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)

Acute liver dysfunction after Fontan operations may result from inadequate hepatic perfusion along with low cardiac output and high central venous pressure. We monitored hepatic venous oxygen saturation in 15 patients after Fontan operations to determine whether oxygen saturation predicts the occurrence and severity of acute liver dysfunction. We measured oxygen saturation from hepatic venous blood samples every 4 to 5 hours for at least 24 hours after the operation and used the mean hepatic venous oxygen saturation value for the first 24 hours after the operation to analyze the relationship between oxygen saturation and hepatic function. As indices of hepatic function, we measured serum alanine aminotransferase, total bilirubin, blood lactate (arterial, hepatic venous, and the difference between them), and the arterial ketone body ratio (the ratio of aceto-acetate to beta-hydroxybutyrate). For alanine aminotransferase and bilirubin, we used the maximal values during the first week in the analysis, and for blood lactate and ketone body ratio, we used the mean values for the first 24 hours after the operation. Significant broken-line regression relationship existed between mean hepatic venous oxygen saturation and hepatic function indices (alanine aminotransferase, total bilirubin, and blood lactate). The interpretation of these relationships is that hepatic indices are constant above the critical mean hepatic venous oxygen saturation values but are correlated with mean hepatic venous oxygen saturation below critical points in the range of 21% to 26%. Thus a hepatic venous oxygen saturation value below about 25% during the first 24 hours after a Fontan operation predicts the occurrence and the severity of acute liver dysfunction. We suggest that monitoring hepatic venous oxygen saturation is useful for management of critically ill patients after Fontan operations.
 ...
PMID:Monitoring of hepatic venous oxygen saturation for predicting acute liver dysfunction after Fontan operations. 793 6

The metabolism of pyruvate by Helicobacter pylori was investigated employing one- and two-dimensional 1H and 13C nuclear magnetic resonance spectroscopy. Generation of pyruvate from L-serine in incubations with whole cell lysates indicated the presence of serine dehydratase activity in the bacterium. Pyruvate was formed also in cell suspensions and lysates from phosphoenol pyruvate. Metabolically competent cells incubated aerobically with pyruvate yielded alanine, lactate, acetate, formate, and succinate. The production of alanine and lactate indicated the presence of alanine transaminase and lactate dehydrogenase activities, respectively. Accumulation of acetate and formate as metabolic products provided evidence for the existence of a mixed-acid fermentation pathway in the microorganism. Formation of succinate suggested the incorporation of the pyruvate carbon skeleton into the Kreb's cycle. Addition of pyruvate to various liquid culture media did not affect bacterial growth or loss of viability. The variety of products formed using pyruvate as the sole substrate showed the important role of this metabolite in the energy metabolism of H. pylori.
 ...
PMID:Pyruvate metabolism in Helicobacter pylori. 797 73

Rat liver was kept at 4 degrees C or 37 degrees C in MEM, and reperfused through a closed circulation from the hepatic vein to the portal vein at 37 degrees C with the same solution. Although purine nucleoside phosphorylase and ALT activities were increased in the perfusate, depending on the duration of ischemia at both 4 degrees C and 37 degrees C, the ratio of the latter to the former was significantly higher after 37 degrees C-ischemia than after 4 degrees C-ischemia. The stimulation stage of Kupffer cells evaluated in situ by formazan deposition after liver perfusion with nitro blue tetrazolium and phorbol myristate acetate was elevated after 4 degrees C-ischemia longer than 1 h, but not after 37 degrees C-ischemia. In contrast, the degree of oxidative stress in hepatocytes assessed by formazan deposition after liver perfusion with nitro blue tetrazolium alone was greater after 37 degrees C-ischemia than after 4 degrees C-ischemia. These results suggest that oxidative stress in hepatocytes and the stimulatory state of Kupffer cells after ischemia-reperfusion may differ between 4 degrees C-ischemia and 37 degrees C-ischemia, probably leading to different development of liver damage.
 ...
PMID:Oxidative stress in hepatocytes and stimulatory state of Kupffer cells after reperfusion differ between warm and cold ischemia in rats. 799 81

Two main equal groups of clinically healthy, non pregnant rabbits were classified into 4 subgroups (5 rabbits each). The 1st and 2nd subgroups were treated with sulphaquinoxaline or sulphadiazine in a single oral dose of 100 mg/kg b. wt., while the 3rd and 4th subgroups received a repeated oral dose of 100 mg/kg b. wt., daily for 5 successive days, respectively. The second main group received lead acetate in a dose of 4.2 mg/kg b. wt. per day for 2 months, then was classified as in case of the 1st main group and administered the respective sulphonamides in their recommended doses. The experimental lead intoxication was found to decrease the free delta-aminolevulinic acid dehydratase (delta-ALA-D) activity in blood of lead intoxicated rabbits after 4 and 8 weeks. Also, the ratio of free and with glutathione reactivated delta-ALA-D was increased 2.9 and 2.2 after 4 and 8 weeks, respectively as compared with before lead administration (1.19), indicating toxicity. The sulphonamide/creatinine ratio was increased after administration of both sulphonamides but higher in lead intoxicated rabbits as compared with healthy ones. The AST/ALT ratio was decreased 4 and 8 weeks after lead exposure. The AST, ALT and AST/ALT ratio, alkaline phosphatase, urea and creatinine were not altered in healthy rabbits. Repeated oral administration of sulphadiazine caused a significant increase in serum AST, ALT, alkaline phosphatase and creatinine level in healthy and lead intoxicated rabbits. On the other hand, AST/ALT ratio in both healthy and lead intoxicated rabbits was found to decrease 1 h after the last dose as compared with before treatment.
 ...
PMID:Interaction between lead toxicity and some sulphonamides in rabbits: effect on certain blood constituents and serum enzymes. 801 95

