Impaired Induction of the Apoptosis-Protective Protein Bcl-xL in Activated PBMC from Asymptomatic HIV-Infected Individuals

Progression to AIDS in asymptomatic HIV-infected individuals is characterized by a gradual but progressive loss of CD4⁺ T cells. While the mechanisms underlying this decline are currently unknown, recent evidence suggests that these cells are abnormally sensitive to apoptosis in response to activation signals. Recent work has implicated downregulation of Bcl-2 with the increased spontaneous apoptosis in lymphocytes from HIV-infected patients. We have evaluated the roles of the apoptosis-protective proteins Bcl-2 and Bcl-x in stimulated PBMC from asymptomatic HIV-infected and HIV-uninfected individuals. We found that Bcl-2 was constitutively expressed in PBMC from both HIV-infected and uninfected samples. However, Bcl-x induction was delayed and responses were decreased in stimulated HIV-infected samples. Additionally, single-cell intracellular staining of Bcl-x revealed a significant inverse correlation between PWM-induced Bcl-x expression and apoptosis (r = –0.695, P = 0.005). This was confirmed at the single-cell level in direct experiments when stimulated cells were sorted based on Bcl-x induction and then measured for apoptosis. Furthermore, low Bcl-x expression was not due to reduced lymphocyte activation following PWM stimulation. Our data indicate that the induction of Bcl-x is markedly impaired in asymptomatic HIV-infected patients and that stimuli which induce inadequate expression of Bcl-x are associated with increased levels of apoptosis in these cells.     

Divergent effects of classical inducers on rat plasma and microsomal fraction paraoxonase and arylesterase

The effects of three different enzyme-inducing agents (phenobarbital, 3-methylcholanthrene and rifampicin) on plasma and liver microsomal fraction paraoxonase and arylesterase were studied in rats. Although phenobarbital and 3-methylcholanthrene each increased the esterase activities in microsomal fraction, only 3-methylcholanthrene was capable to increase them in plasma. By contrast, the administration of rifampicin decreased both enzyme activities in liver and plasma. The results indicate that at least there exists two esterase activities in rat liver microsomes which hydrolyse both paraoxon and phenylacetate, but only one of them is released into the blood.     

Who is Hispanic? Definitions and their consequences.

What is the appropriate method for classifying Spanish-speaking-origin inhabitants of the United States? This paper presents relevant data from the first wave of a longitudinal study of adolescents in the greater Miami area. As expected, the broadest definition--"up to third generation" Hispanic--identified the largest proportion of the sample as Hispanic, whereas parent self-report placed the smallest proportion into the Hispanic category. When policymakers are concerned about enumerating the entire Hispanic population, a definition broader than self-identification should be used; in estimating prevalence rates, however, the use of self-identification may be adequate.     

Efficacy of topical gentamicin treatment after 193-nm photorefractive keratectomy in an experimental Pseudomonas keratitis model

Background: The treatment of Pseudomonas keratitis has many limitations, and further investigation to identify more effective approaches is required. We therefore studied the possible contribution of the debridement effect of 193-nm excimer laser on Pseudomonas keratitis in rabbit eyes. Methods: Pseudomonas keratitis was induced in 30 rabbit eyes by inflicting controlled central corneal scratches and applying a drop of Pseudomonas aeruginosa suspension. After 24 h, one cornea of each animal was photo-ablated (excimer laser: fluency 90 mJ/cm², 10 Hz, 213 pulses), yielding 50 m of tissue ablation, while the follow cornea served as control. Five groups of six animals each were formed and received: a subconjunctival injection of gentamicin 20, mg (group 1), topical 14 mg/ml gentamicin hourly (group 2) or every 2.5 h (group 3), or NaCl 0.9% hourly (group 4) for 8 h. In group 5, animals were sacrificed without additional treatment. After 9 h corneas were excised, homogenized, serially diluted, and plated on agar blood plates. The numbers of colony-forming units (CFU) per cornea were statistically evaluated (Mann-Whitney test). Results: In control eyes, a greater decrease of CFU was observed in group 2 than in group 3 (P = 0.03). In laser-ablated eyes, there was no difference in CFU between groups 2 and 3. Comparison of the excimer-treated and control eyes revealed a greater number of bacteria (CFU) in controls only in group 3 (P=0.02). Conclusion: Our study suggests that controlled debridement of cornea with excimer laser may improve the effect of topical antibiotics.Presented at ECORA First Annual Meeting, 5 October 1993, Bonn, Germany     

Olive oil- and fish oil-enriched diets modify plasma lipids and susceptibility of LDL to oxidative modification in free-living male patients with peripheral vascular disease: the Spanish Nutrition Study

The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease (Fontaine stage II) were given specific lipid supplements. Designed as a longitudinal intervention study, patients were provided with olive oil for 3 months, followed by a 3 month wash-out period, then supplemented with a combination of fish oil and olive oil for the final 3 months. Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined. Furthermore, lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake. In addition, thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group. A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months. Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients. The intake of the fish-oil supplement resulted in significantly increased plasma levels of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) in comparison with baseline concentrations, olive-oil and control groups. Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period, control and reference groups. The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group, and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil. In conclusion, consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation.