Lipid Apheresis by Hemoperfusion: In Vitro Efficacy and Ex Vivo Biocompatibility of a New Low-Density Lipoprotein Adsorber Compatible with Human Whole Blood

Abstract: To date, selective extracorporeal low-density lipoprotein (LDL) removal can only be performed from plasma; that is, a plasma-cell separation step using a centrifuge or a plasma membrane separator is necessary initially. This article characterizes a new polyacrylate-based LDL adsorber directly applicable to whole blood . In vitro single-pass hemoperfusion tests using pooled donor blood showed quantitative adsorption of atherogenic LDL-cholesterol (LDL-C) and complete recovery of protective high-density lipoprotein C. Fibrinogen, another independent risk factor of atherosclerosis, was also adsorbed to a lesser extent. Single-pass ex vivo biocompatibility using fresh donor blood on-line was excellent and resulted in minimal cell loss. Neither signs of hemolysis nor activation of monocytes (interleukin-l production) were detected. Only slight activation of leukocytes (elastase release) and thrombocytes (platelet factor 4 secretion) as well as of coagulation (thrombin-antithrombin complex formation) and complement (C3a, C5a generation) was observed. Under the experimental conditions used, the optimal anticoagulation regimen was 0.5 IU heparin plus 0.375 mg citratelml blood. Priming the column with a buffer of pH 7.4 containing heparin, citrate, and Ca²⁺ is recommended. In conclusion, this new adsorber exhibited selective LDLC adsorption in vitro combined with excellent ex vivo biocompatibility and thus holds great promise for a successful clinical application in a closed-loop system in patients.     

LDL Hemoperfusion-A New Procedure for LDL Apheresis: First Clinical Application of an LDL Adsorber Compatible with Human Whole Blood

Abstract: To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 ± 8% and triglycerides by 23 ± 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 ± 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future.     

LDL Hemoperfusion-A New Procedure for LDL Apheresis: Biocompatibility Results from a First Pilot Study in Hypercholesterolemic Atherosclerosis Patients

Abstract: Current lipid apheresis techniques can remove atherogenic lipoproteins only from plasma. The initial mandatory separation of plasma and blood cells renders the extracorporeal circuit complex. We recently described the first clinical application of a new lipid adsorber that adsorbs low-density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) directly from whole blood. In continuation of our work, this paper describes the clinical biocompatibility of this new LDL hemoperfusion system. In a 2 center phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation protocol consisted of an initial heparin bolus followed by an acid citrate dextrose-A (ACD-A) infusion during the treatment. One patient blood volume was treated per session. All sessions were clinically un eventful. No signs of hemolysis or extracorporeal clot formation could be detected, and cell counts remained virtually constant. In a subgroup of patients (n = 4–6), further biocompatibility parameters were studied. Activation of leukocytes (elastase release), thrombocytes (β-thrombo-globulin [β-TG] extrusion), and monocytes (interleukin (IL)-1β and IL-6) were minimal. Complement activation (C3a and C5a generation) was negligible. The chosen anticoagulation protocol was both safe (constant ionized calcium levels) and effective (low thrombin-antithrombin formation). In summary, within the scope of a first pilot study. this new LDL hemoperfusion procedure combined the features of excellent clinical tolerance, good biocompatibility, and ease of handling. Phase III clinical trials will have to show whether these encouraging preliminary results can be corroborated in a larger patient population.     

State of the Art of Lipid Apheresis

Abstract: Currently, 5 different lipid apheresis procedures are available for routine clinical treatment of hy–percholesterolemic patients. Unselective plasma exchange is a technically simple extracorporeal circuit, but albumin substitution fluid must be used and there is no high–density lipoprotein (HDL) recovery. Semiselective double filtration with improved size selectivity because of a small–pore secondary filter combines good elimination of low–density lipoprotein (LDL), lipoprotein (a) (Lp[a]), and fibrinogen with adequate HDL recovery; modifications such as thermofiltration, predilution/backflush, or pulsatile flow have been proposed for the improvement of this system. Three highly selective procedures are basedon immunologic or electrostatic interactions: immunoad–sorption using anti–low–density lipoprotein (LDL) antibodies, chemoadsorption onto dextran sulfate, and hep–arin–induced LDL precipitation (HELP) apheresis. The features of each system are discussed critically. Lastly, two new developments, Lp(a) immunoadsorption and LDL hemoperfusion using a polyacrylate LDL adsorber compatible with whole blood, are described     

