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Objectives: Severe hyperlipoproteinaemia (increased LDL, light density lipoproteins, and VLDL, very light density lipoproteins) in patients with high body mass index (BMI) is positively associated with the occurrence of coronary heart disease. This condition requires combined drug regimen because high lipid levels frequently remain after monotherapy and diet. The aim of our study was to investigate the efficacy of combined therapy utilizing the following association: HMG CoA reductase inhibitors plus fibrates., Methods: We examined 50 patients, males, affected by obesity (BMI > 30) and hyperlipoproteinaemia (phenotype IIB, Fredrickson). The first group, 20 obese subjects with severe dislipidaemia, and the second group, 10 mildly hyperlipidaemic obese patients received bezafibrate 600 mg/d and pravastatin 40 mg/d. The other subjects, all obese and highly dyslipidaemic patients, received monotherapy: 10 patients, bezafibrate 600 mg/d and the rest pravastatin 40 mg/d. Weekly, for ten weeks, we evaluated the following serum parameters: total cholesterol and HDL-cholesterol, triglycerides and apolipoprotein A1 and B., Results: We observed no significant changes in HDL-cholesterol and apolipoprotein levels, while an important reduction in total cholesterol and triglycerides, induced by combined therapy, was particularly evident in those patients with the higher lipidic alterations, compared with the additive effects of single drugs., Conclusions: The data show that this combined treatment could be proposed for these subjects to reduce hyperlipidaemia and the risk of premature atherosclerosis.

We studied 56 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg/day) or pravastatin (20 mg/day) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL cholesterol, triglycerides, and apolipoprotein A-1 and B. At the same time intervals we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity, and the fluidity of erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin and pravastatin treatments: (1) an initial increase in cholesterol concentration and in cholesterol/phospholipid molar ratio, with a significant decrease only after 4 months; (2) a similar behavior of membrane fluidity, with an initial decrease and an elevation after 4 months; (3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin and pravastatin not only inhibit the hepatic synthesis of cholesterol, but also modify the cholesterol exchange between plasma and the erythrocyte membrane.

We studied 10 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg die) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL-cholesterol, triglycerides, apolipoprotein A1 and B. At the same time intervals, we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity and the fluidity of the erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin treatment: 1) an initial increase in the cholesterol concentration and in the cholesterol/phospholipid ratio, with a significant decrease only after 4 months; 2) a similar behaviour of membrane fluidity, with an initial decrease and an elevation after 4 months; 3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin not only inhibits the hepatic synthesis of cholesterol, but also modifies the cholesterol exchange between plasma and the erythrocyte membrane.

The aim of the present work was to evaluate the action of cyclosporin (CsA) both in vivo and in vitro on the active sodium transport across the erythrocyte membrane of rheumatoid arthritis (RA) patients. The in vivo study was performed on 20 patients affected by refractory RA and treated with CsA (5 mg/kg/die) or with azathioprine (2 mg/kg/die) before and after 7 days' therapy. The control group was formed of 25 healthy subjects. RA patients before treatment showed increased intra-erythrocyte Na+ concentration and decreased Na+, K+ ATPase activity in comparison with normal subjects. A rise in the activity of the sodium pump and a reduction in the intra-erythrocyte Na+ concentration were observed after cyclosporin treatment, but not after azathioprine. The in vitro study was performed on intact RBCs and on erythrocyte membranes from 15 healthy subjects and from 12 patients affected by classical RA, in the presence or absence of CsA (0.5-1-2 micrograms/ml). CsA (0.5 micrograms/ml) increased the Na+, K+ ATPase activity in intact RBCs and in erythrocyte membranes from both groups of subjects. Intracellular Na+ was decreased only in erythrocytes from RA patients after addition of 0.5 micrograms/ml CsA. A direct action of CsA on the membrane hydrophobic environment of the Na+, K+ ATPase is hypothesized on the basis of the present results.