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Biomedical subjects

P Avogaro

Publications and source records attributed to P Avogaro.

At least 19 recordsLinked to original sources

Relationship of triglycerides and HDL cholesterol in hypertriglyceridemia.

Hypoalphalipoproteinemia (plasma HDL-cholesterol concentration at or below 35 mg/dl as reported in the National Cholesterol Education Program Guidelines) is a well known risk factor for premature coronary artery disease (CAD). In hypertriglyceridemic patients, hypoalphalipoproteinemia is commonly believed to be linked to the derangement of triglyceride metabolism. In this study the occurrence of primary hypoalphalipoproteinemia has been investigated in a cohort of hypertriglyceridemic patients whose plasma triglyceride concentration had been normalized either through diet or diet plus drug treatment. Following the initial visit, 115 hypertriglyceridemic patients received dietary advice and returned for the second visit four months later. Diet reduced plasma triglycerides in all the patients. HDL-cholesterol increased in 76 patients whereas in the others, it remained unchanged or even decreased. Plasma triglyceride concentration was normalized (less than 200 mg/dl) in 54 patients by diet alone, but among these 11 remained hypoalphalipoproteinemics. Patients in whom, despite dietary restrictions, triglycerides exceeded 200 mg/dl, were considered for pharmacological treatment with Bezafibrate (300 mg t.i.d.) for 4 months. Thirty-nine concluded the study. Treatment significantly decreased plasma triglyceride concentration in all the subjects. Normalization was achieved in 32 patients. Four of them, however, remained hypoalphalipoproteinemic. These results indicate that a subgroup of hypertriglyceridemic patients remained hypoalphalipoproteinemic even after normalization of triglyceride levels. In these patients hypertriglyceridemia and hypoalphalipoproteinemia may occur as expression of two distinct primary metabolic defects.

Adult

Some questions concerning a small, more electronegative LDL circulating in human plasma.

Atherosclerosis and its complications are prevalent worldwide with a high prevalence in western societies. The disease may sometimes be explained by a defect of low density lipoprotein (LDL) specific receptors. However, the prevalence of receptor defect is rather rare and a large body of evidence supports the possibility that an alternative pathway, the so-called "scavenger pathway", constitutes the gate through which cholesterol enters into the parietal wall and gives origin to the "foam cell". Experimental work has clearly demonstrated that LDL may be modified under the action of chemical and biological offenders, all of which make the LDL an "alien". Some papers suggest that the modifications of LDL may occur also "in vivo" in the microenvironment of the vascular vall. In 1988 we were able to record two LDL subfractions in human plasma; the more electronegative minor subfraction shares many of the peculiar traits of LDLs modified "in vitro". The present article stresses all the points which support the hypothesis that the small more electronegative LDL circulating modified LDL, may represent a certain amount of possibly oxidative in origin.

Animals

Characterization of a more electronegatively charged LDL subfraction by ion exchange HPLC.

Low density lipoproteins (LDL), collected from 32 normal male subjects (aged 30-60), were subfractionated by high resolution ion exchange chromatography (IE-HPLC). By this procedure two LDL subfractions were eluted. The first corresponds to normal LDL (nLDL); while the second one corresponds to a more electronegative subfraction, called LDL-. The mean percentage contribution of LDL- to native plasma LDL was of 3.9% (range 0.5-9.8%). The percentage concentration of LDL- in total native LDL did not correlate with plasma total cholesterol, triglycerides, and LDL cholesterol, whereas a significant negative correlation with high density lipoprotein cholesterol was found (r = -.38; p less than .05). LDL- was negatively correlated with LDL phospholipids (r = -.59; p less than .001), and with the LDL vitamin E content (r = -.63; p less than .001), and positively correlated with LDL proteins (r = -.35; p less than .05) and the content of thiobarbituric acid reactive substances (TBARS) in total LDL (r = .43; p less than .05). The TBARS molar content of LDL- was three times higher than in nLDL, with a mean concentration in LDL- of 7.3 mol/mol lipoprotein. By preparative IE-HPLC significant differences of the LDL- chemical composition were observed. The percentage content of cholesterol esters and of phospholipids was decreased, whereas proteins and free cholesterol were increased. Analysis by sodium dodecyl sulphate polyacrylamide gel electrophoresis revealed that besides apolipoprotein B-100 there was evidence of peptides with a higher molecular weight in LDL-.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I.

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.

Adult

A cross-over controlled study on beclobrate versus bezafibrate in the treatment of type IIb hyperlipoproteinaemia.

The effects of the new fibric acid derivative beclobrate (100 mg) on some plasma lipidic and apoproteic parameters in 20 patients with type IIb hyperlipoproteinaemia were matched in a randomized cross-over study to a sustained release formulation of bezafibrate (400 mg). Inclusion criteria were: total cholesterol (TC) plasma levels greater than 260 mg/dl and triglyceride (TG) levels greater than 200 mg/dl, after a 2-month period of isocaloric diet. The drugs were administered once a day for 8 weeks, and then crossed-over after 8 weeks of wash-out for another 8 week period of treatment. Both drugs were significantly effective in reducing TC and TG, and in increasing HDL-C plasma levels, but only beclobrate significantly decreased Apo B and LDL-C whereas bezafibrate seemed to be more active in increasing HDL-C levels. The electrophoretic pattern of LP in patients treated with beclobrate revealed a decrease of VLDL, a normalization of the LDL fraction and an increase of HDL. The tolerability was generally good.