Previous studies have demonstrated that alpha-tocopheryl hemisuccinate (TS) protects hepatocyte suspensions from chemical-induced toxicity. It has been suggested that TS cytoprotection is related to unique properties of the TS molecule or is dependent on the cellular release and activity of unesterified alpha-tocopherol (T). To test the unique cytoprotective nature of TS in vivo, the protective ability of T and tocopherol esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats was examined. Hepatoprotection [determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and histopathology] was not observed after T (or tocopheryl acetate and tocopheryl nicotinate) administration, even though this treatment resulted in a fivefold elevation in hepatic T content. Only pretreatment with TS (100 mg/kg, intraperitoneally) resulted in partial hepatoprotection against CCl4 (2.9 g/kg, orally) toxicity. These findings suggest that hepatoprotection results not from the cellular accumulation of T but rather from the intact TS molecule. To test this hypothesis, the hepatoprotective capacity of cholesteryl hemisuccinate (CS), unesterified cholesterol, and cholesteryl acetate (CA) was examined against CCl4 toxicity. As observed with the tocopherol derivatives, pretreatment with unesterified cholesterol or CA demonstrated no protective ability. However, when rats were pretreated with CS (100 mg/kg), the hepatotoxic effects of CCl4 (elevated serum AST and ALT levels and centrilobular necrosis) were completely prevented. The prevention of CCl4-induced hepatotoxicity by CS and TS do not appear to result from an alteration in hepatic drug metabolism. These data clearly demonstrate that CS and TS are unique and powerful cytoprotective agents against CCl4 hepatotoxicity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Protection against carbon tetrachloride-induced hepatotoxicity by pretreating rats with the hemisuccinate esters of tocopherol and cholesterol. 813 82

Subclinical nutritional myopathy was induced in 5-month-old sheep by feeding them a diet low in vitamin E and selenium. Subsequently clinical myopathy was induced by dosing with protected polyunsaturated fatty acids. Plasma activities of creatine kinase (CK), pyruvate kinase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase and aldolase, enzymes of muscle origin, all remained above their reference ranges in clinically affected sheep, but fluctuated widely. Similar fluctuations occurred in subclinically affected animals, resulting in some activities being within the reference ranges and some above, at different times. Plasma malondialdehyde, an indicator of lipid peroxidation, proved of no diagnostic value. Terminal plasma CK activities were significantly correlated with microscopic damage in the vastus lateralis (VL), but not the vastus intermedius (VI) or the tensor fascia lata (TFL) muscles. AST was the most highly correlated with damage in VI and VL. In two clinically affected sheep successfully treated with an oral dose of alpha-tocopherol acetate all enzymes decreased steadily to within their reference ranges, at rates probably related to their plasma half-lives. These results suggest that measurement of plasma CK activity would be useful in monitoring recovery of treated sheep.
 ...
PMID:Plasma indicators of muscle damage in a model of nutritional myopathy in weaner sheep. 817 46

The absence of breast development and the prevention of osteoporosis in Ullrich-Turner syndrome (UTS) require oestrogen/gestagen substitution therapy. In 8 out of 35 (23%) patients with UTS treated with conjugated equine oestrogens and cyclically with norethisterone acetate, the serum liver enzymes increased to conspicuous levels (AST 35; 20-73 U/l, ALT 92; 37-141 U/l, GGT 77; 25-227 U/l, [median; min-max]). These findings were compared with those in 41 tall girls who received a six-fold larger dose of conjugated equine oestrogens for the reduction of final height. None of these 41 girls showed abnormal serum liver enzyme levels. The conspicuous rise in serum liver enzyme levels occurred in the majority of the UTS patients before norethistherone acetate was added to the oestrogen replacement therapy. No essential morphological equivalent was found in liver sonography and biopsy studies. During the follow up the elevated serum liver enzyme levels showed reversibility when medication was temporarily discontinued and either a slow decrease or a steady state after therapy was continued. CONCLUSION. Patients with UTS on oral oestrogen replacement therapy are more susceptible to develop increased serum liver enzyme levels as compared with eukaryotic females treated with the same oestrogen preparation for other disorders. As the underlying pathomechanism is unknown and adverse long-term effects cannot be ruled out, avoiding the portal vein and using the transdermal application of oestrogen may represent a viable solution to the problem.
 ...
PMID:Effect of oestrogen/gestagen replacement therapy on liver enzymes in patients with Ullrich-Turner syndrome. 1119 21

