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)

Studies were carried out to determine the effects of the toxic principle linamarin, a cyanogenic glucoside, in a diet containing cassava (Manihot esculenta Crantz) in the form of gari fed to growing dogs for 14 weeks. There were three groups of dogs, each comprising six animals. One group was fed on a control diet with rice as the carbohydrate source, the second group was fed on cassava (gari) as the carbohydrate source and which was expected to release 10.8 mg HCN/kg cooked food, the third group was fed on the control diet to which enough NaCN was added at feeding time to release 10.8 mg HCN/kg cooked food in order to monitor the effects of the HCN released from gari. All diets contained 130 g crude protein (N x 6.25)/kg and were supplemented with vitamins and minerals. Each animal was given approximately 100 g diet/kg body weight for the duration of the experiment. The biochemical variables investigated were plasma electrolytes, serum proteins, plasma-free amino acids, plasma enzymes and urine protein, and the histology of some metabolically active tissues, namely liver, kidney, myocardium, testis and adrenal gland, was studied. The gari diet caused an elevated plasma thiocyanate concentration (P < 0.01), elevated 24 h urinary thiocyanate excretion and elevated urinary protein excretion (P < 0.01), lowered serum albumin (P < 0.05), a plasma-free amino acid profile which resembled that found in kwashiorkor, lowered plasma K and Ca (P < 0.05). The rice + cyanide diet caused an elevated plasma thiocyanate (P < 0.01) and a 24 h urinary thiocyanate excretion that was significantly higher (P < 0.01) than that of the dogs fed on gari, but caused a urinary protein excretion that was significantly lower than that of the dogs fed on gari (P < 0.01), lowered serum albumin (P < 0.05), a plasma-free amino acid profile that indicated that the amino acids were not being utilized to the same extent as in the control (rice) group but were accumulating. Neither diet had an effect on plasma gamma-glutamyltransferase (EC 2.3.2.2), alanine aminotransferase (EC 2.6.1.2) or isocitrate dehydrogenase (EC 1.1.1.42) activities, plasma Na, Mg, and P concentrations. The gari diet caused generalized congestion and haemorrhage, periportal vacuolation of the liver, swelling, vacuolation and rupture of the epithelial cells of the proximal convoluted tubules of the kidney, myocardial degeneration and adrenal gland degeneration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathological changes in growing dogs fed on a balanced cassava (Manihot esculenta Crantz) diet. 832 65

To evaluate the clinical applications of serum thymidine kinase (TK) activity, we compared the results obtained with this parameter with those of other liver function tests in 27 patients with acute viral hepatitis and 16 normal controls. In those in the acute stage, the serum TK activity increased significantly to 55.5 +/- 66.5 U/L. There was no significant correlation between serum TK activity and findings for serum albumin, bilirubin, alkaline phosphatase or r-glutamyl transpeptidase. However, it did correlate significantly well with the serum activity of aspartate aminotransferase (AST) (r = 0.621, P < 0.01), alanine aminotransferase (ALT) (r = 0.551, P < 0.01), and lactate dehydrogenase (LDH) (r = 0.620, P < 0.01). Serum TK activity reached higher than 70 U/L in 8 of 11 patients with hepatitis A; however, no patients with the other types of hepatitis reached such a high level. During the recovery stage, the serum TK activity decreased significantly to 5.9 +/- 1.7 U/L (P < 0.01), and did not correlate with AST, ALT, LDH or other conventional liver function parameters. The data suggest that an elevation of serum TK in patients with acute viral hepatitis results from hepatocellular damage. A marked elevation of serum TK activity may thus provide a marker for acute hepatitis A infection.
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PMID:Elevated serum thymidine kinase activity in patients with acute viral hepatitis. 844 Apr 24