Low–Density Lipoprotein Removal Methods by Membranes and Future Perspectives

Abstract: Since the application by Thompson et al. in 1975 of plasma exchange for the treatment of 2 patients with familial hyperlipidemia, plasma purification techniques for selective low–density lipoprotein (LDL) removal (i.e., LDL apheresis) have been developed and adopted for the management of this disease. Thermofil–tration is one of the LDL apheresis systems that utilizes membrane techniques developed by Nose and Malchesky's group in 1985. This article reviews its rationale, in vitro studies, animal studies, and clinical investigation. Thermofiltration effectively and selectively removes LDL cholesterol while retaining in the plasma physiologically important macromolecules such as albumin and high–density lipoprotein (HDL) cholesterol. Based on the global view of the treatment of atherosclerosis by LDL apheresis, membrane techniques are as effective, safe, and simpler to apply than other methods. Additionally, these methods are effective for the removal of lipoprotein (a) and fibrinogen; thus, they can address the needs in these application areas.     

LDL Apheresis: A Novel Technique (LIPOCOLLECT 200)

Therapeutic means to lower Lp(a) are limited. The most effective method to reduce plasma Lp(a) concentration significantly is therapeutic apheresis, namely, low‐density lipoprotein (LDL) lipoprotein(a) (Lp(a)) apheresis. A novel technique based on reusable LDL adsorber called Lipocollect 200 (Medicollect, Rimbach, Germany) allows the removal of both LDL and Lp(a) from plasma. Two male patients with hyperLp(a)lipoproteinemia and angiographically established progressive coronary heart disease, without rough elevation of LDL‐cholesterol, who did not respond to diet and medication were submitted to 50 LDL Lp(a) aphereses with Lipocollect 200 LDL Lp(a)‐adsorber at weekly and biweekly intervals. Total cholesterol and LDL cholesterol plasma levels fell significantly by 48.3% (±6.7) to 61.6% (±12.7) (first patient), and 42.5% (±6.3) to 60.6% (±14.3) (second patient), respectively (all differences: P ≤ 0.001). High‐density lipoprotein (HDL)‐cholesterol concentration in plasma did not show statistically significant change. Plasma triglycerides were also significantly reduced by 43.6% (±24.4) (first patient) and 42.3% (±13) (second patient) (both differences: P ≤ 0.001). Plasma Lp(a) showed a statistically significant percent reduction in plasma as expected: 64.7 ± 9.5 (first patient), and 59.1 ± 6.7 (second patient) (both differences: P ≤ 0.001). Plasma fibrinogen concentration was decreased by 35.9% (±18.7) (P ≤ 0.05) (first patient) and 41.8% (±11.5) (second patient) (P ≤ 0.005). Considering the reduction rate between the first and the last procedures, we have compared the mean percent reduction of the first five treatments (from session #1 to #5) with the last five treatments (from session #21 to #25). We have observed an increasing reduction of all activity parameters on both patients apart from HDL‐cholesterol (first patient) and triglyceride (second patient) that showed a decreasing reduction rate. Both patients followed the prescribed schedule and completed the study. Clinically, all sessions were well tolerated and undesired reactions were not reported. The Lipocollect 200 adsorber proved to have a good biocompatibility. In this study, the adsorber reusability for several sessions was confirmed.     

Treatment of Homozygous Familial Hypercholesterolemia with Low Density Lipoprotein Apheresis: A 4 Year Follow-Up Study

Abstract: Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50–60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70–75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.     

Short–and Long–Term Effects on Serum Lipoproteins by Three Different Techniques of Apheresis

