Modification of serum and membrane lipid composition induced by diet in patients with chronic renal failure

Disorders of lipid metabolism during chronic renal failure (CRF) play a crucial role in the pathogenesis of early cardiovascular complication of this syndrome. In addition, some experimental evidence suggests that hyperlipidemia may accelerate progression of renal disease. We have studied 65 patients with CRF (S-creatinine 1.5-9.0 mg/dl), 52.3% of whom were hypertensive. Patients were divided in 2 groups matched for age, sex and degree of renal failure: group 1 was kept for 36 +/- 8 months on a free diet; group 2 was kept for 39 +/- 6 months on a low-protein diet with an elevated polyunsaturated/saturated fatty acid (PUFA/SFA) ratio. We found significantly higher levels of triglycerides (TG) and lower levels of esterified cholesterol in high density lipoprotein (HDL-C) in group 1 than in group 2. Patients on the diet had a lower percentage of membrane SFA and a higher percentage of PUFA than patients on free diet. Only in group 1 a direct correlation between cholesterol/phospholipid (Chol/P) ratio and age was observed; in group 2, a negative correlation between levels of PUFA and TG and between linoleic/oleic (Lin/Ol) ratio and serum Chol was shown. S-creatinine levels were directly correlated with Chol/P ratio in group 1 and indirectly with Lin/Ol ratio and PUFA in group 2. These data show that a low-protein diet, containing an elevated PUFA/SFA ratio, is able to counteract lipid abnormalities in patients with CRF and the normalization of this pattern is associated with significant improvement of membrane lipid composition and, presumably, of "functional" activity of cell membranes with a better control of supposed "renal lipoprotein toxicity".     

Lipid and apolipoprotein patterns during erythropoietin therapy: roles of erythropoietin, route of administration, and diet

Background. Long term effects of rHuEpo on the blood lipid profile have not been well documented. The aim of this paper is to prospectively evaluate whether rHuEpo therapy affects lipid metabolism, and whether these effects are influenced by changes in dietary habits and by route of rHuEpo administration. Methods. The study was performed in 33 maintenance haemodialysis patients (MHP) treated for one year with rHuEpo either intravenously (n = 15) or subcutaneously (n = 18), three times per week at the end of each dialysis session. The doses were 50 IU/kg intravenously or 35 IU/kg subcutaneously during the first 6 months and 20 IU/kg during the following months. The control group consisted of 17 MHP not treated with rHuEpo. Total cholesterol, LDL-cholesterol and HDL-cholesterol, triglycerides, apolipoproteins A1 and B, haemoglobin, serum albumin, blood urea nitrogen, serum creatinine, Kt/V, protein catabolic rate, and plasma erythropoietin were assessed at months 0, 2, 4, 6, 9, 12 and 2 weeks after rHuEpo discontinuation. Changes in food intake were evaluated on the basis of weekly dietary diaries before, and 3 and 9 months after treatment. Patients were divided into two groups: group A consisted of 19 patients who showed an increase in their energy intake (10% or more of basal value), and group B was formed by 14 patients without or with slight changes in their food intake. After the 6th month, dialysis schedules were adapted to new protein catabolic rate values in patients who increased their food intake. Results. During follow-up, there were no significant changes in any of the parameters in the control group. In group A, blood urea nitrogen, serum creatinine, protein catabolic rate, cholesterol, LDL cholesterol, triglycerides and apolipoprotein B increased significantly since the first months of rHuEpo treatment, and changes in cholesterol and apolipoprotein B correlated significantly with changes in protein catabolic rate. In group B, cholesterol, LDL cholesterol, and apolipoprotein B decreased significantly after the 6th month of treatment, without changes in blood urea nitrogen, serum creatinine and protein catabolic rate values. In both groups A and B, HDL cholesterol decreased significantly until the 6th month and returned to basal values in the following months and apolipoprotein A1 decreased until the 4th month and rose to levels higher than basal values in the following months. First rHuEpo administration and rHuEpo suspension at end of follow-up did not show any acute effect on lipid profile, despite significant changes in plasma erythropoietin values. Changes in lipid profile were similar with intravenous and subcutaneous administration of rHuEpo. Conclusions: We infer that long-term rHuEpo treatment positively affects the lipid profile, but in some patients who show exaggerated increase in their food intake these effects may be balanced and overcome by increment in some atherogenic blood lipid fractions. The changes in lipid and apolipoprotein patterns during rHuEpo therapy are not influenced by route of rHuEpo administration.     

Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol.

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.     

Tacrolimus as intervention in the treatment of hyperlipidemia after liver transplant

BACKGROUND: To measure the effect on serum lipids and other risk factors for cardiovascular disease, we converted the primary immunosuppression of dyslipidemic stable liver transplant recipients from cyclosporine A to tacrolimus. METHODS: Patients underwent a four-month dietary stabilization period (American Heart Association Step II diet) and serum lipid samples were collected for analysis at a central laboratory. After conversion, dietary counseling and lipid analyses were performed over a six-month postconversion observation period. RESULTS: Enrollment was terminated prematurely due to low patient recruitment rates. Thirteen patients were enrolled and provided postconversion data showing surprisingly strong results. At six months postconversion, total cholesterol (C) was reduced by a mean of 0.61 mmol/L (P=0.017), high density lipoprotein cholesterol (HDL-C) remained unchanged; the mean total C:HDL-C ratio was reduced by 0.87 (P=0.001). Low density lipoprotein cholesterol (LDL-C) reductions were not statistically significant, but we observed a significant and persistent decrease in apolipoprotein B (-0.15 g/L six months postconversion, P=0.031). No changes in homocysteine or in vitamins B6 and B12 were discerned, but although red cell folate remained stable, serum folate increased after conversion. We observed no rejection episodes or any other clinically notable events following conversion. CONCLUSIONS: In this study, conversion from cyclosporine to tacrolimus provided a safe and well-tolerated alternative that reduced hyperlipidemia and other recognized cardiovascular risk factors.     

Vitamin A deficiency results in dysregulation of lipid efflux pathway in rat kidney

The mechanisms of action of vitamin A deficiency (VAD) on lipid metabolism in the rat kidney were investigated in adult female rats and their offspring. The rats were randomized into three groups: (1) control, in which the mother and offspring received a normal diet (4000 retinol IU/kg diet) for 8 weeks; (2) VAD group, in which the mothers and offspring received a VAD diet (400 retinol IU/kg diet) for 8 weeks; (3) vitamin A-refed group, in which a group of pups on a VAD diet for 8 weeks received a complete diet (6500 retinol IU/kg diet) for 15 days. The lipid metabolism of the offsprings’ kidneys and its relation to the expression of apolipoprotein B100 (Apo-B100), liver X receptor α (LXRα), and retinoid X receptor-α/β (RXRα/β) mRNA was analyzed. VAD was found to alter renal lipid metabolism and its immune environment due to the expression of Apo-B100. Compared with the control, VAD rats had significantly higher levels of transforming growth factor-beta 1 and lower levels of ABCA1, a key gene involved in cholesterol efflux and tissue lipid homeostasis. The expression of LXRα and RXRα/β mRNA also decreased in the VAD rat kidney. Vitamin A refeeding reversed all of the changes. Lipid metabolism involved in renal reverse cholesterol transport may be mediated by decreasing the signaling through the ABCA1 cholesterol efflux pathway, which is significantly modified in kidneys of vitamin A-deficient rats.     

Lipid and apolipoprotein profiles of uremic dyslipoproteinemia--relation to renal function and dialysis

To study the effect of renal function on the development of lipid and apolipoprotein abnormalities in human renal disease, we have investigated 75 patients at different stages of renal insufficiency. The patient population consisted of 19 patients with less advanced renal failure (CRF:1) characterized by a mean glomerular filtration rate (GFR) of 37.4 +/- 14 ml/min, 31 patients with advanced renal failure (CRF:2) having a mean GFR value of 7.9 +/- 7.3 ml/min and 25 patients on maintenance hemodialysis (CRF:HD). Patients in the CRF:1 group had normal plasma triglyceride (TG) and total cholesterol (TC) levels. In the CRF:2 and CRF:HD group, TG levels were increased two- to threefold, together with a moderate elevation of TC levels. All patient groups had elevated levels of VLDL cholesterol and slightly decreased levels of HDL cholesterol. The apolipoprotein profile of all patient groups was characterized by significantly reduced levels of apolipoprotein (Apo)A-I and ApoA-II and significantly increased levels of ApoC-III. CRF:2 and CRF:HD patients had also moderately elevated levels of ApoB, ApoC-I and ApoC-II. Levels of ApoE were only elevated in CRF:HD patients. All patients, regardless of TG levels, had significantly lower ApoA-I/ApoC-III ratios than controls. GFR was positively correlated with ApoA-I and inversely correlated with TC, TG and ApoC-III. CRF:HD patients had slightly higher ApoA-I and ApoA-II and lower ApoB levels compared to CRF:2 patients. Patients with vascular disease had higher TC, TG, ApoB, ApoC-II and ApoE than patients without vascular disease. These results demonstrate that the dyslipoproteinemia with CRF is already manifested at the early stages of disease through its abnormal apolipoprotein rather than lipid profile.     

Carnitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients

There have been conflicting reports concerning the effect of carnitine supplementation on lipid metabolism in patients on peritoneal dialysis (PD). We investigated several parameters of lipid metabolism in pediatric PD patients supplemented with carnitine. The study included 20 patients receiving PD (treatment group) aged 2–18 years and a matched healthy control group. In the treatment group, baseline triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and apolipoprotein B levels were higher than in the control group. High-density lipoprotein cholesterol, free fatty acid, phospholipids, and apolipoprotein A-I levels were not different from those in the control group. The baseline plasma free carnitine level was lower and acyl-carnitine level was higher in the treatment group. No difference was found between the groups with respect to plasma total carnitine levels. Oral l-carnitine supplementation (50 mg/kg per day for 30 days) led to a significant decrease (from a baseline value of 146.6±51.8 mg/dl to 63.6±22.2 mg/dl, P<0.001) in apolipoprotein B levels, and no significant change in the other lipid parameters of the treatment group. Oral l-carnitine supplementation does not ameliorate the lipid profile in pediatric PD patients, but it causes a significant decrease in apolipoprotein B levels. Hence, carnitine supplementation may be recommended for decreasing apolipoprotein B levels in this patient population.     

Lipid metabolism in young males with hypotestosteronaemia and oligospermia prior to,during, and after treatment

Relationships between plasma testosterone levels and selected parameters of lipid metabolism were studied in a group of young sterile males prior to, during, and after hormone therapy. Initial hypertriacylglycerolaemia and decreased concentrations of HDL cholesterol returned to normal values after 30 days of methyltestosterone administration. LDL cholesterol concentrations decreased significantly as did plasma apolipoprotein B levels. These changes persisted also one month after cessation of treatment. The results suggest that restoration of initially decreased testosterone levels in the studied group of sterile males is associated with the restoration of the lipid profile.     

The clinical and biochemical effects of two combination oral contraceptive agents.

A comparison of the effects of two low-dose oral contraceptives on lipid metabolism was undertaken in an open-group comparative design study at the Family Planning Clinic, Groote Schuur Hospital, Cape Town. Sixty healthy women aged 18-35 years requesting oral contraception were allocated alternately to use a monophasic oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel (Marvelon, group A), or a triphasic oral contraceptive containing 30-40 micrograms ethinyloestradiol and 50-125 micrograms levonorgestrel (Triphasil, group B). The changes in the lipoprotein profile elicited by the two preparations differed significantly. Group A subjects had a much greater triglyceridaemic response (42.4%) than group B (14.6%) and had a significant increase in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (Apo-A1). In group B, HDL-C decreased and Apo-A1 showed little change. Non-HDL-C (NHDL-C) and Apo-B levels hardly changed in either group. The atherogenic ratios, NHDL-C/HDL-C and Apo-B/Apo-A1 were higher in group B. This study confirmed a significant difference in the response of plasma lipoproteins to the two oral contraceptive preparations. The evidence suggests that the desogestrel-containing oral contraceptive elicits a less atherogenic lipoprotein profile than does the levonorgestrel-containing preparation. Although unsupported by direct clinical evidence that changes in the lipoprotein pattern induced by oral contraceptives cause atherosclerosis, these effects should be considered when prescribing oral contraceptives for women who have risk factors for cardiovascular disease.     

雌性激素及脂质代谢异常在胆囊结石发病中的作用

目的 探讨雌性激素及脂质代谢异常在胆囊结石发病中的作用.方法 测定比较胆囊结石及胆囊息肉患者血清雌激素(E2)和孕激素(P)水平,血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和载脂蛋白A(APoA1)水平.采用免疫组化检测胆囊组织中雌激素受体(ER)及孕激素受体(PR)的表达.结果 胆囊结石患者血清E2和P水平明显高于胆囊息肉患者,胆囊结石组血清TC、TG、LDL-C水平高于胆囊息肉组,而HDL-C和APOA1水平在两组间差异无统计学意义.胆囊结石患者胆囊组织中ER及PR的阳性率明显高于胆囊息肉组.结论 E2和P通过作用于相应受体.使调控胆囊肌肉收缩的信号分子表达降低,导致胆囊收缩运动受损,胆囊胆汁淤积,同时雌激素可通过对肝脏脂质代谢的影响,使胆汁中胆固醇的饱和度增加,胆汁成石指数提高,可能在促进胆囊结石的形成中具有重要作用.     

