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PubMed1989

[Metabolic studies of 5-ethyl-2'-deoxyuridine with liver extract, liver cells and liver cell culture].

5-Ethyl-2'-deoxyuridine (EtUdR) was converted with rat liver extract, rat liver cells and rat liver cell cultures into its metabolites 5-ethyluracil and 5-(1-hydroxyethyl) uracil. The analytical identification of the metabolites as well as the investigation of the biotransformation process was performed by thin layer chromatography, autoradiography and high pressure liquid chromatography.

Animals↗

PubMed1997

Carrier-mediated active transport of the glucuronide and sulfate of 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) into rat liver: quantitative comparison of permeability in isolated hepatocytes, perfused liver and liver in vivo.

The hepatic uptake of glucuronic acid and sulfate conjugates of 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040), a dual inhibitor of 5-lipoxygenase and thromboxane A2 synthetase, was investigated in rats. The biliary excretion clearance values for the glucuronide and the sulfate, obtained after i.v. administration of E3040, were similar and corresponded to approximately 30% of the hepatic blood flow rate. The influx clearance values of E3040 conjugates in the presence of 3% bovine serum albumin, measured by a multiple indicator dilution method in the perfused liver, were 1.20 ml/min/g liver for the glucuronide and 0.74 ml/min/g liver for the sulfate, which were twice and equal to the normal hepatic plasma flow rate, respectively, which suggests the presence of an efficient transport system(s). The uptake of E3040 conjugates into the isolated hepatocytes is mediated by Na(+)-independent active transport system(s), which is inhibited by dibromosulfophthalein and bile acids. The uptake for the sulfate had high-affinity and high-capacity transport activity (Km = 25 microM; Vmax = 7.8 nmol/min/10(6) cells) compared with that for the glucuronide (Km = 59 microM; Vmax = 2.2 nmol/min/10(6) cells). The uptakes of E3040 conjugates (glucuronide, sulfate) exhibited a mutual competitive inhibition. It is suggested that both conjugates share a multispecific organic anion transporter located on the sinusoidal membrane.

Animals↗

PubMed1997

Prediction of postoperative decompensated liver function by technetium-99m galactosyl-human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicating chronic liver disease.

BACKGROUND: Preoperative technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy may predict postoperative decompensated liver function and its value has been investigated in patients having resection of hepatocellular carcinoma (HCC). METHODS: Hepatic uptake ratio of Tc-GSA (LHL15) was measured before operation in 30 patients. Postoperative complications were analysed retrospectively and compared with LHL15 values and other indicators evaluating hepatic function. RESULTS: The LHL15 of 22 patients without complications was 0.91 or more, compared with 0.90 or less in the eight patients who had complications. Multifactorial analyses showed that LHL15 and Child-Pugh grade significantly predicted postoperative complications (P < 0.0001 and P = 0.0111 respectively). LHL15 was a significant predictor of complications in patients with Child-Pugh grade B disease (n = 15, P = 0.0011). CONCLUSION: LHL15 was a reliable preoperative indicator of the risk of major postoperative complications in patients who had resection for HCC.

Aged↗

PubMed2006

Selection of liver-transplant candidates for adult-to-adult living donor liver transplantation as the only surgical option for end-stage liver disease.

The selection of living donor liver transplantation (LDLT) recipients in regions where deceased donor liver transplantation (DDLT) is rarely performed might be different from that in other centers at which LDLT is an alternative option to DDLT. Records of adult (age > or = 18 yr) patients referred to our center were reviewed to analyze the selection process of LDLT candidates. Among the 533 LDLT candidates, 165 (31%) were rejected due to recipient issues. Advanced hepatocellular carcinoma (HCC) was the most common reason for rejection (n = 55). Among the remaining recipients, 120 patients (22%) were rejected due to donor issues. LDLT was eventually performed in 249 (47%) of the evaluated recipients. There are few options for candidates who are unable to find live donors in regions where DDLT is unrealistic. A more effective and precise approach to recipient and donor evaluation should be pursued.

Adolescent↗

PubMed2003

Liver enzyme activity and histological changes in the liver of silver foxes (Vulpes vulpes fulva) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis.

Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose, species of flukes and individual peculiarities. The highest individual deviation of infected from control animals was registered in the case of GLDH, reaching increases of up to 200-fold. In contrast, AST showed the lowest deviation from control values (less than 10-fold). By the end of the study period, enzyme activities had declined. The prepatent periods for M. bilis and O. felineus in foxes were 2 weeks and 4 weeks, respectively. High egg per gram values were established at the beginning of the patent period. At necropsy, chronic inflammatory reactions were found in the bile ducts and in the wall of the gall bladder. The number of flukes at the end of the study was low.

Alanine Transaminase↗

PubMed2003

Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver.

Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor alpha, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci.

Animals↗

PubMed1994

Changes in ornithine metabolic enzymes induced by dietary protein in small intestine and liver: intestine-liver relationship in ornithine supply to liver.

Compared with the activity obtained with a high-protein diet in rats, a low-protein diet doubled the activity of ornithine aminotransferase [EC 2.6.1.13] (OAT), a key enzyme for citrulline synthesis, in the small intestine. The induction of ornithine aminotransferase in the small intestine by the low-protein diet and its suppression by the high-protein diet, and the converse in the liver, were immunohistochemically verified with anti-OAT antiserum. The immunohistochemical studies revealed that ornithine aminotransferase molecules localized in the villous surface epithelia, but not in the cryptic epithelia, were most responsive to the changes in dietary conditions, these results indicating that intestinal ornithine aminotransferase may be involved in the ornithine supply to the liver, with the reversal of the enzyme reaction occurring with a low-protein diet. Reconstituted model experiments on citrulline synthesis revealed that the addition of ornithine carbamoyl-transferase and carbamoyl phosphate was essential to overcome the unfavorable equilibrium of the reverse reaction, and the further addition of glutamate dehydrogenase and ammonia resulted in a stimulating effect.

Animals↗

PubMed1983

The degradation of urate in liver peroxisomes. Association of allantoinase with allantoicase in amphibian liver but not in fish and invertebrate liver.

Allantoinase and allantoicase were co-purified from frog (Rana catesbeiana) liver. The ratio of the two enzyme activities remained constant during purification and was unchanged by a variety of treatments of the purified enzyme. These results suggest that allantoinase and allantoicase are located in the same protein. It was found that the two hepatic enzyme activities are also associated with the same protein in other frogs (Xenopus laevis and Rana nigromacultata), tadpoles (R. catesbeiana), and newts (Triturus pyrrhogaster). In contrast, allantoinase and allantoicase were found to be different proteins in marine fish and invertebrate liver.

Amidohydrolases↗

PubMed2005

Large liver cell dysplasia in hepatitis B virus x transgenic mouse liver and human chronic hepatitis B virus-infected liver.

OBJECTIVES: Large liver cell dysplasia (LCD) is frequently associated with hepatitis B virus (HBV), but it remains uncertain whether it is reactive, senescent or preneoplastic. METHODS: The HBX transgenic mice and normal control mice were sacrificed at 1, 3, 5, 7, 9, 11, 13 and 15 months after birth. Twenty-three cases of human B viral chronic hepatitis/cirrhosis with prominent LCD were selected. The immunohistochemical stain of proliferating cell nuclear antigen (PCNA), transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and senescence-associated beta-galactosidase (SA-beta-Gal) were evaluated. RESULTS: In HBX transgenic mice, LCD was developed since 3 months and formed small nodules of hepatocellular adenoma, which progressed to hepatocellular carcinoma. The hepatocytes with LCD in HBX transgenic mice showed significantly higher PCNA-labeling index (LI) and lower TUNEL-LI than normal hepatocytes of control mice (p < 0.05). In the majority of human B viral chronic hepatitis/cirrhosis, the hepatocytes with LCD revealed higher PCNA-LI and lower TUNEL-LI than those without, when compared in each case using the same tissue block. SA-beta-Gal staining showed no difference between hepatocytes with and without LCD. CONCLUSION: It is suggested that LCD, related to HBV, might not be just an innocent bystander, but closely related to hepatocarcinogenesis.

Adult↗

PubMed1968