Abstract: Low–density lipoprotein (LDL) apheresis is applied in patients with coronary heart disease because of severe inherited forms of hypercholesterolemia, for which dietary and combined drug treatment cannot lower LDL cholesterol concentrations less than 130 mg/dl. The following article describes the changes in lipoprotein levels in a total of 19 patients undergoing weekly LDL apheresis. Immunoadsorption, operating with polyclonal antibodies against apolipoprotein B–100, was used in 6 patients. Five patients were put on heparin–induced extracorporeal LDL precipitation (HELP) therapy; 6 received dextran sulfate adsorption treatments. Under steady–state conditions a single treatment reduced LDL cholesterol by 149 ± 3 m/dl with immunoadsorption, 122 ± 2 mg/dl with HELP, and 124 ± 18 mg/dl with dextran sulfate adsorption. Lipoprotein (a) (Lp[a]) declined by 52 to 65%. Very low density lipoprotein (VLDL) cholesterol and VLDL triglycerides declined by 45 to 55% because of the activation of lipoprotein lipase and precipitation during the HELP procedure. In all procedures, there was a small reduction in the different high–density lipoprotein fractions, which had returned to normal after 24 h. The long–term HDL3 cholesterol levels increased significantly. During all procedures there was a decrease in the molar esterification rate of lecithin cholesterol acyltrans–ferase activity. All changes in lipid fractions were paralleled by changes in the corresponding apolipoprotein levels. It is concluded that all three techniques described are powerful tools capable of lowering LDL cholesterol in severe hereditary forms of hypercholesterolemia. In HELP and dextran sulfate adsorption, the amount of plasma is limited by the elimination of other plasma constituents. Immunoadsorption may thus be preferred in very severe forms of hypercholesterolemia.     

DALI apheresis in hyperlipidemic patients: biocompatibility, efficacy, and selectivity of direct adsorption of lipoproteins from whole blood

Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.     

Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.     

Efficacy and safety of a new whole-blood low-density lipoprotein apheresis system (Liposorber D) in severe hypercholesterolemia

Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole-blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/- 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01), while high-density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high-risk patients.     

Catabolism of lipoprotein-X (Lp-X) induced by infusion of 10% intralipid]

In order to clarify the metabolism of Lipoprotein X (Lp-X) induced by intravenous Intralipid 10%, in vitro experiments using purified Lp-X from the sera of the patients receiving Intralipid 10% were carried out. 1) Lp-X or high density lipoprotein (HDL) was incubated with J-774 macrophages laden with [3H] cholesterol. Marked extraction of cholesterol from macrophages by Lp-X as well as HDL was observed. 2) [3H] cholesterol labelled Lp-X or oxidized LDL (o-LDL) was incubated with J-774 macrophages. Incorporation of Lp-X into macrophages was negligible comparing to o-LDL. 3) [3H] cholesterol labelled Lp-X, low density lipoprotein (LDL), or HDL was incubated with Hep G2 cells was less than LDL, but similar to that of HDL. These results indicated that Lp-X extracted cholesterol from peripheral tissues during its formation, and it was not catabolized by the scavenger pathway, but catabolized by the LDL pathway of hepatocytes.     

Extracorporeal Removal of Lipids by Dextran Sulfate Cellulose Adsorption

Abstract: Extracorporeal removal of low–density lipoprotein (LDL) cholesterol by dextran sulfate adsorption is indicated in patients with diet and drug resistant hypercholesterolemia to prevent or to regress coronary heart disease. Plasma separation is the first step in the process, followed by adsorption of LDL cholesterol and lipoprotein (a) (Lp[aJ) to negatively charged dextran sulfate co–valently bound to cellulose beads. The reduction per treatment in LDL cholesterol is 65–75% and in Lp(a) 40–60%. In most patients one treatment per week is sufficient to reduce mean LDL to 100–150 mg/dl. Minor side effects occur in 2–6% of treatments. Major side effects are rare. In uncontrolled studies long–term treatment was associated with inhibition of progression and induction of regression of coronary artery disease. LDL apheresis by dextran sulfate may increase blood perfusion of some tissues, and preliminary results indicate a beneficial effect on therapy resistant nephrotic syndrome with hypercholesterolemia.     

Lipid Apheresis: From a Heroic Treatment to Routine Clinical Practice

Abstract: Lipid apheresis has developed from a heroic treatment into a routine clinical therapy and currently is the major indication for performing extracorporeal plasma therapy. Whereas it was once reserved for patients with homozygous familial hypercholesterolemia, today it has a place in the secondary prevention of severe coronary heart disease when low-density lipoprotein (LDL)-cholesterol levels exceed 150 mg/dl, despite conservative treatment, in any type of primary hypercholesterolemia. Unselective plasma exchange has been replaced by a variety of selective procedures. The efficacy of the treatment can be maximized by combining LDL apheresis with the use of cholesterol synthesis enzyme inhibitors. Clinical studies have shown that drastic cholesterol reduction can result in regression of coronary atherosclerosis as well as in reduced cardiac morbidity and mortality. Technical progress comprises improved selectivity, online regeneration of adsorbers, and LDL adsorption from whole blood. Recently, a new LDL hemoper-fusion procedure was successfully tested in a clinical pilot study; blood is passed directly over a lipid sorbent without prior plasma separation. If this system is demonstrated to be safe and effective in clinical Phase III trials, a further qualitative step in the rapid development of LDL apheresis will have been made.     

