Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to evaluate the effect of cirrhosis on the disposition of the haemoglobin-based oxygen carrier, diaspirin cross-linked haemoglobin (DCLHb). Cirrhosis was induced in male Sprague-Dawley rats (200-250 g) by inhalational exposure to carbon tetrachloride (CCl4), over a period of 6 weeks. Pharmacokinetic evaluation was performed after a single intravenous bolus administration of DCLHb (400 mg kg(-1)). Serum biochemistry, including aspartate transaminase, alkaline phosphatase, bile acids, serum albumin, and serum creatinine, were measured in CCl4-treated (n = 6) and age-matched control (n = 6) rats. After 6 weeks, the jugular vein and carotid artery were cannulated for bolus DCLHb administration (400 mg kg(-1)) and blood sampling, respectively, in both groups of rats. Cirrhosis produced significant (P < 0.05) elevations in alkaline phosphatase (497.4 +/- 84.8 U L(-1) vs 241.2 +/- 5.1 U L(-1)), aspartate transaminase (920.5 +/- 190.9 U L(-1) vs 238.2 +/- 118.1 U L(-1)) and bile acids (333.8 +/- 77.3 mg dL(-1) vs 43.8 +/- 4.2 mg dL(-1)) compared with the control group. No significant renal dysfunction was observed as a result of CCl4 exposure. Plasma DCLHb concentrations declined approximately log-linearly. Systemic clearance of DCLHb was estimated to be 2.2 +/- 0.7 mL h(-1) in the treatment group and was slightly, but not significantly, less in the control group (3.6 +/- 1.7 mL h(-1)). There was also a trend toward a longer elimination half-life in the treatment group (4.7 +/- 2.2 h) compared with the control group (3.8 +/- 0.8 h), although this difference was not statistically significant. Cirrhosis does not significantly alter the disposition of DCLHb perhaps due to increased extra-hepatic metabolism by the reticulo-endothelial system.
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PMID:Pharmacokinetics of diaspirin cross-linked haemoglobin in a rat model of hepatic cirrhosis. 1127 13

Primary biliary cirrhosis (PBC), autoimmune cholangitis (AIC = AMA-negative PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholestatic liver diseases. Overlap syndromes combine characteristics of cholestatic liver diseases and autoimmune hepatitis. In PBC, alkaline phosphatase and gamma-glutamyl transferase are elevated, to a lesser degree aminotransferases. Histology shows bile duct lesions. Anti-mitochondrial antibodies are typical. Ursodeoxycholic acid (UDC) is established therapy that slows or even stops the disease progression, at least in early stages of the disease. In non-responders immunosuppression is recommended. PSC is mostly associated with chronic inflammatory bowel diseases. P-ANCA are frequent. Bile duct lesions revealed by retrograde cholangiography are characteristic. UDC is given as therapy. Bile duct strictures or bacterial cholangitis may be late sequelae and should be treated by antibiotics or bile-duct dilatation. Cirrhosis may ultimately develop in PBC and PCS. In progressed PBC or PSC liver transplantation is indicated.
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PMID:[Cholestatic liver diseases]. 1545 69

