Biomedical subjects
Publications and source records attributed to S K Majeed.
The chronic toxicity of O,S-dibenzoyl thiamine hydrochloride (DBT) was studied by prolonged dietary administration to rats at dosages of 1000 and 10 000 ppm. The study confirmed the low toxicity of this compound and absence of carcinogenicity.
Histological examination of 753 Beagle dogs showed renal foci of calcification in 27.9% of males and 21.5% of females. In contrast, stomach calcification was observed in 6.2% of males and 5.2% of females examined. It is suggested that the focal calcification seen in both organs was possibly of dietary origin and may have been related to the phosphate content.
Male chicks of an egg-laying strain were injected with 0, 1, 2 or 4 micrograms/100 g b. wt thyroxine s.c. daily from 7 to 12 weeks of age. Increasing dose suppressed testicular development and puberty was completely blocked by the highest level. Live weight gain was enhanced by thyroxine treatment. Similar treatment of females prevented normal development of the ovaries at puberty.
A variety of changes was seen in the respiratory tract of European hedgehogs (Erinaceus europaeus) infected with a Capillaria species. The main lesions were those of bronchopneumonia and tracheitis.
A rare type of mixed mammary tumour, described in a CD female rat, represents the first record of a mixed mammary tumour in a rat with both epithelial and chondroid components.
The lesions associated with parasitic infestation in 1156 wild-caught, laboratory-maintained nonhuman primates (Macaca fascicularis, Macaca mulatta, and Papio spp) are described. The two most common parasites seen were lung mites (Pneumonyssus spp) and nodular worms (Oesophagostomum spp). In addition, in cynomolgus monkeys (Macaca fascicularis) only, Nochtia nochti was a frequent pathogen. The etiology of mineralized fibrotic nodules in the mesentery of cynomolgus monkeys was thought to be infection with Paragonimus westermani, the oriental lung fluke.
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.
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.
The relationship between blood lead concentration and nerve conduction velocity has been examined, using the cynomolgus monkey as a model for human lead poisoning, with lead dose and blood lead concentration maintained under controlled conditions, to determine whether nerve conduction velocity could be used as an objective measure of the effects of lead on the nervous system at subclinical concentrations. Five cynomolgus monkeys were maintained at a blood lead concentration of 90-100 micrograms Pb/100 ml for nine months by daily oral dosing with lead acetate (12-15 mg Pb/kg body weight). Motor nerve conduction velocity in the ulnar nerve was measured, together with blood lead concentrations. Blood lead concentrations were proportional to lead intake, reaching a stable level within one to two weeks. Lead did not accumulate in the blood, and blood lead concentrations were found to decrease to a maintained plateau from initial high concentrations during the first seven days of dosing. The animals showed no clinical or behavioural evidence of lead poisoning at any time during the study, although there was a progressive decrease in blood packed cell volume, haemoglobin concentration, and erythrocyte concentration. The maximal motor nerve conduction velocity of the ulnar nerve remained constant throughout the study, although changes were observed in the conduction velocity of slowly conducting nerve fibres. At termination, intranuclear inclusions were found in the renal tubular cells of all animals as were focal areas of myelin degeneration in the ulnar and sciatic nerves.
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The relationship between the acute toxicity of orally-administered chloroform and its long-term tumorigenic potential was studied in male mice of the CFLP outbred Swiss albino mouse strain. A single dose of approximately 18 mg CHCl3/kg had no detectable acute toxic effect on the liver or kidneys and did not stimulate regenerative activity, whereas both toxicity and subsequent tissue regeneration were observed with single doses of about 60 mg/kg or higher. The severity of the toxic effects and regenerative changes was greater when corn oil was used as a vehicle for chloroform than when the vehicle was a toothpaste base. In earlier long-term studies in mice of the same strain, kidney tumours occurred in males given 60 mg/kg/day throughout life but not in mice given 17 mg/kg/day. The tumour response was greater when the 60-mg/kg/day dose was given in an oily vehicle than when it was given in toothpaste. The findings are consistent with the hypothesis that early acute toxic change and subsequent repair are a sine qua non for tumorigenesis in the kidney and liver in response to chloroform.
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Adrenal calcification occurred in 52.6% of rhesus monkeys, 4.7% of cynomolgus monkeys and 2.4% of baboons examined. In contrast, ovarian calcification was observed in 62.3% of baboons, 38% of cynomolgus and 22.3% of rhesus monkeys examined.
Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle dogs at dosages of 2.5, 5.0, 10.0 or 25.0 mg/kg/day for 13 weeks. Physiological saline was given as a control. Some dogs given 5.0 or 10.0 mg/kg/day were retained undosed for a further 5 weeks in order to assess recovery. Premature deaths from acute renal tubular nephrosis occurred in dogs given 25.0 and 10.0 mg/kg/day. Dogs which survived treatment at 10.0 mg/kg/day showed marked elevation of circulating urea and creatinine concentrations after 4 weeks' treatment but thereafter the increases became less obvious. Varying degrees of renal cortical tubular dilatation, basophilia, degeneration or necrosis were seen in the kidneys of all dogs examined after 13 weeks treatment although no clinical impairment of renal function was detectable at dosages up to 5.0 mg/kg/day. These changes had essentially regressed in dogs examined 5 weeks after the last dose of DKB at 5.0 mg/kg/day. All the adverse clinical and histological effects noted, following any dose level of DKB tested, could be attributed to renal changes.
The effect of repeated (4 weeks) oral administration of 2,4-, 2,5- or 2,6-xylidine (at dose levels of 400--500 mg/kg/day) on the morphology and microsomal drug metabolising enzyme activity of the liver was studied in rats. All 3 isomers caused hepatomegaly which was considered to be due to proliferation of the smooth endoplasmic reticulum. Decreases in glycogen content and glucose-6-phosphatase activity were demonstrated histochemically. Biochemical investigations showed increases in microsomal protein and cytochrome P-450 content in rats dosed with 2,4- or 2,5-xylidine and in glucuronyltransferase activity in rats given 2,4-, 2,5- or 2,6-xylidine. Aniline hydroxylase activity was increased in all treated rats except males dosed with 2,6-xylidine. The results of the study indicate that all isomes of xylidine can be inducers of microsomal drug-metabolising enzyme activity, that they may be metabolised by oxidation and that the xylidine molecule may be eliminated as a conjugate with glucuronic acid.
11 cases of spontaneous pituitary neoplasms in rats, which showed infiltration into brain tissue, are reported. This represents an incidence of about 0.42%.