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Enzyme
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Target Concepts:
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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)
The efficacy and safety of 20 mg simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) and of 16 g cholestyramine daily in the treatment of 34 hypercholesterolaemic patients have been compared after dietary treatment and stratified randomization. The effect of combined treatment with the two drugs was studied in 5 patients with severe
hypercholesterolaemia
. After 6 weeks of treatment the simvastatin group showed a significantly greater (p less than 0.05) decrease in the mean total plasma cholesterol concentration from 7.88 to 5.48 mmol/l than in the cholestyramine group in whom there was a fall from 7.82 to 6.73 mmol/l. Simvastatin decreased the mean plasma LDL cholesterol concentration from 6.07 to 3.76 mml/l and cholestyramine decreased it from 6.16 to 4.46 mmol/l. Simvastatin also reduced the mean plasma total triglycerides by 24%, VLDL triglycerides by 20% and VLDL cholesterol by 36%, while cholestyramine led to increases in these parameters by 64%, 85% and 63%, respectively. Mean plasma HDL cholesterol concentration and the subfractions HDL2 and HDL3 cholesterol were significantly increased by simvastatin. Simvastatin and cholestyramine reduced the mean plasma apolipoprotein B concentration by 28% and 13%, respectively. The mean plasma apolipoprotein A-I concentration was significantly higher only on simvastatin treatment. Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients. Small increases in serum
alanine aminotransferase
(S-ALT) activity were seen with both drugs. Cholestyramine significantly raised the serum alkaline phosphatase (S-ALP) although to a level still within the normal range. It is concluded that 20 mg simvastatin was more effective than 16 g cholestyramine in the treatment of
hypercholesterolaemia
.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia. 250 17
Normal reference values for total serum protein, albumin, cholesterol,
alanine aminotransferase
(
ALT
), aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (GGT), alkaline phosphatase (AP), and total bilirubin were established in 48 clinically healthy woodchucks. To validate the use of these biochemical tests in the woodchuck for assessment of liver injury, carbon tetrachloride was administered to produce hepatocellular necrosis and the common bile duct was surgically occluded to produce cholestasis. Biochemical tests were performed prior to experimental treatment and thereafter in surviving woodchucks for a period of 6 weeks. There were marked increases in the serum activities of AST,
ALT
, and SDH following carbon tetrachloride administration and all 3 enzymes appeared to be useful markers of acute hepatocellular injury. The predominate biochemical abnormalities in woodchucks with bile duct obstruction were hyperbilirubinemia,
hypercholesterolemia
and increased serum AP and GGT activities. The increase of GGT occurred earlier following bile duct obstruction and the magnitude of increase was greater than that of AP, suggesting that GGT would be the preferred serum enzyme test in the woodchuck for assessment of cholestatic liver injury.
...
PMID:Laboratory assessment of hepatic injury in the woodchuck (Marmota monax). 286 72
The effects of synvinolin (MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, were investigated in 43 patients with heterozygous familial
hypercholesterolaemia
in a double-blind, placebo-controlled, dose-finding study. Synvinolin was given in doses ranging from 2.5 mg to 80 mg per day for 4 weeks. 8 patients received placebo. Low-density-lipoprotein cholesterol fell on average by 18% on 2.5 mg/day and 42% on 80 mg/day. The drug was as effective whether it was given once or twice daily. Serum high-density-lipoprotein cholesterol tended to increase and serum triglycerides to decrease on the higher doses. The drug was tolerated well. Except for a slight rise in
alanine aminotransferase
in 3 patients no objective side-effects were observed.
...
PMID:Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolaemia. 287 29
The effects of simvastatin, an inhibitor of cholesterol synthesis, was studied in 50 patients with
hypercholesterolaemia
. In the first study, 24 patients with serum cholesterol levels of 10.74 +/- 1.59 mmol/l were treated with simvastatin 40 mg daily for 6 months. Serum cholesterol levels decreased within 4 to 8 weeks to stable values 30 to 36% below the basal value. Serum triglycerides decreased by 16 to 28% and high density lipoprotein (HDL) cholesterol increased by 6 to 11% on average. In the second study, 26 patients with serum cholesterol levels of 12.35 +/- 2.05 mmol/l were treated with simvastatin 40 mg daily as monotherapy or combined with a bile acid binding resin for 2 years. Cholesterol levels decreased to values which remained stable throughout the entire study period; after 2 years the decrease amounted to 43%. Compared with monotherapy, combination with a bile acid binding resin yielded a further 12% decrease of cholesterol. In the entire group, triglycerides decreased by 16% and HDL cholesterol increased by 9% on the average. Side effects were limited to slight increases in
alanine aminotransferase
and creatine phosphokinase occurring in some patients. Simvastatin appears to be an important asset in the treatment of
hypercholesterolaemia
.
...
PMID:[Efficacy and safety of simvastatin, a new cholesterol-lowering drug]. 292 55
We report the biochemical results in 90 women presenting to an eating disorders clinic: 61 who had bulimia, 22 with anorexia nervosa and seven unclassified. The results were compared with 30 control women. The group of women with an eating disorder had significantly higher concentrations of total CO2, calcium, AST,
ALT
, ALP, albumin and cholesterol and significantly lower concentrations of potassium, chloride and phosphate in the plasma. The elevated calcium could be accounted for in part by an increase in total CO2 and an increase in albumin. Hypokalaemia was strongly associated with self-induced vomiting and laxative abuse. Biochemical abnormalities occurred in both forms of eating disorders; however,
hypercholesterolaemia
was more common in anorexia nervosa and abnormal liver enzymes were more common in bulimia.
