Pathophysiologie und Therapie von Lipidstoffwechselstörungen bei Nierenerkrankungen

Summary Nephrotic syndrome, uremia, hemodialysis, peritoneal dialysis, and renal transplantation are accompanied by alterations in lipoprotein metabolism (Table 1). In nephrotic patients, total cholesterol, LDL, VLDL and triglycerides are elevated, while HDL may be increased, normal, or decreased. The pathophysiology includes increased hepatic synthesis of VLDL and cholesterol, decreased activity of lipoprotein lipase, and increased urinary excretion of HDL (Fig. 1). The risk of coronary heart disease (CHD) is increased in nephrotic patients, and elevated LDL-cholesterol may contribute to this risk. Cholesterol lowering diet and drugs are indicated. Presently, Lovastatin and Simvastatin are the most potent cholesterol lowering drugs in nephrotic patients with good evidence of long-term safety. Most patients with impaired renal function or on hemodialysis have moderate hypertriglyceridemia due to decreased lipoprotein lipase activity (Fig. 2). HDL may be slightly decreased. Although the risk of CHD is increased in these patients, triglyceride lowering drugs are not indicated, since no benefit can be expected. Peritoneal dialysis is accompanied by elevated VLDL in addition to hypertriglyceridemia. Reabsorption of large amounts of glucose from peritoneal dialysis fluid increases the carbohydrate load and stimulates hepatic VLDL synthesis. Cholesterol lowering therapy may be advantageous, but the experience is very limited. Side effects of lipid lowering drugs may be aggravated in renal failure. Total cholesterol, LDL, VLDL, and triglycerides are elevated in 50% of patients following renal transplantation. Corticosteroides and cyclosporin are major causes of hyperlipidemia. Cholesterol lowering therapy is indicated since the incidence of CHD is increased. Lipid lowering diet, triple immunosuppression with low dose cyclosporin, azathioprim, and prednisone, or conversion from cyclosporin to azathioprim are valuable measures to reduce cholesterol. Low-dose lovastatin (20 mg/24 h) seems to be an effective and safe cholesterol lowering drug in renal transplantation, while higher doses may induce rhabdomyolysis.

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Abkürzungsverzeichnis NS Nephrotisches Syndrom - LDL Low Density Lipoprotein Cholesterin - VLDL Very Low Density Lipoprotein Cholesterin - HDL High Density Lipoprotein Cholesterin - KHK Koronare Herzerkrankung - HMG-CoA 3-Hydroxy-3-Methylglutaryl-Coenzym A - NIH National Institute of Health - GFR Glomeruläre Filtrationsrate     

The effect of enalapril and timolol on blood lipids. A randomized multicenter hypertension study in general practice in Norway

In a 24-week randomized, single-blind study Timolol (n = 63) and Enalapril (n = 57) proved to be potent and safe antihypertensive drugs. However, the effect on lipid metabolism was fundamentally different, despite the fact that the effect on total serum cholesterol did not significantly differ between the two groups. Enalapril had no adverse effect on any lipid fractions, while Timolol increased very low (VLDL) + low (LDL) density lipoprotein cholesterol by 7.6% (p less than 0.001) and total triglycerides by 34.5% (p less than 0.001), and decreased the favorable high density lipoprotein (HDL) cholesterol by 11.3% (p less than 0.001). Thus, the ratio HDL/VLDL + LDL cholesterol was reduced by 17.1% (p less than 0.001). Enalapril reduced uric acid by 3.4% (NS), while Timolol increased uric acid by 4.0% (p less than 0.05). The difference between the groups was statistically significant (p less than 0.01). The first steps in any attempt to solve the hypertension-coronary dilemma should be to take into consideration all pharmacologic effects of antihypertensive drugs.     

