The risk of metabolic syndrome as a result of lifestyle among Ellisras rural young adults

The study aimed to investigate the association between metabolic syndrome (MetS) and lifestyle risk factors among Ellisras adults. A cross-sectional study was conducted on 624 adults (306 males and 318 females). MetS was defined according to the criteria of the International Diabetes Federation. The prevalence of MetS was 23.1% (8.6% males and 36.8 % females). Females appeared to have higher mean values for waist circumference (WC), fasting blood glucose (FBG), total cholesterol (TCHOL) and low-density lipoprotein cholesterol (LDL-C), while males had high mean values for high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP). No significant age and gender differences were observed for dietary intake. Significantly more females (51.9%) presented with increased WC than males (4.6%). Participants who had a high dietary energy intake were significantly less likely to present with larger WC (OR: 0.250 95% CI [0.161; 0.389]), low HDL-C (OR: 0.306 95% CI [0.220; 0.425]) and high LDL-C (OR: 0.583 95% CI [0.418; 0.812]) but more likely to present with elevated FBG (OR: 1.01 95% CI [0.735; 1.386]), high TCHOL (OR: 1.039 95% CI [0.575; 1.337]), high TG (OR: 1.186 95% CI [0.695; 2.023]) and hypertension (OR: 5.205 95% CI [3.156; 8.585]). After adjusting for age, gender, smoking, and alcohol status, high energy intake was more than two times likely to predict MetS in adults with a large WC (OR: 2.766 95% CI [0.863; 3.477] and elevated FBG (OR: 2.227 95% CI [1.051; 3.328]). Therefore, identifying groups that are at an increased risk and those that are in their early stages of MetS will help improve and prevent the increase of the MetS in the future

Characterisation of Human Cytochrome P450s Involved in the Bioactivation of Clozapine

Clozapine is known to cause hepatotoxicity in a small percentage of patients. Oxidative bioactivation to reactive intermediates by hepatic cytochrome P450s (P450s) has be proposed as a possible mechanism. However, in contrast to their role in formation of N-desmethylclozapine and clozapine N-oxide, the involvement of individual P450s in the bioactivation to reactive intermediates is much less well characterized. The results of the present study show that 7 of 14 recombinant human P450s were able to bioactivate clozapine to a glutathione-reactive nitrenium ion. CYP3A4 and CYP2D6 showed the highest specific activity. Enzyme kinetical characterization of these P450s showed comparable intrinsic clearance of bioactivation, implicating that CYP3A4 would be more important because of its higher hepatic expression, compared with CYP2D6. Inhibition experiments using pooled human liver microsomes confirmed the major role of CYP3A4 in hepatic bioactivation of clozapine. By studying bioactivation of clozapine in human liver microsomes from 100 different individuals, an 8-fold variability in bioactivation activity was observed. In two individuals bioactivation activity exceeded N-demethylation and Noxidation activity. Quinidine did not show significant inhibition of bioactivation in any of these liver fractions, suggesting that CYP2D6 polymorphism is not an important factor in determining susceptibility to hepatotoxicity of clozapine. Therefore, interindividual differences and drug-drug interactions at the level of CYP3A4 might be factors determining exposure of hepatic tissue to reactive clozapine metabolites. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics