Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology.

N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors critical for synaptic transmission and plasticity, and for the development of neural circuits. Rare or de-novo variants in GRIN genes encoding NMDAR subunits have been associated with neurodevelopmental disorders characterized by intellectual disability, developmental delay, autism, schizophrenia, or epilepsy. In recent years, some disease-associated variants in GRIN genes have been characterized using recombinant receptors expressed in non-neuronal cells, and a few variants have also been studied in neuronal preparations or animal models. Here we review the current literature on the functional evaluation of human disease-associated variants in GRIN1, GRIN2A and GRIN2B genes at all levels of analysis. Focusing on the impact of different patient variants at the level of receptor function, we discuss effects on receptor agonist and co-agonist affinity, channel open probability, and receptor cell surface expression. We consider how such receptor-level functional information may be used to classify variants as gain-of-function or loss-of-function, and discuss the limitations of this classification at the synaptic, cellular, or system level. Together this work by many laboratories worldwide yields valuable insights into NMDAR structure and function, and represents significant progress in the effort to understand and treat GRIN disorders. Keywords: NMDA receptor , GRIN genes, Genetic variants, Electrophysiology, Synapse, Animal models.

Therapeutic yoga reduces pro-tumorigenic cytokines in cancer survivors.

INTRODUCTION: Chronic inflammation can remain many years after the completion of cancer treatment and is associated with cancer recurrence. The purpose of this study was to examine how a 16-week therapeutic yoga program (TYP) modulates the cytokine profile in heterogeneous cancer survivors. METHODS: Eligible participants were 18 years of age or older and clinically diagnosed with cancer. Consenting participants were asked to attend three, 75-min sessions weekly of TYP with meditation. Seventeen patients provided blood samples at baseline and end of study. Eight cytokines (interferon (IFN)-γ; interleukin (IL)-1b, IL-1ra, IL-4, IL-6, IL-8, IL-10; and tumor necrosis factor (TNF)-α), three receptors (sIL-6R, sTNFRI, sTNFRII), and C-reactive protein (CRP) were quantified. RESULTS: Patients were 59.6 ± 7.3 years old; over half (56%) were overweight or obese BMI ≥ 25 kg/m2); majority were female (71%) and breast cancer survivors (65%), of which 44% were Hispanic. Marked reductions were observed in all cytokines except IL-4, with significant reductions (p < 0.05) found in IL-1b (- 13%) and IL-1ra (- 13%). No significant changes were observed in soluble cytokine receptors or CRP. CONCLUSIONS: TYP led to significant reduction in circulating cytokines associated with chronic inflammation in a heterogeneous sample of cancer survivors.

Body-weight goals, trends, and weight-loss techniques among patients with peripheral arterial disease.

BACKGROUND:: Obesity contributes to negative outcomes in peripheral arterial disease (PAD). Little is known about the body-weight goals and trends among patients with PAD. AIM:: The aim of this study was to explore self-reported body-weight trends and methods used to achieve weight loss in patients with PAD. METHODS:: Data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) was utilized to compare individuals with PAD who were overweight and obese ( n = 240), to matched individuals without PAD ( n = 480). Self-reported body weight at age 25 years, 10 years prior and 1 year prior to the current assessment, and age and weight of heaviest body weight were compared. Self-reported weight-loss techniques during the past year were compared between groups. RESULTS:: Individuals with PAD and controls reported similar weights 10 years prior (79.2 kg vs 78.5 kg; p = 0.60) and weight gain over the last 10 years of 5.7 kg. There was no significant difference in reported body weight at age 25 years, 10 years prior, 1 year prior, or heaviest weight. Compared with the control group, fewer participants with PAD reported attempted weight loss in the last year (27.50% vs 36.04%; p = 0.02) and were half as likely to report utilizing exercise as a weight-loss method (12.5% vs 21.7%; p = 0.003). CONCLUSIONS:: These data indicate that those with PAD are less inclined to attempt weight loss, especially through means of increased physical activity. Future research is needed regarding the effectiveness of intentional weight-loss programs in this population.

Diet as a Risk Factor for Cognitive Decline in African Americans and Caucasians with a Parental History of Alzheimer's Disease: A Cross-Sectional Pilot Study Dietary Patterns.

