Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.
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PMID:University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial. 173 83

Eight patients with severe peripheral vascular atherosclerosis scheduled for abdominal aortic surgery were investigated to detect coexisting coronary artery disease. None of the patients had a history of angina pectoris or previous myocardial infarction. Preoperative computerised thallium-201 dipyridamole myocardial scintigraphy was abnormal in all patients, showing either myocardial scar tissue and/or ischaemia with redistribution and/or low washout. In all but one patient, the serum level of creatin kinase was elevated during the first postoperative days. In two patients, the serum concentrations of aspartate aminotransferase and lactate dehydrogenase were elevated. None of the patients showed clinical or electrocardiographical signs of acute myocardial infarction. Thallium-201 dipyridamole myocardial imaging is a new noninvasive method for detection of ischaemic heart disease in patients with severe peripheral atherosclerosis who are unable to perform a bicycle exercise test. The new programme for determination of regional washout appeared to be very precise and may be especially applicable in the case of low washout values.
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PMID:Thallium-201 myocardial scintigraphy during dipyridamole-induced coronary hyperaemia. First experiences with a new regional washout programme. 321 87

The effect of variable doses of ethanol on plasma lecithin: cholesterol acyltransferase (LCAT) activity was examined in male, atherosclerosis-susceptible squirrel monkeys over a 12-month period. Primates were divided into three groups: 1) Controls fed isocaloric liquid diet; 2) Low Ethanol monkeys given liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) High Ethanol animals fed diet plus vodka at 24% of calories. There were no significant differences between the treatments in serum glutamate oxaloacetate transaminase (SGOT), a measure of liver function. However, plasma LCAT activity (% esterification/min) measured in vitro was significantly reduced in High Ethanol monkeys while cholesterol esterification was elevated in the Low Ethanol group and intermediate in Controls. Similarly, the in vivo appearance of radiolabeled cholesteryl ester in high density lipoproteins (HDL) following the intravenous injection of 3H mevalonolactone was highest in the Low Ethanol primates, intermediate in Controls and significantly lower in monkeys fed the high alcohol diet. In vitro measurement of LCAT enzyme efficiency was similar for the three groups while substrate efficiency was lower in the High Ethanol treatment. Although LCAT activator (apoprotein A-I) was not markedly altered by dietary ethanol and the concentration of LCAT substrates (HDL free cholesterol and phosphatidyl choline) was significantly elevated in the High Ethanol group, subtle modifications in substrate-product composition may account for the observed reduction in cholesterol esterification. These include potential substrate and/or product LCAT inhibition resulting from increased concentrations of plasma free cholesterol, HDL lysophosphatidyl choline, and higher HDL2/HDL3 subfraction ratios, as well as alterations in HDL phospholipid fatty acid profiles in the High Ethanol group. Results from this study provide the first evidence of an anomalous enhancement in LCAT activity in nonhuman primates fed ethanol at 12% of calories and a marked depression in cholesterol esterification at the 24% dose which may be due to substrate alterations and product inhibition prior to overt biochemical evidence of liver dysfunction.
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PMID:Effect of ethanol on lecithin:cholesterol acyltransferase (LCAT) activity. 399 6

Ultrasonic and laboratory studies were performed in 816 white-collar workers over 35 years old who received health examination. Prevalence of fatty liver diagnosed by ultrasonography was 17.9% in all subjects and was maximum (24.4%) in males 45-49 years of age. Obesity index and body mass index were higher in fatty liver than in normal controls. Serum levels of glutamate pyruvate transaminase (GPT), cholinesterase, glutamate oxaloacetate transaminase (GOT), gamma-glutamyl transpeptidase (gamma-GTP), triglyceride, total cholesterol, uric acid, HbA1c and glucose were significantly higher, and a serum level of HDL-cholesterol was significantly lower in males with fatty liver than in controls with obesity. Prevalence of abnormal laboratory findings in fatty liver was also shown, and prevalence of fatty liver was prominently high in males with severe obesity or with mild elevation of GPT. A major cause of fatty liver was considered as obesity. In conclusion, fatty liver was a common cause of liver dysfunction and was closely related to risk factors for atherosclerosis especially in white-collar workers.
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PMID:[Ultrasonic and laboratory studies on fatty liver in white-collar workers]. 764 60

