Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical and laboratory examination of abnormalities not attributable to atherosclerosis has been performed on 188 male and 126 female adult subjects with hyperlipidaemia. The sample was recruited from 20000 subjects screened at a health control centre who had an initial serum cholesterol and/or triglyceride (TG) concentration above 350 mg/100 ml and 3.50 mmol/l. All were subjectively healthy and had no history of atherosclerotic disease. Known cases of secondary hyperlipidaemia were excluded. Lipoprotein (LP) analysis with preparative ultracentrifugation and electrophoresis was made on all subjects including control group with "nonelevated" serum lipids. Typing of hyperlipoproteinaemia (HLP) was performed according to the modified system of Fredrickson et al. Compared to controls, subjects who had elevated very low density ?LP (VLDL) (types II B, III, IV and V) were more obsese, while subjectI B and women with type IV HLP than in the control groups. Arcus corneae was seen in 29% of control groups. Arcus corneae was seen in 29% of controls and in higher frequencies in types II A and II B. A positive correlation existed between the frequency of arcus corneae and the mean low density LP cholesterol in the different types. Multiple tendon xanthomata (n equals 11) were found exclusively in type II A HLP, palmar xanthomata (n equals 3) only in the presence of floating beta-LP and eruptive xanthomata in one male with type V HLP. The mean ESR was increased in all types of HLP. The mean S-GPT and uric acid concentrations were higher in type IV HLP in both sexes than in the control groups. In men with type IV HLP S-GPT was positively correlated to tvldl tg. the uric acid level was correlated to both the VLDL TG concentration and body weight independently. Of the male subjects with HLP 1/3-1/2 had a diabetic or borderline i.v. glucose tolerance.
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PMID:Studies in asymptomatic primary hyperlipidaemia II. Clinical findings. 16 37

ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, significantly reduced both serum cholesterol and phospholipid levels in dogs, when used at a dosage higher than 10 mg/kg per day. Triglyceride levels were not consistently changed, but beta- and pre-beta-lipoproteins were preferentially reduced. Serum cholesterol levels were reduced by 44--45% at the higher dosage of 100--400 mg/kg per day (for 5 weeks) but ML-236B caused no significant changes in the cholesterol content of the liver and aorta and in the activities of serum GOT, GPT, CPK and lecithin : cholesterol acyltransferase. Fecal excretion of neutral sterols was unaffected but that of bile acids was markedly elevated by the drug. Under these conditions, hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, showed no detectable changes.
Atherosclerosis 1979 Mar
PMID:Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. 22 90

To develop the prophylactics and the curatives for atherosclerosis, thyroxine derivative, CG-635, was assayed for its physiological activities in experimental atherosclerosis in rabbits fed with cholesterol. It was found that CG-635 possessed serum TC/TP value lowering activity (total cholesterol/total phospholipid) in normal and cholesterol fed rabbits for 3 weeks, and prevented the elevation of the value of cholesterol fed rabbits by daily injection for 7 weeks. CG-635 also depressed the hyperlipemia induced by cholesterol feeding, and its inhibitory effect was shown to be more marked on the increase of cholesterol than triglyceride, phospholipid and free fatty acid in serum. CG-635 did not, however, influence GOT, GPT and G-6-Pase activities in serum with increased cholesterol intake. From the histological findings it was proved that this compound prevented to a high degree the occurrence of atherosclerosis and fatty liver of cholesterol fed rabbits. Furthermore, it was recognized that thyroid hormone and the thyroid simulating hormone-like activities of CG-635 were much weaker than thyroxine, except for the action in the lipid metabolism.
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PMID:[Effect of d,l-alpha-methyl-3, 5, 3, 5-tetraiodothyronine ethylester hydrochloride (CG-635) on experimental hypercholesterolemia and atherosclerosis in rabbits (author's transl)]. 117 Oct 31

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.
Atherosclerosis 1992 May
PMID:Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet. 163 55

