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W Leonhardt

Publications and source records attributed to W Leonhardt.

At least 19 recordsLinked to original sources
PubMed1995

Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition.

A very short run time and small sample volumes in the separation of lipoproteins by preparative ultracentrifugation are needed for several investigations. Recently, a very fast sequential separation method was described that needs only 100 min for one run in a centrifugal field of 625,000 x g. We studied the influence of centrifugal fields of this dimension on lipoprotein separation and lipoprotein particle integrity using a Beckman Optima TLX ultracentrifuge with a TLA-120.2 rotor. Rotor speed (120/90/60/30.10(3) rev./min) and run time (100 min/3 h/6.7 h/27 h) were selected in such a way that the product of centrifugal field and run time remained constant. The first conditions correspond to the very fast ultracentrifugation (VFU) procedure with a centrifugal field of 625,000 x g. Thirty different plasma samples covering a wide range of lipid and protein concentrations were separated in the course of two centrifugal runs at densities of 1.006 and 1.063 kg/l which yielded very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and the subnatant of low-density lipoproteins, including high-density lipoproteins (HDL) and concomitant sedimented plasma proteins. The major lipid components of the lipoproteins, triacylglycerols, free and esterified cholesterol, phospholipids and the apolipoproteins B and A-I, were estimated considering the masses of the tube contents after a slicing procedure. Measurements of lipids and proteins showed a very good recovery of better than 94% and 91%, respectively, and precision-within-series (coefficient of variation) of better than 4.2% and 6.5%, respectively. The effects of the rotor speed on the lipoprotein structure appeared to be weak. With increasing rotor speed, VLDL and LDL lipid constituents principally tended to decrease, whereas they increased in the subnatant of the LDL-run. The mean lipoprotein mass composition, considering the mass percentage of each measured particle constituent, did not show significant alterations. Total protein decreased in VLDL and in LDL and increased in the subnatant of the LDL-run. As checked by an enzyme-linked immunosorbent assay (ELISA) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the protein effects were due to nearly complete disappearance of contaminating plasma proteins, especially albumin as the major contamination of VLDL and LDL. The apolipoproteins (apo) B-100, A-I, E and C-I to C-III remained nearly unaffected. The main advantages of VFU were the very short run time (cumulative flotation time is 3.4 h) and the elemination of albumin without repeated runs. The procedure was suitable for the assessment of lipid and protein constituents in lipoproteins from very small plasma samples (500 microliters).

Adult↗
PubMed1994

Very-fast ultracentrifugation of human plasma lipoproteins: influence of the centrifugal field on lipoprotein composition.

A short run-time in separation of lipoproteins by preparative ultracentrifugation is desirable for several reasons. Recently, a method was described that needs only 100 min for one run in a centrifugal field of 625,000 x g. It is assumed that lipoprotein separation depends on the rotor speed but this has not been systematically studied in centrifugal fields of this order. We performed such a study. Rotor speeds of 120, 90, 60 and 30 x 10(3) rev./min and run-times of 100 min, 3 h, 6.7 h and 27 h were selected in such a way that the product of centrifugal field and run-time remained constant. The first conditions correspond to the 'very fast ultracentrifugation' (VFU) procedure with a centrifugal field of 625,000 x g. The Optima tabletop ultracentrifuge, the rotor TLA-120.2 and thick wall open tubes for 1 ml were used. Thirteen different plasma samples covering a wide range of cholesterol and triglyceride concentrations were separated into VLDL, LDL and HDL in the course of two centrifugal runs at densities of 1.006 and 1.063. The constituents of the lipoproteins were calculated considering the mass of the tube contents after slicing. Recoveries of cholesterol, triglycerides and protein were 97%, 98% and 90%, respectively. The influence of the rotor speed on the apparent composition of the lipoproteins was small. With increasing rotor speed, VLDL-cholesterol became higher (by 14%, P < 0.001), VLDL-triglyceride became lower (by 6%, P < 0.012), LDL-cholesterol became lower (by 9%, P < 0.000). The effects on LDL-triglyceride and on HDL-cholesterol and HDL-triglyceride, did not reach statistical significance. Protein in VLDL and in LDL decreased and increased in 'HDL' (the subnatant of the LDL run). As checked by SDS-PAGE the protein effects were due to complete disappearance of albumin from VLDL and LDL while the apolipoproteins B-100, E and C-I to C-III remained unaffected. It is concluded that the main advantages of VFU are the short run-time and the disappearance of albumin from VLDL and LDL. The other compositional changes need to be further investigated.

