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Glucosyltransferase inactivation reduces dental caries.

Dental caries has been an intractable disease in spite of intense dental research. The metabolic acids produced by mutans streptococci demineralize the tooth surface and lead to dental caries. The enzyme glucosyltransferase (GTF) produced by mutans streptococci is the key factor in this process. Oral bacterial GTFs use sucrose as a substrate in synthesis of either water-soluble or insoluble glucans. In this investigation, kinetic studies with divalent metal ions revealed their strong binding affinity to GTF. The metal ions also proved to be strong inhibitors of the enzyme. Here we describe a simple method of inactivating the enzyme that actively participates in dental caries by taking advantage of a Fenton reaction which requires metal ions such as iron or copper and peroxide. The hydroxyl radical ions produced via the Fenton reaction inactivate GTF, a factor in the production of dental caries.

Binding, Competitive↗

Adhesion to and decalcification of hydroxyapatite by carboxylic acids.

Fundamental to the processes of decalcification of or adhesion to mineralized tissues is the molecular interaction of acids with hydroxyapatite. This study was undertaken to chemically analyze the interaction of 1 mono-, 2 di-, 1 tri-, and 2 polycarboxylic acids with hydroxyapatite in an attempt to elucidate the underlying mechanism. Maleic, citric, and lactic acid decalcified hydroxyapatite, in contrast to oxalic acid and the two polycarboxylic acids that were chemically bonded to hydroxyapatite. Solubility tests showed that the calcium salts of the former were very soluble, whereas those of the latter could hardly be dissolved in the respective acid solutions. Based on these data, an adhesion/decalcification concept was advanced that predicts that carboxylic acids, regardless of concentration/pH, either adhere to or decalcify hydroxyapatite, depending on the dissolution rate of the respective calcium salts in the acid solution. This contrasting behavior of organic acids most likely results from their differential structural conformations.

Acrylic Resins↗

The effect of study design on in situ treatment of carious enamel lesions.

The aim of this exploratory study was to investigate the influence of several factors on changes in the mineral content of carious enamel lesions treated in situ. The study involved 36 adult volunteers who used either a non-fluoride toothpaste or one of two fluoride toothpastes (1000 or 1500 ppm F). Human enamel specimens were prepared and attached to partial dentures as described previously (Schäfer, 1989) and treated in situ for between three and six weeks. The mineral content of lesions was determined by microradiography and computerized densitometry. The factors investigated in this study included study length, frequency of treatment, trial design, patient compliance, patient diet, and previous caries experience of the patient. The effects observed were small, relative to that of the treatment, and not statistically significant (p greater than 0.05). However, the trends in the data were all as would be intuitively predicted. Study duration correlated positively with observed lesion mineral content. Lesions worn by panelists using a fluoride toothpaste for six weeks contained greater levels of mineral with respect to placebo than did those in panelists on a three-week study. The residual variations in the three phases of the study were found to be similar, suggesting that there is no advantage in these studies having a cross-over design. Brushing frequency also correlated positively with observed lesion mineral content, with panelists brushing three times per day with a fluoridated dentifrice having lesions with greater levels of mineral, with respect to placebo, than those brushing twice per day. Overall, no clear relationship between reported diet and changes in lesion mineral levels was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sample size considerations in designing studies with intra-oral models.

Especially during recent years, the use of pre-clinical models for predicting the efficacy of fluoride systems has assumed greater importance within the scientific community. Originally utilized primarily to screen experimental fluoride delivery systems, preclinical models are now being considered as predictors of clinical efficacy in lieu of controlled clinical caries trials. Of the various preclinical models presently available, human intra-oral models have the greatest potential for reflecting intended usage conditions and therefore may be the most meaningful models for predicting clinical efficacy. However, only with the proper consideration of numerous critical variables can studies using intra-oral models be appropriately designed to achieve the desired objectives. Clearly, these models must provide relevant information in a manner which reflects clinically established cariostatic activity and be capable of detecting established differences in the amount of cariostatic activity, i.e., dose-response effects. Three sources of variation must be considered before an appropriate study design and sample size can be chosen. Based on fluoride uptake data from an intra-oral model with proximally-located enamel specimens, estimates of variation among subjects, within subjects, and among specimens within subjects were obtained. Multiple specimens per panelist do not affect the first two sources of variation. Thus, the number of panelists, and not the number of specimens, is of primary importance when pre-test data are used to choose the appropriate study design and calculate the required sample size.

