Erosion Prevention Potential of an Over-the-Counter Stabilized SnF2 Dentifrice Compared to 5000 ppm F Prescription-Strength Products.

OBJECTIVE: To determine the relative ability of various F-containing products to protect enamel against the initiation and progression of tooth surface loss due to erosive acid challenges. METHODS: Cores of enamel were prepared from extracted human teeth, soaked in pooled human saliva (pellicle formation), and then treated in a 1:3 slurry (product:saliva) of either OTC level (1100 ppm F) or prescription level (5000 ppm F) products, followed by a standardized erosion cycling procedure (five days of cycling) that included 10-minute challenges with an erosive dietary acid (1% citric acid at pH 2.3) applied 60 minutes after each dentifrice treatment (repeated four times per day). Enamel surface loss was measured using transverse microradiography. Two studies were conducted. Study 1 included: A) 1100 ppm F as NaF; B) 1100 ppm F as stabilized SnF; C) 5000 ppm F as NaF; and D) 5000 ppm F as NaF + acidulated phosphate. Study 2 included: 1) 1100 ppm F as stabilized SnF; 2) 5000 ppm F as NaF + tricalcium phosphate; and 3) 1100 ppm F as NaF. RESULTS: Study 1: Treatment B (1100 ppm F as SnF), where specimens lost only 8.0 µm of the enamel surface, was significantly more effective than Treatments A, C, and D at protecting enamel against the initiation and progression of erosive acid damage (p < 0.05). Specimens treated with product A exhibited 22.8 (1.25) µm (mean ± sem) of enamel loss; 20.0 (0.71) µm of enamel loss with treatment C and 24.0 (1.4) µm of enamel loss with Treatment D. Study 2 also demonstrated significantly greater erosion protection with the stabilized SnF2 dentifrice (p < 0.05), with only 5.8 (1.93) µm of tooth surface loss, while groups 2 and 3 lost 19.8 (0.75) µm and 18.0 (2.16) µm, respectively. CONCLUSION: Results from both studies demonstrated the OTC dentifrice formulated with stabilized SnF2 provides significantly greater protection against erosive acid attack compared to some of the most popular prescription level (5000 ppm F) fluoride treatments available.

Observation and quantification of nanoscale processes in lithium batteries by operando electrochemical (S)TEM.

An operando electrochemical stage for the transmission electron microscope has been configured to form a "Li battery" that is used to quantify the electrochemical processes that occur at the anode during charge/discharge cycling. Of particular importance for these observations is the identification of an image contrast reversal that originates from solid Li being less dense than the surrounding liquid electrolyte and electrode surface. This contrast allows Li to be identified from Li-containing compounds that make up the solid-electrolyte interphase (SEI) layer. By correlating images showing the sequence of Li electrodeposition and the evolution of the SEI layer with simultaneously acquired and calibrated cyclic voltammograms, electrodeposition, and electrolyte breakdown processes can be quantified directly on the nanoscale. This approach opens up intriguing new possibilities to rapidly visualize and test the electrochemical performance of a wide range of electrode/electrolyte combinations for next generation battery systems.

A new model for demonstrating enamel protection benefits relative to acid challenge.

OBJECTIVE: To determine the applicability of a modified US FDA Caries Monograph test method for measuring the protective benefits of fluoride (F) against erosive, dietary acids. METHODS: Acid-challenged teeth were treated in two studies with a dentifrice, rinsed, and then re-challenged in a series of tests using three dietary acids. Study 1 included dentifrices containing 1450 ppm F as sodium fluoride (NaF) + triclosan [A], 1450 ppm F (NaF) + potassium nitrate (KNO3) [B], 1000 ppm F as sodium monofluorophosphate (SMFP) [C], and 0 ppm F (placebo) [D]. Study 2 included dentifrices containing 1450 ppm F (NaF) [A]; and 0 ppm F (placebo) [B]. Acids were analyzed for phosphate removed during tooth challenges, with post-treatment results compared to baseline. Results were averaged and reported as a % protection value for each product, with higher values indicating greater protection. RESULTS: Study 1: % protection for A = 16.4; B = 13.0; C = 7.1; and D = -5.2. Study 2: A = 15.2; B = -10.5, with A = B > C > D: Study 1; and A > B: Study 2. In each study, p < 0.05, ANOVA. CONCLUSIONS: The model provides a viable tool for initially assessing the potential for fluoride-containing oral care products to protect teeth against erosive, dietary acids. This can then lead to further and more elaborate testing with reasonable expectations for outcomes.

Enamel protection from acid challenge--benefits of marketed fluoride dentifrices.

