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

The increase of activity of the enzymes AP, Gamma-GT, GlDH and GPT was investigated in this study with regard to its pathomechanism. The increase of AP is known to be caused by a de novo-protein synthesis in the liver, as several investigators have demonstrated using protein synthesis inhibitors. In this study female Wistar rats were partly sham-operated, partly bile duct-obstructed. One half of each group received the protein synthesis inhibitor ethionine, 24 h after bile duct obstruction in the group with ethionine the following enzyme activities were measured in the serum: AP 216 +/- 80 U/l; gamma-GT 4.5 +/- 1.9 U/l; GlDH 85 +/- 26 U/l; GPT 375 +/- 163 U/l. In the group without ethionine the activities were: AP 459 +/- 69 U/l; gamma-GT 4 +/- 0.9 U/l; GlDH 120 +/- 81 U/l; GPT 417 +/- 191 U/l. Because the differences between the groups with and without ethionine were not significant with the exception of AP, it is concluded that in the early phase of bile duct obstruction up to 24 h no influence of de novo-protein synthesis can be demonstrated in the elevation of the activities of gamma-GT, GlDH and GPT.
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PMID:The serum activities of AP, gamma-GT, GlDH and GPT after bile duct obstruction and ethionine in the rat. 197 81

Following sham operation and bile duct obstruction (BDO), Wistar rats received ethionine, which inhibits protein synthesis in the liver. Earlier studies revealed, that the increase of activity of AP after BDO is the result of a de novo-synthesis of enzyme protein in the liver. With regard to serum activities of the enzymes G1DH, GPT and gamma-GT, no influence of de novo-synthesis after BDO has so far been certified, but these enzymes have only been investigated in the early phase after BDO, for up to 24 h under protein synthesis inhibition. In the present study, the protein synthesis inhibition was extended up to the fourth day after BDO. Signs of de novo-synthesis after BDO could also be detected in G1DH, GPT and gamma-GT.
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PMID:Serum activities of AP, gamma-GT, G1DH and GPT in the first four days after bile duct obstruction and ethionine in the rat. 197 50

Serum ferritin, prealbumin, pseudocholinesterase, alpha-1-antitrypsin and caeruloplasmin were determined in control subjects and patients with pancreatic cancer, chronic pancreatitis or extra-pancreatic disease mainly of gastrointestinal origin, in order to investigate the different hepatic changes which influence serum ferritin in chronic pancreatic and other digestive diseases. Increased circulating ferritin was found in pancreatic cancer and extra-pancreatic disease when compared to controls. Correlations were detected between ferritin and the other proteins investigated and between ferritin and total bilirubin, alkaline phosphatase and alanine aminotransferase. Multiple regression analysis demonstrated that cholestasis accounts for 45% of circulating ferritin, the acute-phase response accounted for 18% and decreased liver function accounted for 11%. We conclude that the increase in serum ferritin in chronic pancreatic and other gastrointestinal diseases largely depends on liver changes, with cholestasis probably playing a primary role.
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PMID:Hepatic changes and serum ferritin in pancreatic cancer and other gastrointestinal diseases: the role of cholestasis. 202 31

S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.
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PMID:S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results. 205 Mar 26

Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transaminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A (N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P less than 0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increases thereafter.
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PMID:Serum transaminase levels in the acute phase of chronic extrahepatic cholestasis. 210 Oct 66

Because of the liver's dependence on arterial blood to exert its metabolic functions in cirrhosis of the liver, with or without thrombosis of the portal vein, the interruption of hepatic arterial flow for the palliative treatment of malignant tumors of the liver is counterindicated. However, the effects of arterial devascularization on the cholestatic liver are not fully understood. The objective of the present study was to investigate hepatic alterations due to hepatic artery ligation in rats with chronic extrahepatic cholestasis. Serum alkaline phosphatase, bilirubin and alanine aminotransferase were measured in rats 3 h after sham operation (group A, N = 29) or ligation of the hepatic artery (group B, N = 29). Alanine aminotransferase activity was significantly higher (P less than 0.05) in group B, demonstrating acute hepatocellular damage in animals with chronic extrahepatic cholestasis.
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PMID:Effect of hepatic artery ligation in rats with chronic extrahepatic cholestasis. 210 Oct 73