The liver synthesizes prokallikrein and is the main organ to clear the active enzyme (plasma-kallikrein) from circulation. This clearance, a receptor-mediated endocytosis, is calcium-independent and not affected by the blockade of Kupffer cells. The effects of endothelial cells blockade and of acetaminophen intoxication on the clearance of 10 nM rat plasma-kallikrein (RPK) by the isolated, exsanguinated and perfused rat liver are now reported. Endothelial cells blockade obtained by the addition of large excess (30 uM) of formaldehyde-treated serum albumin to the perfusion fluid does not affect the hepatic clearance of RPK (the half-lives of hepatic uptake were 15.5 +/- 1.0 min in the absence versus 16.5 +/- 1.4 min in the presence of the treated protein, p > 0.05). Some livers were perfused 24 hours after acetaminophen intoxication: 6.6 mmol/kg given i.p. after a 42-hour period of fast. Hepatocyte injury suggested by elevated aminotransferase activity (ALT 10 times control value, AST 30 times control value), acute phase inflammatory response (serum alpha 2-macroglobulin increase) and reduced synthetic function (serum albumin decrease), was confirmed histologically and only zone 3 hepatocytes were necrotic. A 66-hour period of fast does not affect by itself the hepatic clearance of RPK (16.9 +/- 1.3 min of half-life of hepatic uptake) when compared with the control group (15.5 +/- 1.0 min, p > 0.05). On the other hand the RPK clearance by the livers of rats previously intoxicated with acetaminophen was markedly deficient (the half-life of hepatic uptake was 39.2 +/- 3.2 min). These findings suggest that RPK is internalized by hepatocytes, preferentially by those of the perivenular zone of the hepatic acinus.
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PMID:Plasma-kallikrein clearance by the liver of acetaminophen-intoxicated rats. 846 45

Except for increased serum alkaline phosphatase (AP) levels, the changes in liver function test (LFT) values during normal pregnancy have not been clearly established, mainly because most studies do not include matched controls. We therefore measured the serum values of routine liver tests including 5'-nucleotidase and total bile acids in 103 healthy pregnant women (first trimester, n = 34; second trimester, n = 36; third trimester, n = 33) and in 103 age-matched controls not receiving oral contraception. Fasting blood samples were taken. Because of hemodilution, serum albumin levels were significantly lower during all trimesters. As expected, AP activity was significantly higher in the third trimester. Serum aspartate transaminase (AST) activity and total bile acid (TBA) concentrations did not differ between pregnant and nonpregnant women. Serum alanine transaminase (ALT) activity was slightly higher in the second-trimester pregnant women than in controls (6.8 +/- 4.5 vs. 8.2 +/- 5.8, P = .04), although all values remained within normal limits. In pregnant women, total and free bilirubin concentrations were significantly lower during all three trimesters, as was conjugated bilirubin during the second and third trimesters. Serum gamma-glutamyl transpeptidase (GGT) activity was significantly lower in the second and third trimesters. Serum 5'-nucleotidase activity was slightly but significantly higher in the second and third trimesters. The knowledge of these results is useful for the interpretation of LFT values and the management of liver diseases during pregnancy.
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PMID:Liver function tests in normal pregnancy: a prospective study of 103 pregnant women and 103 matched controls. 862 Nov 29

We have reported the efficacy of intraarterial-combined immunochemotherapy including interleukin-2 (IL-2) for unresectable hepatocellular carcinoma (HCC). To further test this therapy for prevention of intrahepatic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In addition, gap junction appearance, which may change during liver regeneration, was analyzed using a monoclonal antibody (HAM8). Serum albumin, alanine transaminase, and total bilirubin (TB) levels were also evaluated. IL-2 (45,000 Japanese reference units [JRU]/d) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. We also examined the influence of IL-2 on liver regeneration after hepatectomy with splenectomy. No difference in the weight of the liver, serum albumin, alanine transaminase, or TB was observed in any groups at 1, 2, or 4 days after hepatectomy. Neither IL-2 nor splenectomy influenced MI and BrdU LI at all three points. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline with or without splenectomy. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of IL-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. These results suggest that the liver regeneration after partial hepatectomy may be suppressed by the administration of IL-2, even though the suppression may not be harmful for overall recovery of the resected liver. However, it seems that hepatic IL-2 administration can be performed without serious complications after hepatectomy.
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PMID:Influence of continuous interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats. 867 80