OBJECTIVE: To determine the ability of various marketed dentifrices containing stabilized stannous fluoride (SnF2), sodium fluoride (NaF), or sodium monofluorophosphate (SMFP) to protect enamel against the earliest stages of erosive dietary acid damage using an in vitro enamel protection model. METHODS: Acid-challenged, extracted human teeth were treated with a 1:3 dilution of dentifrice, rinsed, and then challenged in a controlled series of tests using four dietary acids considered potentially erosive to teeth. Each acid was collected and analyzed to determine the level of mineral (phosphorous) removed from the teeth during the challenge. Post-treatment results were compared to baseline values for each acid. Results for the four acids were averaged and reported as an average percent protection value for each of the dentifrices tested, with higher values representing greater acid protection. The study included six dentifrices formulated with (A) sodium fluoride (NaF), (B) stabilized stannous fluoride (SnF2), (C,D) NaF plus 5% potassium nitrate (KNO3), (E) sodium monofluorophosphate (SMFP), or (F) SMFP plus 8% arginine bicarbonate. RESULTS: The stabilized SnF2 dentifrice demonstrated an average protection score of 39.3%, while products formulated with NaF resulted in protection scores between 11 and 13%. The SMFP dentifrice was rated at -3.5%, and the SMFP + arginine bicarbonate dentifrice resulted in a net average score of -5.0%. Results of this test were statistically significant (p < 0.05, ANOVA: B > A = C = D > E = F), in favor of the stabilized SnF2 dentifrice. CONCLUSIONS: These results suggest the stabilized SnF2 dentifrice has the potential to provide significantly better overall acid protection versus any of the other dentifrices included in the study.

Anticaries potential of commercial fluoride rinses as determined by fluoridation and remineralization efficiency.

OBJECTIVE: The objective of this work was to compare the anticaries potential of several currently marketed fluoride-containing mouthrinse products using two in vitro approaches: 1) fluoride uptake studies of demineralized human enamel samples after exposure to rinse products; and 2) microhardness studies of sound enamel samples after exposure to the rinse products and demineralizing agents. METHODS: Four currently marketed rinse products, formulated at 100 ppm F, were evaluated in fluoride uptake studies relative to a negative (water) rinse control (Study 1). The same rinse products were evaluated in microhardness studies (Study 2) against a positive control, ACT Anticavity rinse, which is formulated with 225 ppm F and carries the ADA Seal of Acceptance as an effective anticavity mouthrinse. Test products included ACT Total Care rinse (pH = 6.34), Listerine Total Care rinse (pH = 3.57), Crest Pro-Health for Me rinse (pH = 3.33), and Crest Pro-Health Complete rinse (pH = 3.43). RESULTS: Study 1-Samples treated with any of the fluoride-containing rinses showed significantly higher (p < 0.05) levels of fluoride uptake than the negative (water) control. Two of the products (Crest Pro-Health for Me and Crest Pro-Health Complete) showed significantly higher (p < 0.05) levels of fluoride uptake into demineralized enamel than the other marketed rinses (Listerine Total Care and ACT Total Care). Study 2-Samples treated with the same two rinse products (Crest Pro-Health For Me and Crest Pro-Health Complete) showed significantly lower mineral loss than the other rinse products, as well as the positive control. CONCLUSION: Results of these in vitro studies indicate that the Crest mouthrinse products evaluated here are capable of providing significantly better fluoridation of demineralized enamel, as well as significantly better protection against the initiation and progression of demineralization, compared to the other marketed fluoride-containing mouthrinse products tested.

Water replacement hypothesis in atomic details: effect of trehalose on the structure of single dehydrated POPC bilayers.

We present molecular dynamics (MD) simulations to study the plausibility of the water replacement hypothesis (WRH) from the viewpoint of structural chemistry. A total of 256 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) lipids were modeled for 400 ns at 11.7 or 5.4 waters/lipid. To obtain a single dehydrated bilayer relevant to the WRH, simulations were performed in the NP(xy)h(z)T ensemble with h(z) > 8 nm, allowing interactions between lipids in the membrane plane and preventing interactions between neighboring membranes via periodic boundary conditions. This setup resulted in a stable single bilayer in (or near) the gel state. Trehalose caused a concentration-dependent increase of the area per lipid (APL) accompanied by fluidizing the bilayer core. This mechanism has been suggested by the WRH. However, dehydrated bilayers in the presence of trehalose were not structurally identical to fully hydrated bilayers. The headgroup vector was in a more parallel orientation in dehydrated bilayers with respect to the bilayer plane and maintained this orientation in the presence of trehalose in spite of APL increase. The total dipole potential changed sign in dehydrated bilayers and remained slightly positive in the presence of trehalose. The model of a dehydrated bilayer presented here allows the study of the mechanisms of membrane protection against desiccation by different compounds.