内源性高甘油三酯血症患者血浆VLDL、LDL及HDL对血凝的影响

目的：研究内源性高甘油三酯血症(HTG)患血浆极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL)是否发生了氧化修饰及其对血凝的影响。方法：对2l例内源性高甘油三酯血症患与2l例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆VLDL、LDL及HDL，测定这三种脂蛋白的234nm光吸收、相对电泳迁移率(REM)和硫代巴比妥酸反应物质(TBARS)，分别将这三种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中，按试剂盒分别测定凝血酶原时间(PT)及活化部分凝血酶原时间(APIT)。结果：内源性HTG患血浆TG含量平均升高2．73倍，HDLC下降l.7l倍，同时LPO升高1．22倍;HTG组VLDL、LDL及HDL的REM、234nm光吸收值、TBARS含量均较对照组显增加(P＜0．01)，表明内源性HTG患血浆VLDL、LDL及LDL均发生了氧化修饰生成Ox—VLDL、Ox-LDL.PT及APTT在分别加入HTG组的VLDL、LDL及HDL后均比加入相应正常组脂蛋白明显缩短(P均＜0．05)。相关分析表明，HTG组血浆VLDL及HDL相对电泳迁移率(REM)与PT呈负相关(P＜0．01)。结论：HTG患血浆VLDL、LDL及HDL发生了氧化修饰，并使PT及APTT明显缩短。     

Effect on lipids, lipoproteins and apoproteins of labetalol prescribed in doses of 400 mg/day in hypertensive patients. Double-blind versus placebo study

The effects of labetalol on plasma lipoprotein metabolism were evaluated in a 3-month double-blind drug versus placebo study conducted on 30 consenting hypertensive patients, 15 of whom had normal plasma lipid levels and 15, minor type II hyperlipoproteinaemia; 20 patients received labetalol 400 mg/day and 10 the placebo. All patients remained in stable nutritional status throughout the study. Full clinical examination and blood sampling were carried out 30 days before, and on days 0, 30 and 90 of treatment. Whole blood was collected after 12 hours' fasting and immediately centrifuged prior to determination of plasma lipids (total cholesterol and triglycerides, by enzymatic assay), lipoprotein lipids (HDL, HDL2, HDL3, LDL, VLDL separated by ultracentrifugation in density gradient), apoproteins A1 and B (by laser immunonephelometry) and post-heparin lipoprotein lipase activity (PHLA). Significant changes in heart rate and systolic and diastolic blood pressures were noted in patients under labetalol but not in patients under placebo. Lipid and apolipoprotein levels were similar in both groups on day 0, and no significant variation in lipids, lipoprotein lipids and apolipoproteins were observed after 30 and 90 days of treatment with either labetalol or the placebo. At the end of treatment PHLA was unmodified in the group under placebo and raised in the group under labetalol (p = 0.05). The absence of changes in blood lipid values was found both in patients with normal lipidemia and in those with hyperlipidaemia. This study confirms that labetalol in doses of 400 mg/day has notable anti-hypertensive activity and, as previously reported and in contrast with other beta-blocking agents, is devoid of any adverse effect on lipid metabolism.     

Separation of bovine plasma lipoproteins by a rapid ultracentrifugation method

The recently described method of centrifugation with iodixanol for the rapid separation of human plasma lipoproteins was adapted to separate bovine plasma lipoproteins. Density gradients were generated by mixing plasma with iodixanol 12% (w/v), followed by centrifugation at 350,000 g and 16 degrees C for 3 h 10 min in a vertical rotor. Gradients were unloaded dense-end first into 10 fractions. Human very low density lipoprotein (VLDL; density < 1.011 g/ml), low density lipoprotein (LDL; density = 1.016-1.039 g/ml) and high density lipoprotein (HDL; density = 1.039-1.090 g/ml) were resolved well at densities considerably lower than those traditionally reported in salt gradients. In gradients generated from 12% iodixanol, bovine LDL and HDL exhibited even lower densities (1.016-1.028 and 1.016-1.048 g/ml, respectively) with all lipoproteins occurring at the lower density region of the gradient. In contrast, density gradients generated from layers of equal volumes of 6% and 12% iodixanol readily separated bovine HDL from VLDL, whilst LDL still overlapped with HDL. The latter accounts for >80% of all bovine lipoproteins and exists as two populations, namely light and heavy HDL. Gradients generated from two layers of iodixanol recovered bovine HDL in five fractions. The hypercholesterolaemia associated with lactation resulted in a modest shift in the profile of HDL cholesterol towards lipoprotein particles of lower density (light HDL). Significant between-farm differences were also detected in the density profiles of bovine plasma cholesterol. This new method is suitable for use in research and diagnosis in relation to lipoprotein metabolism disorders in cows.     

Effects of fish oil concentrate on lipoproteins and apolipoproteins in familial combined hyperlipidemia

Summary The effects of two moderate doses of long-chain n-3 fatty acids (3.0 and 4.5 g EPA + DHA per day for 4 weeks each) on serum lipids and lipoproteins of patients with familial combined hyperlipidemia (FCH) were studied in a double-blind, placebo-controlled clinical trial. In nine patients with FCH n-3 fatty acids led to a statistically significant, dose-dependent fall in very low density lipoprotein (VLDL) triglycerides (3 g/day: –42%, 4.5 g/day: –55%) VLDL cholesterol (3 g/day: –41%, 4.5 g/day: –47%), and VLDL apolipoprotein (apo) B-100 (3 g/day: –40%, 4.5 g/day: –56%). No overall change in low-density lipoprotein (LDL) cholesterol was found, as confirmed statistically. However, when analyzing the data of single patients LDL cholesterol and LDL apo B did not change in five patients but increased dose dependently (from pretreatment 4.80±0.93 mmol/l to 5.70+0.93 mmol/l LDL cholesterol after 4.5 g/day) in four. LDL and VLDL composition as indicated by cholesterol/apo B-100 and triglyceride/apo B-100 ratios did not change significantly. High-density lipoprotein (HDL) cholesterol was unchanged; the HDL cholesterol/apo A-I+apo A-II ratio increased by 19% (P<0.05) during fish oil treatment. We conclude that in FCH moderate doses of long-chain n-3 fatty acids are highly effective in lowering pathological VLDL triglycerides, VLDL cholesterol, and VLDL apo B. LDL cholesterol must, however, be monitored during treatment as it may rise substantially in some although not in all patients with this disease.Abbreviations EPA eicosapentaenoic acid - DHA docosahexaenoic acid - FCH familial combined hyperlipidemia - VLDL very low density lipoprotein - LDL low-density lipoprotein - HDL high-density lipoprotein - apo apolipoprotein Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

The effects of trimazosin and pindolol on serum lipids, blood glucose and serum insulin levels

The effects on plasma lipids, blood glucose and serum insulin levels of oral administration of trimazosin and pindolol over a 6-month period were studied in 11 patients with essential hypertension. Total plasma cholesterol and LDL cholesterol concentrations were higher (p less than 0.05) after one month's treatment with trimazosin than basal values, but the significance of changes disappeared with continuation of treatment. The concentrations of plasma triglycerides, VLDL cholesterol, HDL cholesterol and free fatty acids and the HDL cholesterol/total cholesterol ratio remained about constant during treatment with trimazosin. During pindolol treatment the plasma levels of total cholesterol and LDL cholesterol were slightly but not significantly lowered at 3 and 6 months. The levels of plasma triglycerides, VLDL cholesterol and HDL cholesterol remained about constant and the ratio of HDL cholesterol to total cholesterol had increased slightly (p less than 0.05) at 3 months. Serum free fatty acid concentration decreased significantly. There were no significant differences between plasma lipid levels during either trimazosin or pindolol treatment. Blood glucose concentrations showed a slight tendency to increase during the treatment periods, but no impairment in insulin release was found.     

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.Abbreviations: CEE conjugated equine estrogens - HDL high-density lipoproteins - HRT hormone replacement therapy - LDL low-density lipoproteins - TG triglycerides - VLDL very low density lipoproteins Correspondence to: U. Julius     

Unterschiedliche Werte von Lipoprotein Lp(a) bei erwachsenen Diabetikern in Abhängigkeit von der Therapieform

Summary A total of 60 newly admitted hospital patients with maturity onset diabetes mellitus and normal kidney function were studied. They were either treated only with a diet (group I), or also with blood-sugar lowering sulfonylureas (group II). Some patients had become insulin-dependent (group III). It was found that the mean serum concentration of lipoprotein Lp(a) was significantly increased in patients in groups II and III, but not in group I, as compared to the median of the group of 51 normal controls. All three groups of diabetics showed normal LDL cholesterol levels but lowered HDL cholesterol values, most pronouncedly in group II. Groups I and II, but not group III, showed a significant increase of the mean serum concentration of triglycerides and of the mean values for the LDL/HDL ratio as compared to normal controls. A correlation between the serum concentration of Lp(a) on the one hand, and the HbA₁ value, LDL cholesterol, VLDL, HDL cholesterol, phospholipids, triglycerides and total cholesterol on the other, cannot be found for any of the three groups of diabetics.

