Abstract.A clinically normal, 3-year-old female rhesus monkey (Macaca mulatta), which was part of a routine toxicology study, had a mass in the right ovary with metastases to the adjacent mesentery and lungs. The histologic features and immunohistochemistry results were consistent with the diagnosis of choriocarcinoma. Neoplastic cell types included cytotrophoblast (positive for cytokeratin), syncytiotrophoblast (positive for human chorionic gonadotropin), and extravillous trophoblast (positive for human placental lactogen). Because the neoplasm was present in the ovary, the uterus was normal, and the animal was not currently pregnant, this was considered a primary ovarian neoplasm of germ cell origin. The monkey had elevated serum levels of chorionic gonadotropin at the beginning of the study, indicating that, as in women, choriocarcinomas in monkeys can be associated with increased gonadotropin levels and that the tumor was preexisting at the start of the toxicology study.
Evidence for the presence of cortisol and corticosterone in equine plasma and cortisol in equine urine is presented. The mean morning concentration of plasma cortisol was 7 \g=m\g/100ml, and that of corticosterone 0\m=.\5 \ g=m\ g/ 100 ml.A diurnal rhythm of small amplitude was found.Administration of corticotrophin, induction of hypoglycaemia and surgery produced marked increases in plasma cortisol levels, but only small increases were seen after normal exercise. The changes in plasma cortisol were not invariably accompanied by significant alteration of the eosinophil count.
Some tissues contain more than one enzyme exhibiting 'acid-phosphatase' action and the partial separation of such enzymes has been reported, e.g. from rat liver (Goodlad & Mills, 1957; Barka, 1961 a, b) and from Escherichia coli (Rogers & Reithel, 1960). Among the factors that make the interpretation of experimental observations on 'acid-phosphatase activity' difficult are (a) in the earlier work, lack of knowledge of the lysosomal sequestering of acid P-glycerophosphate phosphohydrolase (/3-glycerophosphatase) and the conditions in which it is released, (b) the variety of substrates used for assay coupled with a lack of information concerning the identity of the enzyme(s) responsible for the hydrolysis of any given substrate and (c) the wide diversity of properties of 'acid phosphatases', both from different tissues within a species and from similar tissues in different species. Some of these inherent difficulties are illustrated by the work of Macdonald (1961) on the phenyl phosphate-phosphohydrolase (phenyl phosphatase) activity of mouse-liver homogenates and the subsequent interpretations of the results obtained (Neil, 1961; Macdonald, 1962). The present work is concerned principally with the differentiation of guinea-pig-liver enzymes that hydrolyse /-glycerophosphate and p-nitrophenyl phosphate in acid solution. Some of the results of this work have been briefly reported (Neil & Horner, 1962). MATERIALS AND METHODS Animals. Laboratory-stock adult albino guinea pigs were used throughout. The stock consisted of an inbred colony derived from that maintained at the Research Institute (Animal Virus Diseases), Pirbright, Surrey. Chemical&. ,B-Glycerophosphate was laboratory-reagent grade (British Drug Houses Ltd., Poole, Dorset) containing less than 3% of the a-isomer. Phenolphthalein mono-,Bglucuronic acid was obtained from Sigma Chemical Co., St Louis, Mo., U.S.A. Sucrose was Tate and Lyle Co. Ltd. caster sugar. Alloxan was obtained from Hopkin and Williams Ltd., Chadwell Heath, Essex. All other chemicals were of AnalaR or laboratory-reagent grade from British Drug Houses Ltd.
[phenyl-14C]-Phenylbutazone was administered to 2 horses p.o. and i.v. on separate occasions. Plasma levels and urinary and faecal elimination of 14C were monitored for up to 7 days after dosing. Phenylbutazone was rapidly and extensively absorbed after oral administration, and its bioavailability was 91% assessed by comparison of plasma AUCs of unchanged drug after p.o. and i.v. administration. The plasma elimination half-life of phenylbutazone was 9.7 h and this was independent of the route of administration. The pattern of elimination of phenylbutazone was independent of the route of administration, with 55% of the dose being found in the urine in 3 days and a further 39% in the faeces in 7 days. These data, which are the first reports of the absolute bioavailability and excretion pathways of phenylbutazone in the horse, are discussed in terms of their significance for the gastrointestinal toxicity of this drug.
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