Molecular dynamics simulations of polystyrene brushes in dry conditions and in toluene solution.

The properties of polystyrene brushes in dry conditions and in toluene solution are studied as a function of grafting density using molecular dynamics simulations. Both, individual brushes and double layers of opposing brushes are considered, the structural properties of which were found to be similar. The density profiles show very pronounced density oscillations which extend up to approximately 1.8 nm and fall into two groups of three peaks each. These features are observed regardless of grafting density and solvent conditions. In the absence of solvent, the chains undergo a transition from an oblate to a spherical shape as the grafting density increases. In contrast, in good solvent, the chains remain spherical independent of the grafting density. Solvation also increases the extension of the polystyrene chains roughly by a factor 2.5. Isotropic and two-dimensional radial distribution functions are used to characterize the structure of the polystyrene brushes. Toluene is observed to form up to four layers at the base of the grafted chains irrespective of grafting density.

The protective effects of toothpaste against erosion by orange juice: studies in situ and in vitro.

OBJECTIVES: There has been a monumental increase in the consumption of soft drinks, fruit juices and sport drinks in the UK, the US, and many other countries. Previous investigations have demonstrated the erosive nature of these acidic soft drinks. The aim of this investigation was to determine the protective effects of an experimental fluoride-based toothpaste, containing sodium hexametaphosphate, against an erosive challenge on tooth enamel. METHODS: The erosion of enamel by orange juice compared the experimental toothpaste with a benchmark sodium fluoride paste and negative control, water, in a 15-day in situ model; and the same in an in vitro enamel erosion model. Flat, polished human enamel samples with a surface profile of +/-0.1mum, were exposed to the three regimens in the single blind, crossover clinical study mimicked in vitro. Depths of the resulting eroded areas were measured using a profilometer. RESULTS: There was significantly more erosive damage on the specimens exposed to the benchmark paste and water compared to the test paste in both the in situ and in vitro studies. CONCLUSIONS: The data provide further support for tooth brushing before meals. Results of this study further suggest the sodium hexametaphosphate containing paste could be used to provide significant erosion protection in susceptible individuals over that provided by conventional fluoride products.

A comparative molecular simulation study of the glass former ortho-terphenyl in bulk and freestanding films.

We performed molecular dynamics simulations of the low-molecular weight organic glass former ortho-terphenyl in bulk and freestanding films. The main motivation is to provide molecular insight into the confinement effect without explicit interfaces. Based on earlier models of ortho-terphenyl we developed an atomistic model for bulk simulations. The model reproduces literature data both from simulations and experiments starting from specific volume and diffusivity to mean square displacement and radial distribution functions. After characterizing the bulk model we form freestanding films by the elongation and expansion method. These films give us the opportunity to study the dynamical heterogeneity near the glass transition through in-plane mobility and reorientation dynamics. We finally compare the model in bulk and under confinement. We found qualitatively a lower glass transition temperature for the freestanding film compared to the bulk.

Neutron and X-ray scattering studies of cholera toxin interactions with lipid monolayers at the air-liquid interface.

Using neutron/X-ray reflectivity and X-ray grazing incidence diffraction (GID), we have characterized the structure of mixed DPPE:GM(1) lipid monolayers before and during the binding of cholera toxin (CTAB(5)) or its B subunit (CTB(5)). Structural parameters such as the density and thickness of the lipid layer, extension of the GM(1) oligosaccharide headgroup, and orientation and position of the protein upon binding are reported. Both CTAB(5) and CTB(5) were measured to have approximately 50% coverage when bound to the lipid monolayer. X-ray GID experiments show that both the lipid monolayer and the cholera toxin layer are crystalline. The effects of X-ray beam damage have been assessed and the monolayer/toxin structure does not change with time after protein binding has saturated.

Cholera toxin assault on lipid monolayers containing ganglioside GM1.

Many bacterial toxins bind to and gain entrance to target cells through specific interactions with membrane components. Using neutron reflectivity, we have characterized the structure of mixed DPPE:GM(1) lipid monolayers before and during the binding of cholera toxin (CTAB(5)) or its B-subunit (CTB(5)). Structural parameters such as the density and thickness of the lipid layer, extension of the GM(1) oligosaccharide headgroup, and orientation and position of the protein upon binding are reported. The density of the lipid layer was found to decrease slightly upon protein binding. However, the A-subunit of the whole toxin is clearly located below the B-pentameric ring, away from the monolayer, and does not penetrate into the lipid layer before enzymatic cleavage. Using Monte Carlo simulations, the observed monolayer expansion was found to be consistent with geometrical constraints imposed on DPPE by multivalent binding of GM(1) by the toxin. Our findings suggest that the mechanism of membrane translocation by the protein may be aided by alterations in lipid packing.

Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.

There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.

Reduction in dental caries with four concentrations of sodium fluoride in a dentifrice: a meta-analysis evaluation.

Information on the effects of fluoride concentrations above 1,100 ppm in dentifrices is not extensive in the literature. The objective of this meta-analysis was to examine and compare the anticaries effectiveness (in terms of DMFS scores) of 1,700 ppm, 2,200 ppm and 2,800 ppm F- ion (as sodium fluoride) dentifrices vs. an 1,100 ppm F- ion (as sodium fluoride) control dentifrice based on results from six double-blind, randomized clinical studies, each conducted over a two- to three-year period. The studies each enrolled approximately 1,200-2,000 male and female school children per treatment group in grades I through 8, and were conducted in areas with low fluoride content water supplies in the states of Indiana, Pennsylvania, Ohio and Oregon. Separate meta-analyses were performed on the study results (DMFS increment scores determined by visual-tactile examinations supplemented with radiographs) for the one-year, two-year and three-year examinations. Comparisons of the 1,700 ppm F-, 2,200 ppm F-, and 2,800 ppm F- groups vs. the 1,100 ppm F- group were based on pooling the effect sizes for these comparisons from the individual studies. The effect sizes were calculated in two different ways, reflecting the analyses that were performed in the original studies: 1) effects based on the sample means and variances; and 2) effects based on the adjusted sample means and mean squared error from an analysis of covariance. The results obtained from this meta-analysis provide evidence that the use of a 2,800 ppm F- ion, as sodium fluoride, dentifrice results in statistically significantly lower caries increment than the use of an 1,100 ppm F- ion, as sodium fluoride, dentifrice. This result was noted after one, two, and three years of dentifrice use. The 1,700 ppm F- and 2,200 ppm F- dentifrice groups showed some directional advantages over the 1,100 ppm F- dentifrice group, however the analysis did not establish these groups as statistically significantly better than 1,100 ppm F-. The meta-analysis based on analysis of covariance results was somewhat more sensitive to treatment group differences than the analysis based on sample means and variances, as was expected.

Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial.

Experimental evidence has clearly demonstrated that the early stages of lesion formation (enamel demineralization) are reversible following exposure to saliva and/or fluoride. Clinical evidence for remineralization has also been reported extensively in the literature. However, the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries. Retrospective analysis of an existing clinical trial database provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled, double-blinded caries clinical study. The clinical study examined three treatment groups: 1) 0.243% sodium fluoride/silica dentifrice, 2) 0.4% stannous fluoride/calcium pyrophosphate (positive control) dentifrice and 3) non-fluoridated placebo/calcium pyrophosphate (negative control) dentifrice. Clinical measures in this study included both radiographic and visual-tactile assessments of caries. Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3, for both total and radiographic caries. In contrast, while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3, for both total and radiographic caries, the differences were not statistically significant. When only subjects who were "at risk" for potential reversals (i.e., those with a minimum of one carious lesion at baseline) were examined, a statistically greater frequency in caries reversals was observed in both the sodium fluoride (total, incipient, and radiographic caries) and stannous fluoride (total and radiographic caries) groups as compared to the placebo group at Year 3. Collectively, these data confirm the ability of both 0.243% sodium fluoride/silica and 0.4% stannous fluoride/calcium pyrophosphate dentifrices to clinically reverse caries. The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride, although these treatments were not found to be significantly different.

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.

The application of in situ models for evaluation of new fluoride-containing systems.

Many in situ models have assessed the anticaries potential of fluoride-containing systems (Stookey et al., 1985; Mellberg et al., 1986, 1992a,b; Corpron et al., 1986; Featherstone and Zero, 1992; Ogaard and Rolla, 1992; Stephen et al., 1992). Several models have reportedly been validated according to guidelines proposed by Proskin et all. (1992). The proposed guidelines cover only dentifrices containing sodium fluoride (NaF) or sodium monofluorophosphate (SMFP) as active ingredients. These compounds are the most widely used sources of fluoride in dentifrices, and dose-response clinical standards are available for both. Other fluoride compounds, such as amine fluoride (AmF) and stannous fluoride (SnF2), have also been proven effective in reducing caries (Muehler et al., 1957, 1958; Marthaler, 1968; Lu et al., 1980; Cahen et al., 1982). Profile standards for these fluorides were not included in the proposed guidelines, primarily due to the lack of clinical data necessary to establish a dose response for these ingredients. Criteria for demonstrating the efficacy of these ingredients, along with methods to assess new fluoride compounds, need to be established. In situ models are used to evaluate the anticaries potential of new compounds added to mouthrinses, gums, slow-release devices, etc. (Creanor et al., 1992; Manning and Edgar, 1992; Lamb et al., 1993; Toumba and Curzon, 1993; Wang et al., 1993). Ingredients are often added to dentifrices previously proven effective against caries in order to provide additional benefits of gum health, tartar control, cleaning, etc. Proposals are made regarding the in situ testing of new dentifrices containing clinically proven fluoride compounds other than NaF and SMFP, as well as alternative delivery systems, in order to assist in their evaluation.