Beneficial effects of fluvastatin on progressive renal allograft dysfunction

To assess the time-dependent changes in renal function in relation to antioxidant and lipid-lowering effects of fluvastatin in hyperlipidemic renal transplant recipients, 20 patients were treated with fluvastatin 40 mg/d for 12 months, after failure of a dietary program. Plasma malondialdehyde (MDA) levels and lipid profiles were evaluated in relation to serum creatinine and calculated creatinine clearances 18 months before and during the fluvastatin treatment. Mean baseline lipid values were: total cholesterol 318 mg/dL, triglycerides 212 mg/dL, LDL cholesterol 219 mg/dL, HDL cholesterol 58 mg/dL, apolipoprotein A 176 mg/dL, and apolipoprotein B 145 mg/dL. During 12 months of treatment, fluvastatin produced consistent and significant reductions in total and LDL cholesterol (-18.4% and -24.1%), triglycerides (-17.7%), and apolipoprotein B (-22.7%) as well as an increase in HDL cholesterol (12.3%) and apolipoprotein A (9.2%). Plasma MDA levels decreased by 41.8% (from 3.5 +/- 0.3 to 1.8 +/- 0.1 nmol/mL, P =.00002). Creatinine clearance, which had been declining at a rate of 0.32 mL/min/month during the previous 18 months before treatment, progressively improved during treatment, giving a positive slope of the creatinine clearance, which increased by 0.35 mL/min/month, (P =.016; 53.3 +/- 4.2 mL/min vs 49.8 +/- 4.1 mL/min pretreatment). Multiple linear regression analysis revealed that MDA was the parameter most closely associated with the variability in creatinine clearance. In conclusion, renal transplant patients with lipid abnormalities display renoprotective activity of fluvastatin, possibly due to its lipid-lowering and antioxidant effects.     

瘦素在胆囊胆固醇结石形成中的作用

目的 通过临床病例研究,探讨血清及胆汁中的瘦素在胆囊胆固醇结石形成中的作用与影响.方法 选取2016年3月1日-11月30日在内蒙古自治区人民医院肝胆胰脾外科住院行腹腔镜下或开腹胆囊切除术患者共91例,分为胆囊胆固醇结石组(A组)58例和非胆囊胆固醇结石组(B组)33例,以体重指数=24 kg/m2为标准,又将A组分成A1组30例(体重指数≥24 kg/m2)和A2组28例(体重指数＜24 kg/m2);B组分成B1组18例(体重指数≥24 kg/m2)和B2组15例(体重指数＜24 kg/m2).对A、B两组病例一般情况、体重指数、血清瘦素含量、胆汁瘦素含量、高密度脂蛋白、低密度脂蛋白、脂蛋白(a)、载脂蛋白AI、载脂蛋白B、载脂蛋白AI/载脂蛋白B比值、血清总胆固醇、血清总胆汁酸、三酰甘油等指标进行检测.计量资料用均数±标准差(-x±s)表示,组间比较使用t检验或t’检验.计数资料用频数和百分数表示,组间比较使用x2检验.体重指数和血清瘦素的相关性采用Pearson相关系数描写.结果 胆囊胆固醇结石组患者血清瘦素含量与非胆囊胆固醇结石组血清瘦素含量分别为(7.92 +7.34) ng/ml和(4.81±1.79) ng/ml,差异有统计学意义(P＜0.05),同时该组血清瘦素水平与体重指数呈正相关(r=0.65,P=0.01),当体重指数≥24 kg/m2时相关性明显(r =0.73,P ＜0.01).胆囊胆固醇结石组血清总胆固醇、低密度脂蛋白、载脂蛋白B、三酰甘油水平分别为(4.85±0.74) mmol/L、(2.53±0.69) mmol/L、(0.97±0.3) g/L、(1.92±0.61) mmol/L,非胆囊胆固醇结石组分别为(4.47±0.8) mmol/L、(2.22±0.50) mmol/L、(0.8 ±0.2) g/L、(1.49 ±0.69) mmol/L,与后者相比前者含量显著性增高(P＜0.05).胆囊胆固醇结石组高密度脂蛋白和载脂蛋白AI含量分别为(0.93±0.28) mmol/L、(1.38±0.27) g/L,与非胆囊胆固醇结石组(1.24 ±0.26) mmol/L、(1.53±0.21) g/L相比显著性降低(P＜0.05);两组胆汁瘦素含量、总胆汁酸、脂蛋白(a)差异无统计学意义(P＞0.05).结论 血清瘦素含量的改变,可能通过影响血液脂质、脂蛋白水平,以及胆汁中瘦素的含量,最终影响胆固醇结石的形成过程.     