BACKGROUND: African Americans (AA) are more likely to develop Alzheimer's disease (AD) than Caucasians (CC). Dietary modification may have the potential to reduce the risk of developing AD. OBJECTIVE: The objective of this study is to investigate the relationship between Southern and Prudent diet patterns and cognitive performance in individuals at risk for developing AD. DESIGN: Cross-sectional observational study. PARTICIPANTS: Sixty-six cognitively normal AA and CC individuals aged 46-77 years with a parental history of AD were enrolled. MEASUREMENTS: Participants completed a Food Frequency questionnaire, cognitive function testing, which consisted of 8 neuropsychological tests, and cardiovascular risk factor assessments, including evaluation of microvascular and macrovascular function and ambulatory blood pressure monitoring. RESULTS: Results revealed a relationship between the Southern diet and worse cognitive performance among AAs. AAs who consumed pies, mashed potatoes, tea, and sugar drinks showed worse cognitive performance (p<0.05) compared with CCs. In addition, gravy (p=0.06) and cooking oil/fat (p=0.06) showed negative trends with cognitive performance in AAs. In both CC and AA adults, greater adherence to a Prudent dietary pattern was associated with better cognitive outcomes. Cardiovascular results show that participants are overall healthy. AAs and CCs did not differ on any vascular measure including BP, arterial stiffness and endothelial function. CONCLUSION: Research shows that dietary factors can associate with cognitive outcomes. This preliminary cross-sectional study suggests that foods characteristic of the Southern and Prudent diets may have differential effects on cognitive function in middle-aged individuals at high risk for AD. Results suggest that diet could be a non-pharmaceutical tool to reduce cognitive decline in racially diverse populations. It is possible that the increased prevalence of AD in AA could be partially reduced via diet modification.

Reduced LPL and subcutaneous lipid storage capacity are associated with metabolic syndrome in postmenopausal women with obesity.

OBJECTIVES: This study examines the hypothesis that lower adipose tissue lipoprotein lipase (LPL) activity and a limited capacity for subcutaneous adipocyte expansion will be associated with metabolic syndrome (MSyn) in postmenopausal women who are overweight and obese. METHODS: Women (N = 150; age 60 ± 1 year; BMI: 31.5 ± 0.3 kg m-2; mean ± standard errors of the means [SEM]) with and without MSyn had dual-energy X-ray absorptiometry scans for total body fat, CT scans for visceral and subcutaneous abdominal adipose tissue areas, lipid and glucose metabolic profiles, and abdominal and gluteal fat aspirations for subcutaneous fat cell weight (FCW; N = 150) and LPL activity (N = 100). RESULTS: Women with MSyn had similar total body fat, but 15% larger abdominal and 11% larger gluteal FCWs and more visceral fat (179 ± 7 vs. 134 ± 6 cm2) than women without MSyn (P's < 0.05). Abdominal LPL activity was 13% (P = 0.18) lower in women with than without MSyn and correlated with abdominal FCW (r = 0.49, P < 0.01) only in those without MSyn. Visceral fat and abdominal and gluteal FCWs correlated with MSyn components, and subcutaneous adipose tissue correlated with abdominal FCW (r = 0.43, P < 0.01) and LPL activity (r = 0.18, P < 0.05), independent of total body fat. CONCLUSIONS: These results show that women with MSyn have lower LPL activity, limited capacity for subcutaneous adipocyte lipid storage and greater ectopic fat accumulation in viscera than women without MSyn of comparable obesity. This suggests that the development of novel therapies that would enhance adipocyte expandability might prevent the accumulation of ectopic fat and reduce the risk for MSyn in postmenopausal women with obesity.

Influence of Vitamin D and Parathyroid Hormone on Bone and Metabolic Risk in Women with Previous Gestational Diabetes.