Apolipoproteins↗
PubMed1994

Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women.

In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11-21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL2 and HDL3, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect.

Dietary Fats↗
PubMed1994

Efficacy of alpha-glucosidase inhibitors on lipids in NIDDM subjects with moderate hyperlipidaemia.

This paper summarizes literature data concerning the action of acarbose, an alpha-glucosidase inhibitor, on the concentrations of plasma lipids. Clinical trials in which acarbose has been used in the treatment of non-insulin-dependent diabetics have sometimes shown that it reduces serum triglycerides while it has little or no effect on serum cholesterol levels. The results of a randomized double-blind placebo-controlled study lasting 24 weeks are discussed in more detail. Under the controlled conditions, the effects of acarbose treatment on fasting concentrations of cholesterol, HDL-cholesterol, and triglycerides did not reach statistical significance for the entire patient group. However, in the highest tertile of initial cholesterol concentrations acarbose treatment led to significant lowering of the cholesterol concentration and of the total-to-HDL-cholesterol ratio. The most important benefits of acarbose were observed after a test meal given on day 0 and on week 24 of treatment. The triglyceride increment 1 h postprandial was significantly lowered. This was associated by a significant decrease of the insulin increment. Reduction of hyperinsulinaemia appears to be the mechanism by which acarbose treatment can improve plasma lipid concentrations.

Acarbose↗
PubMed1994

Recovery of cholesterol and triacylglycerol in very-fast ultracentrifugation of human lipoproteins in a large range of concentrations.

Very-fast ultracentrifugation using a benchtop ultracentrifuge was applied to the analysis of lipoproteins in 0.5 ml of human plasma. VLDL, IDL and LDL were flotated at densities of 1.006, 1.019 and 1.063 kg/l in runs lasting 30, 100 and 100 minutes. Chylomicrons, if present, were flotated in a separate run. HDL were isolated by precipitation of the apolipoprotein B-containing lipoproteins from total plasma using polyethylene glycol. Three series of separations were routinely performed: 1. VLDL run alone (632 samples), 2. VLDL run + LDL run (122 samples), and 3. Chylomicron separation + VLDL run + IDL run (92 samples). The concentrations of cholesterol and triacylglycerol were obtained for plasma, chylomicrons, VLDL, IDL, LDL and HDL. Plasma values ranged from 1.8 to 37.1 mmol/l cholesterol and 0.26 to 50.2 mmol/l triacylglycerol. The plasma triacylglycerol concentrations were corrected for free glycerol by 3% (for triacylglycerols < 2.5 mmol/l) and by 2% (for triacylglycerols > or = 2.5 mmol/l). The recovery rate of lipids after ultracentrifugation was determined by comparing the concentrations in lipoproteins and in plasma. It was near to 100% and decreased for samples with extremely high lipid concentrations.

Cholesterol↗
PubMed1991

Beneficial effects on serum lipids in noninsulin dependent diabetics by acarbose treatment.

Acarbose (Bay g 5421, Glucobay; CAS 56180-94-0) inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. It is therefore efficient as a first-line drug in the treatment of noninsulin-dependent diabetics (NIDDM) insufficiently treated with diet alone. Information is scarce whether under acarbose treatment the lipid metabolism can also be improved. Therefore the changes of triglycerides, cholesterol and HDL-cholesterol were analyzed in a randomized double-blind placebo-controlled trial. In brief, 94 NIDDM aged 43 to 70, after a pretreatment period of at least 3 months, were treated with 100 mg acarbose t.i.d. or placebo for 24 weeks. The patients were recruited after a 4-week screening phase with reinforcement of diet. The most impressive results of acarbose treatment were lowering of blood glucose and insulin, especially in the postprandial state, and of HbA1 (glycosylated hemoglobin). Results on lipids: The initial serum cholesterol levels showed a broad spectrum. Low concentrations remained unchanged under acarbose, while high concentrations (the upper tercile) decreased from 273 to 251 mg/dl. This effect was statistically significant compared to placebo. HDL-cholesterol levels increased continuously under acarbose and placebo as well thus indicating some study effect. Similarly, fasting triglycerides leveled down under acarbose and placebo. However, drastic differences appeared in postprandial triglycerides which were checked 1 and 5 h after a test meal given at entry and at finish of the study. The lowering by acarbose compared to placebo was highly significant for the 1 h postprandial concentrations. It is concluded that acarbose treatment can reduce elevated cholesterol concentrations and postprandial triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗
PubMed1990

Efficacy of a combined bezafibrate retard-colestyramine treatment in patients with hypercholesterolemia.

