Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The morphological and biochemical studies were performed on the injured livers of female rats produced by chronic administration of D-galactosamine (GALN) (250 mg/kg, i.p.) for 7 months. Light microscopically, cirrhotic changes were observed in most of the animals characterized by the proliferation of the connective tissues from portal triads into hepatic lobules. The electron microscopic study demonstrated mitochondrial proliferation and irregularities with crenated membranes, focal hypertrophy of the smooth endoplasmic reticulum, decrease of the rough endoplasmic reticulum with partial detouchment of ribosomes, slight loss of compactness of nucleoli and no remarkable accumulation of lipid droplets in the cytoplasm. The proliferation of collagen fibers was observed around the hepatocytes and acid mucopolysaccharides were seen in the space of Disse and partly in the sinusoids histochemically using electron microscope. Biochemically chronic GALN administration, which increased hepatic weight significantly, resulted in a significant decrease in microsomal protein concentration, whereas cytochrome P450 content significantly increased. There was no change in phospholipid contents. After GALN, plasma albumin concentration was significantly decreased and the value of zinc turbidity test was increased. However, there was no change in plasma GPT level and total cholesterol concentration.
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PMID:D-galactosamine induced hepatic cirrhosis: its ultrastructural and biochemical studies in rat. 65 50

Treatment of 24 male patients with 3 g/day of xanthinol nicotinate did not change the in vitro measurements of ADP-induced platelet aggregation but produced a marked inhibition of collagen-induced platelet aggregation. This effect may be connected with the drug-induced depression of the ATP level in platelet-rich plasma. Changes in the platelets in the patients' blood or in the lipid composition and the concentration of uric acid in their serum were ruled out as reasons for the decrease of the collagen-induced aggregation. The activity of the three serum enzymes y-GT, GOT, and GPT and the concentration of the blood sugar did not change.
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PMID:Effect of xanthinol nicotinate treatment on platelet aggregation. 84 33

Female Swiss mice were treated for 24 weeks, with 3-hydroxy-4-pyrone (Py) added to their powdered diet at 0.5% (wt/wt), and the effects of this agent on the liver were examined. Serum transaminases (especially GPT) rose continuously, while the GOT/GPT ratio remained at approximately 1.0 throughout the study period. The characteristic changes found from 8 weeks onward were piecemeal necrosis and bridging necrosis of the hepatocytes with dense lymphocytic infiltration. Proliferation of collagen fibers in the portal tracts and formation of narrow fibrous septa dividing the lobules into pseudolobules were also noted from 12 weeks onward. A large number of the infiltrating lymphocytes were identified as T cells by immunohistochemical and electron microscopic studies. These lymphocytes often surrounded or were closely attached to degenerating hepatocytes. Focal apoptosis and necrosis accompanied by a granulomatous reaction of the centrilobular hepatocytes were noted as early changes in the liver. Our findings indicate that the hepatic changes produced in mice by long-term Py administration have characteristics in common with those of human chronic active hepatitis. Immunological cytotoxic mechanisms, especially T cell-mediated ones, appear to play an essential role in the development of hepatic lesions in this murine model of chronic active hepatitis.
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PMID:Pathology of chemically induced chronic active hepatitis in mice. 142 59

Eighteen immuno-compromised children (malignancies, hematological diseases, collagen diseases) with neutropenia and infections were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and the safety of the drug were evaluated. 1. Responses to IPM/CS were excellent in 13 patients, good in 1, and fair in 4. None of the patients displayed a poor response to the treatment thus the efficacy rate was 77.8%. 2. Of 5 patients with sepsis, 4 had excellent or good responses. IPM/CS was effective against sepsis caused by Enterococcus faecalis and Pseudomonas aeruginosa. 3. In patients with severe neutropenia (WBC less than 100/mm3), the efficacy rate was 70%. 4. As for side effects, elevations of GOT and GPT were observed in 1 patient with liver cirrhosis. These results indicate that IPM/CS is safe and effective in immuno-compromised children with neutropenia and infections.
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PMID:[Clinical evaluation of imipenem/cilastatin sodium against infections in compromised children (malignancy, hematological disease, collagen disease)]. 143 90

The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol-containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid-reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine-induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid-reactive substances in liver homogenates under the lipid peroxidation-stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short-term exposure of 21 days of treatment.
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PMID:Chronic ethanol and cocaine-induced hepatotoxicity: effects of vitamin E supplementation. 144 28