Effects of fluvastatin on plasma lipid abnormalities in hemodialysis patients with chronic renal failure

Fluvastatin, an HMG-CoA reductase inhibitor, was administered at a dosage of 20 mg/day for 24 weeks to 11 hemodialysis patients with a high plasma total cholesterol (TC) level (> or = 220 mg/dl). Serum lipids, apolipoprotein, and malondialdehyde (MDA) levels were measured every 12 weeks. After 24 weeks of fluvastatin administration, the TC level had decreased by 10.5% (238 +/- 15 mg/dl-->203 +/- 25 mg/dl), the low density lipoprotein cholesterol (LDL-C) level had decreased by 16.2% (142 +/- 32 mg/dl-->119 +/- 26 mg/dl), and the HDL-C level had increased by 23.4% (47 +/- 15 mg/dl-->58 +/- 19 mg/dl). These changes were statistically significant and resulted in a reduction of the atherogenic index (AI: TC-HDL-C/HDL-C). The triglyceride (TG) level did not change significantly. The apolipoprotein A1 level increased by 9.1% (121 +/- 22 mg/dl-->132 +/- 20 mg/dl) and the apolipoprotein B level decreased by 20.2% (114 +/- 25 mg/dl-->91 +/- 20 mg/dl). The MDA level also decreased significantly (1.16 +/- 0.92 nmol/ml-->0.58 +/- 0.38 nmol/ml). No particular side effects were observed during the 24 weeks of fluvastatin administration. In conclusion, fluvastatin may play an important role in preventing significant oxidative stress and was shown to be safe and effective in reducing the TC, LDL-C, MDA and AI levels in dialysis patients with hypercholesterolemia. The possibility that this improvement in the plasma lipid profile of dialysis patients may decrease atherogenic complications requires further investigation, including long-term clinical observations.     

Dyslipidaemia and hyperlipidaemia following renal transplantation

The lipid metabolism of 93 patients with renal transplantation was prospectively studied. It was characterized by the serum levels of cholesterol, HDL, LDL, triglyceride, apolipoprotein A1, Apo B and lipoprotein (a) as well as by lipid electrophoresis. In addition to the examination of lipid concentrations, the authors looked for correlations with other metabolic changes, immunosuppressive treatment and the changes of body weight and hypertension following transplantation. Their conclusion is that hyperlipidaemic and dyslipidaemic changes, as reflected by the levels of total cholesterol, LDL and Apo B, are more considerable in women than in men. The levels of pre-beta and beta lipoprotein were not significantly lower in men than in women. With the passing of time after transplantation and with the reduction of the doses of cyclosporine and corticosteroids, the values of hypertension, hyper-lipidaemia and dyslipidaemia decreased. According to the follow-up results, the lipid values measured in the winter and autumn months are higher than those found in the summer. The importance of early and follow-up examinations and of the reduction of pathological metabolic alterations is emphasized. Based on the paper presented at the Hungarian Nephrological Congress, Debrecen, October 15, 1994.     

Conversion from cyclosporine microemulsion to tacrolimus-based immunoprophylaxis improves cholesterol profile in heart transplant recipients with treated but persistent dyslipidemia: the Canadian multicentre randomized trial of tacrolimus vs cyclosporine microemulsion.

