UDP-glucuronosyltransferase genetic variation in North African populations: a comparison with African and European data

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases.

Aim: To examine genetic variation in UGT in North African populations.

Subjects and methods: Allele frequencies of SNPs UGT1A4^24Thr, UGT1A4^48Val, UGT2B15^85Tyr, UGT2B15^523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations.

Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A4^48Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of the populations.

Conclusion: North African populations show a high frequency of carriers of UGT2B15^523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17^del, a variant associated with high concentrations of testosterone and oestradiol.     

Verapamil prevents the effect of calcium-sensing receptor activation on the blood glucose and insulin levels in rats

BackgroundThe Ca²⁺ triggered insulin exocytosis in β cells of the pancreatic islets may be the result of Ca²⁺ influx through L-type voltage dependent calcium channels (VDCC) localized in the plasma membrane, as well as of liberation of Ca²⁺ from intracellular storages, induced by activation of the calcium receptor (CaR) coupled with the PLC enzyme present in the pancreatic islets. The present study was designated to determine, in in vivo experiments, the effects of CaR activation by R-568 and inhibition of the receptor by NPS 2143 on the plasma glucose and insulin levels in the presence of verapamil, a calcium channel blocker.MethodsWistar rats, after fasting for 14 h before the experiment, were anesthetized with inactin and loaded ip with 1 g/kg glucose.ResultsIn comparison to the control group, the verapamil-induced blockade of the calcium channels in glucose loaded animals increased the blood glucose level and decreased the insulin level, whereas CaR activation with R-568 induced opposite effects. However, in the presence of verapamil, R-568 did not change the concentration of glucose or insulin versus the control animals. Verapamil infusion did not alter elevated glucose concentration in the NPS 2143 animals. At the same time, verapamil reduced the plasma insulin level and potentiated the drop of insulin concentration induced by NPS 2143.ConclusionThe observations suggest that under the in vivo conditions, calcium channel blockade may prevent changes in the blood glucose and insulin concentrations induced by the CaR activation.     

Period of gestational diabetes mellitus diagnosis and maternal and fetal morbidity

BACKGROUND: The aim of the study was to analyze the association between the period of diagnosis of gestational diabetes mellitus (GDM) and maternal and neonatal outcome. METHODS: In this retrospective study, 1708 offspring (1571 singleton, 119 twins, and 18 triplets) born to women with GDM who attended the Diabetic and Pregnancy Clinic were included. Pregnancies were divided into three groups according to the gestational age at GDM diagnosis. The association of the period of diagnosis with maternal and fetal outcome was assessed adjusting for potentially confounding variables (logistic regression analysis). RESULTS: The period of diagnosis was a predictor in two out of three maternal outcomes (pregnancy-induced hypertension and insulin treatment) and in four out of 12 fetal outcomes (preterm birth, 5-min Apgar <7, perinatal mortality, and hyperbilirubinemia). Whereas pregnancy-induced hypertension was higher in women diagnosed with GDM in the second period, the other outcomes displayed higher occurrences with earlier diagnosis. CONCLUSIONS: Diagnosis of GDM earlier in pregnancy is a predictor of adverse maternal and neonatal outcome.     

Protective effect of ascorbic acid after single and repetitive administration of cadmium in Swiss mice

The aim of the study was to delineate the protective effect of ascorbic acid with plausible mechanism after single and repetitive cadmium administration to Swiss mice. The effects of single high dose administration of CdCl(2) (6?mg/kg) or ascorbic acid (AsA) (50?mg/kg) and chronic (three times) administration of Cd at low dose (2?mg/kg) or AsA at same dose (50?mg/kg) were compared in Swiss albino mice. Changes of lipid peroxidation [determined by the malonyldialdehyde (MDA) concentration] were taken as a measure of the oxidative stress intensity. Lipid fatty acid's unsaturation related to the permeability of cell membranes was also examined. Mobilization of the immune system was determined by analyzing changes in antioxidant concentrations of AsA and glutathione (GSH), and by measuring the activation of antioxidant enzymes SOD, GPx and CAT. In addition, the level of free polyamines and variation in their proportions were examined. In conclusion, exposure to higher levels of cadmium will have more deleterious effects on the body rather than chronic exposure at lower levels with this toxic metal, while this study clearly demonstrated the protective effects of AsA in a mouse model.     

Promovision: designing a capacity-building program to strengthen and expand the role of promotores in HIV prevention

This article describes the development of Promovisión, a program based on the utilization of promotores in community-based organizations (CBOs) to improve the provision of HIV prevention services to recent immigrants and Latinos who are less acculturated. Promovisión aims to demonstrate the contribution of promotores as a cost-effective strategy in HIV prevention efforts, and how promotores facilitate the formation of community, regional, and national CBO networks working collaboratively to prevent the spread of HIV in Latino communities. In addition, this article examines the interpersonal, organizational, community, and sociocultural dimensions that facilitate or hinder community mobilization, and coalition formation and growth, and how these findings shaped the final design of the program. Finally, the Promovisión program seeks to demonstrate that a promotor-based program is a culturally appropriate model for HIV prevention and care, which can be successfully implemented in community and clinical settings among ethnic populations with limited English proficiency.     

NMDA receptor antagonism does not inhibit induction of ischemic tolerance in gerbil brainin vivo

Effects of high and moderate affinity uncompetitive NMDA receptor antagonists (+)MK-801 and memantine on ischemic tolerance were compared in relation to telemetrically controlled brain temperature. The tolerance to an injurious 3 min test of global forebrain ischemia in Mongolian gerbils was induced 48 h earlier by 2 min preconditioning ischemia. Normothermic preconditioning was virtually harmless, and greatly reduced neurodegeneration evoked by test ischemia. In hyperthermic animals it was injurious and failed to induce tolerance. Memantine (5 mg/kg) and (+)MK-801 (3 mg/kg) injected i.p. 1 h before preconditioning did not inhibit ischemic tolerance in the normothermic gerbils, while in hyperthermic animals treated with (+)MK-801 ischemic tolerance was partially restored. Subchronic 3 day infusion of memantine (30 mg/kg/day) significantly decreased neurodegeneration, and preconditioning in the normothermic gerbils further reduced neuronal damage. Hyperthermia exacerbated preconditioning ischemia and in this way reduced expression of tolerance, while (+)MK-801 partially reversed this effect. Our results do not confirm previous reports on the role of NMDA receptors in the induction of ischemic tolerance in gerbils.