Development of a Potassium-Specific Adsorbent for Direct Hemoperfusion

Abstract: Direct hemoperfusion (DHP) over an exchange resin for sodium is capable of rapidVVly lowering an vated serum potassium level but has not been used clin- ically because of subsequent electrolyte abnormalities. After the completion of detailed in vitro studies, we de- veloped a sodium/calcium/magnesium exchange resin mixture specifically to remove potassium from the blood. The mixture, which consisted of exchange resins for so- dium (48%), calcium (48%), and magnesium (4%), gave the most satisfactory results in vitro. DHP through these resin-mixture columns for 2 h reduced elevated plasma potassium levels (6.7 ± 1.1 to 3.5 ± 0.6 mEq/L, p < 0.001) in anephric dogs without including any significant change in the levels of sodium, calcium, magnesium, al- bumin, total protein, or cholesterol. The platelet losses and changes in the plasma free hemoglobin levels ob- served were similar to those found with activated char- coal hemoperfusion. These results suggest that this resin hemoperfusion may be useful in patients with acute hyperkalemia.     

HMG-CoA reductase,cholesterol 7alpha-hydroxylase,LCAT, ACAT,LDL receptor,and SRB-1 in hereditary analbuminemia

BACKGROUND: Hereditary analbuminemia is associated with hypercholesterolemia, which has been shown to be primarily caused by increased extrahepatic production of cholesterol. Nagase rats with hereditary analbuminemia (NAR) have been used as a model to dissect the effect of primary hypoalbuminemia from that caused by proteinuria in nephrotic syndrome. The present study was undertaken to explore the effect of hereditary analbuminemia on protein expression of the key factors involved in cholesterol metabolism. METHODS: Hepatic tissue protein abundance of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7alpha-hydroxylase (a rate-limiting enzyme in cholesterol catabolism), low density lipoprotein (LDL) receptor, high density lipoprotein (HDL) receptor (SRB-1), acyl-coA cholesterol acyltransferase-2 (ACAT-2), and plasma concentration of lecithin cholesterol acyltransferase (LCAT), as well as HMG-CoA reductase, ACAT, and LCAT activities were determined in fasting male NAR and Sprague-Dawley control rats. RESULTS: The NAR group exhibited significant up-regulation of HMG-CoA reductase protein abundance but normal HMG-CoA reductase enzymatic activity. This was coupled with a significant up-regulation of cholesterol 7alpha-hydroxylase and a mild up-regulation of ACAT protein abundance and activity. However, hepatic LDL receptor and HDL receptor and plasma LCAT protein concentration and activity were normal in NAR. CONCLUSION: Hypercholesterolemia in NAR is associated with elevated hepatic HMG-CoA reductase protein abundance, but normal HMG-CoA reductase activity. These findings point to post-translational regulation of this enzyme and favor an extrahepatic origin of hypercholesterolemia in NAR. The observed up-regulation of cholesterol 7alpha-hydroxylase represents a compensatory response to the associated hypercholesterolemia. Unlike nephrotic syndrome, which causes severe LDL receptor, HDL receptor, and LCAT deficiencies, hereditary analbuminemia does not affect these proteins.     

非创伤性股骨头坏死与血浆脂蛋白的相关性研究

目的　研究非创伤性股骨头坏死与血浆脂质变化的相关性。方法　研究对象 12 0例 ,其中 60例非创伤性股骨头坏死患者和 60例正常人 ,采用奥林帕斯 (Olypas)AU 40 0全自动生化分析仪 ,检测总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白 (HDL)、低密度脂蛋白 (LDL)、载脂蛋白AI(ApoAI)、载脂蛋白B(ApoB)等指标。结果　股骨头坏死组与正常对照组血浆脂质及载脂蛋水平比较 ,TC、TG、LDL、ApoB明显升高 (P <0 0 5 ) ,HDL、ApoAI明显降低 (P <0 0 5 ) ,ApoB/ApoAI比值显著升高 (P <0 0 0 1)。结论　非创伤性股骨头坏死的发生和发展与血浆中的脂蛋白有密切关系 ,ApoB/ApoAI比值升高对估计非创伤性骨坏死的发生具有一定的临床意义     