BACKGROUND: Tacrolimus improves lipid profile in renal and liver transplant recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported. METHODS: One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion-treated heart transplant recipients with low-density lipoprotein cholesterol >2.5 mmol/liter and/or a total cholesterol/high-density lipoprotein cholesterol ratio >4 were recruited for the study. Complete lipid profile was assessed before (baseline) and after 6 months of treatment with either cyclosporine microemulsion maintenance (n=64) or tacrolimus conversion (n=65). RESULTS: At 6 months, tacrolimus-converted patients exhibited a greater decrease in total cholesterol (from 5.51 +/- 0.16 to 4.88 +/- 1.22 mmol/liter [tacrolimus], vs 5.61 +/- 1.36 to 5.38 +/- 0.87 mmol/liter [cyclosporine]; p = 0.0078). This decrease in cholesterol was caused largely by a decrease in low-density lipoprotein cholesterol (-0.41 +/- 0.54 [tacrolimus] vs -0.13 +/- 0.55 [cyclosporine]; p=0.0018). There were no changes in high-density lipoprotein cholesterol and triglyceride levels, but apolipoprotein B therapy was reduced in tacrolimus-converted vs cyclosporine-maintained patients (p=0.0003). By 6 months, 23.7% of tacrolimus- vs 6.7% of cyclosporine-treated patients met the target lipid levels for high-risk patients (p=0.0094). Conversion from cyclosporine to tacrolimus resulted in decreases in blood urea nitrogen, creatinine, and uric acid without any changes in glucose, HbA(1C), and insulin levels. CONCLUSIONS: Conversion from cyclosporine microemulsion- to tacrolimus-based immunoprophylaxis resulted in decreased cholesterol, apolipoprotein B, urea, creatinine, and uric acid without any clinically evident perturbation of glucose metabolism in stable heart transplant recipients with treated but persistent mild dyslipidemia.     

Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients

BACKGROUND: The effects of pancreas transplant alone (PTA) on cardiovascular risk factors (CRF) and cardiac function in type 1 diabetes mellitus (T1DM) patients are still unsettled. METHODS: We studied 13 T1DM patients who received PTA with portal drainage and 11 matched control patients. Parameters of glucose and lipid metabolism and several additional classic CRF were assessed before and up to 6 months posttransplant. Cardiac morphology and function were assessed by Doppler echocardiographic examination. RESULTS: Insulin independence was promptly achieved and then maintained after PTA. Total and low-density lipoprotein cholesterol levels were significantly lower after transplantation, whereas high-density lipoprotein cholesterol and triglyceride concentrations did not change. Both systolic and diastolic blood pressure values and fibrinogen levels improved significantly. In addition, PTA determined a significant amelioration of several morphologic and functional cardiac indices. None of the measured parameters changed in the control patients. CONCLUSIONS: PTA with portal drainage induces an early improvement of CRF and ameliorates cardiac function in patients with T1DM.     

Low-molecular-weight heparin (LMWH): influence on blood lipids in patients on chronic haemodialysis

A low-molecular-weight heparin (LMWH) has been compared to conventionalheparin in haemodialysis in a 12-month study. In a group of22 patients who had been on chronic haemodialysis for longerthan 12 months, the conventional, unfractionated heparin wasreplaced by a low-molecular-weight analogue (LMWH) (Fragmin,Kabi-Pharmacia Erlangen) for 6 months. Baseline values of lipoproteinprofile prior to the intervention were compared with resultsobtained after 2, 4 and 6 months of LMWH. Control values wereobtained 3 and 6 months after switching back to conventionalheparin. During the LMWH treatment total cholesterol decreasedsignificantly. This coincided with a significant decrease inLDL cholesterol and a minor decrease in total HDL cholesterol.There was no noticeable change in the HDL cholesterol subfractions.The decrease of LDL and HDL was accompanied by a distinct andcontinuous decrease of apolipoprotein B throughout the LMWHperiod while the apolipoprotein Al declined during the first2 months and then stabilized at this lower value. Triglyceridesincreased significantly during the first 2 months and then reboundedto the initial values by the end of the LMWH treatment period.After switching back again to conventional heparin the lipoproteinparameters returned to the starting values. We conclude thatthe long-term use of low-molecular-weight heparin instead ofconventional heparin for anticoagulation during dialysis maycontribute to a reduction of the cardiovascular risk factorsof haemodialysis patients.     

