Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HELP procedure provides a new means of treating high LDL concentrations in severe hypercholesterolemia with the unique additional effect of lowering Lp(a) and fibrinogen. In combination with HMG-CoA-reductase inhibitors a mean interval value of -75% for LDL as compared to the starting concentration may be achieved. The treatment has the advantage that the patient is not exposed to foreign proteins or compounds with attendant immunological problems. It displays a high degree of reproducibility and an almost unlimited capacity guaranteeing a constant therapy independent of the clinic performing the treatment. The first coronary angiographies after 2 years of HELP treatment in over 50 patients (to be reported elsewhere) give support to the hope that regression of coronary heart disease is possible in humans. Further studies and observations should eventually tell us at what level of LDL, Lp(a) and fibrinogen this may be expected. We trust that the clinical benefit of this treatment regimen will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL-levels by the development of premature coronary sclerosis.
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PMID:The HELP-system in the treatment of severe hypercholesterolaemia: acute and long-term experience. 185 46

Apolipoprotein (a)-Lp(a)-is reported to be an independent risk factor for coronary artery disease and for hemodialysis (HD) access occlusion. Homology with plasminogen may predispose to thrombosis. High concentrations usually have been reported in patients on HD and on continuous ambulatory peritoneal dialysis (CAPD), but near-normal values in many kidney transplants (TP). We used Pharmacia immunoradiometric assay in 52 patients on HD, 58 on CAPD, 94 after TP, and 56 controls. The Lp(a) mean levels for CAPD, HD, TP, and control groups were 738, 647, 348, and 368 U/l and the medians were 542, 537, 96 and 143 U/l, respectively. The means and medians for CAPD and HD were significantly greater than those for TP and controls (p < 0.003 for means and < 0.005 for medians). We found no significant difference between: (1) Lp(a) means or medians comparing HD and CAPD or TP and controls; (2) Lp(a) means for the 33 patients with insulin-dependent diabetes mellitus and the 171 without; (3) number of occlusions of HD fistulae or grafts in patients with high Lp(a) values and without; (4) mean Lp(a) for CAPD patients on gemfibrozil and also for TP patients on 3-hydroxy-methylglutaryl coenzyme 1 reductase inhibitors, or diet alone, before and after treatment, and (5) mean Lp(a) values for HD and CAPD patients with and without myocardial infarction. Lp(a) did not correlate significantly with fractional shortening or left ventricular end systolic or diastolic diameter by echocardiogram or with ejection fraction. For TP patients, Lp(a) and serum creatinine correlated (p = 0.004), and mean Lp(a) for 71 TP on ciclosporin A exceeded that for the other 23 patients (p < 0.03). Lp(a) fell in 13 of 14 patients after TP (mean fall 77%). The dominant Apo(a) isoform in 10 of 13 patients on CAPD or HD with high Lp(a) values was the equivalent of S2 (Utermann). Lp(a) in HD or CAPD is often elevated and regulated by both genetic and renal failure factors, but falls after TP with return of renal function and mainly genetic regulation. Lp(a) was not a risk factor for coronary artery disease in HD or CAPD patients and did not fall significantly with two drugs or diet.
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PMID:Comparison of Lp(a) concentrations and some potential effects in hemodialysis, CAPD, transplantation, and control groups, and review of the literature. 756 98

The problem of hypercholesterolemia following heart transplantation (HTx) is often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivates of nicotinic acids and fibrates were not successful due to Cyclosporin A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial, we investigated the effects of monotherapy with the HMG-CoA-reductase inhibitor Simvastatin in heart transplant recipients. The study included 70 patients (Simvastatin n = 37, control group n = 33). Eight patients died within the first 3 month postoperatively following HTx. Purpose of the study was adjustment of LDL-cholesterol-values in the Simvastatin-treated group to < 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol-plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < .001). In the same period the mean HDL-cholesterol values increased by approximately 15% in both groups. The ratio of LDL-/HDL-cholesterol was significantly lower in the Simvastatin treated group (2.28) than in the control group (2.94) (p < .01). There was no significant difference in Lp(a)-values. No adverse effects were observed within the following period of 24 months, particularly no increase in the frequency of rejection episodes. The drug induced hypercholesterolemia following HTx could be treated safely and effectively by low-dose Simvastatin.
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PMID:[Therapy of hypercholesterolemia after heart transplantation with the HMG-CoA reductase inhibitor simvastatin in long-term follow-up]. 771 16