The hepatotoxicity of acetaminophen is believed to be mediated by the reactive metabolite N-acetyl-p-benzoquinone imine; however, the mechanism by which this metabolite produces the toxicity is unknown. The metabolite, which is both an electrophile and an oxidizing agent, may covalently bind to critical proteins, or it may initiate oxidative damage. We have previously developed a Western blot assay for detection of acetaminophen covalently bound to protein and have reported the relationship between covalent binding and the development of hepatotoxicity. Recently, we developed a Western blot assay for protein aldehyde formation, which may occur via the reactive oxygen species, the hydroxyl radical. In this paper, we have compared covalent binding to protein aldehyde formation. Toxic doses of acetaminophen (400 mg/kg) were administered to mice, and the mice were subsequently killed at 0, 1, 2, 4, and 6 h. Since the oxidizing agent FeSO4 has been reported to potentiate lipid peroxidation when administered with acetaminophen, other mice received FeSO4 (100 mg/kg) plus acetaminophen. Compared to saline-treated control mice, acetaminophen treatment significantly increased serum alanine aminotransferase levels, an index of hepatotoxicity, at 4 and 6 h, but not at 1 or 2 h. Acetaminophen plus FeSO4 treatment of mice significantly increased serum alanine aminotransferase levels at 2, 4, and 6 h compared to controls. Levels of alanine aminotransferase in serum of acetaminophen plus ferrous sulfate-treated mice were higher at 4 and 6 h than those of acetaminophen-treated mice, but not significantly different. FeSO4 alone did not increase alanine aminotransferase levels. Western blot assays revealed that acetaminophen did not cause an increase in protein aldehydes over control at any time, nor did acetaminophen plus FeSO4; however, FeSO4 alone increased the intensity of staining of the immunoblot for protein aldehydes over control at all times after 0 time. Acetaminophen-protein adducts were detected in acetaminophen- and acetaminophen plus FeSO4-treated mice. In vitro experiments indicated that FeSO4 plus tert-butyl hydroperoxide in the presence of bovine serum albumin increased protein aldehyde formation. Inclusion of acetaminophen in the incubation mixture inhibited protein oxidation of bovine serum albumin in a concentration dependent manner. The data indicate that acetaminophen quenches protein oxidation, presumably by reacting with the hydroxyl radical. These data are consistent with the theory that acetaminophen covalent binding is the primary mechanism of toxicity and argue against a role for protein oxidation in acetaminophen hepatotoxicity.
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PMID:Mechanism of acetaminophen-induced hepatotoxicity: covalent binding versus oxidative stress. 872 1

Chronic non-A, non-B hepatitis (NANBH) is a common and often progressive liver disease. Based on current serological tests, hepatitis C virus (HCV) infection is responsible for most cases. Interferon-alpha (IFN) treatment at a dose of 3 x 10(6) units given three times per week for 24 weeks has been shown to be effective in normalizing serum alanine aminotransferase (ALT) levels and reducing hepatic inflammation in approximately 40% of these patients. The purpose of this study was to identify pretreatment characteristics in patients with chronic hepatitis C(CH-C) which would best predict a favourable response to IFN treatment (normalization of serum ALT). One hundred and sixty-three adult patients who had participated in a large multicentre treatment trial were included in the study group; 84 had been treated with 3 x 10(6) units of recombinant IFN-alpha-2b (rIFN) subcutaneously three times per week for 24 weeks and 79 patients had been treated with 1 x 10(6) units rIFN in the same dosage schedule. Forty-one pretreatment historical, clinical, laboratory and histological variables were evaluated. In addition, early biochemical improvement during treatment was evaluated as a predictor of ultimate response. Univariate analysis identified six variables (dose, dose m-2, weight, body surface area, ongoing ethanol use, white blood cell count and the presence of symptoms) as potential predictors of response (two-tailed, P < 0.15). By multivariate analysis, however, only the 3 x 10(6) dose of rIFN was independently predictive of response (P < 0.01). When the analysis of response was confined to those patients who received treatment with 3 x 10(6) units of rIFN, seven variables [body weight, surface area, dose m-2, current ethanol use, serum albumin and the presence of chronic persistent hepatitis (CPH) on entry liver biopsy] were more frequent in patients who responded to therapy. In a multivariate model, only CPH and body weight predicted an increased likelihood of response (P < 0.01). However, the model was not a sensitive predictor of response as only 18% of the study group had CPH on liver biopsy. A decrease in serum ALT levels within the first 12-16 weeks of rIFN treatment was found to be the strongest indicator of an ultimate response to treatment. Thus, assessment of early response to IFN treatment is the only practical means of predicting complete response and avoiding prolonged and unnecessary therapy in those with little chance of response.
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PMID:Clinical predictors of response to recombinant interferon-alpha treatment in patients with chronic non-A, non-B hepatitis (hepatitis C). The Hepatitis Interventional Therapy Group. 879 May 60