About 50 mg of silver leaf (metallic silver) was given daily by mouth to 30 healthy volunteers for 20 days. A statistically significant hypophospholipidemic, hypotriglyceridemic, hypocholesterolemic and hypoglycemic effect was observed. This was accompanied by a less marked fall in total lipids and significant rise in HDL-cholesterol. In addition, a decrease in plasma enzymes - alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatine phosphokinase (CPK), gamma glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH) was noted. This was statistically significant for all enzymes except CPK. The safety of ingested silver foil is indicated by absence of pathology in urine and unaltered levels of protein and albumin in the plasma. These observations suggest that silver could be beneficial in conditions like diabetes mellitus, obesity and atherosclerosis.
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PMID:Effect of silver leaf on circulating lipids and cardiac and hepatic enzymes. 1023 75

Preliminary data suggest that fluvastatin may be safely combined with fibrates. The Fluvastatin Alone and in Combination Treatment Study examined the effects on plasma lipids and safety of a combination of fluvastatin and bezafibrate in patients with coronary artery disease and mixed hyperlipidaemia. A total of 333 patients were randomly allocated in this multicentre double-blind trial to receive 40 mg fluvastatin alone (n=80), 400 mg bezafibrate (n=86), 20 mg fluvastatin+400 mg bezafibrate (n=85) or 40 mg fluvastatin+400 mg bezafibrate (n=82) for 24 weeks. Low-density lipoprotein (LDL)-cholesterol decreased >20% in all fluvastatin-containing regimens, with significantly greater decreases compared with bezafibrate alone (P<0.001). Bezafibrate alone and fluvastatin+bezafibrate combinations resulted in greater increases in high-density lipoprotein (HDL)-cholesterol and decreases in triglycerides compared with fluvastatin alone (P<0.001). Fluvastatin (40 mg)+bezafibrate was the most effective for all lipid parameters with a decrease from baseline at endpoint in LDL-cholesterol of 24%, a decrease in triglycerides of 38% and an increase in HDL-cholesterol of 22%. All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy, or between combination regimens. No clinically relevant liver (aspartate aminotransferase [ASAT] or alanine aminotransferase [ALAT]) greater than three times the upper limit of normal) or muscular (creatine phosphokinase (CPK) greater than four times the upper limit of normal) laboratory abnormalities were reported. This large study shows 40 mg fluvastatin in combination with 400 mg bezafibrate to be highly effective and superior to either drug given as monotherapy in mixed hyperlipidaemia, and to be safe and well tolerated.
Atherosclerosis 2000 Jun
PMID:Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study). 1129 92

Hyperlipidemia, a condition normally observed in cholestatic liver disease, is also a risk factor for the development of atherosclerosis. The relationship between the elevation of lipoproteins in cholestatic liver diseases and atherosclerosis formation has not been elucidated. In this study, we propose that the impairment of endothelium-dependent relaxation (EDR) of blood vessels in cholestatic liver diseases may lead to the development of atherosclerosis. Using bile duct ligation (BDL) in rats as a model, we examined the liver function, serum lipid profile, EDR and morphologic change of the aorta from both sham operated and BDL rats. Significant increases in liver and spleen weights, serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and the bilirubin level were observed in BDL rats. Upon bile duct ligation, the total and low-density lipoprotein cholesterol levels were increased but the high-density lipoprotein cholesterol and triglyceride levels were reduced. Less contractility and lowered response to acetylcholine-induced relaxation were found in aorta segments. In addition, the acetylcholine-induced relaxation was blocked by both L-NAME and 15 mM KCl. Our results suggest that both nitric oxide and endothelium-derived hyperpolarizing factor are important elements for the impairment of the EDR in BDL rats. In addition, a mild atrophy of the media of the aorta was detected in BDL rats. We conclude that the alterations of lipid profile and the mild atrophy of the media may lead to the impairment of EDR in the aorta in BDL rats, and these factors may potentiate the development of atherosclerosis.
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PMID:Change in lipid profile and impairment of endothelium-dependent relaxation of blood vessels in rats after bile duct ligation. 1285 Feb 41

