreds with amelogenesis imperfecta. To improve our understanding of the roles of enamelin in normal enamel formation, and to gain information related to possible genotype/phenotype correlations, we have identified 2 ENAM mutations in kindreds with hypoplastic ADAI, 1 novel (g.4806A>C, IVS6-2A>C) and 1 previously identified (g.8344delG), and have characterized the resulting enamel phenotypes. The IVS6-2A>C mutation caused a severe enamel phenotype in the proband, exhibiting horizontal grooves of severely hypoplastic enamel. The affected mother had several shallow hypoplastic horizontal grooves in the lower anterior teeth. In the case of the g.8344delG mutation, the phenotype was generalized hypoplastic enamel with shallow horizontal grooves in the middle 1/3 of the anterior teeth. In general, mutations in the human enamelin gene cause hypoplastic enamel, often with horizontal grooves, but the severity of the enamel defects is variable, even among individuals with the same mutation.
Statistical Power for Analyses of Changes in Randomized Controlled Trials
Authors: Tu Y.-K. , Blance A. , Clerehugh V. , Gilthorpe M.S.
Published: January 2009

Randomized controlled trials (RCTs) are widely recommended as the most useful study design to generate reliable evidence and guidance to daily practices in medicine and dentistry. However, it is not well-known in dental research that different statistical methods of data analysis can yield substantial differences in study power. In this study, computer simulations are used to explore how using different univariate and multivariate statistical methods of analyzing change in continuous outcome variables affects study power, and the sample size required for RCTs. Results show that, in general, analysis of covariance (ANCOVA) yields greater power than other statistical methods in testing the superiority of one treatment over another, or in testing the equivalence between two treatments. Therefore, ANCOVA should be used in preference to change score or percentage change score to reduce type II error rates.
Vesiculo-erosive Oral Mucosal Disease—Management with Topical Corticosteroids: (1) Fundamental Principles and Specific Agents Available
Authors: González-Moles M.A. , Scully C.
Published: January 2009

Vesiculo-erosive diseases of the oral mucosa pose a major challenge in oral medicine, because they are chronic, painful, and interfere with the daily activities and quality of life of the patients, including disturbing eating, drinking, talking, and personal relationships. Many are autoimmune diseases, and corticosteroid therapy is currently central to their treatment. These diseases present with inflammation and alterations to epithelial integrity, through cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets. Until recently, despite their serious adverse effects, it was necessary to prescribe systemic corticosteroids to control severe erosive oral diseases. Now, however, many of these diseases can be controlled by high-potency topical corticosteroids, which have proved to be highly efficacious and to cause fewer adverse effects compared with systemic corticosteroids. Nevertheless, although topical corticosteroids are still the most widely used drugs in the practice of oral medicine, the scientific body of evidence for their use in the oral cavity is virtually non-existent, and therefore many of the protocols followed are, of necessity, drawn from experience of their use in a dermatological setting. This review aims to set out the key aspects of the use of topical corticosteroids in oral medicine. The issues covered include the indications and basic rules for their use, the types of corticosteroids, the drug selection, and the specific formulations.
Vesiculo-erosive Oral Mucosal Disease—Management with Topical Corticosteroids: (2) Protocols, Monitoring of Effects and Adverse Reactions, and the Future
Authors: González-Moles M.A. , Scully C.
Published: January 2009

Although topical corticosteroids (TCs) are the most widely used drugs in oral medicine, and specifically in the treatment of vesiculo-erosive oral mucosal disease, there are few evidence-based data for the correct use of these drugs. In this review, we outline the most widely used protocols, the most common reasons for treatment failure, and the adverse effects documented in the literature.
Inflammation is More Persistent in Type 1 Diabetic Mice
Authors: Graves D.T. , Naguib G. , Lu H. , Leone C. , Hsue H. , Krall E.
Published: January 2009

Whether diabetes enhances or diminishes the host response to bacteria has been controversial. To determine how diabetes alters the inflammatory response, we inoculated P. gingivalis into the scalps of mice rendered diabetic with multiple low-dose streptozotocin treatment. On day 1, a moderate to severe inflammatory infiltrate was noted in both the diabetic and normoglycemic mice. After 3 days, the inflammatory infiltrate was significantly higher in the diabetic compared with the control group (P < 0.05). The mRNA expression of chemokines macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 was strongly and similarly induced 3 hrs and 1 day post-inoculation. By day 3, the levels were reduced in normoglycemic mice but remained significantly higher in the diabetic group (P < 0.05). To determine whether persistent inflammation was specific for the streptozotocin-induced diabetic model, we directly compared the expression of TNF-α in streptozotocin-induced and db/db diabetic mice, which developed type 2 diabetes. Both exhibited prolonged TNF-α expression compared with controls. These results suggest that diabetes alters bacteria-host interactions by prolonging the inflammatory response.
Parathyroid-hormone-related Protein Induces Expression of Receptor Activator of NF-κB Ligand in Human Periodontal Ligament Cells via a cAMP/Protein Kinase A-independent Pathway
Authors: Fukushima H. , Jimi E. , Kajiya H. , Motokawa W. , Okabe K.
Published: January 2009