黄芪注射液对原发性慢性肾小球疾病的治疗作用

目的:观察黄芪注射液辅助治疗慢性肾小球疾病的临床疗效.方法:随机将66例慢性肾小球疾病患者分为对照组(33例)和黄芪注射液治疗组(33例).对照组按原发性肾小球疾病常规治疗,治疗组在常规治疗的同时加用黄芪注射液,疗程14 d.分别在治疗前及14 d疗程后观察并记录血常规、24 h尿蛋白定量、血浆总蛋白、白蛋白、血尿素氮、肌酐、血总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白及血压.结果:黄芪注射液治疗组24 h尿蛋白定量明显降低(P＜0.01),血总蛋白及白蛋白明显升高(P＜0.01,P＜0.05),总胆固醇、甘油三酯、低密度脂蛋白明显降低(P＜0.05),高密度脂蛋白、血压、红细胞及血红蛋白比较无统计学差异(P＞0.05).结论:黄芪注射液不仅能明显的降低蛋白尿,而且具有降低血脂及升高血浆蛋白作用.     

Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins,C-reactive protein and in vivo oxidized LDL

BACKGROUND: Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-stage renal disease (ESRD). Dyslipidemia may be a major contributor in this process and can be influenced by lipid-lowering drugs (statins). Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP). METHODS: We evaluated in a single-blind randomized trial of 28 ESRD patients on hemodialysis, the dose-depending effects of both atorvastatin and simvastatin on lipids, lipoproteins, LDL particle heterogeneity, high sensitive-CRP, and markers of in vivo LDL oxidation. RESULTS: Both statin therapies significantly lowered total plasma cholesterol and LDL-cholesterol concentrations to the same extent, whereas reduction in the concentrations of triglyceride-rich particles was less pronounced. Furthermore, statin therapy reduced LDL cholesterol in all LDL subfractions, without altering the overall LDL particle density. After both statins plasma hs-CRP concentrations were not significantly reduced; parameters of in vivo LDL oxidation (plasma ox-LDL concentration and the oxidation level of isolated LDL), were significantly decreased. Autoantibodies against ox-LDL, however, did not change during this trial period. CONCLUSIONS: These results show that atorvastatin and simvastatin exhibit comparable favourable effects on lipid profiles in ESRD. Moreover, the reduction of in vivo oxidatively modified LDL as shown in this ESRD population, may indicate that these statins exhibit favourable effects on oxidative stress in vivo.     

Apolipoprotein E-containing lipoproteins and lipoprotein remnants in experimental canine diabetes

The effects of diabetes on plasma lipoproteins were examined in a cohort of control and streptozocin-alloxan diabetic beagles fed either standard rations or an atherogenic cholesterol-supplemented diet. Lipoprotein cholesterol, triglyceride, and retinyl ester concentrations were measured in fractions separated by density gradient ultracentrifugation. Individual lipoprotein classes and apolipoproteins were assessed by electrophoresis. Postheparin plasma lipoprotein triglyceride lipase activities were also examined. In the absence of added dietary cholesterol, diabetic animals became hypercholesterolemic with relatively increased low-density (LDL) and decreased high-density (HDL) lipoprotein cholesterol concentrations. Apolipoprotein E-containing beta- to alpha 2-migrating HDL1 (HDLc) appeared in rho = 1.020-1.080 g/ml subfractions, whereas alpha 1-migrating typical HDL (rho = 1.06-1.21 g/ml) was reduced. In comparison to nondiabetic cholesterol-fed animals, diabetic cholesterol-fed animals had increased cholesterol (but not triglyceride) concentrations in very-low- and intermediate-density classes. These classes contained retinyl esters and low-molecular-weight apolipoprotein B (components of intestinal lipoprotein remnants) as well as apolipoprotein E and high-molecular-weight apolipoprotein B. These findings could not be explained by decreased postheparin plasma lipoprotein lipolytic activities. Increased plasma concentrations of HDLc in poorly controlled diabetic dogs may reflect a pathologic disturbance in the excretory limb of cholesterol transport from peripheral cells to the liver. In addition, exaggerated retention of lipoprotein remnants in cholesterol-fed diabetic dogs may contribute to increased delivery of cholesterol to extrahepatic tissues. This model appears to be suitable for physiologic studies of the effects of diabetes on reverse cholesterol transport.