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Biomedical subjects

R Heywood

Publications and source records attributed to R Heywood.

At least 37 records · Page 2Linked to original sources
PubMed1986

Strain-related susceptibility to nephrotoxicity induced by aspirin and phenylbutazone in rats.

Single doses of aspirin induce scattered foci of necrosis of proximal tubules in some strains of rats, whereas acute or sub-acute administration of phenylbutazone causes renal papillary necrosis. Initially, using Sprague-Dawley rats of CFY and CD strains, it became clear that these rats were not as susceptible to these drugs as the literature suggested. Aspirin-induced necrosis was apparently sex-related, being seen in females but could be induced by hormone treatment in males. Male Wistar and Sprague-Dawley rats had reacted differently to administration of phenylbutazone for two weeks. Two experiments were performed with four rat strains: Wistar, Lister-Hooded, Sprague-Dawley, and Fischer-344. The rats were six weeks old at the start of the experiments. Five males and five females of each strain were gavaged with either a single dose of 1,000 mg/kg of aspirin or 200 mg/kg phenylbutazone once daily for four weeks. The drugs were suspended in methylcellulose, which was given to equal numbers of control male and female rats in each experiment. The rats were maintained under standard conditions. Blood and 18-hour overnight urine samples were collected prior to sacrifice. There were no strain-related differences in the types of renal lesions seen, however there were differences in the degrees of responses to the two drugs. With aspirin the female Fischer-344 rats were the most susceptible showing necrosis of proximal tubules of both kidneys and markedly elevated urinary protein concentration and gamma-GT activity. Other females showed less change. Male rats were affected only slightly and males of the Wistar strain were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The toxicity of beta-carotene.

The safety of beta-carotene, a widely distributed food colorant was assessed in tests with cells and in sub-chronic and chronic experiments with animals. Mutagenicity evaluations which included the standard Ames test and the micro-nucleus test of bone marrow cells from mice showed that beta-carotene exerted no mutagenic properties. Embryotoxicity studies in rats and rabbits showed that there was no evidence of embryotoxicity and a multiple generation study in rats showed that there was no interference with the reproductive function in rats given oral doses of up to 1000 mg/kg/day. Chronic toxicity was studied in a 2-year study with dogs in a toxicity/tumorigenicity study in rats and in a mouse carcinogenicity study. Histological findings in the livers of treated dogs and mice, but not in rats, included vacuolated cells with eccentric nuclei which were distributed in periportal areas and which were frequently associated with minimal lipid deposition. There was no evidence that the vacuolisation was dose-related. It was considered that the vacuolated cells were fat storage cells. There was no effect on the tumor profiles in the rat and the mouse studies.

Abnormalities, Drug-Induced↗
PubMed1983

Phenylbutazone-induced nephrotoxicity in the rat.

Male Wistar rats showed reduced urinary concentrating ability after 2 weeks' administration of phenylbutazone at 200 mg/kg/day. Male Sprague-Dawley rats showed progressive proteinuria and developed renal papillary necrosis when given phenylbutazone at 200 mg/kg/day for 13 weeks. It is suggested that strain differences exist in the nephrotoxic profiles of rats given high doses of phenylbutazone.

Animals↗
PubMed1983

Target organ toxicity II.

Sensitive criteria of toxicity are simple characteristics, such as growth, organ weight analysis and selected histopathological examinations. Appropriate laboratory tests support the clinical observations. Correlation of target organ toxicity across the species is poor.

Animals↗
PubMed1983

Age-related susceptibility to aspirin-induced nephrotoxicity in female rats.

The effect of puberty on aspirin-induced renal necrosis in female Sprague-Dawley rats was observed. Rats aged 31 days were unaffected by aspirin administration, but 55-day-old rats showed segmental cortical tubular necrosis after a single dose of 1000 mg/kg of aspirin. Urinary gamma-glutamyl transpeptidase (gamma-GT) and proteinuria were useful non-invasive indicators of these necrotic changes.

Age Factors↗
PubMed1983

The toxicology of a ganglioside extract (Cronassial).

The accepted animal toxicity studies indicate that the ganglioside mixture extracted and purified from the bovine brain cortex (Cronassial) is without detectable toxicity. It did not induce any adverse effects on any of the characteristics of reproduction and it is not antigenic.

Animals↗
PubMed1983

Toxicity of venalot (a mixture of coumarin and troxerutin) in the baboon.

Venalot, a mixture of coumarin and troxerutin, in the proportion 1 to 6 respectively, was given orally to baboons at dosages of 0, 100, 300 and 1000 mg/kg/day for 26 weeks. Vomiting, usually within 3 h of administration and considered to be of central origin, in addition to vomiting immediately after dosing, was noted in animals receiving 1000 mg/kg/day. At this level, collapse on several occasions in two animals, one of which died, was also observed. Another animal receiving 1000 mg/kg/day was killed for humane reasons following a period of weight loss, reduced appetite and deterioration in body condition. However, no adverse effect on body weight gain, food or water consumption, ophthalmoscopic or electrocardiographic examinations were noted in any other animals during this study. Increased levels of liver function (serum leucine amino-peptidase (LAP), and serum ornithine carbamyl transferase (OCT) were noted during the dosing period, together with slightly increased liver weights terminally for animals receiving 1000 mg/kg/day; however, as no morphological or ultrastructural changes were noted, these findings were considered to be attributable to hypertrophy.

Animals↗
PubMed1982

The LD50 test: some considerations of precision.

Substantial improvements in the statistical aspects of the LD50 test are possible. These include modifications to the design of the experiments (including the use of sequential methods) and the replacement of outdated techniques of statistical analysis with more appropriate methods. With such improvements, it would be possible to reduce appreciably the number of animals used (to about 10 or 12) while still achieving precision similar to that obtained with present methods.

Animals↗
PubMed1982

Histopathological and laboratory assessment of visual dysfunction.

The currently available methods of assessing ocular toxicity are discussed. Manifestations of ocular toxicity are best described clinically; histopathological examination of the eye is beset with problems of preparing the eye for morphological examinations. Electron microscopy is essential to look for chemically induced side effects at the cellular level. Mechanisms of ocular toxicity are poorly understood, and the limitation of animal studies in predicting side effects in man must be appreciated.

Animals↗
PubMed1981

Target organ toxicity.

In a survey of the toxicological profiles of 50 compounds in rodent and non-rodent species, sensitive criteria of toxicity were found to be the simple characteristics, such as clinical observation of the living animal, growth and organ weight analysis, liver and kidney function tests and histological examination of selected tissues. There was poor correlation of target organ toxicity across the species. For this reason safety evaluation should not be based on the demonstration of target organ toxicity, but on the absence of toxic signs. A step by step approach, based on the biological activity of the compound, would provide more meaningful data for safety evaluation than the standard toxicological studies in a rodent and non-rodent species.

Animals↗
PubMed1981

Sub-acute toxicity studies on a new piperidine derivative (HSR-902) in dogs.

The administration of a new piperidine antispasmodic agent (HSR-902) to the dog by the oral and intravenous routes, induced clinical signs attributable to parasympathetic blockage. The only significant toxicological finding was rarefied appearance and enlargement of the hepatocytes at the high dose level (50 mg/kg/day); this was shown to be reversible.

Administration, Oral↗
PubMed1981

Chronic intravenous administration of lentinan to the rhesus monkey.

The prolonged effects of overdosage with lentinan in the rhesus monkey are associated with foam cell reactions in lung, liver, kidney, spleen, lymph nodes and bone marrow and with varying degrees of vasculitis and associated reactions. A dose level of 0.5 mg/kg/day was without adverse effect.

Animals↗