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Biomedical subjects

H Greim

Publications and source records attributed to H Greim.

At least 91 records · Page 5Linked to original sources
PubMed1984

Short-term studies with the cryptating agent hexaoxa-diaza-bicyclo-hexacosane in rats.

In short-term experiments rats received single doses of 50, 100, and 500 mumoles/kg of the cryptating agent A 222. A dose-related increase in the activities of GOT and GPT in the serum was observed 6 h after treatment, reaching values up to eleven and three times that of the controls, respectively. However, the enzyme activities returned to the control levels within 3 days. The activity of alkaline phosphatase and the levels of protein and cholesterol in serum were not altered during the observation period of 7 days. Histopathological examinations did not show any changes in the liver, kidney, heart, lung, thymus, spleen, or intestine. The elevations of GOT and GPT seem to be due to a transient liver lesion, since no histopathological alterations of the liver became apparent. These results show, that after single applications of A 222 at all doses used, no severe lesions occur in the observed organs.

Alanine Transaminase↗
PubMed1984

Formation of dichloroacetylene from trichloroethylene in the presence of alkaline material--possible cause of intoxication after abundant use of chloroethylene-containing solvents.

Inhabitants of a private home suffered from symptoms possibly due to dichloroacetylene intoxication. Subsequent anamnesis revealed that abundant amounts of trichloroethylene had been used to remove a wax coating from a concrete-lined stone floor. This prompted us to examine whether dichloroacetylene could have been formed. Incubation of two commercial samples of trichloroethylene with aqueous alkaline solutions between pH 11 and 13, with mortar and tile filling material resulted in the formation of dichloroacetylene. This finding suggests formation of dichloroacetylene, when trichloroethylene comes into contact with moderately alkaline material, such as moist concrete.

Acetylene↗
PubMed1984

Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced toxicity.

Chemical thyroidectomy effectively protected athyroid rats from mortality during 45 days after dosing with 100 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, whereas 70 to 80% of nonthyroidectomized-euthyroid and thyroidectomized-T4 (thyroxine)-maintained-euthyroid rats died within the same period of time. There was a significant decrease in body weight of all TCDD-treated groups compared to vehicle controls. However, body weight loss was much slower in thyroidectomized-athyroid (congruent to 1 g/day) than in nonthyroidectomized-euthyroid or in thyroidectomized-T4-euthyroid (congruent to 8 g/day) rats. TCDD significantly reduced feed intake in nonthyroidectomized-euthyroid and thyroidectomized-T4-euthyroid rats, but no altered feed consumption was observable in thyroidectomized-athyroid animals. These data indicate that thyroid hormone(s) play(s) an important role in mediating the toxicity of TCDD.

Animals↗
PubMed1983

Stimulation of nonbiliary, intestinal excretion of hexachlorobenzene in rhesus monkeys by mineral oil.

Four rhesus monkeys were administered various doses of hexachlorobenzene (HCB) po, to achieve widely varying adipose tissue levels. One month later, each animal was provided with a bile duct bypass allowing for interruption of the enterohepatic circulation (EHC). Effects of mineral oil-supplemented diet and/or interruption of the EHC on urinary, biliary, and fecal excretion of HCB and its metabolites were quantified. Urinary excretion of HCB was not affected by mineral oil but was reduced 20 to 60% by interruption of the EHC. Similarly, biliary excretion of HCB was also reduced 25 to 60% by interruption of the EHC and was not altered by mineral oil. Fecal excretion was increased about fivefold by mineral oil, whereas interruption of the EHC had no effect on the amount of HCB in feces. Results demonstrate that interruption of the EHC reduced urinary and biliary excretion of HCB metabolites, whereas mineral oil specifically stimulated intestinal excretion of the parent compound.

Animals↗
PubMed1983

Enhanced intestinal excretion of hexachlorobenzene in rats by intraluminal injection of hexadecane.