In a placebo-controlled randomized study the effect of combined bezafibrate-colestyramine therapy in comparison with monotherapy with both drugs was investigated. 47 patients with primary hypercholesterolemia received 400 mg bezafibrate (Cedur) retard/d, subsequently bezafibrate retard plus colestyramine (24 g/d) or colestyramine plus placebo in a double-blind fashion. The combination therapy was most effective (LDL decrease 36%, HDL-C increase 31%, apoprotein B decrease 28%), bezafibrate and colestyramine were equally effective with regard to LDL-C and apoprotein B, but only bezafibrate decreased triglycerides (-37%) and increased HDL-C (+24%). Bezafibrate was well-tolerated, but gastro-intestinal side-effects were frequent during therapy with colestyramine, and 16 patients tolerated only a reduced dosage of this drug. From the results presented it can be concluded that combined therapy with bezafibrate retard plus colestyramine is highly effective in the treatment of severe hypercholesterolemia.

Bezafibrate↗
PubMed1988

[Intraindividual comparison of the elimination kinetics of Lipofundin S and Intralipid in consecutive lipid tolerance tests].

Two intravenous fat tolerance tests (IVFTT) were performed in 16 healthy volunteers and 8 patients suffering from hypertriglyceridemia (HTG). We compared Lipofundin S (Braun, Melsungen) with Intralipid (Kabi Vitrum, Stockholm), using both 10- and 20% concentrations. Time intervals between the tests were 1 h for the volunteers and 2 h for the patients with HTG, respectively. Fractional elimination rates were obtained from light scattering intensity of serum samples. They were significantly higher for Lipofundin S (9.61%/min for healthy men and 12.48%/min for healthy women) compared to Intralipid (7.09%/min for healthy men and 9.41%/min for healthy women). This difference occurred independently of (1) serum triglyceride concentrations and sex of the volunteers, (2) concentrations of lipid emulsions (10 vs. 20%), and (3) the test sequence (Lipofundin S or Intralipid first). This means that the elimination kinetics during an IVFTT are not influenced by a foregoing test. Similar features of both emulsion types were: (1) Faster elimination in women compared to men, and in healthy volunteers compared to HTG patients; (2) inverse correlation between fractional elimination rates and serum triglyceride concentrations. Fractional elimination rates of Lipofundin S and Intralipid were closely interrelated. Obviously there exists an intra-individually characteristic elimination capacity for exogenous triglycerides.

Adult↗
PubMed1988

Effects of a bezafibrate sustained release formulation on plasma lipoproteins in patients with hypercholesterolemia. Importance of timing of tablet intake for efficacy.

The therapeutic effect of a single sustained release tablet of bezafibrate (Cedur retard, 400 mg) in primary hypercholesterolemia type IIa and type IIb was investigated in a placebo-controlled randomised study comparing the efficacy of morning vs. evening intake. The decrease in total cholesterol with the morning intake was 18.5% vs. 16.5% for the evening intake (n.s.). HDL-cholesterol increased more in patients taking bezafibrate retard at morning (29.6% vs. 22.4%, p less than 0.05). Bezafibrate was well tolerated. Animal experiments and precursor studies of cholesterol synthesis in man indicate peak activity of HMG-CoA reductase between 1 a.m. and 3 a.m. The data suggest that with normal eating habits during day time other modes of action of bezafibrate besides HMG-CoA reductase inhibition such as reduction of VLDL-synthesis in the liver and an increased fractional catabolic rate, could contribute to the therapeutic effect.

Alkaline Phosphatase↗
PubMed1988

More exercise for the hyperlipidaemic patients?

Epidemiological studies have left no doubt that moderate to vigorous physical training (PT) of endurance type decreases atherogenic lipoprotein fractions and increases vasoprotective lipoproteins. Depending on the underlying metabolic abnormality in various dyslipoproteinaemias a different response to endurance training was observed. PT is particularly effective in most forms of primary hypertriglyceridaemias. PT acts on both excessive VLDL production and fractional catabolic rate of TG--rich lipoproteins. However, improved removal seems to be of dominating importance. In primary hypercholesterolaemia LDL--cholesterol levels did not change during a 4 weeks exercise regimen with standardized isocaloric lipid lowering diet. In observational studies with hyperlipidaemic patients with stable body weight and under lipid lowering diet, during the first 4-6 weeks no significant effect on HDL was seen, whereas longterm studies clearly demonstrate an increase in HDL--cholesterol. Further beneficial effects of PT in hyperlipidaemic patients are improved glucose tolerance, down--regulation of hyperinsulinaemia, lowering of blood pressure and correction of hypercoagulability of the blood.

