Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary human hepatocytes were used to study bile salt hepatotoxicity and the hepatoprotective potential of ursodeoxycholate in vitro. Hepatocytes were obtained by collagenase perfusion of healthy human liver tissue and were treated with glycochenodeoxycholate for 24 hr 1 day after plating. Clear signs of cytotoxicity were observed at concentrations of about 100 mumol/L glycochenodeoxycholate. Toxicity was determined by release of alkaline phosphatase, gamma-glutamyl transferase, AST, ALT or lactate dehydrogenase into the culture medium, by measuring DNA synthesis of the cultured liver cells and by testing the viability of the hepatocytes using trypan-blue dye exclusion. Addition of ursodeoxycholate, which by itself proved to be of little toxicity, significantly reduced the hepatotoxic effects of glycochenodeoxycholate: 72% +/- 6% of the cells survived treatment with 500 mumol/L glycochenodeoxycholate alone, but addition of 100 mumol/L ursodeoxycholate increased the survival rate to 87% +/- 4% (p less than 0.05). Moreover, all enzymes tested were secreted at a significantly lower level when ursodeoxycholate was present. Similarly, the cellular DNA synthesis was maintained at significantly higher levels as a result of ursodeoxycholate treatment. We conclude that (a) primary human hepatocytes are a suitable model for studying hepatotoxicity of bile salts in vitro, (b) ursodeoxycholate reduces hepatotoxicity of other bile salts and (c) ursodeoxycholate can act hepatoprotectively by itself (i.e., alteration of the metabolism of other bile salts is not necessarily required).
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PMID:Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. 240 54

The authors report a study in which they evaluate the efficacy of some laboratory parameters for monitoring intrasplenic hepatocyte xenotransplantation (mouse to rat) as an alternative to 99Tc-HIDA dynamic scan and histologic exam. Swiss mouse and wistar rat hepatocytes were obtained with collagenase digestion. Wistar male rats were used as recipient and were allocated into three groups: A) omotransplanted rats; B) xenotransplanted rats; C) xenotransplanted and immunosuppressed (Cyclosporin A: 20 mg/kg/daily orally) rats. All rats underwent > 70% hepatectomy. Blood samples were obtained daily from a femoral vein and AST, ALT, ALP, bilirubin, albumin and urea were measured. No statistical differences were observed among groups and the laboratory parameters tested can't be considered a valid technique to xenotransplant rejection monitoring.
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PMID:[Monitoring of hepatocyte xenotransplantation. Usefulness of various laboratory parameters]. 761 63

Alcoholic and, to a lesser extent, nonalcoholic patients with liver disease have serum antibodies to acetaldehyde-protein adducts produced in vitro. These antibodies presumably reflect the presence of adducts in the liver, but the protein that triggers this immune response has not been identified. To study this, we measured the reactivity of cytosolic proteins to rabbit IgG developed against a P-450 2E1-acetaldehyde adduct, isolated from alcohol-fed rats, that recognizes acetaldehyde-modified epitopes in proteins. Adducts were determined on Western blots by scanning densitometry of antibody-linked alkaline phosphatase activity in 4 normal livers and in needle biopsy specimens from subjects with liver disease, 17 alcoholic and 14 nonalcoholic. In all livers, except for a normal one, we found a reactive protein of at least 200 kD, similar to the collagen-acetaldehyde adduct we reported to be markedly increased in rats with experimentally induced cirrhosis. The immunostaining intensity in the alcoholic patients with liver disease was eightfold (p < 0.01) and that in nonalcoholic patients with liver disease was fourfold, greater (p < 0.02) than the weak staining in normal livers; it correlated with the degree of inflammation and serum AST or gamma-glutamyl transpeptidase activities. The adduct was reproduced on incubation of normal cytosolic proteins with 2.5 mmol/L acetaldehyde, whereas higher concentrations yielded many additional adducts; the adduct also reacted with IgG antibody to rat collagen type I and disappeared after digestion with collagenase, suggesting that the target protein is a form of collagen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Collagen-acetaldehyde adducts in alcoholic and nonalcoholic liver diseases. 791 86

This article presents the design of a bioreactor using hollow fiber membrane and, isolated hepatocytes of suckling pigs, and the experimental study of its efficacy in vitro. Liver cells were harvested from suckling pigs with collagenase perfusion in situ, and parenchymal and non-parenchymal hepatocytes were cocultured in a hollow fiber module which was rotated sporadically. Bioartificial liver(BAL) was developed using this bioreactor,and the BAL was perfused with ascites of patients suffering from liver cirrhosis. The yield of viable hepatocytes was (6.29 +/- 0.37) x 10(8) cells, and cell viability was greater than 84%. Hepatocytes aggregated to multi-cells spheroids after being rotated every thirty minutes for three hours. The hepatocytes in the bioreactor could synthesize urea. Total billirubin was decreased, and AST was significantly increased in the group of bioreactor, as compared with that in the control group. Glucose decreased in the group of bioreactor,whereas there was no significant descent in the control group; and the difference between the two groups was significant. The above results demonstrate that this bioreactor is effective for decreasing total bilirubin and glucose.
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PMID:[Design of a hollow-fiber bioreactor and perfusion study in vitro]. 1653 33

Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis.
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PMID:Enzymatic debridement in necrotizing pancreatitis. 2601 Dec 12