Perinatal mortality in Marondera district.
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Biomedical subjects
Publications and source records attributed to P Olsen.
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Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex were formed from 40, 29, 30 and 44 litters, respectively. After weaning, the highest dose (500 mg BHT/kg/day) was lowered to 250 mg/kg/day for the F1 rats. The numbers of litters of ten or more pups at birth decreased with increasing BHT dose. At weaning, treated F1 rats had lower body weights than the controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found in the haematological parameters. F1 females on the highest dose showed an increase in serum cholesterol and phospholipids, and serum triglycerides were reduced in this group in both sexes. Dose-related increases in the numbers of hepatocellular adenomas and carcinomas were statistically significant (at P less than 0.05 or lower) in male F1 rats when all groups together were tested for heterogeneity or analysis for trend. The increase in hepatocellular adenomas and carcinomas in treated female F1 rats was only statistically significant for adenomas (at P less than 0.05) in the analysis for trend. All hepatocellular tumours were detected when the F1 rats were more than 2 yr old. Tumours were found in many other organs of some of the treated rats, but their incidence was not significantly different from that in controls. The role of BHT in the development of hepatocellular tumours requires further elucidation.
Radiological findings were analysed in 56 young patients with proven Schistosoma haematobium infection. In 31 patients (55%) changes were present in both the bladder and the ureters but in seven patients (13%) only ureteric changes were seen. Hypertrophy of the mucosa, mild stenosis, linear calcification, punctate calcification or 'ureteritis calcinosa' and polyps are highly suggestive features of an early involvement of the upper urinary tract in this insidious disease.
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The oral LD50 for malachite green oxalate was found to be 275 mg/kg in rats while the approximate lethal dose for NMRI mice was 50 mg/kg. No systemic effects were seen after dermal application of 2,000 mg/kg. Repeated administration in the diet for 28 days to rats produced only minor changes in serum urea and aspartate aminotransferase levels. The rats at the highest dose level showed decreased weight gain and appeared clinically to have elevated motor activity. No sex differences were observed in either acute or prolonged experiments. In accord with human experience malachite green was irritating to mucous membranes, but no effects were seen on intact skin nor was it shown to be sensitizing. It was found to be a mutagen in the Salmonella/microsome test after metabolic activation but without clastogenic activity when tested at maximally tolerated levels in mice in the micronucleus test.
In order to detect possible formation of carcinogenic N-nitroso compounds from nitrite and nitrosatable compounds in meat, studies were carried out with 70 male and 140 female F0 rats, divided into six groups, and 60, 100, 70, 60, 60 and 66 of their male and female offspring. One control group received casein and other groups chopped pork as the sole protein source (45%, mass/mass) on a fresh basis, either salted (sodium chloride) or not. For test groups, nitrite was also added to the meat before autoclaving and storing the diet and represented mass fractions of 200, 1 000 and 4 000 mg/kg, as sodium nitrite. The results do not demonstrate any effect on reproduction and no significant carcinogenic effect was revealed. However, an observed tendency toward an increased number of tumour-bearing rats in the highest dose group, plus the possible formation of carcinogenic N-nitroso compounds in nitrite-treated meat products, led to a recommendation to reduce the use of nitrite. Results from a concomitant study demonstrate that it is possible to produce many cured-meat products with the addition of only 50 mg/kg nitrite.
Butylated hydroxyanisole (BHA) was given to pregnant SPF pigs (Danish Landrace) in doses of 0, 50, 200 and 400 mg/kg body wt per day for 110 days. BHA was mixed in the diet (pelleted). Hyperkeratotic and parakeratotic proliferative changes of the stratified epithelium of the stomach were found at various degree in both control and dosed pigs. Papillomas were not found and no changes of the glandular part of the stomach were observed.
Pulegone and menthol, components of peppermint oil, were investigated in rats. The substances were administered by gavage for 28 days at 0, 20, 80, 160 mg pulegone and 0, 200, 400, 800 mg menthol/kg body wt./day, respectively. At the two highest doses, pulegone induced atonia, decreased blood creatinine content, lowered terminal body weight and caused histopathological changes in the liver and in the white matter of cerebellum. For menthol at all dose levels a significant increase in absolute and relative liver weights and vacuolisation of hepatocytes was found. No sign of encephalopathy was observed in rats given menthol. The no effect level for pulegone was 20 mg/kg body wt./day and for menthol less than 200 mg/kg body wt./day.
Peppermint oil was given p.o. to groups of 10 male and 10 female rats at dosage levels of 0, 10, 40 and 100 mg/kg bw/day respectively for 28 days. Histopathological changes in the white matter of the cerebellum especially were seen at dose levels of 40 and 100 mg/kg bw/day and consisted of cyst-like spaces scattered in the white matter. There were no obvious signs of clinical symptoms due to the encephalopathy.