...
PMID:Biochemical abnormalities in anorexia nervosa and bulimia. 310 18
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
.
...
PMID:Simvastatin (MK-733): a potent cholesterol synthesis inhibitor in heterozygous familial hypercholesterolaemia. 327 66
Partial ileal bypass (PIB) surgery is a method for the treatment of familial
hypercholesterolaemia
in man. Since the rabbit is frequently used as an animal model in experimental studies on PIB, we have investigated the long-term effects of this surgical procedure on the health status of rabbits. Forty-eight weeks after surgery plasma and liver cholesterol levels were decreased by about 40%. The inner diameter of the bypassed ileum was drastically reduced, unlike its length. The bypassed segment did not show clear histological abnormalities. The microflora of the caecum was similar in control and PIB rabbits. PIB did not influence liver histology. The bile of the rabbits with PIB was less lithogenic than that of control animals. Blood haemoglobin levels, haematocrit values and plasma concentrations of alkaline phosphatase,
alanine aminotransferase
, gamma-glutamyl transferase and lactate dehydrogenase were not changed after PIB. Plasma levels of albumin, creatinine, calcium, phosphorus, vitamin B12 and folic acid were not significantly affected by PIB. Rabbits with PIB had significantly higher plasma levels of bilirubin and zinc than control rabbits, but plasma vitamin E concentrations were significantly lower. These results may be of importance for further studies on the effects of PIB in rabbits.
...
PMID:Long-term effects of partial ileal bypass on the health status of rabbits. 370 23
A lethal syndrome characterized clinically by growth retardation, progressive acrodermatitis, chronic pyoderma and paronychia, diarrhea, pneumonia, and abnormal behavior was observed in 17 related Bull Terrier pups. Median survival time was 7 months. Laboratory evaluation revealed non-degenerative neutrophilia, consistently low activities of serum alkaline phosphatase and
alanine transaminase
, and frequently,
hypercholesterolemia
. Lymphocyte blastogenic responses were decreased and there was dysgammaglobulinemia in pups in which quantitative studies of immunoglobulins were made. The mean of plasma zinc concentrations in 5 affected pups was significantly lower than the mean of age- and breed-matched controls. Pathologic findings included parakeratosis, hyperkeratosis, and superficial bacterial infections of the skin. There was severe reduction of lymphocytes in T-lymphocyte areas of lymphoid tissue. Bronchopneumonia and dilatation of the cerebral ventricles were found in most affected pups. Family studies indicated that the syndrome is inherited as an autosomal recessive trait. In spite of its similarities to lethal trait A46 in Black Pied Danish cattle and acrodermatitis enteropathica in man, oral or parenteral treatment with zinc failed to ameliorate the clinical signs of the syndrome.
...
PMID:Lethal acrodermatitis in bull terriers. 371 Aug 72
1000 consecutive blood donors had their liver functions studied. 110 donors (11%) were found to have raised
ALT
of more than twice normal levels. 29 donors had liver biopsies done. Histologically 23 had fatty change, 5 had chronic persistent hepatitis and 1 had liver cirrhosis. Fourteen out of the 23 donors with fatty change also had
hypercholesterolemia
and hypertriglyceridemia. Viral serology of the 110 donors showed that 3 donors were HBsAg positive, 5 donors were Anti-HAV (IgM) positive and 20 donors were Anti-HBc (IgM) positive. Majority of donors with raised
ALT
had fatty liver on biopsy with only 6 donors having significant findings of chronic persistent hepatitis and cirrhosis. Serologically, most of the donors (74.5%) with raised
ALT
had no markers of Hepatitis A, Hepatitis B, CMV or EBV. An interesting finding is the high incidence (18%) of positive, Anti HBc (IgM) in donors with raised
ALT
.
...
PMID:Liver disease in blood donors with raised transaminases. 375 95
The effect of a four-week experiment on ten fa/fa Zucker rats (aged seven weeks at the beginning) fed on a lipid-rich diet (HL: 31 per cent w/w lipids, 45.6 per cent starch) was compared to that of a control diet (C: 10 per cent lipids, 66 per cent starch) on control Fa/- rats using a special pair-feeding apparatus that made it possible to obtain an identical intake rhythm. Energy level of the intake was significantly higher for the HL diet than for the C diet. At the end of the experiment, fa/fa rats remained obese and hyperlipemic, and still showed liver steatosis. With equal energy levels ingested, the obesity of fa/fa rats was comparable for both diets; hypertriglyceridemia and
hypercholesterolemia
were identical for both diets. When compared to the C diet, the HL diet modified neither their obesity nor their hyperlipemia. Obese rat liver on the HL diet showed lower levels for triacylglycerols, cholesterol, GGT,
ALT
, LDH and aldolase activities, while hepatic glycerol kinase and AST activities were higher than and comparable to, respectively, the C diet. Thus the HL diet led to a decreased liver steatosis for fa/fa rats as compared to the C diet.
...
PMID:Influence of diet composition on obesity, hyperlipemia and liver steatosis in Zucker fa/fa rats pair-fed with Zucker Fa/- rats. 637 17
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