Showing papers by "Omar Serri published in 1997"

Gliclazide decreases cell-mediated low-density lipoprotein (LDL) oxidation and reduces monocyte adhesion to endothelial cells induced by oxidatively modified LDL.

Abstract: Low-density lipoprotein (LDL) oxidation has been suggested to play a key role in the pathogenesis of atherosclerosis, a major complication of diabetes mellitus. Gliclazide, a second-generation sulfonylurea, is widely used in the treatment of type II diabetes mellitus. Recently, a free-radical-scavenging activity of gliclazide has been reported. In the present study, we examined the effects of gliclazide on cell-mediated LDL oxidation and monocyte adhesion to endothelial cells induced by oxidatively modified LDL. Incubation of human monocytes and bovine aortic endothelial cells (BAE cells) with increasing concentrations of gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) resulted in a dose-dependent diminution of cell-mediated LDL oxidation as assayed by measurement of thiobarbituric acid (TBA)-reactive substances (TBARS). In addition, exposure of BAE cells to gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) induced a dose-dependent diminution of the oxidized LDL-induced monocyte adhesion to BAE cells as measured by the myeloperoxidase (MPO) assay. The effects of glyburide, another second-generation sulfonylurea, were also tested on cell-mediated oxidation of LDL and LDL-induced monocyte adhesion to the endothelium. No significant effect of this drug was observed on these two processes. These results therefore demonstrate that gliclazide is effective in vitro in reducing both cell-mediated LDL oxidation and monocyte adhesion to the endothelium. These findings suggest a potential beneficial effect of gliclazide in the prevention of atherosclerosis in diabetic patients.

Hypothalamic-pituitary-adrenal axis in abdominal obesity: effects of dexfenfluramine†

Abstract: OBJECTIVE Hyperactivity of the HPA axis is a possible mechanism underlying abdominal obesity. We aimed to evaluate in premenopausal women with abdominal obesity, (i) the hypothalamic-pituitary-adrenal (HPA) axis responses to direct pituitary stimulation with corticotrophin releasing hormone (CRH) and to opioid blockade with naloxone, and (ii) the interaction between short-term serotoninergic activation with dexfenfluramine (dF), a serotonin-release agonist, and these responses. DESIGN AND SUBJECTS Eight obese women (mean BMI, 35 kg/m2) with waist to hip ratio (WHR) > 0.85 were tested with CRH (1 μg/kg i.v.) and naloxone (125 μg/kg i.v.) before and at the end of two treatment periods with dF (15 mg twice daily for 7 days) and placebo (washout 7 days) in a cross-over design. Eight normal weight control women were tested with CRH and naloxone. RESULTS Prior to treatment, ACTH and cortisol responses to naloxone (areas under the curve) were significantly higher in obese women then in control women (P=0.027 and P=0.035 respectively). dF treatment resulted in significant (P<0.05) reduction of ACTH and cortisol increments. In contrast, ACTH and cortisol responses to CRH were not significantly different in obese and control subjects and were unaffected by dF treatment. CONCLUSION We conclude that women with abdominal obesity have hyperreactivity of the HPA axis to opiod blockage and that dexfenfluramine treatment reduces this hyperreactivity.