The 3-years efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (S) (previously called synvinolin or MK-733) has been studied in single and combined therapy with cholestyramine (C) in 48 hypercholesterolaemic patients. Plasma lipids, lipoproteins and apolipoproteins A-I and B, and blood safety tests (haematology, liver function, creatine phosphokinase (CPK), creatinine, blood glucose and thyroid function) were determined regularly throughout the study. Extensive ophthalmological examinations with particular focus on the lens were done before initiation of therapy and at every 6 months during drug treatment. Maximal reductions of mean plasma total cholesterol concentration (34% with S; 47% with S + C) and low-density lipoprotein (LDL)-cholesterol concentration (42% with S; 56% with S + C) were achieved after 4 weeks on full-dose therapy. During continued treatment, years 1 through 3, the reduction of mean plasma total cholesterol was 26-29% with S alone, and 31-41% with S + C. Significant reductions of plasma triglycerides (15-27%) and very low density lipoprotein (VLDL) triglycerides (10-27%) were achieved in the group treated with S as single therapy. In this group there was also a significant increase (10-14%) of high-density lipoprotein (HDL)-cholesterol. In liver aspartate (AST) and alanine (ALT) aminotransferases, as well as alkaline phosphatase (ALP), minor and variable, but usually transient, increases were seen. Repeated ophthalmological examinations did not demonstrate any drug-related side effects. It is concluded that simvastatin is a safe and efficient cholesterol-lowering drug for long-term therapy, both as a single drug and in combination with cholestyramine.
Atherosclerosis 1991 Dec
PMID:Long-term efficacy and safety of simvastatin alone and in combination therapy in treatment of hypercholesterolaemia. 178 13

Growing rats were fed ad libitum soy protein isolate (SPI) or its peptic (SPI-P) or tryptic digest (SPI-T) for a month and their sera were examined for cholesterol and triglyceride levels and enzyme activities such as cholinesterase, glutamate-pyruvate transaminase (GPT) and alkaline phosphatase. The rats fed SPI-P or SPI-T were inferior in growth to those fed SPI. Similarly, the serum glyceride level was lower in the SPI-P and SPI-T groups than in the SPI group. On the other hand, a significant difference was found in the serum cholesterol level between the SPI-P and SPI or SPI-T groups but not between the SPI and SPI-T groups. A similar tendency was observed for serum GPT and alkaline phosphatase activities, although there were no significant differences among dietary groups in small intestinal enzyme activities. As for the atherogenic index being a risk factor inducing atherosclerosis, the order of its value was SPI-P less than SPI less than SPI-T.
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PMID:Effect of feeding peptic digest of soy protein isolate on rat serum cholesterol. 310 Jul 38

Simvastatin (MK-733), a new inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, was administered to 38 patients with heterozygous familial hypercholesterolaemia for 24 weeks. A dose of 40 mg per day produced a mean reduction in low density lipoprotein cholesterol of 43-45% and in triglycerides of 21-31%. Mean high density lipoprotein cholesterol increased significantly by 10-13%. There were no major differences in response whether the drug was taken in one or two doses. MK-733 was tolerated well. Adverse effects were infrequent and limited to slight increases of alanine aminotransferase, creatine phosphokinase and bilirubin. This drug appears to be a potent inhibitor of cholesterol synthesis and has produced the largest therapeutic response as monotherapy in patients with familial hypercholesterolaemia.
Atherosclerosis 1988 Feb
PMID:Simvastatin (MK-733): a potent cholesterol synthesis inhibitor in heterozygous familial hypercholesterolaemia. 327 66