The purpose of this study was to compare plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), VO2max, bone (by DXA), and metabolic outcomes across age and race-matched postmenopausal women (54±1 years; mean±SEM): 1) with previous gestational diabetes (GDM) (32±1 kg/m(2); n=17), 2) without previous GDM, but with a similar BMI to GDM (32±1 kg/m(2); n=17), and 3) without previous GDM, but with a higher BMI than GDM (36±1 kg/m(2); n=17; p<0.01). The prevalence of 25(OH)D insufficiency and deficiency was high (~80%), but not different across groups, while PTH tended to be ~30% lower in women with a history of GDM (p=0.09). Women with a history of GDM had lower HDL cholesterol and higher diastolic blood pressure and fasting and 2-h glucose levels (by oral glucose tolerance test) (vs. groups 2 and 3; p<0.05). Bone mineral density (BMD) tended to be slightly higher in women with prior GDM than the BMI matched women with no prior GDM (p=0.09). Overall, higher PTH was associated with lower femoral neck (r=- 0.33) and (r=- 0.38) (p <0.05), while lower 25(OH)D was associated with lower VO2max (r=0.25, p=0.05) and higher fasting glucose (r=- 0.14) and insulin (r=- 0.29 (p <0.05). We observed that the poor metabolic profiles of postmenopausal women with a history of GDM are independent of 25(OH)D and PTH. However, due to associations between 25(OH)D and PTH with bone and metabolic outcomes, maintaining recommended 25(OH)D and PTH concentrations is important regardless of a previous history of GDM.

Dietary prescription adherence and non-structured physical activity following weight loss with and without aerobic exercise.

OBJECTIVES: To compare the effects of weight loss with and without exercise on 1) dietary prescription adherence and 2) non-structured activity in postmenopausal women. DESIGN: Longitudinal study. SETTING: Clinical research setting with facility based exercise and nutrition education. PARTICIPANTS: Overweight and obese women, 45-76 years old. INTERVENTION: 6 months of weight loss alone (WL; N=38) or with aerobic exercise (AEX+WL; N=41). MEASUREMENTS: Cardiorespiratory fitness (VO2max), resting metabolic rate (RMR), seven day food intake, and physical activity (by Actical accelerometers worn in a subset subgroup: WL: N=10; AEX+WL: N=15) were assessed before and after the interventions. RESULTS: Both interventions resulted in similar weight loss (~9%) and no significant changes in RMR, while only the AEX+WL group improved VO2max (~10%). At baseline, the AEX+WL group consumed slightly more protein than the WL group (P<0.01). Macronutrient intake did not change following AEX+WL, but the WL group decreased their fat intake and increased their carbohydrates and protein intakes (Ps<0.05), which resulted in similar macronutrient intakes between groups post-intervention. Weekday total activity counts decreased 22% (P<0.05) following WL. This change tended (P=0.07) to be different than the lack of change in non-structured activity observed following AEX+WL. CONCLUSION: Although similar dietary adherence was observed, these data suggest that postmenopausal women undergoing weight loss may benefit from the addition of exercise to prevent the decline in non-structured activity observed following weight loss alone.

[Mitochondrial and microcirculatory distress syndrome in the critical patient. Therapeutic implications]. / Síndrome de distrés mitocondrial y de la microcirculación en el paciente crítico. Implicaciones terapéuticas.

Mitochondrial and microcirculatory distress syndrome (MMDS) can occur during systemic inflammatory response syndrome (SIRS), and is characterized by cytopathic tissue hypoxia uncorrected by oxygen transport optimization, and associated with an acquired defect in the use of oxygen and energy production in mitochondria, leading to multiple organ dysfunction (MOD). We examine the pathogenesis of MMDS, new diagnostic methods, and recent therapeutic approaches adapted to each of the three phases in the evolution of the syndrome. In the initial phase, the aim is prevention and early reversal of mitochondrial dysfunction. Once the latter is established, the aim is to restore flow of the electron chain, mitochondrial respiration, and to avoid cellular energy collapse. Finally, in the third (resolution) stage, treatment should focus on stimulating mitochondrial biogenesis and the repair or replacement of damaged mitochondria.

IMPACT OF WEIGHT LOSS AND AEROBIC EXERCISE ON NUTRITION AND BONE MINERAL DENSITY IN AFRICAN AMERICAN AND CAUCASIAN POSTMENOPAUSAL WOMEN.

BACKGROUND: Weight loss is often recommended for obese women to reduce fat mass and the risk of developing chronic diseases, but may result in a reduction of bone mineral density (BMD). African Americans have greater BMD than Caucasians, but differences in the decrease in BMD between these races following weight reduction with and without exercise are unknown. OBJECTIVES: The purpose of this study was to investigate the hypothesis that Caucasian women would lose greater amounts of BMD than African American women after undergoing weight loss, but that the addition of aerobic exercise would attenuate the loss in both races. DESIGN: Longitudinal. PARTICIPANTS: African American (n=34) and Caucasian (n=63), overweight and obese postmenopausal (age 45-80 years). INTERVENTION: Six months of weight loss (250-350 kcal/days deficit) alone (WL) or in combination with aerobic exercise consisting of 3 days/week treadmill training at >85% of heart rate reserve for 45 min (AEX+WL). MEASUREMENTS: Femoral neck, total femur, and lumbar BMD, VO2max, urinary calcium, and dietary intake. RESULTS: African American women had a greater body weight, BMI, and BMD all sites and lower dietary protein and calcium intakes than Caucasian women (all P<0.05). Weight decreased 7.5% in both groups and VO2max increased only after AEX+WL (intervention effect, P<0.001). Both races lost ~1% of their femoral neck and total femur BMD following the interventions (P's<0.01). There were no race by intervention interactions. There was a trend for the women undergoing WL to lose greater femoral neck BMD than those in AEX+WL (P=0.07). There were no associations between changes in BMD and changes in VO2max, urinary calcium, or dietary intake. CONCLUSIONS: Our data indicate that despite beginning the interventions with greater BMD than Caucasian postmenopausal women, African Americans were not spared from losses of femoral neck and total femur BMD following six months of weight loss, but that addition of aerobic exercise to weight loss tends to attenuate the decreases in femoral neck BMD in both races.

Microhardness and SEM after CO(2) laser irradiation or fluoride treatment in human and bovine enamel.

BACKGROUND: It remains uncertain as to whether or not CO(2) laser is able to hinder demineralization of enamel. The possibility to use bovine instead of human teeth on anticariogenic studies with laser has not yet been determined. PURPOSE: To compare the ability of CO(2) laser and fluoride to inhibit caries-like lesions in human enamel and to test whether a similar pattern of response would hold for bovine enamel. STUDY DESIGN: Ninety-six enamel slabs (2 × 2 × 4 mm) (48 from bovine and 48 from human teeth) were randomly distributed according to surface treatment (n = 12): CO(2) laser, 5% sodium fluoride varnish (FV), 1.23% acidulated phosphate fluoride (APF) gel, or no treatment (control). Specimens were subjected to a 14-day in vitro cariogenic challenge. Microhardness (SMH) was measured at 30 µm from the surface. For ultrastructural analysis, additional 20 slabs of each substrate (n = 5) received the same treatment described earlier and were analyzed by SEM. RESULTS: ANOVA and Tukey test ascertained that CO(2) laser promoted the least mineral loss (SMH = 252(a)). Treatment with FV resulted in the second highest values (207(b)), which was followed by APF (172(c)). Untreated specimens performed the worst (154(d)). SEM showed no qualitative difference between human and bovine teeth. APF and control groups exhibited surfaces covered by the smear layer. A granulate precipitate were verified on FV group and fusion of enamel crystals were observed on lased-specimens. CONCLUSIONS: CO(2) laser may control caries progression more efficiently than fluoride sources and bovine teeth may be a suitable substitute for human teeth in studies of this nature.

Potential agents to control enamel caries-like lesions.

OBJECTIVES: To assess whether pastes containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and calcium sodium phosphosilicate (CSP) control artificial caries lesion progression. METHODS: Enamel slabs of bovine teeth were embedded in polyester resin and had their enamel surfaces serially polished, and tested for surface microhardness (SMH, 25 g, 5 s). Incipient caries-like lesions were pre-formed and specimens were evaluated by microhardness test (SMH(post-lesion)) and randomly assigned to five treatment groups (n=15): (1) regular dentifrice (RE, 1,100 ppm F); (2) dentifrice with calcium sodium phosphosilicate (CSP); (3) amorphous calcium phosphate stabilized by casein phosphopeptide (CPP-ACP); (4) CPP-ACP with 900 ppm F (CPP-ACP+F) and (5) control group-unexposed to any remineralizing agent. Treatments were applied five times, after the de-remineralization period in the cariogenic challenges. Post-treatments SMH measurements were conducted (SMH(post-treatment)). RESULTS: ANOVA was applied for data evaluation and revealed a significant difference among the treatments (p=0.0161). Tukey's test was conducted and the percentage of mineral loss was calculated. Specimens exposed to CSP (7.1%), RE (6.7%) and CPP-ACP+F (3.8%) showed lower mineral loss than those that in the control group (-11.0%). CPP-ACP group (3.2%) differed from the control, CSP and RE groups. CONCLUSIONS: Depending on the agent used, a remineralizing effect may be expected, which reflects in caries lesions progression.

Low relative skeletal muscle mass indicative of sarcopenia is associated with elevations in serum uric acid levels: findings from NHANES III.

BACKGROUND: Sarcopenia may be related to increases in reactive oxygen species formation and inflammation, both of which are associated with elevations in serum uric acid. OBJECTIVE: To test the hypothesis that a reduced skeletal muscle mass index, indicative of sarcopenia, is related to elevations in uric acid. DESIGN: Cross-sectional analysis of nationally representative data. SETTING: Third National Health and Nutrition Examination Survey, 1988-1994. PATIENTS: 7544 men and women 40 years of age and older who had uric acid, skeletal muscle mass, and select covariate information. MEASUREMENTS: Skeletal muscle mass assessment was based on a previously published equation including height, BIA-resistance, gender, and age. Absolute skeletal muscle mass was calculated for all study population individuals and compared against the sex-specific mean for younger adults. Serum uric acid data were gathered from the NHANES laboratory file. RESULTS: A logistic regression analysis revealed that elevations in serum uric acid are significantly related to sarcopenia status. For every unit (mg/dL) increase in uric acid, the odds ratio of manifesting a skeletal muscle mass index at least one standard deviation below the reference mean was 1.12. Participants in the highest grouping (> 8 mg/dL) of serum uric acid concentration had 2.0 times the odds of manifesting sarcopenia compared to the lowest grouping (< 6 mg/dL) (p < 0.01) after adjusting for the additional covariates. LIMITATIONS: This study design was limited in its cross-sectional nature. Potential selection, measurement, and recall bias may have occurred, and methodology used to classify sarcopenia status based on skeletal muscle mass index is not validated. CONCLUSION: This observation provides support for the theory that elevations in uric acid may lead to sarcopenia, although the proposed mechanism needs further experimental support.

Influence of fluoride-releasing restorative material on root dentine secondary caries in situ.

The usefulness of fluoride-releasing restorations in secondary caries prevention may be questioned because of the presence of other common sources of fluoride and because of ageing of the restorations. This study tested the hypothesis that glass-ionomer cement restorations, either aged or unaged, do not prevent secondary root caries, when fluoride dentifrice is frequently used. Sixteen volunteers wore palatal appliances in two phases of 14 days, according to a 2 x 2 crossover design. In each phase the appliance was loaded with bovine root dentine slabs restored with either glass-ionomer or resin composite, either aged or unaged. Specimens were exposed to cariogenic challenge 4 times/day and to fluoridated dentifrice 3 times/day. The fluoride content in the biofilm (FB) formed on slabs and the mineral loss (DeltaZ) around the restorations were analysed. No differences were found between restorative materials regarding the FB and the DeltaZ, for either aged (p = 0.792 and p = 0.645, respectively) or unaged (p = 1.00 and p = 0.278, respectively) groups. Under the cariogenic and fluoride dentifrice exposure conditions of this study, the glass-ionomer restoration, either aged or unaged, did not provide additional protection against secondary root caries.

Protective effect of the dental pellicle against erosive challenges in situ.

The acquired dental pellicle helps prevent erosion, but the protection level is unknown. This in situ study tested whether a two-hour pellicle protects against different erosive challenges by orange juice. Subjects wore palatal appliances loaded with either enamel or dentin specimens. Pellicle was allowed to form, or not (control), on the surfaces of the specimens intra-orally for 2 hrs before the erosive challenges of 0 (control), 10, 20, and 30 minutes' duration. Specimens were randomly removed from the appliances after each challenge. Percentage of surface microhardness change (%SMC) was determined for the enamel specimens, and that of mineral loss and lesion depth for the dentin specimens. Enamel specimens with the pellicle showed a significantly lower %SMC, only after the 10-minute challenge. No protection was found for dentin. It was concluded that the acquired pellicle reduced dental erosion, but that this effect was limited to the less severe erosive challenge on enamel surfaces.

Influence of the organic matrix on root dentine erosion by citric acid.

This investigation was conducted in an attempt to clarify the role of the organic matrix in bovine dentine demineralisation by 1% citric acid. Dentine slabs (n = 15) were treated for 2 min with 10% sodium hypochlorite (NaOCl, a strong protein solvent), 2% glutaraldehyde (GDA, a protein fixative) or deionised water (DIW, as negative control) prior to each of 5 demineralisation periods of 30 min. The mineral loss (DeltaZ), lesion depth (LD) and surface loss (SL) were determined after each period of demineralisation, by transverse microradiography. The NaOCl-treated group showed higher DeltaZ and LD than the GDA- and DIW-treated groups. No differences between GDA and DIW groups were found. The DeltaZ and LD profiles were explained by quadratic fits (r(2) >0.80; p = 0.001) in all groups. SL was detected only in the NaOCl-treated group. The data suggested that the maintenance of the organic matrix in the lesion might be important to reduce the erosion progression rate.

An in situ investigation into the abrasion of eroded dental hard tissues by a whitening dentifrice.

This crossover study aimed to investigate abrasion of previously eroded hard dental tissues by a whitening dentifrice compared to a regular dentifrice. After a 3-day lead-in period, 14 volunteers were randomly assigned to use one of the toothpastes while wearing a removable appliance, containing 3 enamel and 3 root dentine slabs on each side. On the first day salivary pellicle was allowed to form. Twice daily for the following 3 days, one side of each appliance was immersed in an acidic carbonated drink ex vivo while the other side remained unexposed. Specimens were then brushed with the allocated dentifrice. After a 3-day washout period, new sets of enamel and dentine slabs were mounted in the appliances and the participants commenced period 2 using the alternative toothpaste. Acid-treated specimens always showed more wear than untreated specimens. The whitening dentifrice did not significantly increase the wear of softened enamel compared with the regular dentifrice. Brushing with the whitening toothpaste led to significantly greater wear of sound enamel and of both eroded and sound dentine than the regular dentifrice. The results suggest that whitening dentifrices may not increase the wear of acid-softened enamel but may have a more deleterious effect on dentine than regular toothpastes.

Effect of non-vital tooth bleaching on microleakage of coronal access restorations.

This study evaluated the effect of non-vital tooth bleaching on microleakage of composite resin/bovine tooth interface at different post-bleaching times. A total of 320 teeth were cleaned. A pulp chamber access cavity was made at the lingual surface of each tooth. The teeth were randomly divided into four groups: SPH - sodium perborate + 30% hydrogen peroxide; SPW - sodium perborate + distilled water; CP-37% carbamide peroxide; and CON-distilled water (control). The bleaching agents were replaced every 7 days, over 4 weeks. Following bleaching procedures, the groups were divided into four subgroups (n = 20), according to the post-bleaching times: 0 (baseline), 7, 14 and 21 days. After that, the cavities were restored with an adhesive system (Single Bond; 3M Co., St Paul, MN, USA) and a composite resin (Z100/3M). The specimens were thermocycled, stained with 2% methylene blue solution (pH 7), and sectioned longitudinally. The teeth were evaluated blind and independently by three previously calibrated examiners, to provide representative scores. The data were submitted to Kruskal-Wallis and multiple comparison tests (alpha=0.05). At baseline and 7 days, the SPH group showed a higher degree of dye penetration than the CON (P=0.04). At 14 and 21 days, there were no differences among groups. The association of sodium perborate with 30% hydrogen peroxide or with water may affect the sealing ability of composite resin restorations performed up to 7 days after bleaching procedures.

Caries progression and inhibition in human and bovine root dentine in situ.

Since the use of bovine instead of human dentine to evaluate cariogenic and anticariogenic substances is not well established, this in situ study was conducted. Eleven volunteers wore palatal acrylic devices containing 4 dentine slabs (2 human and 2 bovine). Sucrose solution (20%) was dripped over all slabs 4 times a day, simulating a cariogenic challenge. Dentifrice slurries, fluoridated or not, were dripped over specified dentine slabs 3 times a day to evaluate caries reduction. After 14 days, the biofilm formed on the dentine slabs was collected for microbiological analysis. In dentine, mineral loss (DeltaZ) and lesion depth (LD) were determined by cross-sectional microhardness and by polarized light microscopy, respectively. The total streptococci and mutans streptococci counts in the biofilm formed either on human or on bovine slabs, whether treated or not with fluoride dentifrice, were not statistically different. The DeltaZ and the LD values of dentine treated with fluoride dentifrice were significantly lower than the values of dentine treated with non-fluoride dentifrice. The differences in the DeltaZ and LD values between the human and bovine dentine were not statistically significant. The results suggest that bovine dentine can be used instead of human to evaluate caries development and inhibition.