     

Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia

Hyper-alpha-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (beta-VLDL) and triglyceride enrichment of low density lipoproteins (LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin:cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL2 density fraction. The only brother of the patient also had hyper-alpha-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL2. Deficiency of this enzyme activity thus causes accumulation of HDL2 in plasma leading to hyper-alpha-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.     

Lipid changes in the nephrotic syndrome: New insights into pathomechanisms and treatment

Summary The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apoliproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism.Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipidlowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in polyand monounsaturates fatty acids, has been recently tested by the author, with very promising results.Abbreviations LDL low density lipoproteins - VLDL very low density lipoproteins - HDL high density lipoproteins - Apo Apolipoprotein - LCAT Lecithin cholesterol acyltransferase - HMGCoA Hydroxymethylglutaryl coenzyme A Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)     

Effects on lipids and lipoproteins in women treated with oestradiol and progesterone

Thirty women with climacteric symptoms were treated for 4 months with 2 mg 17β-oestradiol and different doses of progesterone (50, 100 or 200 mg). The concentrations of total and free cholesterol, phospholipids, triglycerides (TG), apoprotein A1 and apoprotein B were determined in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) fractions and in serum. HDL levels increased and LDL levels decreased, while TG levels in VLDL remained unchanged, which indicates that the lipoprotein pattern is oestrogen-induced and that progesterone exerts little or no influence.     

Effect of furosemide on the lipid abnormalities in chronic renal failure

The effect of furosemide on the lipoprotein profile and the activities of postherapin plasma lipases were studied in 12 patients with chronic renal failure. The concentrations of serum total, VLDL and LDL triglycerides were significantly higher and the concentration of HDL triglyceride was significantly lower in the patients with renal failure than in healthy controls. HDL cholesterol was significantly lower in the patients than in the controls. The activity of postherapin lipoprotein lipase was significantly lower in the patients than in the controls. The introduction of furosemide induced a significant increase in the concentrations of VLDL cholesterol and VLDL triglyceride. These changes were reversed when the drug treatment was discontinued. Postherapin lipase activities were not further altered by furosemide.     

Elevated lipoprotein(a) levels in patients with acute myeloblastic leukaemia decrease after successful chemotherapeutic treatment

Summary Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to investigate disease-associated changes in lipid metabolism. Lipoprotein (a) [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23 mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87 and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol and HDL levels increased in all 10 and LDL in 9 cases in which complete remission was achieved. These data suggest that the catabolism of LDL-cholesterol might be even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a) level in acute myeloblastic leukaemia is influenced either directly or indirectly by the leukaemic blasts.Abbreviations AML acute myeloblastic leukaemia - Lp(a) lipoprotein (a) - LDL low density lipoprotein - HDL high density lipoprotein - FAB French-American-British - CALGB cancer and leukaemia group B - CR complete remission - TG triglycerides - VLDL very low density lipoprotein - RIA radioimmunoassay - apo(a) apoprotein (a) - HMG-CoA reductase 3-hydroxy-3-methylglutaryl coenzyme A reductase Supported by the Volkswagen Stiftung with a grant to A.N.     