术中静脉输注不同剂量异丙酚对患者酸碱平衡及脂质代谢的影响

目的 评价术中静脉输注不同剂量异丙酚对患者酸碱平衡及脂质代谢的影响.方法 拟行广泛全子宫加盆腔淋巴结清扫术的宫颈癌患者60例,年龄30～64岁,体重40～75 kg,ASA Ⅰ或Ⅱ级,随机分为3组(n=20),Ⅰ组、Ⅱ组和Ⅲ组分别静脉输注异丙酚50、100、150μg·kg~(-1)·min~(-1).分别于麻醉诱导前即刻、开始静脉输注后1、2、3 h及术毕时行动脉血气分析,记录pH值、总二氧化碳(TCO_2)、碱剩余(BE)、HCO_3~-及乳酸(LA)浓度;取颈内静脉血样2 ml测定血清甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDLL-C)、载脂蛋白A_1(APOA_1)及载脂蛋白B(APOB)的浓度.结果 3组各指标均在正常范围内.与麻醉诱导前即刻比较,静脉输注异丙酚后3组pH值、TC_2、BE、HCO_3~-及APOA_1浓度降低,LA及TG浓度升高,Ⅱ组及Ⅲ组LDL-C浓度降低,Ⅲ组APOB浓度降低(P<0.05或0.01);与Ⅰ组比较,静脉输注异丙酚后Ⅱ组及Ⅲ组pH值、BE、LDL-C及APOB浓度降低,TG浓度升高,Ⅲ组TCO_2、HCO_3~、TC及APOA_1浓度降低(P<0.05或0.01);与Ⅱ组比较,静脉输注异丙酚后Ⅲ组pH值、TCO_2、BE、TC及APOB浓度降低,TG浓度升高(P<0.05或0.01).结论 短时静脉输注异丙酚时患者酸碱平衡及脂质代谢均在正常范围,但有发生代谢性酸中毒及脂质代谢异常的趋势,且与剂量有关.     

Pathogenesis of endogenous endotoxemia in chronic liver disease--with special reference to the experimental fatty liver in germfree animals

The effect of intestinal bacterial flora and endotoxin on fatty liver with germfree (GF) and conventional (CV) rat in the 12th and 24th week was investigated after giving fatty diet which was added 1% cholesterol-0.5% cholic acid to the basic diet. Results are as follows. Serum biochemistry Serum GOT, GPT, ALP and cholesterol values increased after giving the fatty diet in both groups. Limulus Gelation Test In CV group, endotoxin was detected in 2 of 10 cases in portal blood and was completely absent in arterial blood. After the fatty diet, endotoxin increased gradually both in portal and arterial blood. Cyclic AMP values on glucagon challenge (P/B ratio) In both groups, the levels of the P/B ratio maintained low values compared with control. In CV group, the values were lower in endotoxin positive cases than negative ones. Hepatic carbohydrate metabolism Abnormal hepatic F6P , glucose, FDP and PEP values were observed in CV group and reduction of the levels of hepatic F6P , G6P and glucose values were remarkable in GF group. Hepatic G6P in CV group and FDP in GF group remained unchanged. Impairment of F6P and G6P in CV group, was significant in endotoxin positive cases than in negative ones.     

Gene expression of LDL receptor, HMG-CoA reductase, and cholesterol-7 alpha-hydroxylase in chronic renal failure

BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic lipid profile and an increased risk of ischaemic cardiovascular disease. The associated hyperlipidaemia is reportedly ameliorated by erythropoietin (Epo) therapy. According to a recent report, rats studied 3 weeks after 5/6 nephrectomy and fed a high- protein diet exhibited increased activities of hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase (Ch-7 alpha- H), despite normal corresponding mRNA values. DESIGN AND METHODS: This study was designed to examine the effects of naturally progressing CRF of longer duration as well as those of Epo therapy on gene expressions of the key factors involved in hepatic cholesterol metabolism, i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H. Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy), Epo-treated CRF group (given Epo 150 U/kg/twice weekly) and sham-operated, placebo- treated normal controls. They were allowed free access to regular rat chow and studied 6 weeks after surgery. Liver mRNAs and protein mass or activities of the above factors were studied. RESULTS: Plasma cholesterol concentration was significantly increased in the CRF group (P < 0.001) and was modestly lowered (P < 0.05) by Epo therapy. However, microsomal cholesterol concentration and LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA as well as HMG-CoAR activity, and Ch-7 alpha-H and LDLR protein mass measurements were virtually identical in the three groups. Thus, hepatic LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA and protein measurements in rats with CRF were similar to those of the normal control group representing an inappropriate response to the associated hypercholesterolemia. Epo therapy led to partial amelioration of CRF- associated hypercholesterolaemia with no discernible effect on hepatic tissue expression of the above factors.