"Is there any safe and optimal treatment of hyperlipidemia following heart transplantation?" The problem of hypercholesterolemia following heart transplantation if often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivatives of nicotinic acids and fibrates were not successful due to cyclosporine A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial we investigated the effects of the HMG-CoA-reductase inhibitor simvastatin in heart transplant recipients. The study included 70 patients (simvastatin n = 37, control group n = 33). 8 patients died within the first three months following heart transplantation. Purpose of the study was the adjustment of the LDL-cholesterol values in the simvastatin treated group to < or = 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < 0.001). In the same period the mean HDL-cholesterol values increased by approx. 15% in both groups (no significant difference [p > 0.05]). The ratio of LDL/HDL-cholesterol was significant lower in the simvastatin treated group (2.28) than in the control group (2.94) (p < 0.05). There was no significant difference in Lp(a) values. No adverse side effects were observed within the observation period of 24 months, particularly no increase in the frequency of rejection episodes. Summarizing the above, we recommend low-dose simvastatin therapy as a safe and optimal treatment of hypercholesterolemia following heart transplantation.
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PMID:[Can hyperlipidemia after heart transplantation be optimally and safely treated?]. 787 99

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.
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PMID:Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate. 801 68

The influence of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, on quantitative and qualitative changes in lipoprotein metabolism was investigated in 18 patients (group I, 10 with primary kidney disease and group II, 8 with diabetic nephropathy) with nephrotic syndrome. Nephrotic patients exhibited severe hyperlipidemia (serum cholesterol 390 +/- 17 mg/dl and triglyceride 335 +/- 42 mg/dl; mean +/- SEM) and had significantly higher lipoprotein (a) [Lp(a)] levels (54 +/- 12 mg/dl; median 31 mg/dl, p < 0.01) compared with 20 healthy subjects (mean 12 +/- 1.8 mg/dl; median 7 mg/dl). Fifty-six percent of the patients and 15% of the controls had values greater than 30 mg/dl. Treatment with simvastatin in increasing doses over a period of three months (13 patients received 40 mg/day and 5 patients 20 mg/day at the end of the third month) reduced LDL-cholesterol in both groups of patients (35% and 54%) as well as apolipoprotein B (apoB) (31% and 46%) significantly, but Lp(a) levels were not influenced (57 +/- 21 vs 59 +/- 20 and 50 +/- 14 vs 53 +/- 16 mg/dl, respectively). On the other hand a complex change in lipoprotein composition occurred. The ratio of LDL apoB/LDL cholesterol-ester increased significantly (0.75 +/- 0.03 to 0.84 +/- 0.03 and 0.80 +/- 0.03 to 1.02 +/- 0.1, respectively) and cholesterol concentration in VLDL (64 +/- 16 to 39 +/- 7 and 74 +/- 18 to 55 +/- 74 mg/dl, respectively) was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of simvastatin on lipoprotein (a) and lipoprotein composition in patients with nephrotic syndrome. 818 55

The relationship between lipoprotein(a) [Lp(a)] and metabolism of triglyceride-rich lipoproteins (TRL) was studied in 58 untreated patients with familial combined hyperlipidemia (FCH) from eight different kindreds, 17 spouse controls, and 17 unrelated controls. Lp(a) plasma concentrations were not significantly different between FCH subjects (343 +/- 61 mg/L, mean +/- SEM) and controls (249 +/- 52 mg/L). In FCH, log-transformed Lp(a) levels correlated positively with postheparin lipoprotein lipase ([LPL] r = .61, P = .0002) and hepatic lipase ([HL] r = .46, P = .008) activities and total plasma cholesterol level (r = .30, P = .03). In controls, Lp(a) correlated with LPL (r = .50, P = .04) and total plasma cholesterol level (r = .51, P = .003). In eight FCH patients, treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin resulted in significantly increased mean LPL activities and plasma Lp(a) concentrations. In three of these FCH patients, repeated measurements during 1 year demonstrated that changes in Lp(a) concentrations were paralleled by similar changes in LPL activity, but not HL activity. The observed correlation between postheparin plasma lipolytic activities and Lp(a) plasma concentrations suggests a connection between the metabolism of TRL and Lp(a).
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PMID:Lipoprotein(a) plasma concentrations associated with lipolytic activities in eight kindreds with familial combined hyperlipidemia and normolipidemic subjects. 851 May 21

