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W R Gibson

Publications and source records attributed to W R Gibson.

At least 37 records · Page 2Linked to original sources
PubMed1979

Animal models for the comparative assessment of neurotoxicity following repeated administration of vinca alkaloids.

Neurotoxicity is the major side effect occurring during the clinical use of vincristine (VCR). Animal models predictive of potential neurotoxicity would be very useful in the preclinical development of new vinca compounds. To simulate conditions in which neurotoxicity is produced during the clinical use of VCR, experimental animals (except the guinea pig) were given the test compounds by the iv route over a prolonged time period. Doses were selected based on the production of leukopenia. Vindesine (VDS), a chemically modified vinblastine (VBL) product, was compared with VCR and VBL in animal studies. Definite neurotoxic manifestations developed when VCR was given to chickens, cats, and monkeys. The administration of VDS or VBL did not produce neurotoxic signs in these species. The mouse, rat, dog, and guinea pig were not found to be useful models. Thus, it would appear the chicken, cat, and monkey would be appropriate animal models for the preclinical testing of new vinca compounds.

Animals↗
PubMed1979

An evaluation of the toxicity of cefaclor in laboratory animals.

The toxicity of cefaclor, a new orally-administered cephalosporin, was evaluated in laboratory animals given single or multiple doses of the antibiotic. The acute toxicity data for cefaclor in mice, rats, dogs and monkeys were comparable to that previously reported for cephalexin. Rats were maintained on dietary mixtures of cefaclor which provided average daily doses of approximately 230 to 950 mg/kg for 28 days in subacute toxicity tests, and 160 to 675 mg/kg for 1 year in chronic toxicity tests. Treatment-related effects in the above studies were limited to soft stool excretion and caecal dilatation in the subacute test. Effects in dogs given daily oral doses of 50 to 200 mg/kg for 30 days were limited to a transient moderate fall in haemoglobin concentration in the two males at the highest dose. Soft stool excretion and occasional episodes of emesis were observed in dogs given cefaclor for 1 year at oral doses of 100 to 400 mg/kg/day. A reversible thrombocytopenia occurred in one animal at the highest dose. Analysis of various tissue fluids taken 2 hours after the last dose revealed that the concentration of cefaclor in the synovial fluid was approximatley one-half of that in serum. The results of these studies indicate that cefaclor has a low toxic potential in the species tested.

Animals↗
PubMed1978

Toxicologic evaluation of cefamandole nafate in laboratory animals.

The safety of cefamandole nafate in laboratory animals was evaluated in six species. The acute toxicity of cefamandole after intravenous or subcutaneous administration was similar to that of cephalothin sodium. The subacute and chronic toxicity of cefamandole was studied in rats and dogs for periods of two weeks to six months at doses of 250--1,000 mg/kg per day in rats and 125--1,500 mg/kg per day in dogs. No evidence of significant systemic toxicity was observed in these studies. There were, however, various degrees of local injury at the injection sites that resulted in slight decreases in hemoglobin, hematocrit, and red blood cell counts in the animals in which injury at the injection site was most severe. Studies of reproduction in rats and mice indicated that cefamandole nafate had no teratogenic effects and no adverse effects on fertility, gestation, or growth of offspring. Comparative studies of nephrotoxicity in rabbits demonstrated that the nephrotoxicity of cefamandole nafate was considerably less than that of cefazolin.

Animals↗
PubMed1976

Effect of hypophysectomy and insulin on lipogenesis in cockerels.

Hypophysectomy increases hepatic lipogenesis in cockerels. In an attempt to find the possible hormonal mechanism for this we have examined the effects of hypophysectomy, insulin and pituitary homogenates on hepatic lipogenesis. Insulin (5 U/kg) injected intravenously, simultaneously with glucose-14C tracer, increased the amount of 14C found in liver lipids at 30 min after the injection. Similarly, insulin injected 5 min before killing, increased the incorporation of glucose-14C and acetate-14C by liver slices during a 30 min incubation. Hypophysectomy increased lipogenesis within 24 hours. The effect of insulin was most pronounced in hypophysectomized cockerels. The activity of the lipogenic enzyme, acetyl CoA carboxylase was similarly affected. A homogenate of chicken pituitaries added to the medium reduced lipid synthesis from glucose-14C by liver slices. This effect was larger in liver slices in which lipogenesis had been stimulated by insulin. The increased rate of hepatic lipgenesis in hypophysectomized cockerels may be caused partly by increased hepatic sensitivity to the lipogenic action of insulin or by the removal of a direct inhibition by pituitary hormones.

Acetyl-CoA Carboxylase↗
PubMed1976

Toxicology of vindesine (desacetyl vinblastine amide) in mice, rats, and dogs.

Comparative acute intravenous toxicity studies of vinblastine sulfate (VLB), vincristine sulfate (VCR), and vindesine in mice and rats indicated that vindesine was more toxic than VLB and less toxic than VCR. Rats were able to tolerate larger repeated doses of vindesine than dogs. Rats given intravenous doses totaling 0.15 mg/kg-wk vindesine for 3 months developed no remarkable signs of toxicity. Doses of 0.3 mg/kg-wk or greater produced anorexia, depressed blood cell counts, atrophic intestinal mucosa, inhibition of spermatogenesis, extramedullary hematopoiesis, and infections. Dogs were given total weekly intravenous doses of 0.04, 0.08, 0.1, or 0.16 mg/kg vindesine for 3 months. The only observed effect in the two lower dose groups was inhibition of spermatogenesis. Groups receiving 0.1 or 0.16 mg/kg developed leukopenia, slight erythropenia, inhibition of spermatogenesis, focal skeletal muscle degeneration, elevated lactic dehydrogenase, and an increase in bone marrow myeloid: erythroid ratio. No evidence of functional or structural changes in neural tissues was found. The above effects are common to animals given VCR at lower doses and for a shorter test period. It is therefore concluded that vindesine is less toxic in animals than VCR.

Animals↗
PubMed1975

Plasma levels of luteinizing hormone in gonadectomized Japanese quail exposed to short or to long daylengths.

Plasma levels of luteinizing hormone (LH) were measured by radioimmunoassay in gonadectomized male and female Japanese quail, exposed either to 8 h light: 16 h darkness per day (8L:16D; short days) or to 20L:4D (long days). In both sexes, exposure to long days increased LH levels and in the gonadectomized quail LH continued to rise over several weeks. Eventually the castrated quail had levels about five times higher than the control birds and the ovariectomized quail had levels about 14 times higher than their controls. Quail kept on short days had low LH levels while birds kept on long days and returned to short days resumed low levels after a delay of some days. Since very high levels of LH occurred in gonadectomized quail only when they were on long days, we conclude that the photoperiodic regulation of LH secretion does not operate solely by adjusting sensitivity to gonadal feedback, but works in a more direct manner. Ovariectomized females whether on long days (high LH) or short days (low LH) grew masculine plumage and castrated males retained male plumage. This confirms that the ovary is responsible for sexual dimorphism of plumage and shows that the action of the ovary is not mediated by LH (through feedback). The remaining rudimentary (right) gonad in ovariectomized females did not undergo visible hypertrophy and did not secrete enough hormone to stimulate the cloacal gland or oviduct.

Animals↗