[Comparison of the effectiveness of the HMG-CoA-reductase inhibitors pravastatin versus colestyramine in hypercholesteremia]. / Vergleich der Wirksamkeit des HMG-CoA-Reduktase-Hemmers Pravastatin versus Colestyramin bei Hypercholesterinämie.

Comparison of the Efficacy of Pravastatin and Colestyramine in Hypercholesterolemic Patients. We have treated 55 patients with heterozygous familial hypercholesterolemia, familial combined and polygenic hyperlipoproteinemia in a controlled, randomized study to compare the efficacy of pravastatin (CAS 81093-37-0) and colestyramine (CAS 11041-12-6). After an initial therapy of 8 weeks with 20 mg pravastatin doubling of dose led to an additional decrease of the atherogenic lipid fractions (total cholesterol, TC) 21% versus 25%, LDL-C 26% versus 31%, Apo B 12% versus 17%). After 24 weeks of therapy TC decreased by 28%, LDL-C by 33% and Apo B by 14%. Colestyramine reduced cholesterol in 22 FH patients by mean 18%, LDL-C by mean 28% and Apo B by mean 12%. Both drugs did not differ significantly in their lipid-lowering potential. 16 g colestyramine and 20 mg pravastatin did not change the antiatherogenic lipids and apoproteins (HDL-C, Apo AI and AII), however, with 40 mg pravastatin HDL-C increased significantly by 8.4 to 16.5%. The triglycerides remained constant under colestyramine therapy. Pravastatin lowered serum triglycerides after 16 weeks significantly by 11-16%. Pravastatin had no significant effect on liver and kidney function or muscular metabolism. Under therapy with colestyramine well-known complaints like constipation or flatulence were rarely seen.

Lipids, lipoproteins, apolipoproteins, and other risk factors in Chinese men and women with and without myocardial infarction.

One hundred and fifty-four male and 69 female Chinese patients, aged between 40 and 60 years, who had suffered myocardial infarction (MI) were investigated and compared with 216 men and 219 women who had no history or ECG evidence of coronary heart disease. The male MI patients had significantly raised levels of triglycerides (160 mg/dl), cholesterol (194 mg/dl), VLDL-CH (31 mg/dl), apolipoprotein B (122 mg/dl) and apolipoprotein E (4.7 mg/dl) and a lower apolipoprotein A-I level (126 mg/dl) than the control group (triglycerides 131, cholesterol 179, VLDL-CH 26, apo B 102, apo E4.2, and apo A-I 138 mg/dl). The women with MI also had higher values for the atherogenic lipids than the control group (triglycerides 175 vs. 134 mg/dl, cholesterol 218 vs. 186 mg/dl, LDL-CH 128 vs. 104 mg/dl, VLDL-CH 32 vs. 26 mg/dl, apo B 121 vs. 103 mg/dl and apo E 5.4 vs. 4.3 mg/dl), as well as lowered apolipoprotein A-I (128 vs. 144 mg/dl). The Lp(a) levels (men and women considered together) were significantly higher for the MI patients (34.3 mg/dl vs. 26.2 mg/dl). Anti-atherogenic lipoproteins such as HDL-cholesterol, HDL2-CH, HDL3-CH, phospholipids and apolipoprotein A-II, C-II and C-III showed no difference between the groups.

[Kinetics of lipids and lipoproteins with determination of the recovery rate in the non-steady state following plasma, membrane filtration and dextran sulfate adsorption apheresis in hypercholesterolemia]. / Kinetik der Lipide und Lipoproteine mit Bestimmung der Recovery-Rate im Non Steady State nach Plasma-, Membranfiltrations- und Dextransulfatadsorptionsapherese bei Hypercholesterinämie.

In the work presented here, the efficiency of the following techniques was determined in the period 1983-1988 with respect to the elimination of lipids, lipoproteins and apoproteins in patients with severe hypercholesterolemia; firstly with plasmapheresis, then with membrane-filtration apheresis, and recently with dextran sulfate adsorption apheresis. Furthermore, the loss resulting from removal by apheresis in lipids, lipoproteins and apoproteins was calculated by means of a single-compartment model from pool size and recovery rates. It could be shown that the individual lipids (TG, CH, LDL-CH, P) in the serum as well as in the lipoprotein fractions (VLDL, LDL, HDL) attained new steady states at differing rates, the recovery times for cholesterol being the longest, those of HDL-CH and apoproteins AI, AII, CII, CIII and E the shortest. The absolute replacement in "mg/kg BW/d" was 35 for beta-lipoprotein, 18-22 for total-CH, 13-17 for LDL-CH, 10-12 for apoprotein B; for the antiatherogenic lipids HDL-CH it was 1.72-2.7 mg/kg BW/d; for alpha-lipoprotein 14-23 mg/kg BW/d; for apoprotein HDL 16-19 mg/kg BW/d. The recovery rates for anti- and atherogenic lipids for women with heterozygous FH were higher than for men with FH. Rates of 0.235; 0.510 and 0.183 mg/kg BW/d were measured for CII, CIII and apoprotein E respectively. Dextran sulphate adsorption apheresis (Kaneka) is a more specific method for eliminating LDL-CH and apoprotein B than plasmapheresis and membrane filtration apheresis. The amounts removed in LDL and apo B with the Kaneka technique are largely identical with those taken out by membrane filtration. Larger relative and absolute recovery rates for LDL-CH, total-CH and apo B were found after Kaneka's DSA-apheresis, which may be explained by the more specific removal in LDL-CH and apo B.

Lack of efficacy of dried garlic in patients with hyperlipoproteinemia.

