[MPPG complex belongs in the first phase of drug-assisted lipid lowering (magnesium-pyridoxal-phosphate-glutamate )].
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Glutamine↗
Biomedical subjects
H Wieland
Publications and source records attributed to H Wieland.
Endocrine and metabolic abnormalities following kidney transplantation.
Various endocrine and metabolic disturbances associated with long standing uremia persist after kidney transplantation or arise from the use of immunosuppressive drugs. Hyperlipidemia for long time being implicated as the cause of corticosteroids is also observed in renal transplant recipients treated with cyclosporin A monotherapy. After conversion from cyclosporin to azathioprine serum cholesterol and triglyceride concentration fall, and elevation of LDL-cholesterol may also be reversed. There is a tendency for higher HDL-cholesterol in azathioprine and prednisolone treated transplant patients. Those patients who are at risk for clinically significant cholesterol elevations can be predicted by their pretransplant lipid levels, specifically the LDL-fraction. Risk-benefit ratio of conversion and of treatment with lipid-lowering drugs, especially with lovastatin, should be carefully examined, also in view of glucose intolerance. Higher incidence of diabetes mellitus requiring insulin therapy in cyclosporin treated transplant recipients has been reported. Cyclosporin may cause toxic effects on pancreatic beta-cells resulting in inhibition of insulin secretion. High doses of cyclosporin induce inhibition of glycogen synthesis in rat liver. Glucose intolerance is reversible after reduction of cyclosporin dose or conversion to azathioprine. Therefore glucose metabolism in kidney transplant recipients treated with cyclosporin should be carefully followed. Immunosuppressive therapy may affect reproductive function, arachidonate metabolism and renin-angiotensin-aldosterone system as well as posttransplant calcium and phosphate metabolism. Endocrine and metabolic abnormalities are associated with long standing uremia. After successful kidney transplantation several observations are normalized but further complications arise from the use of immunosuppressive drugs. The present paper reviews various endocrine and metabolic disturbances described following renal transplantation.
Animals↗
Gangliosides in normal human serum. Concentration, pattern and transport by lipoproteins.
The total content and pattern of gangliosides were determined in the unfractionated sera of 11 healthy human adults and in isolated lipoproteins. The total content of lipid-bound sialic acid was 10.5 +/- 3.2 nmol/ml serum. The ganglioside profile consisted of more than ten different components. The major ganglioside was GM3, followed by GD3, GD1a, GM2, GT1b, MG-3 (sialosyllactoneotetraosylceramide), GD1b and GQ1b. Traces of four additional gangliosides could not be quantified reliably. Ganglioside patterns did not vary in sera taken from healthy adults of different age and sex. Approximately 98% of human serum gangliosides were transported by serum lipoproteins, predominantly by LDL (66%), followed by HDL (25%) and VLDL (7%). The quantitative distribution of individual gangliosides in VLDL and LDL was almost the same as that in the unfractionated serum; some differences existed with the ganglioside profile in HDL.
Adult↗
Ketogenic and antiketogenic effects of L-carnitine in hemodialysis patients.
Eighteen hyperlipidemic hemodialysis patients were treated with 1, 5, and 15 mg L-carnitine/kg body weight (each dose was given for three months) given intravenously at the end of the dialysis therapy. Low dose L-carnitine treatment caused an increase in plasma total carnitine (TC), short chain acylcarnitine (SCC), and long chain acylcarnitine (LCC). An increase in plasma free carnitine (FC) occurred only in the 10 responders who showed a significant decrease in serum triglycerides. Serum VLDL triglycerides, VLDL cholesterol and VLDL phospholipids also decreased in the responders compared to nonresponders. There was no difference in HDL- and LDL-lipoproteins in both responders and nonresponders. L-carnitine in doses of 5 or 15 mg/kg body weight caused markedly elevated plasma levels of all carnitine fractions but no further lipid lowering effect. Moreover, enhanced serum triglycerides were observed in some hemodialysis patients. Thirteen out of 15 patients displayed an increase of HDL triglycerides and 5, an increase of VLDL triglycerides. Our data suggest that low doses of L-carnitine are effective in treating hypertriglyceridemia in selected patients. Low dose L-carnitine also avoids unphysiological high plasma levels of carnitine and carnitine esters and prevents antiketogenic effects in hemodialysis patients.
Acylation↗
High-performance liquid chromatographic separation of human haemoglobins. Simultaneous quantitation of foetal and glycated haemoglobins.
A high-performance liquid chromatographic system, which uses a weak cation exchanger (PolyCATA) together with Bis-Tris buffer (pH 6.47-7.0) and sodium acetate gradients, is described. Samples from adults and newborns were analysed and a clean separation of many minor and major normal and abnormal haemoglobin (Hb) variants was greatly improved. The method allows the separation of minor foetal haemoglobin (HbF) variants and the simultaneous quantitation of HbF and glycated HbA. HbF values correlated well with those obtained by the alkali denaturation method (r = 0.997). The glycated haemoglobin (HbAIc) levels measured in patients with high HbF concentrations correlated with the total glycated haemoglobin determined by bioaffinity chromatography (r = 0.973). The procedure is useful for diagnostic applications and affords an effective and sensitive way of examining blood samples for haemoglobin abnormalities.
Adult↗
[Effects of sex steroids on the lipoprotein profile].
Plasma testosterone levels were measured pre- and postoperatively as well as during estrogen substitution in a 47-year-old woman with excessive hyperandrogenaemia due to a Leydig-cell tumour of the left ovary. In addition, the lipoprotein profile was determined before and 14 days after removal of the tumour and four weeks later during estrogen substitution. The preoperative plasma testosterone level was between 6.25 and 8.50 ng/ml; at the same time there was a hypercholesterolaemia with increased beta-lipoprotein and decreased alpha-lipoprotein fractions: the ratio of beta- to alpha-lipoprotein cholesterol was 3.0, a type IIa hyperlipoproteinaemia. After the testosterone concentration had returned to normal both the beta- and pre-beta cholesterol fell significantly, while the alpha-lipoprotein fraction remained unaltered. The alpha-cholesterol fraction increased significantly after estrogen substitution, the beta- to alpha-lipoprotein ratio being 1.20. It is concluded from these results that hyperandrogenaemia goes together with raised peripheral beta and pre-beta-cholesterol concentration, while estrogens cause a rise in the alpha-fraction.
Cholesterol↗
Lipid metabolic changes during hormonal treatment of endometriosis.
Three groups of patients with pelvic endometriosis were treated with medroxyprogesterone acetate (MPA) 50 mg/day (n = 10), lynestrenol (LYN) 10 mg/day (n = 25) and danazol (DAN) 600 mg/day (n = 25) respectively. Total cholesterol, triglycerides, alpha-lipoprotein, prebetalipoprotein, beta-lipoprotein cholesterol, high-density (HDL) and low-density (LDL) lipoprotein and apolipoprotein A1 and B concentrations were determined before treatment and after 3 and 6 mth of therapy. Whereas lipid, lipoprotein and apolipoprotein levels did not change in the MPA group, the patients on LYN and in particular those on DNA showed marked changes in lipoportein patterns. Alpha-lipoprotein, HDL and apolipoprotein A1 levels fell, while beta-lipoprotein, LDL and apolipoprotein concentrations rose, these changes being statistically significant. No alterations were seen in the serum levels of cholesterol, triglycerides or prebetalipoprotein cholesterol. In view of a possible relationship between high LDL and low HDL levels and a risk of accelerated coronary arteriosclerosis in women it was concluded that progestogen-induced alterations in lipoprotein patterns should be avoided as far as long-term treatment is concerned and where additional risk factors are present.
Adult↗
[Serum lipid and lipoprotein concentrations in pregnancy and at onset of labor in normal and complicated pregnancies caused by hypertensive gestosis and fetal growth retardation].
Cholesterol triglyceride and lipoprotein concentrations were determined in the sera of 220 pregnant women at different periods of their pregnancy. In 197 healthy pregnant women we found besides an increase in cholesterol level and in particular an increase in the beta-lipoprotein fractions, a marked increase in pre-beta-lipoprotein levels and more than twice as high triglyceride concentration in the course of the first to the third trimenon. Nothing abnormal was found on comparing the lipid and lipoprotein parameters of 13 pregnant women having hypertensive toxaemia, with those of healthy gravidae, with the exception of a marked increase in the pre-beta-lipoprotein levels in those patients who suffered from toxaemia. No connection was seen between infantile deficient development below the tenth percentile and the serum lipid and lipoprotein concentrations (n = 10) in the mother. Examinations carried out in 233 pregnant women and their children at the time of birth did not yield any connections between maternal and infantile protein patterns. All infants had definitely lower parameter concentrations than their mothers.
Adolescent↗
Extracorporeal plasma therapy: the HELP system for the treatment of hyper-beta-lipoproteinemia.
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Adult↗
Selective removal of low density lipoproteins (LDL) by precipitation at low pH: first clinical application of the HELP system.
The first clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low-density lipoproteins by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 mu filter, is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter and the clear plasma filtrate is subject to bicarbonate dialysis/ultrafiltration to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low-density lipoproteins from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. The HELP system shows a high degree of specificity with over 80% of total protein being returned to the patient. Over 130 treatment procedures have now been performed. Patient compliance and acceptance have been excellent and no major complications have been observed.
