Effect of bezafibrate on lipids, lipoproteins, apolipoproteins and platelet aggregation in hypertriglyceridemic patients.

Twenty-seven hypertriglyceridemic patients were recruited for an open placebo-controlled, 7-month study of the effect of bezafibrate (CAS 41859-67-0, Bezalip, Cedur) on lipids, lipoproteins, apolipoproteins, and platelet aggregation. Patients received 3 placebo tablets a day for a stabilization period of 2 months, followed by a treatment period of 5 months during which one group received bezafibrate 200 mg 3 times a day, and a control group continued to receive placebo. Values measured at the end of the stabilization period were considered as the baseline values. Bezafibrate therapy significantly reduced triglycerides by 43%, and increased HDL-cholesterol by 22%. Apolipoprotein A-1 increased by 14%, and apolipoprotein A-2 by 42%. There was a small reduction of cholesterol (6%), and of apolipoprotein B (11%). A small increase occurred in LDL-cholesterol (2%), suggesting increased catabolism of high VLDL levels which were converted to LDL-cholesterol. Platelet aggregation was measured by the degree of light transmission through a platelet suspension. The improvement of the lipoprotein profile was associated with significant reduction of platelet aggregation in vitro, stimulated by adenosine diphosphate (ADP) at concentrations of 1.15 mumol/ml and 0.75 mumol/ml, and by collagen 2.0 micrograms/ml. Average decrease of platelet reactivity was 45%, 30% and 42%, respectively. The decrease of light transmission with ADP concentration of 2.3 mumol/ml was not significant, suggesting that the aggregatonic effect of the higher ADP concentration overcame the attenuating effect of bezafibrate. The control groups, displayed no significant changes in the blood constituents and platelet functions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tetanus--the forgotten disease].

Tetanus is preventable by proper immunization, which has almost eradicated the disease in countries with a high standard of living. However, the disease is still prevalent even in the most advanced countries and it often appears in the elderly. We emphasize this fact and alert primary care physicians, and duty physicians in emergency rooms, to the possibility of tetanus developing in older patients. Because of their age, they often do not remember when they last had tetanus immunization, nor are records always adequate. We point out the necessity and feasibility of incorporating a special immunization review program for the elderly, including a cost-benefit analysis.

Isosorbide-5-mononitrate and atenolol in the treatment of stable exertional angina.

Fourteen men and six women, 48-68 years old, with stable angina and effort-induced ST-segment depression (ST-D) were treated with isosorbide-5-mononitrate (IS-5-MN) 2 x 40 mg/day and/or atenolol (AT) 100 mg/day in a double-blind randomized sequence during two 6-week periods. The patients performed ergometer tests. AT caused more decrease of heart rate at rest and at comparable work-load than IS-5-MN. Blood pressure at rest was in the normal range. Decrease of blood pressure at rest and at effort was similar with both agents. Combined administration of the two drugs was not more effective than monotherapy with AT or IS-5-MN in lowering heart rate and blood pressure. The average ST-D at comparable effort was for placebo 2.3 mm, for IS-5-MN after 2, 4, and 6 weeks, 3, 6, and 12 h, respectively, after medication, 1.4, 1.0, and 1.3 mm, and for AT 1.2, 1.4, and 1.4 mm, respectively. Administration of the drugs together caused additional highly significant reduction of ST-D (0.3-0.9 mm). The results indicate that IS-5-MN and AT have a similar beneficial effect on effort-induced myocardial ischemia, which is enhanced by their combined administration. The drugs alone and in combination are effective for as long as 12 h after administration of IS-5-MN, and 24 h after administration of AT. Moderate signs of tolerance to IS-5-MN were found after 6 weeks of therapy.

Effects of glibenclamide on serum lipids, lipoproteins, thromboxane, beta-thromboglobulin, and prostacyclin in non-insulin-dependent diabetes mellitus.

A study was conducted to determine the effects of glibenclamide on serum lipoproteins, apolipoproteins, thromboxane (TXA2), prostacyclin (PGI2), and beta-thromboglobulin (B-TGL) in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). In 20 NIDDM patients, aged 34 to 67 (mean, 53.6) years, without clinical signs of atherosclerotic disease and whose blood sugar level was over 140 mg/dl after four weeks of dietary treatment, fasting blood samples were taken before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glibenclamide treatment. Pretrial levels of total serum cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the diabetic patients did not differ from those in nondiabetic controls, whereas high-density lipoprotein cholesterol (HDL-C) levels and the percentage of TC bound to HDL (HDL-C%) were significantly lower in the patients than in controls. After combined dietary and glibenclamide treatment and the normalization of blood sugar, both HDL-C (mg/dl) levels and HDL-C% levels increased significantly. TC, TG, and LDL-C levels decreased. Levels of apolipoproteins A1 and A2 rose and apolipoprotein B fell, but differences were not significant. TXB2 and 6-keto-PGF1-alpha (the inert metabolites of TXA2 and PGI2) and B-TGL were determined by radioimmunoassay. TXB2 and B-TGL levels decreased significantly after glibenclamide administration, indicating attenuation of platelet aggregation. No changes in PGI2 were observed. The results demonstrate the favorable effect of glibenclamide on lipoproteins and apolipoproteins in NIDDM patients, especially in increasing HDL-C levels and HDL-C%, and in attenuating platelet aggregation as indicated by reduction of TXB2 and B-TGL.

Effects of glyburide treatment on serum lipoprotein and apolipoprotein concentrations and ratios in non-insulin-dependent diabetes mellitus.

Lipoproteins and apolipoproteins were studied in 28 patients with newly detected non-insulin-dependent diabetes mellitus (NIDDM) before and after combined dietary and glyburide treatment. The patients, aged 33 to 67 years and without coronary or other atherosclerotic diseases, displayed fasting blood sugar levels of over 140 mg/dl after four weeks of dietary treatment. Overnight fasting blood samples were collected before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glyburide treatment. The pretrial levels of total serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 and A2, and apolipoprotein B were similar to or even lower than those of nondiabetics; however, high-density lipoprotein cholesterol (HDL-C) levels and HDL-C% (the percentage of TC bound to HDL) were significantly lower in the diabetic patients. After combined dietary and glyburide treatment and normalization of blood sugar, apolipoprotein A1 and A2, HDL-C levels, and HDL-C% increased significantly. TC, TG, and LDL-C levels, although not exceeding the normal range, decreased significantly. HDL-C2 and HDL-C3 levels also increased, but the differences did not reach significance. Among the lipid, lipoprotein, and apolipoprotein ratios in the patients, only the ratios HDL-C:LDL-C, apolipoprotein A1:apolipoprotein B, and HDL-C: apolipoprotein B increased significantly as a result of the opposing responses of the protective lipoprotein HDL-C and apolipoprotein A1 and the atherogenic lipoprotein LDL-C and apolipoprotein B. The results demonstrate the favorable effects of combined dietary and sulphonylurea drug treatment on lipoproteins and apolipoproteins in NIDDM patients, thereby reducing coronary and atherosclerotic risks.