Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interpretation of the morphological features of alcoholic hepatitis is discussed in terms of a comparison with the results of an ultrastructural and histoenzymological study of the liver biopsies of nine patients. In these patients liver biopsies were performed in the initial stage of the illness and fifteen days after five were re-biopsied, when the clinical and biological signs were improved. The correlations between morphological and biological data were good, especially for the levels of serological and histoenzymological alkaline phosphatase and gamma-glutamyltranspeptidase evaluations. However, when histological appearances had returned to normal, after two weeks of abstinence from alcohol several histological and ultrastructural features of the initial hepatitis persisted. The presence of evolving cirrhosis was a contributing factor to the severity of the changes seen. Morphologically, apart from the changes due to chronic alcoholic intoxication (steatosis, mitochondrial alteration), the hepatitic lesions comprise Mallory's bodies, cytoplasmic oedema and mitochondrial swelling. Cholestasis was invariably present. Histo-enzymologically there was a reduction in ATPase activity suggesting a metabolic failure in the energy producing pathways. In addition, in the periphery of lobules an active cirrhotic process was present, with tubular de-differentiation of hepatocytes and an increase in gamma-glutamyltranspeptidase on the cytoplasmic membrane. Because of the absence of any topographical relationship between hepatitis and cirrhosis, the presence of lymphocytes in the neighbourhood of the ductules suggested an indirect relationship between both processes, perhaps an autoimmune response initiated by Mallory's bodies.
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PMID:[The hepatocyte in acute alcoholic hepatitis. Histoenzymological and ultrastructural analysis (author's transl)]. 3 Oct 27

Studies were undertaken to determine if cholestasis in alcoholic or viral hepatitis is related to immunologic hyperreactivity as suggested for cholestasis due to type-II drug-induced hepatitis, and evaluate possible mechanisms involved in lymphokine-induced cholestasis. Results indicate that a cholestatic factor exists in alcoholic and acute viral hepatitis. Supernatants of lymphocytes from patients with alcoholic hepatitis stimulated by an extract of alcoholic hyalin evoked a 28% +/- 7.3 SEM reduction in rat bile flow (P less than 0.03). Supernatants of lymphocytes from patients with acute viral hepatitis activated by liver-specific protein caused a reduction in rat bile flow of 24% +/- 5.9 SEM (P less than 0.03). A decrease in bile flow also occurred following injections of sera from patients with alcoholic or acute viral hepatitis. In contrast, injection of supernatants of non-stimulated lymphocytes or those from chronic active hepatitis or healthy subjects did not produce a significant change in bile flow. Supernatants of stimulated lymphocytes from tuberculin-sensitized guinea pigs caused a similar decrease in rat bile flow and reduced excretion of human secretory immunoglobulin A (IgA). Despite reductions in rat bile flow there were no alterations in liver morphology, liver plasma membrane Na-K-ATPase activity, microsomal cholesterol-7 alpha-hydroxylase activity or low-dose indocyanine green clearance during the period of observation.
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PMID:Studies of the influence of immunological and serological factors from patients with cholestasis due to alcoholic or viral hepatitis on biliary function in the rat. 609 1

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/QO2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents. Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.
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PMID:Hypermetabolic state and hypoxic liver damage. 632 88