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S Badiou

Publications and source records attributed to S Badiou.

6 recordsLinked to original sources

Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed during highly active antiretroviral therapy (HAART) including protease inhibitor. Apolipoprotein (apo) CIII could be involved in this HTG by inhibition of triglyceride (TG) hydrolysis, which leads to the occurrence of small dense low density lipoprotein (sdLDL), a recognized cardiovascular risk factor. OBJECTIVE: To characterize the influence of lopinavir/ritonavir-containing regimen on lipoprotein profile. DESIGN AND METHODS: 24 antiretroviral-experienced HIV infected adults (including 14 patients in therapeutic interruption of at least 2 months) and 14 HIV uninfected healthy controls were enrolled. Serum lipid parameters (total cholesterol (TC), HDL-C, LDL-C, TG, apoA1, apoB, apoCIII), lipoprotein composition and LDL size were determined before initiation of lopinavir/ritonavir-containing regimen, and at 1 and 3 months thereafter. RESULTS: At baseline an atherogenic lipid profile was evidenced, characterized by a moderate HTG associated to a smaller mean LDL size (25.16 vs 25.93 nm, P<0.001), an enrichment in TG of LDL (11.4 vs 6.0%, P<0.01) and a high prevalence of sdLDL (75 vs 7%, P<0.01) when compared to controls. After 1 month of lopinavir/ritonavir-containing regimen, a significant reduction of LDL size (24.81 vs 25.16 nm, P<0.05) and a significant increase in cholesterol total (5.53 vs 4.49 mmol/l, P<0.001), in TG (4.20 vs 2.01 mmol/l, P<0.001), in apoA1 (1.28 vs 1.11 g/l, P<0.001), in apoB (1.08 vs 0.94 g/l, P<0.01), in apoCIII (0.16 vs 0.10 g/l, P<0.001), in TG percentage in LDL (14.4 vs 11.4, P<0.05) and in TG percentage in HDL (10.2 vs 8.3, P<0.05) were observed. CONCLUSIONS: Advanced stage of HIV infection is associated with an atherogenic lipid profile including a high prevalence of sdLDL. Lopinavir/ritonavir-containing regimen accentuates the reduction of LDL size. Since fibrates decrease TG and increase LDL size, they appear as a logical option to manage HAART-induced HTG.

Adult↗

Discrepancies between apolipoprotein E phenotyping and genotyping in the elderly.

We estimated the frequencies of phenotype (isoelectric focusing; IEF) vs. genotype (PCR/Hhal) discordance in a sample of an aged population (> 65 years). Both phenotype and genotype techniques have been used in the study of apolipoprotein E (apoE) polymorphism in 125 elderly subjects. The discordance between phenotype and genotype was unresolved in 11 (8.8%) of the 125 unrelated subjects studied. We observed a significant association between the presence of the E4 allele and both Alzheimer's disease (chi2 = 13, p < 0.001) and increased cholesterol concentration (Mann Whitney, p < 0.03). These relationships were not affected by the techniques used. Our results indicate that transcriptional modulation and post-transductional modifications in normal ageing and in aged-related diseases may explain in part discrepancies between gene analysis and protein characterisation.

Aged↗

Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation.

Oxidative stress can produce profound alterations to cellular membrane lipids, impairing cell metabolism and viability. This phenomenon, previously observed in haemodialysis patients, has been proposed as a significant factor in regard to haemodialysis-related shortened red blood cells (RBC) survival. In the present study, several parameters associated with oxidative stress were evaluated in a group of haemodialysis patients either receiving erythropoietin therapy (n = 12, mean erythropoietin dose 88 +/- 24 U/kg/week) or not receiving such therapy (n = 30), and in 38 controls. Malonyldialdehyde (MDA, nmol/ml), an end-product of lipid peroxidation, and RBC antioxidant systems were measured, including RBC alpha-tocopherol (RBC vitamin E, mg/l), RBC glutathione (GSH, nmol/mgHb), and RBC superoxide dismutase activity (SOD, U/mgHb). Plasma vitamin E concentrations were also evaluated. Finally, oral vitamin E supplementation (500 mg daily), an exogenous antioxidant, was administered for 6 months to seven patients from the dialysis group receiving erythropoietin while oxidative parameters were repeatedly evaluated and erythropoietin requirements monitored, in order to appreciate the therapeutic relevance of an antioxidant supplementation. An elevation of serum MDA was observed in all haemodialysis patients and a significant decrease in RBC vitamin E, despite normal serum vitamin E levels. Furthermore, the reduction in RBC vitamin E was more important in patients treated with erythropoietin. Vitamin E supplementation resulted in a significant increase in RBC vitamin E (from 0.3 +/- 0.1 to 1.2 +/- 0.2 mg/l of pellet) and a reduction in erythropoietin dose (from 93 +/- 24 to 74 +/- 26 U/kg/week) while maintaining stable haemoglobin concentrations. These results suggest that the oxidative stress could be one of the resistance factors to erythropoietin response in haemodialysis and that vitamin E supplementation could have a sparing effect on erythropoietin dosage requirement.

Adult↗

[Oxidative stress and chronic renal insufficiency: what can be a prophylactic approach?].

Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.

Antioxidants↗

The relationship between apolipoprotein E4 and lipid metabolism is impaired in Alzheimer's disease.

BACKGROUND: Human apolipoprotein (Apo) E4 (ApoE4) is an important determinant of lipid metabolism and cell-to-cell cholesterol transport. It is also a major genetic risk factor for both vascular disease and familial and sporadic late-onset Alzheimer's disease (AD). Since vascular pathology could dramatically reduce neuronal reserve capacity, a biological chain of events between ApoE4, hypercholesterolemia and AD has been postulated. The aim of the present study is to explore the relationship between lipid metabolism and ApoE isoforms in a large series of elderly subjects in relation to the presence or absence of AD. METHODS: Of 332 referrals to a neurology clinic specializing in memory disorders, 146 were given a diagnosis of AD (age, mean +/- SD 76 +/- 13.1 years, 64.4% women) according to DSM-IIIR criteria. One hundred and seventy-six subjects were included as controls (age 80 +/- 5.6 years, 58% women). The ApoE phenotype was determined by the isoelectrofocalization method, cholesterol, triglycerides, phospholipids, ApoA and ApoB were determined by routine chemistry. FINDINGS: A significant association was observed between the E4 allele and AD (chi2 = 13, p < 0.001) only below age 80. In the control group, cholesterol levels were found to be significantly higher in men but not in women with an E4 allele (6.35 +/- 1.3 mmol/l) as opposed to those without (5.8 +/- 1.2 mmol/l). ApoB levels were also found to be higher in the presence of ApoE4, with no gender effect. Within the AD group no significant relationship was found between ApoE4 and cholesterol levels (mean 6.05 +/- 0.9 mmol/l in E4-AD subjects versus 5.8 +/- 1.21 mmol/l in non-E4-AD subjects). Similar observations were made in relation to triglycerides and phospholipids. INTERPRETATION: Our results demonstrate the disappearance of the ApoE4-raising effect on serum cholesterol, triglyceride and phospholipid levels in AD suggesting a more complex relationship between AD and lipid metabolism than has previously been supposed. This lipid abnormality may further contribute to the progression of AD.

Aged↗