Effects of continuous medroxyprogesterone acetate on lipoprotein metabolism in postmenopausal women receiving estrogen

Objective: To investigate the effects of medroxyprogesterone acetate (MPA) on the beneficial effects of estrogen therapy on lipid metabolism in postmenopausal women. Methods: Postmenopausal women were administered either conjugated equine estrogen (CEE) 0.625 mg daily for 3 months (Group 1) or CEE 0.625 mg in conjunction with MPA 2.5 mg (Group 2) or MPA 5.0 mg (Group 3) daily for 3 months. Plasma levels of cholesterol, triglyceride, lipoprotein lipids, apolipoproteins, sex steroid hormones and lecithin cholesterol acyltransferase activity (LCAT) were determined. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activities were measured in postheparin plasma. Changes in the lipid concentrations and enzymatic activities were evaluated in each group. Results: Total, low-density lipoprotein (LDL) cholesterol, apolipoprotein B concentrations and LCAT activity were all significantly reduced by treatment in the three groups. The levels of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol as well as the levels of apolipoprotein AI and AII were significantly elevated in groups 1 and 2. The mean decrease in these parameters was related to the dose of MPA. Levels of triglyceride in the HDL and HDL2 were significantly increased in group 1. The levels of triglyceride in plasma, very low density lipoprotein (VLDL), LDL, HDL3 and VLDL cholesterol and LPL activity were unaffected. H-TGL activity was significantly inhibited only in groups 1 and 2. MPA produced a dose-dependent increase in H-TGL activity. A significant negative correlation was observed between the HDL cholesterol concentration and H-TGL activity (r = 0.58 P < 0.001). Conclusions: The administration of MPA 2.5 mg and 5.0 mg did not adversely affect the changes in VLDL-LDL metabolism produced by estrogen. However, MPA has dose-dependent negative effects on HDL metabolism by increasing H-TGL activity and the 5.0 mg MPA interferes with the favorable effects on lipids of estrogen in postmenopausal women.     

Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women

OBJECTIVE: To investigate the effects of short-term administration of melatonin on lipoprotein metabolism in normolipidemic postmenopausal women. METHODS: Fifteen such women received 6.0 mg melatonin daily for 2 weeks. Blood was sampled before and after treatment. We measured concentrations of total cholesterol and total triglyceride in the plasma, as well as the levels of cholesterol, triglyceride, and protein in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Plasma apolipoprotein levels were determined by immunoturbidimetric assay. Activities of lipoprotein lipase, hepatic triglyceride lipase, and lecithin cholesterol acyltransferase were also determined by enzymatic analysis. RESULTS: Melatonin administration significantly increased the plasma levels of triglyceride by 27.2% (P < 0.05), of VLDL-cholesterol by 37.2% (P < 0.01), of VLDL-triglyceride by 62.2% (P < 0.001), and of VLDL-protein by 30.0% (P < 0.05). However, the plasma total cholesterol level and the concentration of lipid and protein in LDL and HDL were not significantly affected. Melatonin significantly increased the plasma levels of apolipoprotein C-II by 29.5% (P < 0.005), of C-III by 17.1% (P < 0.001), and of E by 7.6% (P < 0.05). The plasma levels of apolipoprotein A-I, A-II, and B were not altered. Melatonin significantly inhibited the activity of lipoprotein lipase by -14.1% (P < 0.05), but did not significantly affect the activities of hepatic triglyceride lipase or of lecithin cholesterol acyltransferase. CONCLUSIONS: Findings indicate that melatonin increases the plasma level of VLDL particles by inhibiting the activity of lipoprotein lipase, but may not affect the plasma levels of LDL and HDL particles in postmenopausal women with normolipidemia.     

Effect of anti-hypertensive treatment on plasma lipids and lipoproteins (author's transl)

The authors attempted to evaluate through a literature review, lipid and lipoprotein changes induced by anti-hypertensive drugs (especially diuretics and beta-blockers). Generally, these drugs induce a modification of the lipid and lipoprotein profile towards profile atherogenicity by a moderate increase in total cholesterol, a marked increase in triglycerides and very-low-density lipoprotein triglycerides, and a decrease in high-density lipoprotein cholesterol. In theory, these changes could decrease or cancel the reduction in cardio-vascular risk obtained through the antihypertensive treatment but current data do not allow to confirm or disprove this hypothesis. However, it is certain that adherence to a suitable life-style and good dietary habits tend to reduce the associated risk factors and compensates, at least in part, for the effects of hypotensive drugs on the lipids and lipoproteins.     