Periodontal ligament (PDL) cells play important roles in root resorption of human deciduous teeth by odontoclasts (osteoclast-like cells). However, it is unclear how PDL cells regulate osteoclastogenesis. We examined the effects of PTHrP, TGF-β, and EGF, which are all secreted by the tooth germ, on tartrate-resistant acid-phosphatase-positive (TRAP+) cell formation using co-cultures of human PDL cells and mouse spleen cells. Only PTHrP promoted TRAP+ cell formation in co-cultures. PTHrP induced receptor activator of NF-κB ligand (RANKL) mRNA expression and slightly reduced osteoprotegerin (OPG) expression in PDL cells. The cAMP/PKA inhibitors Rp-cAMP, H89, and PKI did not affect PTHrP-induced TRAP+ cell formation. The PKC inhibitor, Ro-32-0432, suppressed RANKL expression in PDL cells and PTHrP-induced TRAP+ cell formation. However, this inhibitor directly modulated the number of osteoclast precursors. Thus, PTHrP induces osteoclastogenesis by increasing the relative expression level of RANKL vs. OPG in PDL cells via a cAMP/PKA-independent pathway. Abbreviations: PTHrP, parathyroid-hormone-related protein; TGF-β, transforming growth factor-β; EGF, epidermal growth factor; RANKL, receptor activator of NF-κB ligand; OPG, osteoprotegerin; PDL, periodontal ligament; TRAP, tartrate-resistant acid phosphatase; PKA, protein kinase A; PKC, protein kinase C; MAP, mitogen-activated protein; ERK, extracellular signal-regulated kinase; cAMP, cyclic Adenosine 3′5′-Monophosphate.
Painful Tooth Stimulation Elevates Matrix Metalloproteinase-8 Levels Locally in Human Gingival Crevicular Fluid
Authors: Avellan N.-L. , Sorsa T. , Tervahartiala T. , Mäntylä P. , Forster C. , Kemppainen P.
Published: January 2009

Recent studies have demonstrated that pulpal pain can induce neurogenic inflammatory reactions in gingiva and the expression of pro-inflammatory neuropeptides in gingival crevicular fluid (GCF). Neuropeptides co-ordinate the activity of immuno-effector cells and may influence the secretion of matrix metalloproteinase (MMP)-8, the major tissue-destructive protease in GCF. With this background, we studied whether experimental pulpal pain can trigger changes in GCF MMP-8 levels. The molecular forms of MMP-8 in the GCF of stimulated and non-stimulated teeth were analyzed by Western immunoblot, and MMP-8 levels by quantitative immunofluorometric assay. Painful stimulation of the upper incisor provoked significant elevations in GCF MMP-8 levels of the stimulated tooth. Western immunoblot revealed elevations in both neutrophil- and mesenchymal-type MMP-8 isoforms. At the same time, the GCF MMP-8 levels of the non-stimulated teeth were not changed. Analysis of these data indicated that pulpal pain can induce local elevations in MMP-8 levels in GCF.
Introduction to Cumulative Meta-analysis in Dentistry: Lessons Learned from Undertaking a Cumulative Meta-analysis in Periodontology
Authors: Moles D.R. , Needleman I.G. , Niederman R. , Lau J.
Published: January 2009

Improving health and well-being from the consideration of isolated studies is problematic. Systematic reviews have been developed to address this problem and may include a quantitative data synthesis in the form of a meta-analysis, or a cumulative meta-analysis. The value of systematic reviews depends greatly on the availability and quality of the results of primary research. The objective of the current project was to demonstrate the technique of cumulative meta-analysis in dentistry using data from a previously published systematic review. The process highlights an issue that some trials could not be synthesized due to the lack of reporting of measures of variation. This represents a potential source of bias. Investigators are encouraged to consider their trials as part of an information continuum and to report sufficient detail to permit the trials’ incorporation into subsequent syntheses.
Continuing Etching of an All-in-One Adhesive in Wet Dentin Tubules
Authors: Wang Y. , Spencer P.
Published: January 2009

Self-etch adhesives that etch and prime simultaneously are becoming more acidic. We hypothesized that the degree of acidic monomer conversion at the interface and within the tubules was high enough that the acidic reaction would be very self-limiting. Dentin surfaces prepared from extracted, unerupted human third molars were treated with Prompt L-Pop (3M ESPE). The prepared teeth were stored in normal saline, and specimens retrieved at intervals ≤ 4 wks were randomly selected for light, scanning electron microscopic and micro-Raman spectroscopic analysis. Morphologic and spectroscopic analyses indicated dentin demineralization and adhesive penetration throughout the demineralized layer and tubules. Increased dentin demineralization and loss of adhesive integrity were noted after aqueous storage. The degree of monomer conversion at the interface was consistently greater than conversion within the tubules. Fluid within the tubules may inhibit monomer conversion. The acidic characteristics of this adhesive may be retained and, thus, continue to affect/demineralize the surrounding dentin.