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An embryotoxicity study on butylated hydroxyanisole (BHA) was carried out in SPF pigs (Danish Landrace). BHA was incorporated in the diet and administered to pigs in doses of 0, 50, 200 and 400 mg/kg body wt/day from mating (artificial insemination) to day 110 of the gestation period, when the foetuses were removed. Significant lower weight gain was observed in the dams dosed 400 mg/kg body wt/day. Absolute and relative organ weight for the liver and thyroid gland showed a dose-related increase, BHA neither affected the reproduction data nor the incidence of defects in the foetuses.
Butylated hydroxytoluene (BHT) was given to rats in the diet at levels of 500 and 5000 ppm for different periods of time up to 90 days. Iodine uptake by the thyroids, the half life of thyroxine and the weights of liver and thyroid were determined when 5000 ppm BHT was given in commercial or semisynthetic diets containing different amounts of iodine. Iodine uptake was significantly increased in those animals given BHT into the diet, but the half-life of thyroxine was unchanged or slightly prolonged. Thyroid weight was enhanced at both 500 and 5000 ppm BHT, while liver weight was increased ony in the latter. No explanation of the pathogenesis of the effect can be suggested.
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A case of lymphangiomatosis of bone in a 12-years old boy is presented. First bone lessions were seen at 6 1/2 years of age and the case had a progressive course. The only associated lymphatic malformation was a submandibular lymphangioma. The lymphography performed at the patient was normal. Literature about this subject is revised and evolutive possibilities and therapy are described.
Organochlorine pesticides were found in all samples of livers, kidneys, mammary glands, and fetuses of eastern water rats (Hydromys chrysogaster) collected in the Murrumbidgee irrigation areas of New South Wales in 1970 and 1972. DDE was the predominant residue. Livers contained 0.01--3.10 ppm sigma DDT air-dried weight; kidneys, less than 0.01--1.12 ppm; mammary glands, 0.14--23.75 ppm; fetal liver, 0.28--0.66 ppm. Variations in residue levels are discussed in relation to the possible effects of environmental and physiological factors.
Earlier experiments with Orange RN in rats have shown several changes in the blood i.g. induction of Heinz bodies, methaemoglobinaemia and reduction of RBC (J.F. Gaunt et al., Fd. Cosmet. Toxicol., 1971, 9, 619). Similarly induction of Heinz bodies, reduction of RBC and a rise in reticulocytes were demonstrated at our institute in pigs following a few weeks administration of Orange RN (P. Olsen et al., Toxicology, 1973, 101, 249). The purpose of this study has been to investigate the degree and the induction time of Heinz bodies and changes in the number of reticulocytes and RBC in pigs during the first 18 days. After a few days marked alterations in the blood picture were seen. Heinz bodies increased from a few or none to 65% of the erythrocytes in the highest dose group (320 mg/kg bw/day) and to 30% in the lowest dose group (160 mg/kg bw/day). In addition a marked decrease in RBC and a rise in reticulocytes were seen in the highest dose group.
In a recent review on the role of fats in human nutrition Vergroesen and Gottenbos (1975) emphasize, that the presence of erucic acid isomers in hydrogenated marine oils (HMO) may constitute a toxicological problem as serious as erucic acid in rapeseed oil (RSO). On the contrary Christophersen et al. (1976) stress, that these fatty acids in HMO represent a minor toxicological problem, and that conclusions drawn from HMO to RSO are questionable. Preliminary studies at our institute indicate lipidosis in the heart both in rats fed RSO and HMO, containing equivalent amounts of erucic acid and erucic acid isomers respectively. Further experiments of longer duration are performed with HMO and RSO in order to compare the effect on the heart, especially in relation to the formation of cell necrosis.
The laboratory animal is susceptible to biological variation due to a variety of causes. Thus genetic variation and nutrition have become recognized to influence the reaction of the animal to experimental procedures. Severe kidney injury was observed at our institute in preliminary studies with 1% butylated hydroxytoluene (BHT) incorporated in a semisynthetic diet fed to Wistar rats for one month. These lesions together with nephrocalcinosis, a common finding in rats fed a semisynthetic diet might suggest that the animals in our experiment were predisposed to kidney damage. In order to show the influence of the rat strain and the type of diet a study was performed with both Wistar and Sprague-Dawley rats fed a semisynthetic or commercial diet mixed with 1% BHT. It was observed that the semisynthetic diet had a marked effect on the severity of the kidney lesions and that the lesions were independent of the rat strain used. In addition, an apparent sex variation was found.