Forty male cynomolgus monkeys were fed a nutritionally complete diet containing butter and 0.5% cholesterol for 18 months to ensure development of atherosclerosis. Timefurone was administered daily at 10 mg/kg/day. Lipoprotein cholesterol parameters were measured every 4 weeks and clinical chemistries were done at approximately 8-week intervals. Low density lipoprotein cholesterol [LDL-C] was significantly reduced 24-45% at all time periods and total-C was lowered 17-23% at weeks 12, 16, and 24-40 in the timefurone group. Very low density lipoprotein cholesterol [VLDL-C] was increased 68-156% from weeks 40-78 and triglycerides [TG] were significantly elevated 52-220% on weeks 4-16, 24, 28, and 36-78 by timefurone. Timefurone caused small but significant changes in several clinical chemistry parameters including: creatinine, total bilirubin, albumin, glucose, serum glutamic-oxalacetic transaminase, and serum glutamic-pyruvic transaminase during the test. Significant reductions in arterial cholesterol were observed in thoracic aorta (-24%) and carotid arteries (-29%) in treated monkeys when compared to placebo. Arterial cholesterol in treated monkeys was positively correlated to LDL-C (R = 0.54, p less than or equal to 0.05). Timefurone, therefore, appears to have a significant beneficial effect against the development of atherosclerosis in cholesterol-fed male monkeys and possesses excellent potential for clinical experimentation.
Atherosclerosis 1985 Sep
PMID:Evaluation of timefurone, a new anti-atherosclerotic drug, for its effects on lipoprotein cholesterol in male cynomolgus monkeys fed an atherogenic diet for 18 months. 386 22

In a group of Egyptian lead tank welders who were exposed to lead fumes for periods to 22 years the changes in serum lipids and some of the liver function tests which may elucidate the effect of lead on the liver were investigated. The results revealed increased blood lead level associated with decreased blood haemoglobin and increased urinary excretion of delta amino levulinic acid. However, no clinical abnormalities were recorded in the exposed group of the present work. Thus the increase in serum triglycerides and B-lipoprotein together with the lowering of the phospholipid/cholesterol ratio which were found may indicate premature development of atherosclerosis. Indirect evidence of the beginning of liver fattening was also provided by the increase in serum GOT, GPT, LDH enzymes and decreased albumin/globulin ratio besides the changes in serum lipid values. It is concluded therefore that lead poisoning may have a vascular as well as hepato-toxic action.
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PMID:Evaluation of the effect of lead exposure on the liver in Egyptian lead tank welders. 738 20

The long-term efficacy and tolerability of simvastatin, a 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitor, was assessed during a 24-month follow-up period in 168 elderly hypercholesterolemic patients. After completing a 4 week double blind dose ranging study with simvastatin, 47 males and 122 females over 62 years of age with type II hyperlipidemia, a total cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease were included in this extended study. A total of 159 patients completed the 12-month follow-up period and 141 patients were monitored over the full 24 months. All patients were started on 10 mg simvastatin once daily and the dosage was increased until the target levels of low density lipoprotein (LDL) cholesterol between 2.3 mmol/l (90 mg/dl) and 3.6 mmol/l (140 mg/dl) were reached. Fifty percent of patients reached the targeted LDL cholesterol goal of < 3.6 mmol/l (140 mg/dl) during the study. At study completion, 65 patients (39%) were taking 40 mg simvastatin per day, 56 patients (33%) 20 mg, 42 patients (25%) 10 mg and 5 patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant lipid lowering therapy. Over 2 years, the mean decrease in LDL cholesterol ranged from 36% to 38%, the median decrease in triglycerides was 12% to 19% and the mean increase in high density lipoprotein (HDL) cholesterol ranged from 9% to 10%, respectively. Seven patients discontinued simvastatin because of adverse clinical or laboratory events, but only in two (1.1%) was this considered to be drug-related. Side-effects were mild and most frequently gastrointestinal in nature. Mean changes in asparate aminotransferase (AST) were not significantly different from zero and mean changes in alanine aminotransferase (ALT) and creatine phosphokinase (CPK) showed a small increase. We conclude that simvastatin is an efficacious and well-tolerated treatment for hypercholesterolemia in elderly individuals for extended periods.
Atherosclerosis 1995 Aug
PMID:Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients. 757 71


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