Adult↗
Medroxyprogesterone acetate and lipid metabolic changes.
Lipid metabolic changes under oral treatment with medroxyprogesterone acetate (MPA) were investigated in four groups of patients: group I; 10 patients aged 25-45 (mean 38) years received 50 mg MPA daily for pelvic endometriosis. Group II; 21 patients aged 55-77 (mean 62) years received 200 mg MPA daily for surgically treated endometrial carcinoma stage I. Group III; 14 praemenopausal patients aged 37-52 (mean 47) years received 1000 mg MPA daily for metastasized breast cancer. Group IV; 27 post-menopausal patients aged 53-78 (mean 68) years were treated with 1000 mg MPA daily for metastatic breast cancer as well. A fifth group of initially 86 patients aged 40-86 (mean 63) years after surgery for endometrial carcinoma stage I served as untreated control for groups II and IV. Cholesterol and triglyceride concentrations were measured enzymatically lipoproteins were determined by quantitative electrophoresis and precipitation and apolipoproteins A1 and B were quantified by kinetic rate nephelometry. Whereas in patients of group I no changes of lipid and lipoprotein parameters were observed, daily oral doses of 200 mg MPA and more led to a marked fall in alpha-lipoprotein-, HDL-cholesterol and apolipoprotein A1 levels. beta-Lipoprotein-, LDL-cholesterol and apolipoprotein B concentrations rose significantly in Groups III and IV. The relevance of these findings in terms of athero-genicity is discussed.
Adult↗
The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels.
Lipoprotein(a) concentrations were measured by radial immunodiffusion in a cohort of 40-60 year males who had been classified by coronary angiography as CAD+ with 50% stenosis of one or more of the major coronary arteries or CAD- with no signs of coronary lesions. Sample odds ratios were calculated as a measure of association between serum Lp(a) values and the presence of coronary artery disease. An odds ratio of 2.706 (P less than 0.001) was derived for elevated (greater than or equal to 30 mg/dl) Lp(a) levels vs low (less than 5 mg/dl) Lp(a) levels indicating a strong association between the presence of coronary artery disease and elevated Lp(a) concentrations. This association was independent of the known risk factors smoking, hypertension and diabetes as well as the serum concentrations of total triglycerides, HDL-cholesterol, alpha-Lp-cholesterol and pre-beta-Lp-cholesterol. In contrast to these variables the association between Lp(a) and coronary artery disease was dependent upon the serum concentrations of LDL-cholesterol, beta-Lp-cholesterol and total cholesterol. At concentrations below the respective median for each variable, odds ratios of between 1.42 and 1.67 were calculated whereas at concentrations above the respective medians the odds ratios ranged from 4.50 to 6.33 (P less than 0.001). Our data, therefore, suggest that increasing LDL concentrations markedly increase the risk of coronary artery disease due to elevated Lp(a) levels.
Adult↗
Evaluation of immunoaffinity chromatography for isolating human lipoproteins containing apolipoprotein B.
Because of high specificity, immunoaffinity chromatography is the most suitable procedure for the isolation of lipoprotein (LP) particles defined by their apolipoprotein (Apo) composition. The purpose of the present study was to describe immunosorber methodology and its application to the isolation of ApoB-containing lipoproteins from either plasma or isolated lipoprotein density classes. The exploration of various coupling procedures demonstrated that immunosorbers of highest capacity were obtained by cyanogen bromide activation of Sepharose. Among various dissociating agents tested, 3 M sodium thiocyanate was found to be the most effective desorbent for bound lipoproteins. Studies on the non-specific binding of serum albumin to several different immunosorbers showed a negligible retention (1.9%) of albumin. Good recoveries (80-98%) were obtained with all apolipoproteins tested with both anti-ApoA-I and anti-LP-B immunosorbers. By using the optimal experimental conditions, it was shown that the ApoB-containing lipoproteins retained by immunosorbers with antibodies to LP-B had chemical, physical and immunological properties similar, if not identical, to those of their corresponding parent density classes. The application of an alternative immunoaffinity chromatography procedure with serially connected immunosorbers with antibodies to apolipoproteins other than ApoB resulted in the isolation of LP-B, a lipoprotein containing ApoB as its sole protein constitutent. LP-B had chemical and physical properties very similar to those of subclass 2 of low-density lipoproteins (density 1.019-1.063 g/ml, flotation coefficient 0-12). Based on these studies, we suggest that immunoaffinity chromatography in combination with microanalytical procedures for quantification of lipids and apolipoproteins offers a powerful tool for the isolation and functional characterization of lipoprotein particles defined by their apolipoprotein composition.
