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Biomedical subjects

R Heywood

Publications and source records attributed to R Heywood.

At least 19 recordsLinked to original sources
PubMed1992

Carcinogenicity assessment of lonidamine by dietary administration to Sprague-Dawley rats.

Following chronic dietary administration of 20, 60 and 180 mg/kg per day of lonidamine for 2 years to groups of Sprague-Dawley rats, treatment-related non-tumour findings seen microscopically included the following: atrophy of the testis with associated changes in epididymis and pituitary at all dosages; neuropathy in the sciatic nerve accompanied by skeletal muscle atrophy which was dose-related, particularly in male animals. Neither the incidence of tumour-bearing animals, nor the spectrum of tumours seen, was significantly changed. In the females given 180 mg/kg per day an overall reduction in tumour incidence was noted, which was reflected in a significant reduction (P < 0.001) in mammary tumours.

Administration, Oral↗
PubMed1992

Age-related changes in thyroid structure and function in Sprague-Dawley rats.

Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.

Aging↗
PubMed1990

Morphological assessment of visual dysfunction.

The eye is an isolated unit but with a potentially high degree of sensitivity to toxic substances. The multiplicity of types of reaction to injury reflects the unique anatomical, physiological and biochemical features of the eye. The following are examples of such: The albino rat is not a good model for retinal toxicity because of problems of phototoxic retinopathy, the absence of pigment within the pigment epithelial layer and the high incidence of spontaneous retinal pathologies; The ocular toxicity of a compound cannot be anticipated from its chemical structure; Pharmacological side effects are similar between species, and are predictive for man; Mechanisms of ocular toxicity are poorly understood.

Animals↗
PubMed1989

Toxicity studies with quinine hydrochloride.

Three-month studies in the rat, a rat embryo-toxicity study and a specific study to investigate ototoxicity were carried out with quinine hydrochloride. The results of these studies suggest an acceptable daily intake of 40 mg quinine hydrochloride for an adult. There were no indications of teratogenic effects and no indications of interference with auditory function in rats receiving up to 200 mg/kg.

Animals↗
PubMed1987

Summary of the toxicologic profile of iopentol.

Repeat dose toxicity studies, reproductive studies and mutagenicity studies were performed to assess the safety of iopentol. It is concluded that iopentol, a non-ionic contrast medium, is free from significant toxic effects.

Abnormalities, Drug-Induced↗
PubMed1979

Biochemical observations on beagle dog semen.

Semen samples were collected at weekly intervals for six weeks from eight sexually mature beagles previously shown to produce normal ejaculates. Seminal plasma and sperm fractions were separated by centrifugation and the sodium, potassium, alanine and aspartate aminotransferases, acid and alkaline phosphatase concentrations in the two fractions determined. Regression analysis of the mean weekly values obtained from physical and biochemical examination of the ejaculates showed that sodium ion concentration was highest in seminal plasma. The highest levels of aminotransferases were found in sperm fractions. Those enzymes may be indices of abnormal or damaged spermatozoa. Acid and alkaline phosphatase activity was 100 times greater in seminal plasma than in sperm fractions. Phosphatase concentrations are likely to be dependent on prostate activity. Measurement of acid phosphatase in canine semen therefore may be a useful index of prostate function. The motility of the semen samples was independent of the potassium concentration in seminal plasma. However, there was some evidence of a correlation between sperm motility and the enzyme and sodium content of seminal plasma.

Acid Phosphatase↗
PubMed1979

Treatment of rhesus monkeys (Macaca mulatta) with intrauterine devices loaded with levonorgestrel.

The effects of levonorgestrel-loaded plastic intrauterine devices on endometrial morphology were investigated in 15 rhesus monkeys for 14 weeks. The devices were designed to release 25 microgram of the hormone per day and were inserted in the uterus by hysterotomy. Control animals were sham operated or received inert placebo devices. With the levonorgestrel-releasing devices, widespread changes in endometrial morphology were seen. These changes included atrophy of the endometrial mucosal and glandular epithelium and decidualization of the endometrial stroma. With the inert placebo control devices, only minor changes in endometrial morphology were observed.

Animals↗
PubMed1979

Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings loaded with levonorgestrel.

The effects of levonorgestrel-releasing intravaginal rings were investigated in 15 rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either three or ten times the human dose level of the hormone. Untreated placebo rings were used as a control. The devices were well retained. After insertion of the vaginal rings, a dose-related decrease in vaginal bleeding was observed. The vaginal microbial flora were assessed qualitatively and semi-quantitatively and although all groups including controls showed some changes in microbial populations, by the end of the study nearly all animals returned to a normal balanced microflora. Terminal studies showed that, at the high dose level, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular epithelium had occurred. A dose-related increase in mucus within the lumen of the endocervical canal was observed. Focal or diffuse atrophy of the vaginal mucosal epithelium was seen in the majority of levonorgestrel-treated animals.

Animals↗
PubMed1979

Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings impregnated with either progesterone or norethisterone.