Liver fibrosis was induced in rats by repeated peritoneal injections of carbon tetrachloride (CCl4) over a period of 2-11 weeks. Serum procollagen III peptide (SPIIINP), prolidase (SP) and alanine aminotransferase (SALT) levels were monitored during the period of induction. The extent of fibrosis was semi-quantitatively estimated after collagen staining, and the anti-fibrotic effects of 16,16-dimethyl prostaglandin E2 (DMPGE2), colchicine, and zinc sulphate were studied. SPIIINP and SP were increased the first 2 weeks after CCl4 administration and peaked at 6 weeks. Alterations in SPIIINP and SP correlated well to the semi-quantitative histological score of liver sections during the first 6 weeks, and SP was positively related to SPIIINP throughout the whole induction period. DMPGE2 decreased SPIIINP, SP and SALT significantly in addition to a markedly decreased formation of liver collagens. Colchicine had a similar but less dramatic effect, whereas zinc sulphate only reduced SPIIINP without influencing liver damage. In conclusion SPIIINP seems to be a valuable indicator of liver fibrogenesis, and SP may play a limited role in indicating accelerated collagen metabolism in the liver. DMPGE2 obviously inhibited the production of collagens induced by CCl4. Colchicine also had an apparent effect on liver fibrosis, whereas zinc sulphate merely seemed to postpone it.
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PMID:Monitoring of serum markers for fibrosis during CCl4-induced liver damage. Effects of anti-fibrotic agents. 148 4

Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5 or 7 mg paraquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, GOT, GPT and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary hemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electromicroscopic examination on the surviving animals revealed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts.
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PMID:Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections. 150 67

A sandwich ELISA system for detecting vascular basement membrane associated collagen (BAC) was developed. Serum levels of BAC were determined in patients with liver diseases (N = 53), various cancers (N = 65) and other diseases (399). Serum levels of procollagen type III (PIIIP) amino propeptide, type IV collagen.7s domain (7s domain) and other parameters (TP, ALB, GOT, GPT, CHE, gamma-GTP, ALP, LDH, CHE, TG, GLU) were also determined in those patients. In the whole patients, serum concentrations of BAC showed a weak correlation with GOT, GPT, ALB and CHE but not with gamma-GTP and ALP. There was no correlation between BAC and PIIIP or 7s domain. Although serum levels of BAC were elevated in both liver diseases and cancers, the increase in liver diseases was more marked. Markedly increased serum levels of BAC with low levels of CHE were found only in liver cirrhosis and liver cirrhosis plus hepatocellular carcinoma. Increased BAC may reflect capillarization of the liver sinusoid or remodeling of the vascular basement membrane which is observed in the progression of liver fibrosis. Serum BAC is thought to be a promising new marker, different from PIIIP or 7s domain for diagnosing fibrosis state in the organs, particularly in the liver.
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PMID:[Serum level of vascular basement membrane associated collagen by the sandwich ELISA with monoclonal antibodies and its clinical significance in various diseases]. 170 45

In vitro models have shown that metabolites of ethanol (acetaldehyde and lactate) stimulate collagen synthesis, thereby, suggesting that they may be important as fibrogenic mediators. The relevance of these findings for fibrogenesis in the human liver in vivo, however, has not as yet been demonstrated. Serum markers for collagen (PIIINP, using radioimmunoassays employing polyclonal antibodies and Fab-fragments (PIIINP-Fab), respectively) and basement membrane (laminin) metabolism were therefore investigated in 25 alcoholic cirrhotics (Pugh-Score: 6.7 +/- 1.9 S.D.) and in 19 comparable nonalcoholic cirrhotics (Pugh-Score: 6.3 +/- 1.5, n.s.) with only slight evidence for inflammation: GOT 28 +/- 22 vs. 24 +/- 21 U/l; GPT 24 +/- 23 vs. 31 +/- 28 U/l; gamma-globulins 24 +/- 8 vs. 22 +/- 5%, respectively (all n.s.). Severity of the disease was assessed by quantitative liver function tests. Levels of PIIINP, PIIINP-Fab and laminin measured by RIA were 21 +/- 19 micrograms/l, 90 +/- 42 micrograms/l and 2.5 +/- 0.8 U/ml in alcoholic cirrhosis and 10 +/- 6 micrograms/l, 61 +/- 10 micrograms/l and 1.9 +/- 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p less than 0.01). Differences on PIIINP and PIIINP-Fab remained significant even after accurate matching for galactose elimination capacity, aminopyrine breath test and hepatic sorbitol clearance. Laminin levels were higher in alcoholic cirrhosis only after matching for the hepatic sorbitol clearance (p less than 0.01). The higher levels of serum markers for collagen and basement membrane metabolism in alcoholic vs. nonalcoholic patients with cirrhosis at equal severity of the disease and with only minimal signs of inflammation may be the clinical reflection of a specific fibrogenic effect of ethanol metabolites.
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PMID:Higher levels of serum aminoterminal type III procollagen peptide, and laminin in alcoholic than in nonalcoholic cirrhosis of equal severity. 173 19

To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
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PMID:In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. 184 94


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