The high-density lipoprotein (HDL)-Atherosclerosis Treatment Study showed that simvastatin plus niacin (mean daily dose 13 mg and 2.4 g, respectively) halt angiographic atherosclerosis progression and reduce major clinical events by 60% in patients with coronary artery disease (CAD) who have low HDL, in comparison with placebos, over 3 years. How safe and well-tolerated is this combination? One hundred sixty patients with CAD, including 25 with diabetes mellitus, with mean low-density lipoprotein cholesterol of 128 mg/dl, HDL cholesterol of < or =35 mg/dl (mean 31), and mean triglycerides of 217 mg/dl were randomized to 4 factorial combinations of antioxidant vitamins or their placebos and simvastatin plus niacin or their placebos. Patients were examined monthly or bimonthly for 38 months; side effects (gastrointestinal upset, nausea, anorexia, vision, skin, and energy problems, or muscle aches) were directly queried and recorded. Aspartate aminotransferase, creatine phosphokinase (CPK), uric acid, homocysteine, and fasting glucose levels were regularly monitored. A safety monitor reviewed all side effects and adjusted drug dosages accordingly. Patients who received simvastatin plus niacin and those on placebo had similar frequencies of clinical or laboratory side effects: any degree of flushing (30% vs 23%, p = NS), symptoms of fatigue, nausea, and/or muscle aches (9% vs 5%, p = NS), aspartate aminotransferase (SGOT) > or =3 times upper limit of normal (3% vs 1%, p = NS), CPK > or =2 times upper limit of normal (3% vs 4%, p = NS), CPK > or =5 times upper limit of normal, new onset of uric acid > or =7.5 mg/dl (18% vs 15%, p = NS), and homocysteine > or =15 micromol/L (9% vs 4%, p = NS). Glycemic control among diabetics declined mildly in the simvastatin-niacin group but returned to pretreatment levels at 8 months and remained stable for rest of the study. This combination regimen was repeatedly described by 91% of treated patients and 86% of placebo subjects as "very easy" or "fairly easy" to take. Thus, the simvastatin plus niacin regimen is effective, safe, and well tolerated in patients with or without diabetes mellitus.
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PMID:Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). 1475 79

A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [S(i)]), which is important given associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S(i), and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies.
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PMID:Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. 1544 93

To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atherosclerosis and coronary heart disease. The toxic effects of cholesterol on the liver and the relationship between the intake of a high cholesterol diet and hepatic fibrosis, however, have not been investigated clearly or histopathologically. Male Wistar rats were fed a diet supplemented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacrificed and analyzed via blood biochemistry, traditional microscopy and immunohistochemistry. Following the feeding of this diet, the rates of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total cholesterol in the rats were elevated consistently from week 3 and throughout the remainder of the experiment. From microscopic observation, hepatic necrosis, macrophage infiltration and steatosis increased markedly throughout the experiment. Hepatic fibrosis and myofibroblast proliferation were detected at weeks 9 and 12. Mast cell appearance was proportional to the degree of hepatic damage. These findings suggest that hepatic fibrosis is inducible by a high cholesterol diet and is likely the result of the interaction between several different cell types (i.e., macrophages, myofibroblasts, and mast cells) in an inflammatory milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease.
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PMID:Mild hepatic fibrosis in cholesterol and sodium cholate diet-fed rats. 1580 24


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