Biomedical subjects

S A Rice

Publications and source records attributed to S A Rice.

111 records · Page 7Linked to original sources

PubMedDate not supplied

Validation of a developmental swimming test using Swiss Webster mice perinatally treated with methimazole.

The swimming method of Klaus and Hacker, developed for the AB/Jena and DBA2/Jena mouse strains, was evaluated for use with pre-weaned Swiss Webster (SW) mice. All SW mice completed the swimming pattern by postnatal day (PND) 16, but did not conform to all criteria depicted for each stage of the methodology. These swimming differences among strains required modification of the above method for the SW mouse. An expanded and revised swimming methodology included evaluation of limb movement and placement; body position; head position, including nostril and ear positions; and direction of movement. The revised methodology was validated on PND 4 through 20 with offspring of methimazole-treated or untreated SW dams. Methimazole, an antithyroid agent, was administered in drinking water (0.1 mg/ml; day 16 of pregnancy through day 10 postpartum). Untreated dams received tap water. Methimazole pups exhibited significant delays in swimming development on PND 9 through 16. This revised swimming methodology provides another preweaning test for the detection of behavioral teratogens for SW and probably other strains of mice.

Animals↗

PubMedDate not supplied

Effects of isoniazid treatment on selected hepatic mixed-function oxidases.

The hepatic microsomal content of cytochromes P-450 and b5, the defluorination rates of four volatile fluorinated ether anesthetics, and the activities of selected mixed-function oxidases were compared following administration of either isoniazid, phenobarbital, beta-naphthoflavone, or saline to male Fischer 344 rats. Isoniazid treatment significantly increased the rate of metabolism of p-nitroanisole, ethoxyresorufin, aniline, methoxyflurane, enflurane, isoflurane, and sevoflurane, significantly decreased the rate of metabolism of aminopyrine, and did not alter the activity of NADPH-cytochrome c reductase or the microsomal contents of cytochromes b5 and P-450 per mg of microsomal protein. The pattern of catalytic activities associated with isoniazid induction did not resemble that of either phenobarbital or beta-naphthoflavone induction. Furthermore, isoniazid treatment resulted in a shift in the (reduced cytochrome P-450 plus CO) absorption maximum from 450 to 451 nm. This shift in absorption, coupled with the observation that the total microsomal cytochrome P-450 content is not elevated, suggests that there is an increased production of one species of cytochrome P-450. The great enhancement of enflurane defluorination following isoniazid treatment was of particular interest because other enzyme-inducing agents, including phenobarbital, 3-methylcholanthrene, phenytoin, and beta-naphthoflavone, have not been found to increase enflurane defluorination to a clinically significant level.

Anesthetics↗

PubMedDate not supplied

Effects of subchronic intermittent exposure to nitrous oxide in Swiss Webster mice.

Swiss Webster mice were treated to determine whether the inhalational anesthetic, nitrous oxide (N2O), causes organ toxicity and enhances anesthetic defluorination. Two-hundred and sixteen young adult male and female mice were exposed to room air or to 5,000 (.5%), 50,000 (5%) or 500,000 (50%) N2O for four hours per day, five days per week for periods up to fourteen weeks. Body weight was measured twice weekly throughout the experiment. Liver, kidney, spleen and testis were weighed and examined histologically along with brain, stomach, seminal vesicle, and ovary for evidence of drug induced damage. Blood smears were examined microscopically and complete blood count, differential white cell count, and reticulocyte and platelet counts were performed. In addition, liver microsomal cytochrome P-450 content and the rates of defluorination of enflurane and methoxyflurane were determined. The maximum tolerated concentration of N2O was approximately 5000,000 ppm. Even at this high dose, there was no evidence of organ damage. Following N2O exposure, neither the hepatic microsomal cytochrome P-450 content nor the rates of anesthetic defluorination were increased; the rate of in vitro inorganic fluoride production was greater for methoxyflurane than for enflurane. Since there was no evidence of specific organ toxicity or of enzyme induction or inhibition, it was concluded that N2O is a comparatively nontoxic inhalational anesthetic under the conditions of this study.

Anesthetics↗