The effect of hexadecane on the intestinal excretion of hexachlorobenzene was studied in female Sprague-Dawley rats dosed twice with 14C-hexachlorobenzene at 50 mg kg-1 per os. Injection of 75 mg n-hexadecane into ligated and unligated segments of the intestine increased concentrations of hexachlorobenzene in intestinal contents by about two- or three-fold in jejunal and ileal segments, and about two-fold in the cecal-colon segment. The jejunum appeared to be the site of greatest excretion of hexachlorobenzene followed by the ileum, the cecum and the colon. This order is opposite to our previous data from animals with an undisturbed intestinal passage. The apparently greater excretion of hexachlorobenzene into the small intestine is probably due to its much larger surface area than that of the large intestine. However, the residency time of luminal contents in the large intestine normally exceeds that in the small intestine by about 20--40-fold, which apparently more than compensates for the difference in relative surface area between small and large intestine. Thus, residency time appears to be a more important factor than surface area in determining the intestinal elimination of hexachlorobenzene. These results with hexachlorobenzene are probably typical of physiological disposition of lipophilic halogenated hydrocarbons generally.

Alkanes↗
PubMed1982

Hexadecane enhances non-biliary, intestinal excretion of stored hexachlorobenzene by rats.

[14C]Hexachlorobenzene (100 mg/kg) was orally administered to 4 groups of rats. Ten days later the effects of hexadecane (3 x 5 ml/kg by gavage) and/or bile duct ligation on urinary and fecal excretion and tissue levels of hexachlorobenzene were examined. Hexadecane did not affect urinary excretion of hexachlorobenzene, whereas bile duct ligation tripled it. Each of the 3 treatments (n-hexadecane, bile duct ligation and the combination of the two) resulted in a significant increase in fecal excretion of hexachlorobenzene. Moreover, the combination of hexadecane and bile duct ligation produced a greater increase in fecal excretion of hexachlorobenzene than either treatment alone. Concentrations of hexachlorobenzene in blood, fat and kidney were not affected by any of the treatments, but liver concentrations were reduced significantly by bile duct ligation. Concentrations of hexachlorobenzene in intestinal contents indicate that intestinal-wall passage is the primary route of elimination from the body and that enhancement of elimination occurs mostly distal to the jejunum.

Alkanes↗
PubMed1982

Elimination of thioethers following administration of naphthalene and diethylmaleate to the rhesus monkey.

As a measure of glutathione (GSH) conjugation, urinary, fecal and biliary excretion of thioethers and hepatic GSH content were measured in rhesus monkeys following administration of single doses of naphthalene and diethylmaleate (DEM). Naphthalene had little or no effect on hepatic GSH content and the excretion of thioethers into urine, feces or bile of rhesus monkeys which is similar to that observed in chimpanzees and humans and is in contrast to results obtained from rats. Apparently, conjugation of naphthalene and/or its metabolites with GSH does not play a major role in the metabolism of naphthalene in primates, whereas it is one of the major pathways in rodents. Rhesus monkeys, like chimpanzees, excreted about 13% of the various doses of DEM (30, 75 and 200 mg/kg) as thioethers into urine which is half of that excreted by rats. Six hrs after administration of 200 mg/kg DEM, the hepatic GSH content was decreased by 90% in the rhesus monkey. During the first day after this dose (200 mg/kg), the increase in the excretion of thioethers into bile corresponded to about 15% of the dose of DEM administered. Since fecal excretion of thioethers corresponded to only 1% of the dose and urinary excretion represented 12% of the dose, it appears that biliary thioethers of DEM are reabsorbed from the intestine and then excreted into urine. It appears that the rhesus monkey as well as the chimpanzee is, whereas the rat is not, a good animal model to study GSH-related conjugation reactions with predictive value for man.

Animals↗
PubMed1981

Age-, sex-, and strain-dependent differences in the induction of enzyme-altered islands in rat liver by diethylnitrosamine.