Adult↗

Composition of pooled plaque fluid from caries-free and caries-positive individuals following sucrose exposure.

The composition of pooled plaque fluid from five population samples was determined before and at selected times (7, 15, 30, and 60 min) after a 10% sucrose rinse. Subjects were grouped according to caries status (caries-free, CF, DMFS = 0; caries-positive, CP, DMFS > 10). Samples were also studied from white-spot surfaces and from sound surfaces of the same mouths of two additional CP groups. Plaque fluid was isolated by centrifugation and analyzed for organic acids, inorganic ions (ion chromatography), and pH (microelectrodes). Prior to sucrose exposure, plaque fluids from the CF subgroups and from sound surfaces of the CP subjects had higher pH values than samples from CP subgroups and from white-spot surfaces, respectively; the ionic compositions were otherwise similar. Starved plaque fluids were also found to be supersaturated with respect to enamel and to a significantly greater degree in the CF samples, suggesting that CF plaque fluid may have a greater remineralization potential than CP samples. Following sucrose exposure, a rapid decrease in plaque fluid pH was observed, which corresponded primarily to lactic acid production. For all times examined, mean pH and DS(En) values were lower and lactic acid concentrations were higher in the CP samples than in the CF samples; noted differences were statistically significant at 7 min for pH and DS(En), and at 7, 15, and 30 min for lactic acid. Lower values of DS(En) suggest that plaque fluid from CP subjects had a measurably greater cariogenic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Mineral element analysis of carious and sound rat dentin by electron probe microanalyzer combined with back-scattered electron image.

We recently demonstrated the advantages of back-scattered electron images (COMPO) in the visualization of dentinal caries, and the relationship of the change in the dentin fluorescence pattern in caries lesions. However, the exact nature of these changes is not known. In this paper, the nature of the changes in the areas with reduced mineral content in COMPO images was investigated. We examined the relation of changes in mineral elements and the appearance of soft carious and sound dentin in COMPO images using a scanning electron microscope (SEM) equipped with an electron probe microanalyzer (EPMA). Rat molars with small dentinal caries lesions just under the DEJ were chosen for the study. The Ca, P, Na, Mg, Zn, F, and total contents were determined by EPMA from five different dentin sites, and the Ca/P and Mg/Ca ratios were calculated. Generally, the lowest contents were found in caries lesions and highest in mantle dentin, with the exceptions of Mg and Zn. The Ca/P ratio was lowest in mantle dentin and highest in carious dentin. The results confirm that the change in fluorescence in the dentinal caries lesion is correlated with the very initial changes in mineral content, and that EPMA used in combination with COMPO images is a useful tool for determining small changes in mineral elements in the carious and adjacent areas of dentin.

Animals↗

Quantitative diagnosis of small approximal caries lesions utilizing wavelength-dependent fiber-optic transillumination.

The instruments clinically available for the diagnosis of approximal caries lesions are inadequate to detect lesions early and quantitatively. The aim of this study was to investigate whether wavelength-dependent light scattering and absorption of carious tissues may be utilized for the quantitative diagnosis of these small approximal caries lesions. Seventeen extracted premolar teeth were transilluminated at an approximal surface with a glass fiber, which transported the light from a halogen light bulb. Seven approximal surfaces contained a naturally developed small white-spot lesion, and 5 surfaces a small discolored lesion. Five teeth were sound. The occlusal surface was imaged with a CCD camera. Light in the blue and red portions of the electromagnetic spectrum was selected by means of Schott glass filters. From the obtained images, average effective decadic optical thickness differences were determined. These were plotted as a function of average mineral loss assessed by means of wavelength-independent microradiography. The correlation coefficient between the average effective decadic optical thickness difference and average mineral loss was r = 0.79 (95% CI: 0.47 ... 0.93). Different sources of variation that influence the observed correlation were defined and quantified. From these measurements, the correlation coefficient between average effective decadic optical thickness difference and "true' average mineral loss was estimated to be r = 0.92 (95% CI: 0.77 ... 0.97). The results indicate that early and, in principle, also quantitative diagnosis of approximal caries lesions is feasible when wavelength-dependent light propagation through carious tissues is utilized.

Dental Caries↗

Effects of aged fluoride-containing restorative materials on recurrent root caries.

