Biomedical subjects

G J Enderle

Publications and source records attributed to G J Enderle.

4 recordsLinked to original sources

PubMed1996

Bile ductular proliferation and altered leukotriene elimination in thioacetamide-induced fibrosis of rat liver.

BACKGROUND/AIMS: Liver fibrosis is accompanied by both bile ductular proliferation and inflammation under various conditions. The functional consequences and the interrelationships between these changes are unknown. Altered biliary elimination and retention of cholephilic mediators may be a factor in fibrogenesis. Therefore, the relationship between fibrosis, ductular proliferation and functional changes in biliary elimination was studied. METHODS: Micronodular liver fibrosis was induced by thioacetamide in rats. The relative amount of bile ductular epithelial cells was determined by microscopic morphometry. The functional changes in bile secretion and metabolism of leukotriene C4 were assessed in isolated perfused livers of treated rats. RESULTS: Pretreatment with thioacetamide in vivo resulted in enhanced bile fluid formation in subsequently isolated and perfused livers. Infusion of isoproterenol into the portal vein stimulated bile flow. Both unstimulated and isoproterenol-stimulated bile flows were increased in fibrotic livers and were correlated with liver content of bile ductular epithelia. In contrast, biliary secretion of infused leukotriene C4 was lowered in correlation with that of taurocholate. Enhanced metabolism resulted in a shift of the major fraction in bile from leukotriene C4 to leukotriene D4. CONCLUSIONS: Thioacetamide-induced liver fibrosis is associated with an increased number of functionally intact bile ductules that are responsive to isoproterenol stimulating bile fluid formation. In contrast, biliary secretion of cysteinyl-leukotrienes and taurocholate is inhibited and the relative amount of leukotriene D4 is increased. Bile ductular proliferation as well as retention and altered metabolism of leukotrienes are factors associated with the development of liver fibrosis.

Animals↗

PubMed1995

Different pathomechanisms of altered biliary leukotriene C4 elimination in isolated perfused rat livers.

Hepatic retention of cysteinyl leukotrienes is a consequence of impaired bile secretion and may be involved in the pathogenesis of intrahepatic cholestasis. In order to assess the mechanisms of altered biliary leukotriene elimination, we studied the secretion and metabolic pattern of leukotriene C4 (LTC4) in bile early in the alterations of bile formation by xenobiotics. To this end, rats were pretreated with alpha-naphthylisothiocyanate (ANIT), ethionine (ETH), or estradiol valerate (EV) at doses which did not increase serum marker enzymes of cholestasis. Bile secretion was assessed in perfused livers isolated from the treated rats. In all models, the access of [14C]sucrose into bile was increased, indicating increased permeability of the bile tract. Biliary recovery of radioactivity infused as [3H]LTC4 was decreased by ANIT and ETH while 3H-efflux into the perfusate was increased concomitantly. The secretion rate of 3H-radioactivity into bile was correlated with that of [14C]taurocholate infused at the same time. After pretreatment with ANIT (but not in the other models) the venous efflux of [3H]LTC4-ANIT pretreatment was increased [14C]sucrose clearance into bile associated with greatly enhanced biliary access of [32P]phosphate. Thus, altered charge selectivity of the paracellular pathway appears to be a prerequisite for reflux of cholephilic anions. HPLC analysis of [3H]LTC4-derived radioactivity in bile revealed that in all models of altered bile secretion the relative amount of LTD4 in bile was elevated. These results demonstrate differential changes in hepatobiliary transport and metabolism of LTC4 in developing cholestasis. ANIT inhibits leukotriene secretion by increasing paracellular permeability with loss of charge selectivity. In contrast, ETH treatment inhibits transcellular transport while treatment with EV only results in enhanced LTC4 metabolism.

1-Naphthylisothiocyanate↗

PubMed1995

East German uranium miners (Wismut)--exposure conditions and health consequences.

Underground uranium mining was performed in East Germany after World War II on a large scale. East Germany was the main supplier of uranium for the Soviet Union. This review gives a historical summary and describes the broad spectrum of exposure to potential health hazards and the health consequences. Working conditions were very poor during the postwar years from approximately 1946-1955: there was drilling with air floating and a lack of forced ventilation. Dust levels were very high and there was a significant inhalative incorporation of alpha-radiating substances, mostly from short-lived radon progeny. However, long-lived alpha-radiating substances such as uranium-238 contributed considerably to the radiation dose. There was also exposure to toxic chemicals, such as arsenic (in some mines) or crystalline silica, and a variety of other health hazards. From approximately 1956-1970, mining conditions improved: there was drilling with the addition of water and forced ventilation of the mines. As of approximately 1970, compliance with rules of industrial hygiene and international standards of radiation protection was evident. In 1990, uranium production was generally stopped. To date, more than 5,000 cases of bronchial carcinoma are accepted as compensable occupational diseases and more are expected. The extensive data from Wismut uranium mining could improve our understanding of a complex exposure situation resulting in a variety of health impairments other than lung cancer.

Germany↗

PubMed1993

Cholestasis: pathophysiology and pathobiochemistry.

Clinical and morphological diagnosis of cholestasis involves a variety of different parameters, but bile fluid formation and composition of bile are usually not accessible in patients. In contrast, a pathophysiological definition of cholestasis can be based on current knowledge on the mechanisms of bile formation. Hence, causes of cholestasis may be localized in each step of the process of bile formation. 1. Inhibition of fluid formation reduces maximal secretory capacity. 2. Inhibition of the transcellular hepatobiliary transport may involve transport carriers, binding proteins, and the systems of biotransformation. 3. Mechanical obstruction or regurgitation of bile constituents due to increased permeability of the bile tract may inhibit the biliary elimination of cholephilic compounds. Consequences of the inhibition of biliary elimination are retention in the liver and the whole organism of potentially toxic compounds. Among these are endogenous compounds such as bile acids and cysteinyl-leukotrienes, but xenobiotics as well may become more toxic in cholestasis. The composition of bile and portal venous blood is altered. In experimental animals, changes in secretory function can already be observed before clinically used indicator enzymes of cholestasis increase. This functional inhibition of biliary elimination can be characterized as "subclinical" cholestasis that may, nevertheless, inhibit the elimination and potentiate the toxicity of cholephilic endo- and xenobiotics.

Bile↗