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Biomedical subjects

F Coulston

Publications and source records attributed to F Coulston.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of short-term inhalation exposure to 1-nitropropane and 2-nitropropane on rat liver enzymes.

Male Sprague-Dawley rats were exposed to vapors of 1-nitropropane (1-NP) and 2-nitropropane (2-NP) at air concentrations of 100 ppm for 7 hours per day on four consecutive days. Livers were analyzed for enzymatic activities after 1-, 2-, and 4-day inhalation periods. Liver microsomal cytochrome P450 was depressed by 2-NP and elevated following exposure to 1-NP. Levels of cytochrome b5 were slightly increased in rats exposed to 1-NP and remained unchanged after inhalation of 2-NP. Total glutathione (GSH), GSH S-transferase, and UDP-glucuronosyltransferase activities were enhanced by 2-NP. 1-NP induced GSH peroxidase while 2-NP did not. Glutathione reductase was not altered after exposure to either isomer. No changes in the microsomal malondialdehyde content as a measure of lipid peroxidation and in the levels of serum aspartate transferase and serum glutamic oxaloacetic transaminase were observed during a 4-day exposure period in either of the exposed groups compared to control animals.

Animals↗
PubMed1989

Hobson's choice.

Explore the source record for details and available documents.

Animals↗
PubMed1989

Disposition and metabolism of 1-nitropropane in rats and chimpanzees.

The metabolic fate of 1-nitropropane (1-NP) has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-14C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% of the dose in urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and N-methyl-N-2-(methylsulfinyl)ethylpropionic acid amide (NMPA). Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested.

Alkanes↗
PubMed1988

Chronic inhalation exposure of rats to vapors of nitroethane.

Male and female Long-Evans rats were exposed in inhalation chambers to vapors of nitroethane at concentrations of 100 or 200 ppm, 7 hr per day, 5 days per week for 2 years. During the study, general observations were made daily and body weights were obtained weekly for the first 6 months of the study and biweekly thereafter. Any rats that were found dead or sacrificed moribund during the 2-year exposure phase of the study were given a thorough gross examination and tissues were retained for microscopic examination. After 2 years of inhalation of nitroethane, all surviving rats were sacrificed and subjected to the same thorough gross examination. Blood samples were obtained from representative groups of animals for hematology and serum chemistry studies. All rats were examined histopathologically. Exposure of the rats to nitroethane had no pharmacologic effects nor were there any effects on mortality of rats of either sex at either level of exposure. Throughout most of the investigation, body weights of both sexes of both exposed groups were slightly less than those of respective controls, but lack of a well-defined dose-response relationship suggested the involvement of factors other than just exposure to nitroethane. There were no effects of exposure to nitroethane on hematology nor were there any biologically significant effects of exposure to nitroethane on clinical chemistry or on organ weights. No significant nonneoplastic or neoplastic pathology was found as a consequence of exposure of the rats to nitroethane.

Administration, Inhalation↗
PubMed1985

The role of the chimpanzee in the evaluation of the risk of foreign chemicals to man.

Various species of laboratory animals are used to evaluate the efficacy and safety of drugs in man. However, the extrapolation of data from animals to man is often complicated by species differences in the disposition of foreign chemicals. The findings of comparative metabolism studies are used to illustrate species differences in metabolic pathways, rates of biotransformation, kinetics, and excretion routes. Biochemical and structural consequences of the significant differences in enzyme induction between rodents and primate species are discussed. Among the primates, the chimpanzee has been shown to be the most closely related to man not only in the disposition of xenobiotics, but also in the aspects of endocrinology, serology, and immunology. It would, therefore, be the best possible model to predict the fate and effects of foreign chemicals in man. Due to the limited availability of chimpanzees, however, they can only be used for the evaluation of the most critical chemicals and drugs. Comparative metabolism and disposition studies, e.g., of compounds representative of classes of chemicals in chimpanzees and other animals. Only when the pertinent differences between the selected test species and man are known can correct extrapolations to man be made.

Animals↗
PubMed1983

Impaired renal function in diabetic chimpanzees (Pan troglodytes).

Studies were conducted to assess the renal functional state in two recently discovered diabetic chimpanzees. Both were nonobese, adult female animals with the non-insulin-dependent form of impaired glucose tolerance, analogous to the Type II or nonobese, maturity-onset diabetes of humans. Both animals displayed moderate-to-heavy proteinuria and glycosuria in response to intravenous administration of glucose or tolbutamide. Chimpanzee number 333, but not number 1037, had fasting proteinuria and chronic hypertension. Renal function studies, using the inulin clearance method, demonstrated significantly decreased glomerular filtration rates and elevated rates of sodium excretion for both animals. The rate of chloride excretion was also elevated in animal number 1037, but potassium excretion was apparently unaffected in both animals. Abnormal serum biochemical parameters demonstrated for chimpanzee number 333 included elevations in calcium, magnesium, creatinine, urea nitrogen, and uric acid; animal number 1037 had only an elevated serum creatinine. Results are consistent with the occurrence of renal disease similar to the nephropathy that develops in human diabetics. The difference in severity of renal impairment in the two chimpanzees is possibly related to differences in duration and severity of impaired glucose tolerance. A progression of both diabetic and renal disorders is most probable.

Animals↗