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)

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).
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PMID:Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil. 359 Jan 98

Clinicopathologic features of 45 patients with fulminant hepatic failure due to massive or submassive hepatic necrosis were studied. Both percutaneous biopsies and liver explants were available in 23 patients, whole livers only in 11 cases, and biopsies only in 11 cases. An etiologic diagnosis was established in 16 cases (36%). A further 3 cases (7%) were associated with aplastic anemia. Established etiologies included drug reactions (n = 7); autoimmune hepatitis, type 2 (n = 3); halothane hepatitis (n = 1); ischemia/hypotension (n = 1); mushroom poisoning (n = 1); mitochondrial disorder (n = 1); hemophagocytic lymphohistiocytosis (n = 1); and adenoviral hepatitis (n = 1). The extent of necrosis on liver biopsy correlated poorly with that in liver explants (mean difference, 32% +/- 23.8%). Almost all cases could be classified into one of 2 broad patterns of necrosis, namely, (1) zonal coagulative necrosis or (2) panlobular (nonzonal) necrosis. These patterns differed significantly with respect to several clinical parameters including sex ratio, peripheral blood white cell count, serum aspartate transaminase and alanine transaminase, conjugated bilirubin, and alkaline phosphatase levels. Livers with panlobular necrosis showed a spectrum of histopathologic findings that included central venulitis (76%), lymphocytic infiltration of large duct/gallbladder epithelium (54%), and syncytial giant cell transformation (18%). These features were not seen in livers with zonal coagulative necrosis which frequently showed prominent steatosis (91%). Both patterns of necrosis frequently showed ductular proliferation (100%) and cholangiolitis (80%). The diagnostic yield of ancillary studies (histochemistry, immunohistochemistry, and electron microscopy) was very low (<1%). The small proportion of cases with etiologic diagnoses precluded correlation of clinical and histopathological parameters with specific etiologies. In summary, this study describes the spectrum of changes seen in massive and submassive necrosis in children and identifies clinical features that might differentiate between 2 broad patterns of necrosis.
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PMID:Clinicopathologic spectrum of massive and submassive hepatic necrosis in infants and children. 1912 48

We report a case of acute-onset, long-lasting cholestasis induced by atorvastatin. This antihyperlipidaemic drug was taken for 40 days by a 72-year-old male as a treatment for his mixed dyslipidaemia. At that point, the patient presented with asthenia, nausea, painless icterus, acholic stools and hyperchromic urine with biochemical analyses showing a dramatic increase in bilirubin (total bilirubin 22 mg/dL; direct bilirubin 21 mg/dL) and alkaline phosphatase (up to 4-fold over the normal level) with less marked increases in transaminases. Liver histology showed a pattern of cholestasis with evident signs of cholangiolitis and damage of the interlobular bile ducts. Serum transaminase and bilirubin levels returned to normal within 5 months after atorvastatin withdrawal while alkaline phosphatase normalized after only 8 months. Scores on both the Maria and Victorino clinical scale for the diagnosis of drug-induced hepatitis and the Naranjo Adverse Drug Reaction Probability Scale indicated that atorvastatin was the probable cause of prolonged cholestasis in this patient. This is a rare case of cholestasis probably caused by atorvastatin and unusually characterized by bile duct damage.
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PMID:Atorvastatin-induced prolonged cholestasis with bile duct damage. 2015 93