Metabolism in vivo of carbon disulfide to carbonyl sulfide and carbon dioxide in the rat.
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Biomedical subjects
Publications and source records attributed to R A Neal.
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The effect of chronic alcohol administration on the absorption, excretion and metabolism of thiamin in the rat has been examined. In ethanol-fed rats receiving a marginal daily intake of thiamin (10 microgram/day) by stomach tube or by intraperitoneal injection, less of the vitamin and its metabolites were excreted in the urine as compared to controls administered the same diet except that sucrose replaced the energy represented by ethanol. More of the oral dose of thiamin was excreted in the feces of the ethanol-fed as compared to control rats. These data support previous reports of decreased adsorption of thiamin from the gut in animals exposed to ethanol. The studies in which the thiamin was administered by intraperitoneal injection also indicate an effect of ethanol on thiamin excretion in the urine which appears not to be related to absorption of the vitamin from the gut. An examination reveals no difference in the level of thiamin and its metabolites in the tissues of ethanol-fed as compared to control rats receiving thiamin by stomach tube. Thus, the decreased absorption of thiamin from the gut in the ethanol-fed rats seems to be balanced by a decreased excretion in the urine leading to a comparable accumulation of the vitamin in the tissues as controls.
Four strains of Trypanosoma cruzi (Y, BG, M and Peru) retain their ability to infect Rhodnius prolixus and to produce virulent infections in mice for from 12 to 39 years. About 60 or more metacyclic trypomastigotes were consistently lethal to mice. The mean number of metacyclics per bug ranged from 1.2 to 17.3 x 10(3). Comparative studies of virulence of metacyclics and blood trypomastigotes showed the blood forms to be slightly more virulent. The route of injection was shown to be more significant in varying the host response to infection, subcutaneous inoculation being the preferred route.
The immunization of mice with killed epimastigotes or trypomastigotes with saponin SPL as adjuvant was challenged by inoculation of blood or metacyclic trypomastigotes of T. cruzi. Immunogenic preparations were obtained by freeze-thawing of formalin treatment. The protection was effective against homologous and heterologous challenge, and lasted up to 12 weeks after the last immunization. The immunization was also effective against metacyclic trypomastigote challenge. The immunogenicity of the killed T. cruzi suspension was retained after freeze-drying.
Metabolic activation of thioacetamide (CH3CSNH2) to a toxic metabolite which is responsible for its hepatotoxicity and/or its carcinogenicity has been proposed by a number of investigators. In this investigation thioacetamide and one of its metabolites, thioacetamide sulfine (CH3CSONH2), have been compared for their ability to inhibit hepatic mixed-function oxidase enzymes as well as their ability to induce hepatic necrosis. Thioacetamide sulfine was found to decrease aminopyrine N-demethylation and aniline hydroxylation at a lower dose and at an earlier time after administration than was the case with thioacetamide. In addition, at all doses examined, thioacetamide sulfine produced a more severe centrilobular hepatic necrosis than equivalent doses of thioacetamide. To determine whether the hepatic mixed-function oxidase enzyme system was involved in the biotransformation of thioacetamide and/or thioacetamide sulfine to a hepatotoxic compound(s), the severity of liver damage was examined after the administration of an inducer or inhibitors of hepatic mixed-function oxidase enzyme activity. Phenobarbital pretreatment potentiated the hepatic necrosis produced by both thioacetamide and thioacetamide sulfine. In contrast, pyrazole, SKF 525-A, and cobaltous chloride protected against the hepatic necrosis caused by thioacetamide and thioacetamide sulfine. These data suggest that both thioacetamide and thioacetamide sulfine are activated by hepatic mixed-function oxidase enzymes to a hepatotoxic compound(s). These data also suggest that the hepatotoxicity may be mediated by its metabolism to thioacetamide sulfine which, in turn, is metabolized to an ultimate toxic metabolite.
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Varying doses of TCDD ranging from 25 to 1000 mug/kg were administered to the larval and adult forms of the American bullfrog, Rana catesbeiana. Doses of TCDD as high as 1 mg/kg failed to have any significant effect upon survival or completion of metamorphosis in tadpole and doses of up to 500 mug/kg had no effect on survival of adult frogs. Histopathological examination of various tissues from the metamorphosed tadpoles and adult frogs failed to show any abnormalities.
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All antigens (leishmanin) prepared from nine isolates of Leishmania gave positive skin tests in guinea pigs infected with L. enriettii. However, variation in potency was observed and ascribed to batch variation. It is recommended that biological testing of leishmanin is considered before use in field surveys or as an aid to clinical diagnosis.
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