Two unanaesthetized female yellow baboons (Papio cynocephalus cynocephalus) were infused (i.v.) with [3H]oestradiol and two with [3H]progesterone, early in the follicular phases of their cycles. One month later, the two females infused with [3H]oestradiol were simultaneously infused with [14C]progesterone and [3H]dehydroepiandrosterone. All urine and faeces were collected for 96 h after infusion. The proportion of steroid excreted in faeces (versus urine) was 10.0% for oestradiol and 40% for progesterone. Peak excretion in urine occurred 4.5 h after infusion. Peak excretion in faeces occurred an average of 36.4 h after infusion, with remarkable consistency between steroids. