Effect of dolomite oral exposure in Wistar rats during organogenesis period of pregnancy.

The potential of oral exposure to dolomite, a natural product that contains calcium and magnesium, to initiate teratogenesis was analyzed in Wistar rats. Animals received dolomite oral dosages of 500 and 1500mg/kg during the period of gestation from day 6-15 post conceptionem (p.c.). Maternal, embryo and fetal toxicity were evaluated. Dolomite exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, hematology parameters and relative organs weight. Signs of embryo-fetal toxicity were not observed. Skeletal malformations and visceral variations were similar in control and dolomite-treated groups. On the other hand, slight increase was observed in fetal body weight in the dolomite-treated group. Treatment with dolomite resulted in significantly decreased incidences of unossified xiphisternum, incomplete ossification of xiphisternum and sternebrae. These effects could be caused by a beneficial influence of calcium and magnesium salts present in dolomite on ossification process. In conclusion, in this study we found that the oral exposure to rats of up to 1500mg/kg of dolomite during organogenesis did not induce significant maternal and embryo-fetal toxicity.

Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes.

BACKGROUND: Nicotinamide has been used with success to prevent type 1 diabetes in animal models and humans. This vitamin B3 derivative has attracting effects on beta-cell protection and regeneration. AIM/HYPOTHESIS: To evaluate the effect of standard nicotinamide administration on type 1 diabetes prevention in first degree relatives of persons with type 1 diabetes as well as on the concentrations of islet-cell-related autoantibodies, insulin secretion and peripheral sensitivity. SUBJECTS AND METHODS: A randomized double-blind placebo controlled intervention trial was conducted in 40 first degree relatives of type 1 diabetic patients. Persistence of ICA ( >or= 10 JDF units) was among inclusion criteria. Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or placebo for 5 years. Groups were also stratified by age. Islet associated antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT, IVGTT and HLA-DR genotyping were performed in all participants. The main criterion to stop treatment was type 1 diabetes development as defined by WHO. RESULTS: Type 1 diabetes development frequencies were similar between the treatment groups. ICA frequencies at the end of the study, first phase insulin release, and insulin sensitivity did not differ between groups as well. None of the participants suffered from any adverse events described for nicotinamide. CONCLUSIONS: Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.