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Biomedical subjects

P Weisweiler

Publications and source records attributed to P Weisweiler.

At least 19 recordsLinked to original sources
PubMed1994

Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.

Adult↗
PubMed1989

Low-dose colestipol plus fenofibrate: effects on plasma lipoproteins, lecithin:cholesterol acyltransferase, and postheparin lipases in familial hypercholesterolemia.

Effects on plasma lipoproteins, lecithin:cholesterol acyltransferase (LCAT), and postheparin lipase (LPL and HTGL) activities were studied in 18 patients with familial hypercholesterolemia during 8-week treatment periods with colestipol (15 g/d), fenofibrate (0.25 g/d), and colestipol plus fenofibrate. Lipoprotein lipids and apolipoproteins were determined by standard procedures, LCAT by a self-substrate method, and lipases by nonradioisotopic methods. Colestipol and fenofibrate, each given independently, caused similar percentage decreases in LDL cholesterol and apolipoprotein B: -18.4% and -8.6% v -17.4% and -10.6% Colestipol increased the VLDL cholesterol concentration, whereas fenofibrate reduced this parameter but increased HDL cholesterol and apolipoprotein A-I levels. The combination of both drugs led to a substantial fall in LDL cholesterol (-36.8%) and in apolipoprotein B (-28.3%) and maintained the other effects of fenofibrate on VLDL and HDL. Colestipol, given independently or with fenofibrate, produced an increase of the fractional esterification rate of the LCAT enzyme (+25.3% and +36.2%). Fenofibrate stimulated the postheparin LPL enzyme by +16.1% and +21.7%, respectively. This study indicates the complementarity in effectiveness when both drugs were administered together. The appropriate reduction in LDL was combined with the favorable effects on HDL in familial hypercholesterolemia.

Adolescent↗
PubMed1988

Simvastatin and bezafibrate: effects on serum lipoproteins and lecithin: cholesterol acyltransferase activity in familial hypercholesterolaemia.

Sixteen subjects with familial hypercholesterolaemia were randomly assigned to treatment with simvastatin 20-40 mg/day (an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase) or with bezafibrate 600 mg/day (a clofibrate analogue) for 12 weeks. Both drugs produced significant reductions in serum and LDL cholesterol; mean percentage fall -30.5% and -38.1% (simvastatin) and -17.8% and -20.6% (bezafibrate), respectively. Both drugs also caused a decrease in VLDL cholesterol, while only bezafibrate decreased the serum and VLDL triglyceride levels and increased HDL cholesterol and serum apolipoprotein A-I and A-II levels. Serum apolipoprotein B fell by 33.3% (simvastatin) and 15.7% (bezafibrate). Simvastatin and bezafibrate produced significant increases in the mean fractional esterification rate of LCAT, by +124.1% and +20.6%, respectively. Thus simvastatin was clearly more effective than bezafibrate in lowering LDL by enhancing its turnover, but bezafibrate had specific effects on VLDL and HDL that might be favourable in combined treatment regimens.

Adult↗
PubMed1988

Effects of bezafibrate and gemfibrozil on serum lipoproteins in primary hypercholesterolemia.

29 patients with primary hypercholesterolemia were treated for 8 weeks each with either bezafibrate (200 mg t.i.d.) or gemfibrozil (600 mg b.i.d.) in a randomized cross-over trial. Compared to placebo bezafibrate was significantly more effective on low density lipoprotein (LDL)-cholesterol (-28% versus -18%) and the LDL/high density lipoprotein (HDL) ratio (-34% versus -24%) by exploratory statistics. There was also a trend for a more marked reduction of bezafibrate on total cholesterol and apoliproprotein B as well as more pronounced increase in HDL-cholesterol and apolipoprotein A-I. The triglyceride reduction tended to be more extensive with gemfibrozil. Complicance to both drugs was good. No side-effects were observed. The results are considered important with respect to the potential of bezafibrate in reducing the risk of cardiovascular disease.

Adult↗
PubMed1987

Isolation and quantitation of apolipoproteins A-I and A-II from human high-density lipoproteins by fast-protein liquid chromatography.

Apolipoproteins (Apo) A-I and A-II from human high-density lipoproteins (HDL) were isolated and quantified by fast-protein liquid chromatography using a Superose 12 column (gel filtration) followed by a Mono Q column (anion-exchanger). The separation times were 45 min and 15 min, respectively. Identities of both apolipoproteins were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by double immunodiffusion. Peak areas after Mono Q chromatography increased linearly with concentration for samples from 0.5 to 10 mg of protein with a mean ratio of Apo A-I to Apo A-II of 3.46 +/- 0.71 in normolipoproteinemic subjects. This precise technique is an alternative for preparing and quantifying both HDL apolipoproteins.

Apolipoprotein A-I↗
PubMed1987

Relation of hyperlipidemia in serum and loss of high density lipoproteins in urine in the nephrotic syndrome.