There is no one test of liver function. Routine laboratory tests that are useful in screening for liver disease and following its course include serum AST, ALT, alkaline phosphatase, protein electrophoresis, prothrombin time, and bilirubin levels. The transaminase levels give a day-by-day account of the amount of hepatocellular injury and death that occurs. Alkaline phosphatase levels estimate the amount of impedance of bile flow. The prothrombin time and serum albumin level are excellent gauges of hepatic protein synthetic ability, whereas the bilirubin level is probably the best test of overall liver function. Many tests are now available that permit one to diagnose specific diseases of the liver.
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PMID:Evaluation of tests used to screen patients with liver disorders. 888 44

The expansion and differentiation of oval cells in the acetylaminofluorene (AAF)/partial hepatectomy (PH) model was studied utilizing pulse-chase labeling with both tritiated thymidine ([3H]TdR) and bromodeoxyuridine (BUdR). Animals in which a significant decrease in serum albumin and increase in alanine aminotransferase and bilirubin were observed demonstrated the most prominent differentiation of oval cells into hepatocytes. Administration of [3H]TdR or BUdR, either individually or together, to the animals on day 6 after partial hepatectomy resulted in labeling of the majority of the oval cells by days 7 and 9 after PH. A striking difference in the distribution of [3H]TdR- and BUdR-labeled cells in the double labeling experiments was observed on day 11, at which time the number of [3H]TdR-labeled cells increased 6-fold and that of double labeled cells decreased 2-fold. Furthermore, on day 11 the basophilic foci were weakly positive for BUdR and negative at later time points in animals receiving BUdR alone or together with [3H]TdR. In contrast, the cells in basophilic foci as well as transitional cells were positive for [3H]TdR. Cells heavily labeled with both [3H]TdR and BUdR were present at all time points, indicating an inhibition of the proliferative activity. Pulse labeling of rat liver epithelial cells with BUdR in vitro demonstrated that immunodetection of BUdR was lost after three or more cell divisions. We conclude that the BUdR tagging method is particularly sensitive to label dilution during cell cycling and may not be suitable for establishment of a precursor-product relationship between cell lineages when the progenitor population proliferates more than three times.
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PMID:Precursor-product relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers. 889 81

Liver fibrosis was induced by chronically (7 weeks) administering CCl4 to rats. Animals were divided into four groups: (a) controls, (b) treated with CCl4 alone, (c) treated with CCl4 and colchicine and (d) treated with CCl4 and formyl-colchicine bound to lactosaminated serum albumin (FC-LASA). Liver dysfunction was monitored by biochemical tests (alkaline phosphatase [ALP], gamma-glutamyltransferase [gamma GT], aspartate and alanine transaminases [AST and ALT], albumin and total bilirubin). Fibrosis was evaluated by determining hydroxyproline and by microscopic examination. The exposure to CCl4 produced major alterations of liver structure and collagen deposition. These effects were partially counteracted by colchicine and to a greater extent by FC-LASA. Morphological findings paralleled biochemical data. The information reported here indicates that colchicine has an antifibrotic activity on the liver of intoxicated rats and that FC-LASA is more active than colchicine itself as an antifibrotic agent.
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PMID:Formylcolchicine bound to lactosaminated serum albumin is a more active antifibrotic agent than free colchicine. 889 3


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