The effects of dried garlic on blood lipids, apolipoproteins and blood coagulation parameters in hyperlipemic patients were studies in two controlled, randomized, double-blind studies. Both studies comprised placebo and therapy periods of 6 weeks each. The doses administered were 3 X 198 mg in Study I (34 patients) and 3 X 450 mg in Study II (51 patients). In both studies, the following serum parameters were measured every 3 weeks: total cholesterol, HDL (high density lipoprotein)- and LDL (low density lipoprotein)-cholesterol, triglycerides and several safety parameters. In addition, apolipoproteins A and B, euglobulin lysis time, fibrin split products, prothrombin time, whole blood coagulation time and fibrinogen levels were determined in the second study only. The results indicated that neither dosage of dried garlic showed any significant effect on any of the parameters measured. It is therefore concluded that, if there is any effect of garlic on the parameters measured, it is not apparent when using a dried preparation in the dosage studied.

Influence of fenofibrate on cellular and subcellular liver structure in hyperlipidemic patients.

The administration of lipid-lowering drugs to rodents, notably those related to clofibrate, rapidly provokes a hepatic response characterized by hepatomegaly, proliferation of smooth endoplasmic reticulum and proliferation of peroxisomes in hepatocytes. In some studies hepatocellular carcinoma has been found in rats or mice exposed for their entire life-span to high dose levels of various fibrates. In the present study liver biopsy samples were obtained from 38 hyperlipidemic patients, 28 of whom had been receiving fenofibrate for between 2 months and approximately 3 years (mean values: males 1.79, females 1.98 years). The remaining 10 patients had never been treated with a lipid-lowering drug. Examination of the biopsy samples by a variety of optical techniques and by electron microscopy failed to reveal any difference between the groups. Peroxisomes were relatively rare, there being no evidence of the clear proliferation seen in rodent studies. Other microscopic features of interest were some variation of nuclear size, mitochondria containing paracrystalline inclusions, dilated endoplasmic reticulum associated with reduced amounts of rough endoplasmic reticulum, and the presence of lipid droplets in the liver cells. However, these variations from normal were in general not much more apparent in samples from the fenofibrate-treated patients than in the untreated group. Light- and electron-microscopic observations did not suggest liver intoxication or a carcinogenic pattern.

Plasma levels of mepindolol in healthy volunteers after oral doses of mepindolol sulphate.

Three groups of healthy volunteers were given oral doses of 5, 10 and 20 mg, respectively, of the beta-receptor blocking drug mepindolol sulphate (Corindolan). Plasma levels of the active compound mepindolol were measured by means of a sensitive and specific HPLC method. Mepindolol was rapidly absorbed reaching maximum concentrations of 21 +/- 7 ng/ml (5 mg), 47 +/- 23 ng/ml (10 mg) and 54 +/- 29 ng/ml (20 mg) 1--3 h after administration. The AUC ratio of the three doses studied was 1 : 1.9 : 3.0 suggesting incomplete absorption in the 20 mg group. The biological half-life of the drug was calculated to be 3--4 h, independently of the dose administered.

[Changes in serum lipid fractions as a side effect of oral retinoids]. / Veränderungen von Serumlipidfraktionen als Nebenwirkung oraler Retinoide.

Alterations in lipid metabolism have been reported under treatment of various skin disorders with oral retinoids. In 36 patients, mostly psoriatics, under administration of aromatic retinoid (Ro 10-9359) in various dosages serum triglycerides and cholesterol were estimated; in 25 out of 36 patients lipid analysis of the lipoproteins and apoproteins A (HDL) and B (LDL) has been performed. To reveal possible similarities of lipid changes under the two main retinoids we determined the same parameter in 10 patients with conglobate acne treated orally with 13-cis-retinoic acid (isotretinoin/Ro 4-3780 1mg/kg b.w.). Under both drugs serum triglyceride and cholesterol levels were significantly increased. In contrast to the results under the aromatic derivate the HDL- and LDL-cholesterol fractions were changed under isotretinoin. The apoprotein A (HDL) was found significantly increased under aromatic retinoid. Elevated serum lipids mostly occurred in patients having risk factors such as preexisting lipid abnormalities, obesity, diabetes mellitus, heavy smoking, alcohol abuse and hyperlipemia-inducing drugs. Patients to be treated with these drugs should be carefully followed up in order to minimize the risk for atheromatosis.

[The detection of apolipoproteins AI and B in the liver of patients with and without hyperlipoproteinemia (author's transl)]. / Zum Nachweis der Apolipoproteine AI und B in der Leber von Patienten mit und ohne Hyperlipoproteinämie.

Liver sections as well as isolated liver cells from 5 patients with a normal liver and normal serum lipids and patients with familial hyperlipoproteinemia type IIa (n=6), type IIb (n=11), type IV (n=13) and type V (n=2) were studied for the presence of apolipoprotein (apo) AI and B by immunofluorescence technique. At the time of liver biopsy the actual serum concentrations of HDL- and LDL-cholesterol and triglycerides were determined. In patients without metabolic disturbances apo AI was detectable in hepatocytes in 2 out of 5 cases. Apo B was not found in the liver of these patients. The non-parenchymal liver cells did not show depositions of apoproteins. In the group of 32 patients with hyperlipoproteinemia 6 cases showed in the liver apo AI and 2 cases apo B. The apoproteins exhibited a granular fluorescence pattern in the cytoplasm of hepatocytes. There was no correlation between the apoproteins in the liver and the degree of fat depositions in hepatocytes or the concentrations of serum lipids. The results indicate that the fat droplets in hepatocytes of patients with hyperlipoproteinemia represent lipid particles free of apoproteins. The lack of apoproteins in the liver with elevation of lipids in serum can be explained with a disturbed hepatic clearance function for lipoproteins.