The formation of foci with loss of ATPase and emergence of gamma-GTase was studied histochemically in livers of male and female Wistar and Sprague-Dawley rats of 3--4 and 6--7 weeks of age, respectively, after application of diethylnitrosamine. A single dose of 8 mg/kg body weight induced a considerable island formation in weanlings of both sexes. Island induction in adults was observed only after repeated application. No difference in island size and number was observed with the exception of greater island size and Sprague-Dawley females. Sex-dependent differences in susceptibility to island induction were observed in weanlings, females being more sensitivity than males and Sprague-Dawley females being the most sensitive of all. No correlation was seen between monooxygenase activity and the extent of island formation. The coincidence of ATPase-deficiency and emergence of gamma-GTase was highest in Sprague-Dawley females. The importance of this result in respect to cancer formation is discussed. Weanling Sprague-Dawley females seemed to be the most suitable for use in a screening test system for chemical carcinogenicity, especially for testing low doses or weak carcinogens.

Adenosine Triphosphatases↗
PubMed1981

Enhanced fecal elimination of stored hexachlorobenzene from rats and rhesus monkeys by hexadecane or mineral oil.

The effect of various dietary treatments on the fecal excretion of [14C]-hexachlorobenzene (HCB) was studied in rats and rhesus monkeys. Cholestyramine and sesame oil failed to influence fecal excretion of HCB and/or metabolites. However, dietary administration of n-hexadecane (5%) increased fecal excretion of radioactivity 4-13-fold in rats and rhesus monkeys. Similarly, mineral oil in the diet (5%) of rhesus monkeys elicited a 6-9-fold increase in fecal excretion of HCB and/or metabolites. As a result of the mineral oil treatment, and enhanced depletion of HCB from blood and also of the stored HCB from adipose tissue was observed. The concentration of HCB in the blood declined in accordance with decreasing storage levels of HCB in adipose tissue. The major site of elimination of HCB and/or metabolites seemed to be the intestine; in particular, the cecum and the colon ascendens. Both hexadecane and mineral oil appeared to stimulate specifically this elimination path way.

Alkanes↗
PubMed1981

Enhanced fecal excretion of mirex in rhesus monkeys by 5% mineral oil in the diet.

The effect of two dietary treatments upon fecal excretion of Mirex was studied in rhesus monkeys dosed with 14C-Mirex. Administration of 5% mineral oil in the diet during the first month following dosing resulted in about 50% increase in fecal excretion of Mirex. The same treatment repeated 6 months after dosing triggered about a 400% increase in fecal excretion of Mirex. Subsequent dietary administration of cholestyramine resulted in a comparably small effect of fecal excretion of Mirex. The considerable difference in the ability of mineral oil to induce the effect during the first and sixth month after dosage is likely to be due to compartmental redistribution of Mirex. Mineral oil treatment appears to effect primarily the "very deep" compartment (fatty tissues) by enhancing intestinal elimination of Mirex.

Adipose Tissue↗
PubMed1981

Threshold levels in toxicology: significance of inactivation mechanisms.

Metabolic inactivation of chemicals may prevent toxic effects of reactive intermediates when present at low levels whereas inactivation may be overcome at high levels changing dose-effect relation. This is demonstrated in various in vitro test systems: a) Monooxygenase-mediated metabolism causes formation of reactive oxygen species which induce DNA repair in lymphoblastoid cells. DNA damage is suppressed in the presence of glutathione (GSH), catalase or superoxide dismutase. b) Chloroprene is mutagenic in Salmonella typhimurium but not carcinogenic, possibly due to inactivation by GSH-conjugations. c) Chlorodinitrobenzene is not mutagenic is Salmonella typhimurium in the presence of GSH. However it is increasingly mutagenic at concentrations exceeding those of the GSH. d) Suppression of glucuronidation and sulfation in isolated hepatocytes highly increases irreversible binding of naphthalene. It is concluded that information on the metabolism of chemicals is essential for interpretation of toxicity studies in animals and their relevance to man.

Animals↗