De/remineralization from sodium fluoride dentifrices.

PURPOSE: To test the demineralization/remineralization effects of sodium fluoride dentifrices using an in situ single-section crown model system. MATERIALS AND METHODS: A fluoride dose response was evaluated using 0, 1100 and 2800 ppm F-, along with the effects of an enhanced fluoride delivery system (polyampholyte-NaF). The single-section crown model was employed with supervised toothbrushing twice a day. At the end of each 1-month study leg, sections were removed and replaced with new sections for the next leg. Both before and after the double-blind, crossover portion of the study, sections were evaluated by polarized light microscopy and microradiography. The change in mineral content of the enamel and root lesions was analyzed by ANOVA with a Waller-Duncan K-Ratio Test post hoc. RESULTS: The placebo dentifrice group showed a loss of mineral and was statistically different from all groups. The fluoride dentifrices showed increasing amounts of enamel mineral gain, with increasing fluoride concentration. The polyampholyte-NaF delivery system with 1100 ppm F- was equivalent to the 2800 ppm F- dentifrice. Root lesions gave similar rank-order results although all treatments showed demineralization or mineral loss.

Anticaries efficacy of an improved stannous fluoride toothpaste.

A series of laboratory and animal studies were conducted to confirm the anticaries potential of a new, stabilized stannous fluoride (SnF2) dentifrice relative to clinically proven SnF2 controls. Included in this series of assessments were fluoride uptake into demineralized human enamel, remineralization/inhibition of demineralization for both human enamel and roots, and animal caries studies. Each of these studies demonstrate the new, stabilized SnF2 dentifrice (Crest Gum Care toothpaste) is effective at inhibiting and reversing the caries process. These data confirm that this new dentifrice, formulated with a combination of SnF2, and hydrated silica, is predicted to be highly effective against caries. These tests predict that this new stabilized SnF2 dentifrice (Crest Gum Care toothpaste) provides a level of anticaries activity that is equivalent to Crest Regular toothpaste, a sodium fluoride (NaF)/silica product. The data suggest that this new formulation provides enhanced anticaries efficacy relative to previous, unstabilized SnF2 formulations as a result of improved fluoride bioavailability.

Mode of action of fluoride: application of new techniques and test methods to the examination of the mechanism of action of topical fluoride.

Modern techniques in dental research continue to assist in the study of the mode of (anticaries) action of topical fluorides. The Plaque Glycolysis and Regrowth Model (PGRM) facilitates the standardized assessments of antimicrobial effects on plaque following use of test formulations in vivo without complications arising from coincident mineral reactivity. In vivo plaque glycolysis testing demonstrates that topically applied fluoride, at conventional levels found in dentifrices, has only modest effects on the metabolic (acid-producing) activity of dental plaque. Any 'plaque' contribution to fluoride efficacy must come from more subtle effects on plaque acidogenicity than those measured in PGRM. The 19-FMAS NMR (Magic Angle Spinning Nuclear Magnetic Resonance) technique provides unambiguous measures of the reaction products of F-enamel interactions. Studies have revealed a new 'reaction product' of fluoride-enamel interactions--designated as Non-Specifically-Adsorbed Fluoride, NSAF. This species, along with FAP (fluoroapatite), FHAP (fluorohydroxyapatite), and CaF2 (calcium fluoride), contributes to the remineralization/demineralization benefits of fluoride. pH cycling and in situ denture chip studies permit quantitative assessments to be made of the relative benefits of fluoride in promoting remineralization and in inhibiting demineralization. Results from pH cycling/in situ experiments are strongly supportive of Koulourides' 'Acquired Acid Resistance' concept, describing fluoride's decay-preventive effects. The continued application of new analytical/physical techniques and testing regimens to the study of fluoride anticaries mechanisms may lead to the development of improved fluoride agents/treatment modalities for the prevention of dental caries.