The effects of calcitonin (CT) on oxyradical generation and cellular damage induced by carbon tetrachloride (CCl4) were investigated in rat hepatocytes. Addition of CCl4 to the cells concentration dependently increased intracellular production of hydroperoxides and release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatocytes expressed mRNA for a CT receptor, C1b. Coaddition of CT to the cells concentration dependently suppressed the CCl4-induced increase in hydroperoxide production and also decreased the release of AST and ALT. The suppressive effect of CT on hydroperoxide production was reversed by further addition of H7 or by pretreatment with phorbol 12-myristate 13-acetate for 24 h. These results suggest that CT prevents CCl4-induced oxyradical production and cellular damage through activation of protein kinase C in hepatocytes.
 ...
PMID:Calcitonin prevents CCl4-induced hydroperoxide generation and cytotoxicity possibly through C1b receptor in rat hepatocytes. 857 6

Recently, cases of liver damage and liver tumors have been reported after treatment of prostate cancer patients with the antiandrogen cyproterone acetate (CPA). In rat liver, CPA initiates a wave of DNA synthesis that is accompanied by apoptosis. In apoptotic hepatocytes, a latent form of transforming growth factor beta 1 (TGF-beta 1) is detectable by immunohistochemistry. Injection of a single dose of TGF-beta 1 induces apoptosis in the liver of animals pretreated with CPA but has an insignificant effect in untreated animals. In this study, we show by Northern analysis that there is increased expression of TGF-beta 1 in the liver after CPA treatment. Detection of TGF-beta 1 with in situ hybridization showed that TGF-beta 1 was synthesized in the parenchymal cells. Time course and dose-response experiments performed 48 hours after the last application of CPA showed that apoptotic nuclei with chromatin condensed at the nuclear periphery (AN) were already visible 2 hours after injection (0.13%), and apoptotic bodies (ABs) increased 2 to 9 hours after the injection (from 1.28% to 6.67%) after 25 micrograms TGF-beta 1/kg. At 4.5 hours after injection, an induction of apoptosis could be detected with 0.25 microgram TGF-beta 1/kg and after the maximum dose (250 micrograms TGF-beta 1/kg) ANs (0.24%) and ABs (16.74%) were homogeneously distributed throughout the liver lobe. Irrespective of the dose or time after injection of TGF-beta 1, 82% of the ABs were localized within hepatocytes. Liver enzymes were detected in high amounts in the serum (eightfold elevation of glutamate dehydrogenase, fivefold elevation of alanine transaminase [ALT]) 7 hours after the first visible sign of apoptosis. After an additional 20 hours, the liver contained many necrotic figures. These results suggest that the combination of TGF-beta 1 expression coupled with a strikingly enhanced sensitivity to the induction of apoptosis could be responsible both for the liver damage and the development of liver tumors observed after treatment with CPA.
 ...
PMID:The antiandrogen cyproterone acetate induces synthesis of transforming growth factor beta 1 in the parenchymal cells of the liver accompanied by an enhanced sensitivity to undergo apoptosis and necrosis without inflammation. 859 60

Polymorphonuclear leukocytes (PMNS) have been implicated as cellular mediators of hepatic injury in models of inflammation in vivo. In vitro, hepatocyte killing by activated PMNs is mediated in part by proteases, but the role of nitric oxide is unknown. NO is produced by PMNs and hepatocytes and can act either to damage or protect in various models of toxicity. Therefore, we tested the hypothesis that NO is important in PMN-mediated hepatocyte killing in vitro. Freshly isolated hepatocytes from rat liver and PMNs elicited from rat peritoneum were cultured together or alone for 16 hours. Both cell types spontaneously released NO, estimated as its stable breakdown product, nitrite. Accumulation of nitrite in medium from hepatocyte cultures was augmented threefold by incubation with L-arginine and was completely inhibited by treatment with the nitric oxide synthase (NOS) inhibitor NG-methyl-L-arginine (NMA). Nitrite release in PMN cultures was unaffected by L-arginine addition and only partially inhibited by NMA. In PMN:hepatocyte cocultures (10:1), accumulation of nitrite was additive relative to cells cultured separately. Incubation with NMA blocked nitrite production completely in cocultures, whereas L-arginine caused a two-fold increase in nitrite. Addition of PMN stimulants, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate (PMA), caused increased release of alanine aminotransferase (ALT) activity into medium from hepatocytes cultured with PMNs but not from hepatocytes cultured alone; this indicated that injury to hepatocytes was due to activated PMNS. However, neither FMLP nor PMA significantly altered nitrite release from cocultures. Despite the alterations in NO production induced by addition of NMA or L-arginine, neither agent altered the release of ALT from hepatocytes in coculture with activated PMNs. Thus, PMNs and hepatocytes provided NO in vitro, but neither suppression nor elevation of NO production affected PMN-mediated hepatocyte killing. Accordingly, NO is not involved in the mechanisms by which FMLP-or PMA-stimulated PMNs mediate hepatocyte injury in vitro.
 ...
PMID:Nitric oxide is not involved in hepatocyte killing by neutrophils activated by N-formyl-methionyl-leucylphenylalanine or phorbol myristate acetate in vitro. 866 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>