Arteriosclerosis↗
PubMed1987

Loss of fat, water, and protein during very low calorie diets and complete starvation.

The magnitude and composition of weight loss obtained in obese women on two forms of very low calorie protein-supplemented diets (Cambridge diet, Dresden drink) as well as by complete starvation has been investigated. With the VLCD, nitrogen equilibrium was reached on the 10th day of fasting, the cumulative nitrogen balance also being compensated. Nearly half of the body weight loss is due to loss of fat. In order to assess the benefit of fasting regimes, we propose to measure at least two parameters which are independent of each other, e.g., nitrogen balance and total body water. Both types of VLCD were equally effective, safe, and acceptable in achieving rapid body weight reduction.

Adipose Tissue↗
PubMed1987

[Metabolism kinetic characterization of hypertriglyceridemias in drug therapy variations].

In 26 male patients with primary hypertriglyceridemia (HTG) the radioglycerol labelling technique was used to assess triglyceride production rates and fractional catabolic rates pertaining to the rapidly turning-over compartment of endogenously produced triglycerides (TG). On the basis of these data the patients were allotted to 3 groups: group I with predominating TG overproduction, group II with predominating disturbances of TG removal from the bloodstream, and group III with a combination of both dysfunctions. All patients were examined prior to and after 4 weeks of drug intake at the metabolic ward. Each group got a medical treatment aiming at removing the pathogenetic cause of the HTG. Biguanides used in group I decreased TG production rates without affecting fractional catabolic rates. In group II an anabolic steroid (chlormethyltestosterone) proved to be able to improve TG removal, but this improvement was accompanied by a significant lowering of HDL cholesterol and an increase in LDL cholesterol. In contrast, clofibric acid influenced both overproduction and removal impairment in group III. Our results give an insight into mechanisms of action of certain lipid-lowering drugs providing a basis for future improvements in the elimination of the risk factor HTG.

Adult↗
PubMed1987

Testicular cysts: US findings.

Testicular cysts have been considered rare. However, of 307 men who underwent high-resolution ultrasonography (10 MHz) of the scrotum, 30 (9.8%) had testicular cysts. Thirty-three testes were involved, 23 with single cysts, eight with clusters of multiple tiny cysts, and two with more than one focus of cyst. One cyst was aspirated intraoperatively, and one cyst of the tunica albuginea was proved at surgery. Eighty cadaveric testes were scanned also, and cysts were found in one. In two cases, the pathologic report, reviewed retrospectively, failed to mention the cyst, but these cysts could have been overlooked. Further work is needed to determine when or if these testicular lesions need follow-up and what significance they have, if any.

Adult↗
PubMed1987

Predictive value of the index of desirable body weight for total body fat mass as measured by dilution of tritiated water--problems and limitations.

The index of desirable body weight is currently used for classification of patients' weights. We examined how it is related to the degree of adiposity, and whether it can serve in the prediction of body fat to the same degree as Quetelet's index. Sixty-five women and 142 men comprising a wide range of weight indices were studied. Body fat (F) was measured by the tritium dilution technique with a precision of +/- 1.26 kg. Regressions of F/W0 on the index of desirable weight W/W0 gave a correlation coefficient of 0.969 for women and 0.939 for men. Regressions of F/H2 on Quetelet's index W/H2 had correlation coefficients of the same order, i.e. 0.971 for women and 0.936 for men. Hence both indices are equally powerful for calculation of body fat within the study population. Further progress was achieved by multiple regression of F on W and W0 which yielded correlation coefficients of 0.976 for women and 0.953 for men. The residual standard deviation reflecting the mean difference between calculated and estimated fat was 3.4 kg for women and 3.8 kg for men. Despite this self-consistency, prediction of body fat for persons outside the study population is only possible within wide limits. These are given by about twice the residual standard deviation. Therefore, prediction of body fat from weight indices can only be used for detection of larger abnormalities in body composition.

Adult↗