Influence of apolipoprotein E genotype on fat-soluble plasma antioxidants in Spanish children

BACKGROUND: Apolipoprotein (apo) E is a major determinant of plasma lipid concentrations, which in turn influence the plasma concentrations of various fat-soluble vitamins. OBJECTIVE: We aimed to analyze the effect of APOE genotype on fat-soluble antioxidant concentrations in children. DESIGN: A total of 926 healthy boys and girls aged 6-8 y were selected from 4 cities in Spain. APOE genotyping was carried out, and plasma concentrations of lipids, apolipoproteins, and lipid-soluble antioxidants were measured. RESULTS: Plasma lipid concentrations were strongly influenced by APOE genotype. The mean plasma concentration of alpha-tocopherol was 21.3 micromol/L, which is one of the highest values ever reported for a population of children. Although plasma concentrations of alpha-tocopherol, gamma-tocopherol, lycopene, and alpha-carotene varied significantly between subjects with different APOE genotypes, most of these differences disappeared after adjustment for lipoprotein-related covariates. Nevertheless, tocopherol concentrations remained elevated in individuals with the E2/2 genotype. Multivariate regression analysis showed interactions of APOE genotype with triacylglycerol and apo B in determining alpha-tocopherol concentrations. When subjects were stratified according to major apo E groups, apo B appeared to be the most important predictor of alpha-tocopherol concentrations in all groups, whereas triacylglycerol was identified only in carriers of the E2 allele. CONCLUSIONS: The association between APOE genotype and lipophilic antioxidant concentrations is dependent mainly on the effect of the polymorphism on lipoprotein concentrations. However, triacylglycerol plays a role in determining the variability of alpha-tocopherol concentrations in E2 carriers only. This suggests that the alpha-tocopherol content in each lipoprotein class varies according to APOE genotype.     

Marginal structural models for estimating the effect of highly active antiretroviral therapy initiation on CD4 cell count

The effect of highly active antiretroviral therapy (HAART) on the evolution of CD4-positive T-lymphocyte (CD4 cell) count among human immunodeficiency virus (HIV)-positive participants was estimated using inverse probability-of-treatment-and-censoring (IPTC)-weighted estimation of a marginal structural model. Of 1,763 eligible participants from two US cohort studies followed between 1996 and 2002, 60 percent initiated HAART. The IPTC-weighted estimate of the difference in mean CD4 cell count at 1 year among participants continuously treated versus those never treated was 71 cells/mm3 (95% confidence interval: 47.5, 94.6), which agrees with the reported results of randomized experiments. The corresponding estimate from a standard generalized estimating equations regression model that included baseline and most recent CD4 cell count and HIV type 1 RNA viral load as regressors was 26 cells/mm3 (95% confidence interval: 17.7, 34.3). These results indicate that nonrandomized studies of HIV treatment need to be analyzed with methods (e.g., IPTC-weighted estimation) that, in contrast to standard methods, appropriately adjust for time-varying covariates that are simultaneously confounders and intermediate variables. The 1-year estimate of 71 cells/mm3 was followed by an estimated continued increase of 29 cells/mm3 per year (estimated effect at 6 years: 216 cells/mm3), providing evidence that the large short-term effect found in randomized experiments persists and continues to improve over 6 years.     

Redox activity of airborne particulate matter at different sites in the Los Angeles Basin

Epidemiologic studies have shown associations between ambient particulate matter (PM) and adverse health outcomes including increased mortality, emergency room visits, and time lost from school and work. The mechanisms of PM-related health effects are still incompletely understood, but a hypothesis under investigation is that many of the adverse health effects may derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. While the adverse effects from PM have historically been associated with the airborne concentration of PM and more recently fine-particle PM, we considered it relevant to develop an assay to quantitatively measure the ability of PM to catalyze ROS generation as the initial step in the induction of oxidative stress. This ability of PM could then be related to different sources, chemical composition, and physical and spatial/temporal characteristics in the ambient environment. The measurement of ROS-forming ability in relation to sources and other factors will have potential relevance to control of redox-active PM. If oxidative stress represents a relevant mechanism of toxicity from PM, the measurement of redox activity represents a first step in the elucidation of the subsequent downstream processes. We have developed an assay for PM redox activity, utilizing the reduction of oxygen by dithiothreitol which serves as an electron source. We have found that PM will catalyze the reduction of oxygen and have examined the distribution and chemical characteristics of the redox activity of PM fractions collected in different sites in the Los Angeles Basin. Samples of concentrated coarse, fine, and ultrafine PM, obtained with aerosol concentrators, were studied with regard to their chemical properties and redox activity. Redox activity was highest in the ultrafine fraction, in agreement with results indicating ultrafines were the most potent toward inducing that heme oxygenase expression and depleting intracellular glutathione, which has relevance to induction of oxidative stress. Comparison of the redox activity with chemical composition showed a reasonable correlation of redox activity with elemental carbon (r(2)=0.79), organic carbon (r(2)=0.53), and with benzo[ghi]perylene (r(2)=0.82), consistent with species typically found in mobile emission sources.     

"Right-Angled" Stapled Latero-lateral Duodenojejunal Anastomosis in the Duodenal Switch

A simplified technique to perform the duodeno-enteral anastomosis in the duodenal switch is presented. A linear stapled duodeno-jejunal side-to-side anastomosis is performed. The technique is easy and rapid to perform, avoids passing an anvil through the mouth of the patient and is safe for the patient, with satisfactory short-term results.