Accumulated evidence has illustrated that secondary caries is the major reason for the failure of amalgam and resin composite restorations. The purpose of this study was to assess the cariostatic effects of aged fluoride-containing restorative materials on the formation of secondary root caries. Fifty sound human molars were selected and randomly assigned to five material groups: non-fluoride-containing amalgam (NA), fluoride-containing amalgam (FA), non-fluoride-containing composite (NC), fluoride-containing composite (FC), and glass-ionomer cement (GIC). After standardized class V cavity preparations and placement of restorations, teeth within each group were randomly divided into two subgroups, "non-aged" and "aged". The aged subgroup was immersed in an inorganic buffer solution for 2 wks before being thermocycled. After being thermocycled and subjected to four cycles of caries formation in a bacterial model system, the teeth were sectioned. Depths of outer lesions and areas of lesions on the cavity walls were measured by polarized light microscopy. The results showed that the FA and GIC groups, whether aged or not, had significantly smaller outer lesion depth than the non-fluoride-containing NA and NC groups. After aging, the FA group demonstrated significantly greater lesion depth (p = 0.0002), while the GIC group exhibited no significant changes in lesion depths. The NA group had a greater wall lesion area than the NC group, while both demonstrated no significant changes following 2 weeks of aging. The FA and GIC groups had similar inhibition areas along the cavity walls, whereas both inhibition areas increased significantly after the aging process. It is concluded that the fluoride-containing amalgam and the glass-ionomer cement, even after a two-week aging process, can still elicit a significant preventive effect on recurrent root caries in an in vitro bacterial model system.

Analysis of Variance↗

Electron probe microanalysis and transverse microradiography studies of artificial lesions in enamel and dentin: a comparative study.

In cardiology and research involving the interactions between restorative materials and dental hard tissues, it is important for small changes in tooth mineral content to be measurable. Currently, transverse microradiography (TMR) is the most accepted tool for the above purpose. Electron Probe Microanalysis (EPMA) can yield both qualitative identification of elements and quantitative compositional information. The purpose of this study was to compare the mineral distribution in well-defined artificial lesions, in dentin and enamel, by the use of both TMR and EPMA on the same sample. The good correlation between the two sets of data validates EPMA as a technique and helps in the interpretation of its results. The data from TMR analysis are expressed as vol% of mineral, while EPMA gives the levels of Ca and phosphate in wt%. The conversion between the two sets of data is complicated by the fact that local density is, as yet, unknown.

Analysis of Variance↗

The challenges of validating diagnostic methods and selecting appropriate gold standards.

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.

Cariostatic Agents↗

The challenges of validating diagnostic methods relative to a conventional two-year caries clinical trial.

This paper is directed to the question, "What are the appropriate validation criteria for the use of a new clinical trial methodology as a replacement for a conventional two- to three-year caries study?" It is important to recognize that the objective of a two- to three-year randomized, controlled caries trial is to test a precisely framed hypothesis, regarding an experimental product's efficacy relative to a control product. The external validity of conventional two- to three-year caries clinical studies in determining the efficacy and safety of anti-caries products is well-accepted. However, caries clinical trials are not without limitations and have increasingly been viewed as inefficient with respect to measuring the disease process in a holistic manner. The endpoint of a caries lesion with loss of enamel integrity (cavitation) focuses on one end of the caries progression continuum at the expense of early caries initiation and progression. Several early caries detection methods have been developed that correlate with mineral loss of the tooth surface. These diagnostics differ from conventional visual-tactile and radiographic methods in that they are capable of detecting early non-cavitated lesions, and this can generate continuous data. As diagnostic methods become accepted, they will lead to study designs that diverge from the conventional two- to three-year caries studies. Modification of the existing two- to three-year conventional caries design for assessment of product effectiveness, whether by the introduction of a new diagnostic method or by modification of the overall clinical design, must result in a clinical design that is able to differentiate known treatments on the basis of caries prevention efficacy. Given that the fluoride dose response has been characterized in the literature, this should form the basis of any validation package for new methodologies. In conclusion, a minimum expectation for acceptance as a replacement to conventional testing should be that the method or design can differentiate products of known efficacy from one another and that the efficacy relationship observed in a two- to three-year conventional study can be observed with the new method or design.

Cariostatic Agents↗

Visual and visuo-tactile detection of dental caries.

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.

Controlled Clinical Trials as Topic↗

Water concentration in self-etching primers affects their aggressiveness and bonding efficacy to dentin.

Water is required to ionize acid resin monomers for demineralization of tooth substrates. We tested the null hypothesis that altering the water concentration in two-step self-etching primers has no effect on their aggressiveness and bonding efficacy to dentin. Five experimental self-etching primers were prepared with resin-water-ethanol volume ratios of 9-0-1, 8-1-1, 7-2-1, 5-4-1, and 3-6-1. They were applied to smear-layer-covered dentin, followed by a bonding resin and composite build-ups for microtensile bond testing and TEM examination of tracer penetration. Increasing water concentration from 0-60 vol% improved acidic monomer ionization that was manifested as increasing hybrid layer thickness. However, significantly higher bond strength was observed in the 7-2-1 group, with minimal nanoleakage in the corresponding hybrid layer. When self-etching primers are formulated, a balance must be achieved to provide sufficient water for adequate ionization of the acidic monomers, without lowering the resin concentration too much, to optimize their bonding efficacy to dentin.

Acid Etching, Dental↗

The role of sucrose in cariogenic dental biofilm formation--new insight.

Dental caries is a biofilm-dependent oral disease, and fermentable dietary carbohydrates are the key environmental factors involved in its initiation and development. However, among the carbohydrates, sucrose is considered the most cariogenic, because, in addition to being fermented by oral bacteria, it is a substrate for the synthesis of extracellular (EPS) and intracellular (IPS) polysaccharides. Therefore, while the low pH environment triggers the shift of the resident plaque microflora to a more cariogenic one, EPS promote changes in the composition of the biofilms' matrix. Furthermore, it has recently been shown that the biofilm formed in the presence of sucrose presents low concentrations of Ca, P(i), and F, which are critical ions involved in de- and remineralization of enamel and dentin in the oral environment. Thus, the aim of this review is to explore the broad role of sucrose in the cariogenicity of biofilms, and to present a new insight into its influence on the pathogenesis of dental caries.

Biofilms↗

Chemical interaction of phosphoric acid ester with hydroxyapatite.

Among functional monomers used in contemporary dental adhesives, 10-methacryloyloxydecyl dihydrogen phosphate (MDP) has been found to interact chemically with hydroxyapatite (HAp) most intensively and stably. This effect was thought to be the basis of the superior bonding effectiveness of MDP-based self-etch adhesives to enamel/dentin. To elucidate fully the chemical interaction and reactivity of MDP with HAp, we used (31)P CP-MAS NMR spectroscopy and powder x-ray diffraction. In an aqueous ethanol solution, Ca ions were leached from HAp to form, at short term, a MDP-calcium salt (CaMHP(2)) layered structure on the HAp surface. When MDP was allowed to interact for longer time (< 24 hrs), CaHPO(4).2H(2)O precipitated on top of this MDP-calcium salt layered structure. In conclusion, the intense chemical interaction of MDP with HAp must be ascribed to superficial dissolution of HAp induced by the MDP adsorption and subsequent deposition of MDP-calcium salt with a solubility lower than that of CaHPO(4).2H(2)O.

Adsorption↗

Informatics systems to assess and apply clinical research on dental restorative materials.

Dental biomaterials are used clinically for one or more of the following purposes: to restore function, to enhance esthetics, and to prevent or arrest demineralization of tooth structure. Studies of the clinical performance of restorations and prostheses made from these materials have generally focused on quality assessment and survival statistics. Data from these studies should provide probabilities of specific treatment outcomes that are useful for practicing dentists. However, the utility of these data is limited by the lack of national and international standards for assessing these clinical outcomes. Standardized approaches toward clinical informatics and treatment-decision analysis are urgently needed to minimize the variability of clinical outcomes reported in publications associated with direct and indirect restorative materials used for dental restorations and prostheses.

Clinical Trials as Topic↗

Clinical performance of ceramic brackets: a survey of British orthodontists' experience.

Eight-hundred-and-twenty-two British orthodontists were sent questionnaires regarding their use of ceramic brackets. Five-hundred-and-forty-six (66 per cent) responded, and from these, 512 (62 per cent) were analysed. Approximately half of these operators had experience with ceramic brackets, but only 32 operators had treated more than 30 patients. Clinicians' experiences and problems during treatment and debonding are discussed.

Ceramics↗