Adsorption↗
Effects of medrogestone and conjugated oestrogens on serum lipid and lipoprotein concentrations.
Twenty patients, aged 30-60 yr, who had undergone bilateral ovariectomy, were treated orally with 5 mg medrogestone (6,17-dimethylpregna-4,6-diene-3,20-dione) and 1.25 mg conjugated oestrogens per day, according to a constant dosage pattern during the cycle (22 + 6 days). The lipids and lipoproteins were determined twice before the start of therapy and 3, 6 and 12 mth thereafter. The lipids were quantified enzymatically and the lipoproteins by quantitative lipoprotein electrophoresis. Whilst cholesterol and triglyceride concentrations showed no detectable change, a slight but significant increase was seen in the high-density alphalipoprotein (HDL) cholesterol concentrations. The low-density beta-lipoprotein (LDL) cholesterol level showed a moderate fall. There was a resultant reduction in the beta/alpha-lipoprotein ratio. Accordingly, the apoprotein A1 concentrations were found to be elevated, while apoprotein B tended to fall to lower levels during therapy. When these changes are measured by the lipid metabolism risk criterion for the occurrence of coronary heart disease applicable to post-menopausal patients, the effects of the above-mentioned combination may be regarded as entirely favourable.
Adult↗
[Changes in serum lipoproteins under hormonal therapy of breast carcinoma and other endocrine-dependent tumors].
The higher the low-density-lipoprotein cholesterol (beta lipoprotein) level, the greater the risk that coronary heart disease will develop, alpha-lipoprotein fractions (high-density-lipoproteins) are considered to be protective factors. Medroxyprogesterone acetate is responsible for characteristic changes of the lipoprotein patterns indicating enhanced coronary risks. Medroxyprogesterone acetate is applied in the therapy of breast, uterus and ovarian cancer. A statistically significant decrease was observed in alpha-lipoproteins whereas beta-lipoproteins increased without statistical significance. A similar reaction can be observed under the combination therapy of aminoglutethimide and medroxyprogesterone acetate, whereas the combination of cortisone and aminoglutethimide has a distinct influence on beta-lipoproteins but the alpha-lipoprotein level remains uninfluenced. According to these data the effect of an adjuvant application of these drugs must be carefully evaluated due to an increase of coronary risks.
Aminoglutethimide↗
Influence of age, body-weight, smoking habits and alcohol consumption on the lipoprotein profile: preliminary results from a study performed on 6543 male industrial workers aged 40-59 years.
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Adult↗
[Lipoprotein changes during hormonal treatment of endometriosis with lynestrenol and danazol].
The Lipoprotein profile of 24 patients with endometriosis was determined before, during and after the treatment with the two steroid hormones Lynestrenol (10 mg/day) and Danazol (600-800 mg/day). The total cholesterol triglycerides, beta-, prebeta-, and Alphalipo -protein bound to cholesterol were determined. Both hormones cause a marked lowering of the Alpha-Lp-cholesterin. In addition, the beta-LP-cholesterin was elevated and the beta-alpha-LP-ratio was elevated. In the dosage used by us, Lynestrenol showed less effect on the Lipoprotein profile. Danazol caused changed in the beta- and alpha-lipoprotein pattern of highly pathological atherogenic types. The total cholesterol was not influenced. Since women in the fertile age group will suffer a higher risk of arteriosclerosis from an elevation of the beta-LP-cholesterin, the treatment with Danazol calls for a sophisticated monitoring of the lipid metabolism and care in the indication for long term treatment with Danazol or with Lynestrenol.
Adult↗
Influence of smoking on the plasma lipoprotein profile.
Smoking and hypercholesterolemia, or more specifically hyper-beta-lipoproteinemia, are well established risk factors for the early development of atherosclerotic disease. The presence of both factors augments the potential risk. The question arises, therefore, as to whether cigarette smoking has a direct effect on the plasma lipoproteins and, in particular, on the atherogenetic low density lipoproteins. In this study, the influence of cigarette smoking on the lipoprotein profile was investigated in a defined cohort of 6,543 male industrial workers aged 40-59 years, consisting of 2,434 smokers and 3,975 non-smokers. The effect of smoking on the lipoprotein profile showed no significant changes in LDL and only slight changes in the other lipoprotein fractions. Other factors, such as alcohol intake, body weight, and general life style seem to have a greater influence on HDL-cholesterol than smoking. It is concluded that smoking does not significantly alter lipid metabolism and that minor differences observed between smokers and non-smokers are due to a variety of factors, rather than a reflection of a direct metabolic relationship.
Adult↗