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Dihydrofolate reductase (E.C. 1.5.1.3) from Plasmodium falciparum and from its host, the owl monkey (Aotus trivirgatus), were partially purified and characterized. The molecular weight of the parasite enzyme was estimated to be over 10 times as high as that of the host enzyme. The host enzyme had 2 pH optima whereas the parasite enzyme only one. The activity of the host enzyme was greatly stimulated by KCl and urea, while that of the parasite enzyme was inhibited at high concentrations of such chaotropic agents. Km of the parasite enzyme was significantly higher than that of the host enzyme. The parasite enzyme had much lower Ki for pyrimethamine than the host enzyme. Dihydrofolate reductases isolated from pyrimethamine-resistant and pyrimethamine sensitive strains of P. falciparum were found to be similar.

The degradation and excretion of 2-14C-uric acid were examined in three adult woolly monkeys (Lagothrix lagothrichia) to determine the basis for the relatively high serum and urinary uric acid concentrations previously reported in this species. Like man and the great apes which lack uricase, but in distinction to most other mammals, these animals converted very little urate to allantoin. Uric acid turnover, as has been reported for other New World monkeys, was several times that of normal man. Renal urate excretion as well as disposition by extrarenal mechanisms may protect Lagothrix vrom hyperuricemia. The capacity to convert urate to allantoin appears to have been lost late in the evolution of New World monkeys. The woolly monkey deserves further study as a primate model for investigations of enzyme replacement strategies.

Estrogen is concentrated within cellular nuclei in discrete regions of the monkey brain 30 and 60 minutes following intravenous injection of [3H] estradiol. Chromatographic data is provided to suggest that most of the localized estrogen is in the form of estradiol with lesser amounts of estrone and estriol. Three "major" areas of estrogen accumulation include: (1) preopticostrial accumulation: n. preopticus medialis--n. interstitialis striae terminalis, (2) basal hypothalamic accumulation: n. infundibularis--n. ventromedialis--n. premammillaris ventralis, and (3) the amygdaloid accumulation. Several "minor" areas of estrogen accumulation include the tuberculum olfactorium, insulae Calleja, n. triangularis septi, a. hypothalamica anterior, n. anterior hypothalami, n. paraventricularis, n. supraopticus, n. periventricularis and the substantia grisea centralis. The neocortex, rhombencephalon and spinal cord are essentially unlabeled. The major areas of accumulation are similar in several other mammalian and avian species while these, and some minor areas of accumulation, have been shown in neuroanatomical studies to be interconnected by several pathways, especially the stria terminalis. Lesion, implant, stimulation, recording and morphometric studies, in several species, support the concept that this arrangement provides a neuroanatomical substrate which would allow the integration of the various facets of the neuroendocrine reproductive response.

Certain individual squirrel monkeys ("hypo-responders") are able to remain normocholesterolemic when fed diets containing cholesterol (0.5 mg/kcal). Other squirrel monkeys ("hyperresponders") when fed the same diet become hypercholesterolemic. The purpose of these studies was to identify the mechanisms which allow hyporesponders to compensate for dietary cholesterol. Using formula diets and sterol balance techniques, we have compared cholesterol absorption, synthesis, excretion, and turnover in hypo- and hyperresponding monkeys. Cholesterol absorption was essentially identical in the two groups (about 55 mg/day). Cholesterol synthesis was likewise similar in the two groups (about 35 mg/day) and there was no evidence of feedback inhibition at the level of cholesterol fed. Hyporesponders had faster turnover rates and smaller body cholesterol pools than did hyperresponders. Excretion of neutral steroids was similar for hypo- and hyperresponders and did not change with cholesterol feeding. In contrast, hyporesponders increased bile acid excretion shortly after cholesterol feeding was begun. Hyperresponders responded more slowly and to a lesser degree. It is concluded that, in this species, the mechanism of control of plasma cholesterol levels is related to the rate of conversion of cholesterol to bile acids.

The absorption, distribution, and excretion of hycanthone were studied with rats and rhesus monkeys using tritiated materials at the therapeutic dose recommended for man (3.0+/-0.5 mg/kg). Nine pairs of each species received single intramuscular doses of randomly tritiated (specific activity 193.7 mCi/mmol) hycanthone methanesulfonate and were then sacrificed at intervals between 15 min and 72 h after medication. Peak blood and tissue concentrations occurred 30-60 min after administration (plasma half-life-45 min). The highest concentrations were observed in the liver, spleen, kidneys and adrenals, but decreased rapidly (more than 80% of the dose was excreted in 48-72 hours). In monkeys a high concentration of the compound was found in the bile (hours 1-8), probably conjugated to glucuronic acid.Radiochromatography showed only unchanged drug in the blood and tissues, except in the liver where rapid conversion occurred to sulfoxide in the rat and to the deethyl analogue in the monkey.

Activities of the five hepatic enzymes of the urea cycle increased two- to threefold in monkeys on a 60 percent protein diet compared with levels in monkeys on an isocaloric 6 percent protein diet. Equal adaptation occurred in rats on the same diets. These enzyme activities in adult humans approximate those of monkeys on a similar protein intake.