The study was undertaken to show that polymorphic isoniazid elimination in humans is trimodal; that the acetylator genotype and eliminator phenotype of the individual patient are concordant; and that the differences in the pharmacokinetic parameters of fast, intermediate, and slow eliminator subgroups are statistically significant. Sixty adult patients of both sexes and of mixed race with tuberculosis participated in the trial. The apparent elimination rate constant (k, h(-1)) and the area under the isoniazid concentration-time curve (AUC, mg/L/h), over the interval 2 to 6 h after oral isoniazid were determined in all patients; NAT2 allele composition was determined in 47 patients. Serum INH concentrations were determined by HPLC and genotypes by PCR/restriction enzyme analysis. Three eliminator phenotypes could be distinguished, and concordance between the phenotype and the genotype of the individual could be demonstrated. The isoniazid concentration-time profiles of the three eliminator subgroups were significantly different (p < 0.05). The NAT2*12A allele, which codes for fast acetylation, has a high frequency in the population studied, the intermediate acetylator genotype is constituted of codominant fast and slow alleles, and the distribution of phenotypes/genotypes in the population is consistent with Hardy-Weinberg predictions. The therapeutic implications of polymorphic isoniazid metabolism are discussed.
A pilot study was undertaken to investigate the effects of the intake of capsules containing the plant sterols and sterolins (BSS:BSSG mixture) on selected immune parameters of volunteers participating in an ultra-marathon in Cape Town, South Africa. Those runners having received active capsules (n=9) showed less neutrophilia, lymphopenia and leukocytosis when compared to their counterparts having received placebo capsules (n=8): the placebo treated individuals showed significant increases in their total white blood cell numbers as well as in their neutrophils (p=0.03 and 0.03 respectively). Furthermore, statistically significant increases within lymphocyte subsets were observed in the runners having received the active capsules: CD3+ cells increased (p=0.02) as did CD4+ cells (p=0.03). In parallel, the BSS:BSSG capsules decreased the plasma level of IL6 in the runners using the active capsules (p=0.08) and significantly decreased the cortisol: DHEAs ratio (p=0.03), suggesting that these volunteers had less of an inflammatory response and were less immune suppressed during the post-marathon recovery period. These findings justify further investigations into the use of the phytosterols to prevent the subtle immunosuppression associated with excessive physical stress.
A method ofpreparing homogeneous coated vesicles that eliminates the high sucrose concentrations heretofore used is presented. It is shown that sucrose at high concentrations dissociates the coat from coated vesicles. This reaction can explain the presence of empty coats observed with preparations obtained with high concentrations of sucrose. The protein and membrane lipid components have been analyzed by the intrinsic tryptophan and extrinsic diphenylhexatriene fluorescence, respectively. Analysis of mixtures of coated vesicles and baskets resolved the contributions of the two species to the fluorescence curves.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.