Hepatoportal sclerosis (HPS) is one of the causes of noncirrhotic portal hypertension. In general, hepatic synthetic function is preserved and treatment is aimed at relief of the portal hypertension. In this study, we present the clinical and pathologic features of HPS cases who underwent liver transplantation (LT). LT cases with confirmed gross and microscopic diagnosis of HPS are included. Weight of the explanted liver, presence of thrombi in the main blood vessels, and gross and microscopic characteristics were assessed. Clinical information was gathered from chart review. From 1995 to 2004, 8 LT patients were diagnosed with HPS. Cirrhosis resulting from alcohol (2), autoimmune hepatitis (2), and hepatitis B (1), or cryptogenic cirrhosis (3) was the presumed diagnoses pre-LT. Seven patients presented with bleeding varices and 5 had concomitant ascites. At the time of LT, mean values were: prothrombin time of 15.2 seconds, serum albumin 3.2 g/dL, serum bilirubin 3.5 mg/dL, alkaline phosphatase 140 IU/L, aspartate aminotransferase 39.4 IU/L, and alanine aminotransferase 34.7 IU/L. Explanted livers were shrunken, with weights ranging from 715 to 1199 g (mean 934). Nonocclusive portal vein thrombosis was present in 2 patients. On histologic examination, there was dense portal fibrosis, marked phlebosclerosis, and presence of variable degrees of megasinusoid formation. Four livers also had features of incomplete septal cirrhosis. None showed histologic features of the presumed underlying liver disease. In conclusion, HPS can cause hepatic synthetic dysfunction that may necessitate LT. Small liver volume, significant portal fibrosis, and phlebosclerosis may contribute to hepatic parenchymal loss and subsequent synthetic compromise.
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PMID:Liver failure and need for liver transplantation in patients with advanced hepatoportal sclerosis. 1741 9

Current evidence indicates that liver fibrosis is dynamic and can be bidirectional, involving phases of progression and regression, and that in addition to increased matrix synthesis, this pathological process involves major changes in the regulation of matrix degradation. There is also evidence that Kupffer cells participate in both fibrogenesis and fibrolysis. Therefore, the aim of the present work was to study the participation of Kupffer cells on the spontaneous resolution of hepatic fibrosis. Cirrhosis was produced by 3 months of chronic CCl(4) intoxication in male Wistar rats, and then CCl(4) was discontinued and two groups were formed: One group received gadolinium chloride (10 mg/kg, IP, daily) and the other received the vehicle (water) only for 2 months. Serum enzyme activities of alkaline phosphatase and alanine aminotransferase and liver lipid peroxidation increased by CCl(4) treatment but returned to normal by discontinuation of CCl(4). GSH, GSH/GSSG, and GSH+GSSG decreased significantly by CCl(4), but withdrawal of CCl(4) restored normal glutathione parameters. Fibrosis increased five-fold and glycogen decreased significantly by CCl(4) treatment, while discontinuation of CCl(4) reversed completely glycogen depletion and partially fibrosis. Gadolinium chloride showed effects only in the content of glycogen and collagen; the former was decreased further and the latter remained elevated despite discontinuation of the toxic agent. Persistent fibrosis induced by gadolinium chloride, a selective inhibitor of Kupffer cells, indicates that these cells play a pivotal role in fibrolysis.
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PMID:Gadolinium Chloride Inhibits the Spontaneous Resolution of Fibrosis in CCL(4)-Induced Cirrhosis. 2002 Sep 93

The prevalence of infection with hepatitis B virus in Portugal is around 1% of the population; 20-30% of those infected typically develop cirrhosis. The study focuses on the epidemiological profile of patients with hepatitis B infection and liver damage, in particular, cirrhosis. Of the 358 individuals that comprised the study, a liver biopsy was performed in 249 to identify the presence of cirrhosis. Cirrhosis was observed in 59 patients (23.7%) The Child-Pugh classification was used to assess the prognosis of cirrhosis: 3 out of the 59 patients were classified as Child-Pugh grade C, the most severe, 17 (28.8%) as grade B, and 39 (66.2%) as grade A. Patients classified as grade B were older, drank more, and showed higher levels of AST and alkaline phosphatase when compared with individuals classified as grade A. Genotypes A and D were predominant, and no significant differences with respect to genotype distribution were observed. Analysis of the hematological parameters showed that patients classified as Child's grade B had lower levels of platelets and higher levels of prothrombin time than those classified as Child's grade A. The profile of the patients with cirrhosis, including an extended number of individual characteristics, provides useful information, however, only a prospective study could evaluate definitively if liver disease is influenced by these factors. Future studies would benefit from the analysis of the impact of genotypes on liver disease, particularly genotypes A and D, the most predominant genotypes in northern Portugal.
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PMID:Chronic liver disease and cirrhosis among patients with hepatitis B virus infection in northern Portugal with reference to the viral genotypes. 2110 41


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