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.
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PMID:How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? 213 20

A 41 year old woman developed chronic active hepatitis with prominent cholestasis. She was treated with prednisolone over 3 years with symptomatic benefit and improvement in serum biochemistry. However, various steroid-related side effects were encountered and steatorrhoea eventually occurred with very troublesome nocturnal diarrhoea. Therapy with ursodeoxycholic acid 750 mg daily was started. Serum alanine aminotransferase and gamma-glutamyl transferase normalized for the first time since her illness began. Steatorrhoea was abolished. There was good control of symptoms as prednisolone therapy was gradually reduced. However, when prednisolone was completely withdrawn there was a prompt biochemical deterioration. Addition of low-dose azathioprine has maintained normal blood tests over 24 months without return of the original symptoms. There are no side effects of ursodeoxycholic acid in subjects without gallstones and this agent may be effective treatment for cholestatic liver disease.
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PMID:Ursodeoxycholic acid therapy in chronic active hepatitis. 223 18

The purpose of our study was to determine if streptozotocin induced diabetes (SID) in rats produces alterations in hepatic function, as described in poorly controlled diabetic patients, and if islet transplantation (islet-Tx) would subsequently ameliorate this status. Hepatocellular dysfunction was evaluated by the aspartate aminotransferase (SGOT) and the alanine aminotransferase (SGPT) activities in plasma. For the evaluation of cholestasis the plasma alkaline phosphatase (APase) activity was used. These determinations were performed in normal, SID, SID with Islet-Tx, and SID Wistar rats with sham-Tx. Also, glucose was measured in plasma samples, as well as histological studies of the liver were performed. More than 1,000 isogeneic islets (islet-Tx group) or non viable insular tissue (sham-Tx group) were transplanted via mesenteric ileal vein three weeks after SID. The results showed that SID in rats produces alterations in the hepatic function as well as in the structure of the hepatocytes, and the normalization of carbohydrate metabolism by islet transplantation restores normal hepatic function and morphology.
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PMID:Normalization of the altered liver function tests after islet transplantation in diabetic rats. 226 34

49 women of reproductive age were included in the study and were divided in 2 groups. The ovulation inhibitor group (OI) consisted of 37 women aged 33.5-39 exposed to ovulation inhibitors for an average of 13.4 years (Ovosiston, Sequenzovosiston, Non-Ovlon), and the control group consisted of 12 women aged 35.5-41.5 who had taken no OI for at least 5 years. Aspartate-aminotransferase (serum glutamic oxaloacetic transaminase=SGOT) and alanine aminotransferase (serum glutamic pyruvic transaminase) enzymes were determined as indicators of liver damage, and gamma-glutamyl-transferase (gamma-GT) for indication of cholestasis or as a sensitive parameter of hepatopathy. By using a nonradiating, stabile isotop-marked tracer substance, 15 N-ammonium chloride, the uric acid synthesis performance and the ammonium excretion of the liver could be evaluated. The Q-value indicated an excess of ammonium and uric acid as demonstrated by the 15 N test. Significant differences were found between the 2 groups with regard to ALAT, gamma-GT, Q-value, and leukocyte count. The measured values of enzymes and leukocytes studied, however, stayed within the normal range. In the OI group, the decreased gamma-GT activity was surprising. Also, the Q-value showed a slightly pathological median value in 18 women of the OI group. In 4 women who has Q-values of 1.6 to 1.9 (vs. 1.4 median value), liver punction was performed. In each case, liver damage could be shown to be attributed to use of contraceptives. Morphological changes indicating enhanced detoxification activity, and liver cell fat formation of various severity were also found as uncharacteristic alterations. The described increase of the serum activity of aminotransferase, leucine aminopeptidase, alkaline phosphatase, and gamma-GT were interpreted as the expression of cellular adaptation. Long-term use of hormonal contraceptives influences the metabolism of the liver, whose partial disorder can be detected by the 15 N-ammonium test. Normal ALAT and gamma-GT serum enzyme activity in single cases does not allow conclusions on the behavior of the metabolism of the liver.
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PMID:[Use of the stable nitrogen isotope 15N in assessing liver metabolism in hormonal contraception]. 231 86


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