Relative Effects of Insulin Resistance and Protease Inhibitor Treatment on Lipid and Lipoprotein Metabolism in HIV-Infected Patients

Abstract

Background: The relationship between insulin resistance, dyslipidemia, HIV infection, and antiretroviral therapy remains unclear, and the atherogenic nature of lipid and lipoprotein profiles in HIV-infected patients has not been fully characterized. Method: We measured plasma lipid and lipoprotein subfractions using Vertical Auto Profile-II methodology and directly measured insulin-mediated glucose disposal in 45 protease inhibitor (PI)-treated and non-PI-treated HIV-infected patients. Results: PI-treated patients had higher total, LDL, and narrow-density LDL cholesterol (p < .05) and a trend toward higher triglycerides, whereas HDL cholesterol and LDL particle characteristics were unrelated to PI use or history of lipodystrophy. Insulin sensitivity did not differ on the basis of PI therapy, but decreased insulin sensitivity was associated with lower HDL and HDL-3 cholesterol (p < .01); elevated triglyceride (p < .01), VLDL 1+2, and VLDL 3a+3b lipoproteins (p < .01); and smaller, denser (more atherogenic) LDL particle characteristics (p < .01). Thus, the lipoprotein abnormality associated with PI use was increased LDL cholesterol, whereas changes in TG and HDL metabolism were associated with insulin resistance, independent of PI use. Conclusion: The variables of PI-treatment, dyslipidemia, lipodsytrophy, and insulin resistance do not always cluster together in HIV-infected patients, which suggests that the metabolic phenotype emerging in treated patients results from a complex interplay of drug effects, immune restoration, and baseline insulin sensitivity.     

Die Wirkungen gleicher Mengen Linolsäure in oral zugeführten,mehrfach ungesättigten Phospholipiden oder in Safloröl auf die Lipoproteine des Plasmas

Summary The effects of polyenylphosphatidylcholine in a dosage of 10 g per day were compared with an equimolar amount of linoleic acid in 7 g safloroil per day in 8 healthy subjects for 3 weeks. The concentrations of cholesterol, triglycerides, phospholipids, apolipoproteins A-I, A-II and B were measured in serum, as well in VLDL, LDL, HDL, HDL₂, HDL₃ on the day before, after 2 and 3 weeks of application and 6 months after the experiment. The diet was controlled 10 days before and during the experiment using the dietary recall method. According to the dietary records there was an increase of fat supply during application of polyenylphosphatidylcholine inhibiting decrease of LDL cholesterol, which was observed with safloroil. Phospholipid concentrations increased significantly with polyenylphosphatidylcholine in VLDL. Apolipoprotein B in LDL was significantly decreased by both substances. Apolipoprotein A-I and A-II in HDL increased significantly with polyenylphosphatidylcholine. With safloroil this effect was limited to apolipoprotein A-I, but less impressive. The effects of both substances are comparable in the decrease of apolipoprotein B and probably cholesterol. A special effect of polyenylphosphatidylcholine was observed on phospholipids in VLDL and on apolipoprotein A-I and A-II in HDL.

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Abkürzungen PPC Polyenylphosphatidylcholin - VLDL Very low density lipoproteins - LDL Low density lipoproteins - HDL High density lipoproteins - LCAT Lecithin-Cholesterin-Acyl-Transferase     

Changes in lipoproteins and subfractions following oophorectomy and oestrogen replacement in peri-menopausal women

Serum cholesterol concentrations in lipoprotein fractions and subfractions were determined in 11 peri-menopausal women both before and after bilateral oophorectomy, as well as 60 days after commencement of oral oestradiol replacement therapy. Pre-operatively, all subjects were found to have normal lipid and lipoprotein concentrations. There was a post-operative increase in the total cholesterol level, which was attributed to a raised very-low-density lipoprotein (VLDL) cholesterol. Changes in high-density lipoprotein (HDL) subfractions HDL-2 and HDL-3 were noted but since these were compensatory little difference in total HDL cholesterol was observed. Following oral oestrogen replacement, the cholesterol level decreased as a result of a drop in both VLDL and low-density lipoprotein (LDL) cholesterol. The oestradiol-induced HDL cholesterol increment reflected an increase in the levels of both HDL subfractions.