Adult

Plasma lipid lowering activity of acipimox in patients with type II and type IV hyperlipoproteinemia. Results of a multicenter trial.

A multicenter study was carried out in 130 out-patients to assess the plasma lipid lowering activity of acipimox in type IIa, IIb and IV hyperlipoproteinemia. The study consisted of two periods, an 8-week randomized, double-blind comparison of active drug versus placebo and a 16-week open follow-up with acipimox (400 mg and 250 mg t.i.d., respectively, in type II and IV patients). During the double-blind phase acipimox, compared to placebo, showed a highly significant triglyceride lowering effect in type IV patients (-43% vs. +4%, P less than 0.01), while reducing plasma cholesterol significantly in type II patients (-7% vs. -3%, P less than 0.05). Further reductions in plasma lipids were obtained in both types of hyperlipoproteinemia after the 16-week follow-up. In type II patients, total cholesterol fell by 9% in the former acipimox group and 17% in the former placebo group, whereas a 34% reduction in triglycerides was found in type IV patients previously treated with placebo. Treatment had to be discontinued in 4 patients during the double-blind phase and in 5 patients during follow-up, because of adverse events such as skin reactions and gastric disturbances. Statistical analysis of hematological and biochemical variables expressing safety did not show any significant change during treatment.

Adult

Physiologic variables affecting thromboxane B2 production in human whole blood.

Thrombin-induced thromboxane (TX) A2 production in whole blood, as reflected by serum TXB2 measurements, has proven to be a simple and reproducible capacity-related index of platelet TXA2 production ex vivo. In the present study we have determined the influence of a number of physiologic variables on serum TXB2 measurements performed by radioimmunoassay in a group of 177 subjects undergoing evaluation for atherosclerosis risk factors. Serum TXB2 averaged 300 +/- 108 ng/ml in the whole group, with a normal distribution. No statistically significant correlation was found between serum TXB2 and the continuous variables examined (age, BMI, blood pressure, cigarettes, serum cholesterol, triglyceride, glucose and wine consumption) except for the number of platelets. Platelet TXB2 production did not differ between men and women (296 +/- 119 vs 302 +/- 100 ng/ml). We conclude that, within the limits of the examined variables, serum TXB2 is an easily measurable and highly reproducible capacity index primarily related to platelet cyclooxygenase and TX-synthase activity, which can be used for monitoring drug- or disease-induced changes of these enzyme activities.

Adolescent

Effects of pantethine on in-vitro peroxidation of low density lipoproteins.

The effects of pantethine on LDL peroxidation in vitro are reported. LDL isolation by density gradient ultracentrifugation from 12 normal subjects were dialyzed 48 h under conditions allowing oxidation. The LDL peroxides were assayed for the presence of malondialdehyde (MDA) on the lipoprotein. The effect of peroxidation on the LDL protein moiety (apo B) was studied by SDS-gel electrophoresis. The presence in the dialysis buffer of 1 mM reduced glutathione or of an equimolar concentration of pantethine markedly inhibited the MDA formation in LDL. Less effective were 0.5 and 2 mM pantethine, while 10 mM pantethine did not prevent the LDL peroxidation. Both glutathione and pantethine (1 or 2 mM) preserved the original LDL electrophoretic mobility. The electronegative charge of LDL was correlated to the MDA production during the dialysis procedures. Freshly prepared LDL showed a single apo B band by SDS-gel electrophoresis (apo B-100). Following peroxidation 2 or 3 bands with higher molecular weight appeared. Both glutathione and pantethine (1 or 2 mM) strongly inhibited the appearance of higher molecular weight peptides. In appropriate concentrations therefore pantethine inhibits the LDL peroxidation in vitro, thus preserving the molecular integrity of apo B.

Antioxidants

Total plasma apo E and high density lipoprotein apo E in survivors of myocardial infarction.

Total apo E in plasma and the amount of apo E-HDL were measured in 40 normolipidemic male survivors of myocardial infarction and in 40 controls. LDL-C, Lp(a) and apo B were significantly higher and HDL-C and apo A-I were significantly lower in survivors than in controls. Total plasma apo E did not differ between patients and controls, but HDL-E and the ratio HDL-E/apo A-I were lower in survivors. The data support the view that atherosclerotic patients are often characterized by abnormalities in the concentration and distribution of lipoproteins as well as of apoproteins, even in the presence of normal total plasma lipids.

Adult

Effect of the compound "chloridarol" on plasma lipids and apolipoprotein levels.

Eighteen subjects, nine affected with type IIB and nine with type IV hyperlipemia, following since months a "prudent diet" received 750 mg/day of the compound/(2-benzofuryl) (p-chlorophenyl) carbinol/ for two 2-month periods. The results obtained were compared with those obtained following only dietary treatment. The pharmacological treatment significantly reduced the plasma levels of triglycerides and apoB.

Apolipoproteins