The mechanism leading to hyperlipidemia in the nephrotic syndrome is not fully understood but may be related in part to loss of high density lipoproteins in the urine of patients with nephrosis. To prove this hypothesis, we compared serum lipoprotein profiles with the excretion of high density lipoproteins in urine in 19 nephrotic patients. Serum cholesterol ranged from 19-152 (median value 45) mg/dl in very low density lipoproteins (VLDL), from 130-443 (median 186) mg/dl in low density lipoproteins (LDL) and from 19-64 (median 33) mg/dl in high density lipoproteins (HDL). Hyperlipoproteinemia was found in 17 patients, which was classified as phenotype IIa (Fredrickson) in 2, as phenotype IIb in 9 and as phenotype IV in 6 subjects. Two patients showed normal lipoprotein patterns. VLDL- and LDL-cholesterol were not found in detectable amounts in urine, whereas HDL-cholesterol was measured in low concentrations from 0.1-8.3 mg/24 h in all samples. There was no correlation between serum HDL-cholesterol and urinary HDL-cholesterol, but a positive correlation between serum LDL-cholesterol and urinary HDL-cholesterol (r = +0.54, p less than 0.05). However, the total amount of the daily urinary loss of HDL (less than 1% of total plasma HDL) seems not to be sufficient to explain hyperlipoproteinemia in the nephrotic syndrome.

Adolescent↗
PubMed1987

Serum lipoproteins during antihypertensive therapy with beta blockers and diuretics: a controlled long-term comparative trial.

The influence of hydrochlorothiazide and atenolol on serum lipoproteins was investigated in a randomized, prospective study on 68 men with essential hypertension. Cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDH) cholesterol, triglycerides, and the apolipoproteins AI and B were followed up to 42 months after starting therapy. Following atenolol serum (HDL) cholesterol decreased and serum triglycerides increased significantly (p less than 0.01) from 6 to 42 months. After hydrochlorothiazide serum triglycerides, LDL cholesterol and total cholesterol all increased significantly (p less than 0.01) from 12 to 42 months. The changes were more pronounced under higher doses with beta blockade, but not with diuretics. Thus, both atenolol and hydrochlorothiazide have adverse but different effects on serum lipoproteins after long-term administration. Continuing investigation is necessary to determine whether these side effects decrease the benefit of blood pressure reduction in patients with hypertension.

Adult↗
PubMed1987

Type 1 (insulin-dependent) versus type 2 (non-insulin-dependent) diabetes mellitus: characterization of serum lipoprotein alterations.

Serum lipoprotein lipids and apolipoproteins A-I, B, and E were investigated in Type 1 (insulin-dependent) diabetics, Type 2 (non-insulin-dependent) diabetics, and two control groups, twenty subjects each. Lipoproteins were separated and analysed by common methods, apolipoproteins were measured by endpoint immunonephelometry. Compared with controls, Type 2 diabetics had increased serum apolipoprotein E levels (0.116 +/- 0.020 vs. 0.079 +/- 0.014 g 1-1, P less than 0.01) together with an increased content of cholesteryl ester-enriched very low-density lipoproteins. Furthermore, Type 2 diabetics had higher apolipoprotein B concentrations (1.06 +/- 0.21 vs. 0.85 +/- 0.21 g l-1 P less than 0.01), but lower high-density lipoprotein cholesterol concentrations than the controls. Conversely, Type 1 diabetics had elevated serum apolipoprotein A-I values vs. controls and Type 2 diabetics (1.70 +/- 0.33 vs. 1.49 +/- 0.22 and 1.43 +/- 0.21 g 1-1, P less than 0.01). It is concluded that Type 2 diabetics, like other groups at risk for atherosclerotic diseases, are characterized by an increased concentration of partly catabolized very low-density lipoproteins. Sufficiently insulinized Type 1 diabetics have, on the other hand, an increased number of high-density lipoprotein particles.

Adult↗
PubMed1987

Plasma lipoproteins and lipase and lecithin:cholesterol acyltransferase activities in obese subjects before and after weight reduction.

Plasma lipoprotein concentrations and post-heparin lipoprotein lipase, hepatic triglyceride lipase (HTGL), and lecithin:cholesterol acyltransferase (LCAT) activities were determined in 10 obese women before and after weight loss. In period I, a diet was given to maintain constant weight for 3 weeks. In period II, total calories were restricted to 600 kilocalories/day for 3 weeks. In period III, caloric intake was adjusted to maintain weight at the lower level for 6 weeks. The lower calorie diet decreased plasma very low density, low density, and high density lipoprotein (HDL), cholesterol, and apolipoprotein B and A-I concentrations and molar enzyme activities, while the percent conversion of free to esterified cholesterol by the LCAT enzyme was unchanged. During weight stabilization at a lower state (period III), the mean plasma HDL cholesterol level increased, and lipoprotein lipase and LCAT activities increased to values higher than those in period I. The mean HTGL activity remained reduced. I conclude that successful weight loss improves the possibly atherogenic plasma lipoprotein profile of obese subjects. The increase in HDL cholesterol and cholesterol esterification, possibly explained by lowered HTGL enzyme activity, may increase the capacity of HDL to transport cholesterol from peripheral cells to the liver.