The effects of both progesterone- and norethisterone-loaded intravaginal rings were investigated in twenty-five rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either the human dosage level of the hormone or ten times this level. Untreated placebo rings were used for control purposes. The devices were well retained. With the exception of increased plasma fibrinogen levels in animals treated with norethisterone, no marked differences in either local or systemic toxicity between the progesterone and norethisterone intravaginal rings were apparent. Following insertion of the hormone-treated intravaginal rings, a dose-related decrease in vaginal bleeding was recorded. The vaginal microbial flora were assessed qualitatively and semiquantitatively and all groups including the placebo controls showed a changes in mcirobial populations. Terminal studies indicated that at high dose levels, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular endometrial epithelium had occurred. An increase in cervical mucus was observed within the lumen of the endocervical canal in a proportion of hormone-treated animals. In the vagina, a dose-related focal or diffuse atrophy of the mucosal epithelium was found.

Animals↗
PubMed1979

[Decabromobiphenyl : toxicological study (author's transl)].

The paper presents results of experimental studies on a polybrominated flame retardant. Decabromobiphenyl was found not to be irritant to the rabbit skin or eye. The oral and dermal LD 50' in the rat are greater than 5 g/kg. In a 90 days feeding trial in rats no toxic effect were demonstrated at the levels of 100 and 500 ppm. However, hepatic change occured with diet containing 2.000 ppm. In a 4 weeks dust inhalation study, the no effect level was between 0.005 and 0.05 mg/l of air. The higher concentrations induced hepatic changes. Decabromobiphenyl was not teratogenic or embryotoxic to the rat at 10, 100 and 1.000 mg/kg per os. There was no evidence to indicate that the compound has mutagenic potential. Comparing the toxicological profile of decabromobiphenyl with other polybrominated biphenyl flame retardants would indicate that the toxicity decreases when the number of bromine atoms is increased.

Administration, Oral↗
PubMed1979

Canine pituitary-testicular function in relation to toxicity testing.

The physiological onset and establishment of adult pituitary-testicular function has been characterised for Beagle dogs. Testicular measurements, circulating prolactin, luteinising hormone and testosterone concentrations, semen analyses and the histological appearance of testicular biopsies, suggest that male Beagles attain sexual maturity between 35 and 41 weeks of age. The assessment of testicular toxicity is discussed and attention drawn to possible approaches for investigating primary mechanisms of toxic action on the canine testis. Expected values for testicular size, hormone levels and semen characteristics are reported.

Aging↗
PubMed1978

The toxicity of 1-amino-3-chloro-2-propanol hydrochloride (CL88,236) in the rhesus monkey.

The toxicity of 1-amino-3-chloro-2-propanol is associated with acute histopathological change in the medulla oblongata, characterised lesions of focal oedema. Continued administration results in neurological scars. Lesions can be induced at dose levels of 50 mg . kg-1 day-1. Clinical manifestations of neurological involvement are periods of slight incoordination and loss of balance in a few animals only.

Animals↗
PubMed1978

Clioquinol toxicity in the dog.

A number of instances have been reported in the scientific literature in which acute intoxication with halogenated oxyquinolines has led in some species to convlusions, often followed by death. The toxicity of repeated doses of clioquinol has been investigated extensively in the dog. The clinical syndrome induced in this species is characterized by anorexia, weight loss, extremem muscle weakness and emaciation. In some animals surviving this impairment of condition for several weeks, neuropathy of the central nervous system, but not of the peripheral nerves ensued. It is suggested that these toxicological manifestations are less dependent on the dose-level than on the degree of absorption. Some suggestions regarding the aetiology of the lesions are made.

Animals↗
PubMed1978

The oral toxicity of 1-amino-3-chloro-propanol hydrochloride (CL 88236) in rats.

1-amino-3-chloro-2-propanol (CL 88236) was administered by oral gavage for 12 consecutive weeks to rats at dose levels of 50, 250 and 500 mg/kg/day. All levels gave rise to toxicological effects. Epididymal necrosis and/or atrophy of the seminiferous epithelium was found for some males with each dose of CL 88236. The kidney and liver weights of male and female rats given CL 88236 were higher than control values but no histological changes were found in these organs.

Animals↗
PubMed1978

Toxicology studies of linear alkylbenzene sulphonate (LAS) in rhesus monkeys. I. Simultaneous oral and subcutaneous administration for 28 days.

A toxicological investigation was performed with the linear alkylbenzene sulphonate (LAS) using 4 groups of 3 male and 3 female monkeys. Dosages were 0, 30, 150, 300 and 0, 0.1, 0.5, 1.0 mg/kg/day by simultaneous oral (p.o.) and subcutaneous (s.c.) administration respectively, for 28 days. At 300 p.o. and 1.0 s.c. mg/kg/day, the monkeys vomited frequently and usually within 3 hours of administration. An increased frequency of loose or liquid faeces was recorded for animals receiving 150 p.o. and 0.5 s.c. and 300 p.o. and 1.0 s.c. mg/kg/day. Fibrosis of the injection sites was found among all the test groups, the incidence and severity being dose related. Ophthalmoscopy, laboratory examination of blood and urine, organ-weight analysis and histopathological investigation did not detect any further treatment related responses. Previous reports concerning oral administration of tetrapropylene benzene sulphonates (ABS) to dogs record prompt emesis ascribed to local gastro-intestinal effects. Vomiting observed during this investigation was considered to be of possible central origin.

Administration, Oral↗