Hypercholesterolemia is often the cause for the primary heart disease ultimately necessitating heart transplantation (HTx). After transplantation, persisting hypercholesterolemia results in an increased peroxidation of LDL retained by extracellular matrix of the intima. Oxidized LDL accumulates in monocyte derived macrophages, it leads to immobilization of tissue macrophages and provokes the expression of vascular adhesion molecules, growth factors and cytokines. In a prospective open controlled study, the impact of long-term cholesterol reduction by diet in combination with the HMG-CoA-reductase inhibitor Simvastatin on graft vessel disease (GVD) was evaluated. Patients of the control group received only a low fat diet. Simvastatin treatment decreased total and LDL-cholesterol significantly and was not associated with adverse effects. The one year angiographies revealed GVD in 24.1% of the control and 12.1% of the Simvastatin group (Study I). In high risk patients with LDL-cholesterol concentrations above 135 mg/dl, in spite of maximal Simvastatin treatment or plasma fibrinogen concentrations above 400 mg/dl, the heparin mediated extracorporeal low density lipoprotein precipitation (H.E.L.P.)-system was applied. H.E.L.P. was used either for prevention of GVD soon after HTx or for treatment of GVD after development of coronary lesions. Study II proved that the H.E.L.P.-system could significantly lower LDL-cholesterol, Lp(a) and fibrinogen in most high risk patients after HTx, resulting in successful prevention or even treatment of GVD.
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PMID:What is the role of lipid lowering therapy in heart-allograft failure? 858 84

Niacin has been used for many years to treat hyperlipidemia. It has been shown to reduce coronary death and non-fatal myocardial infarction and, in a separate analysis of long-term (15-year) follow-up, all cause mortality. It reduces total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides and increases high density lipoprotein cholesterol (HDL-C). Sustained-release niacin may be associated with more dramatic changes in LDL-C and triglyceride, whereas the short acting preparation causes greater increases in HDL-C. The increase of HDL-C occurs at a lower dose (1500 mg/day) than the reduction of LDL-C (> 1500 mg/day). Niacin also favorably influences other lipid parameters including lipoprotein(a) [Lp(a)], alimentary lipemia, familial defective apolipoprotein B-100 and small dense LDL. Combination of niacin with a bile acid sequestrant or a reductase inhibitor represents a powerful lipid-altering regimen. Whereas the reductase inhibitors and bile acid binding resins primarily affect LDL-C, the combined therapy has a synergistic effect to reduce LDL-C and, in addition, the niacin reduces triglycerides and increases HDL-C. The major drawback in the use of niacin is associated side effects (flushing and palpitations) and toxicity (worsening of diabetes control, exacerbation of peptic ulcer disease, gout, hepatitis). Niacin has a long history of use as a lipid lowering agent and has several attractive features. Unfortunately, the side effect profile of this agent warrants its use only in patients with marked dyslipidemia in whom side effects and potential toxicity are closely monitored.
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PMID:New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. 885 85

The strong familial occurrence of venous and arterial thromboembolic disease has prompted ongoing research to identify novel risk factors. Polymorphisms in the factor VII and prothrombin genes are related to increased thrombosis, but the mechanism of increased risk remains to be elucidated. Elevated levels of plasma homocysteine and of the variant lipoprotein(a) particle also contribute to increased thrombotic risk, due in part to polymorphisms in the apolipoprotein(a) gene and the gene for methylene tetrahydrofolate reductase.
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PMID:Update on genetic risk factors for thrombosis and atherosclerotic vascular disease. 992 32


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