Adult↗
PubMed1986

Separation of apolipoprotein B subfractions by high performance gel permeation chromatography.

Apolipoprotein B has previously been thought to be a homogeneous protein. Recently, it has been shown by SDS polyacrylamide gel electrophoresis that it consists of several species with different molecular weights. The present paper reports the separation of very low density lipoprotein (VLDL) and chylomicron derived apolipoprotein B by high performance gel permeation chromatography in SDS. Apolipoprotein B subfractions B-100, B-48 and B-26 could be identified with molecular weights of 650 000, 278 000, 175 000 and with typical amino acid compositions of apolipoprotein B.

Amino Acids↗
PubMed1986

Fast protein chromatofocusing of human very-low-density lipoproteins.

Using fast protein chromatofocusing, a high-efficiency column chromatography method with a self-generated pH gradient and focusing effects, soluble human very-low-density lipoprotein (VLDL) apolipoproteins were fractionated between pH 6.3 and 4.0. In the presence of 6 mol/l urea and with a flow rate of 1 ml/min, one run (up to 10 mg of protein) took 30 min. VLDL apolipoproteins were separated in seven peaks. As revealed by SDS-polyacrylamide gel electrophoresis, isoelectric focusing and double-immunodiffusion against mono-specific antisera, fractions corresponded to the following proteins: apolipoprotein C-I, albumin, apolipoproteins A-I, E, C-II plus C-III0, C-III1 and C-III2, respectively. Apolipoproteins were eluted in sharp, well-resolved peaks. The recovery of proteins was 78% of the starting material. With fast protein chromatofocusing, an efficient isolation of single apolipoproteins is possible from small amounts of VLDL apolipoprotein preparations. This technique is superior to the commonly used, time-consuming methods for apolipoprotein isolation.

Electrophoresis, Polyacrylamide Gel↗
PubMed1986

Fenofibrate and colestipol: effects on serum and lipoprotein lipids and apolipoproteins in familial hypercholesterolaemia.

Effects on serum lipoproteins were studied in ten patients with familial hypercholesterolaemia (FH) during consecutive eight-week treatment periods with fenofibrate 0.3 g/day, fenofibrate plus colestipol, 15 g/day, and fenofibrate 0.25 g/day plus colestipol. VLDL, LDL, HDL, HDL2, and HDL3 were isolated by ultracentrifugation and precipitation. Lipids and apolipoproteins A-I and B were determined by enzymatic and immunonephelometric techniques, respectively. Administration of fenofibrate alone resulted in decreases in VLDL and LDL cholesterol (-48% and -18%) and in serum apolipoprotein B (-10%), but in increases in HDL, HDL2, and HDL3 (+25%, +26%, and +24%), and in serum apolipoprotein A-I (+6%). Addition of colestipol produced a further reduction in LDL cholesterol (-31%) and in serum apolipoprotein B (-19%). The effects were maintained with less fenofibrate. In FH, an acceptable therapy combines the favourable effects of sufficient lowering of LDL and of a rise in HDL.

Adult↗
PubMed1986

Fat restriction alters the composition of apolipoprotein B-100 containing very low-density lipoproteins in humans.

We investigated effects of fat saturation and fat restriction on very low-density apolipoproteins (VLDL) including the isoforms. Normolipidemic women (22) were given a reference diet, a polyunsaturated diet, and a low-fat, polyunsaturated diet for 6 wk each. The polyunsaturated diet decreased cholesterol and apolipoprotein B levels in VLDL (-33.1% and -23.8%) and in LDL (-13.5% and -8.8%) without affecting HDL. The low-fat, polyunsaturated diet resulted in a reincrease of VLDL triglycerides, but not of VLDL cholesterol. Concentration of VLDL apolipoprotein B fell further (-41.6%). All VLDL apolipoprotein B was in the B-100 region. Though the apolipoprotein E phenotype (E-3/E-3) remained constant, a shift to more (nonsialated) apolipoprotein E isoforms could be confirmed, resulting in an increased apolipoprotein E-3 to apolipoprotein E-2 area ratio (+30.6%). This study indicates that restriction of dietary-fat intake alters the composition of apolipoprotein B-100 containing VLDL that may be favorable for atherogenesis.

Adult↗
PubMed1986

Isolation and quantification of apolipoproteins C-I, C-II, and C-III0-2 in very-low-density lipoproteins by "high-performance" anion-exchange chromatography.

Using "high-performance" anion-exchange chromatography, we isolated and quantified human C apolipoproteins (apo C) from very-low-density lipoproteins (VLDL) in serum. As revealed by isoelectric focusing and double immunodiffusion against monospecific antisera, apo C-I, apo C-II, apo C-III0, apo C-III1, and apo C-III2 were purified to homogeneity. Assay reproducibility (coefficients of variation) ranged between 0.9% and 4.7%. The relative percentages of apo C subspecies in VLDL from normal and hypertriglyceridemic serum samples agreed with data obtained by alternative methods. This precise technique is suitable for detecting and analyzing abnormalities of C apolipoproteins in VLDL.

Apolipoprotein C-I↗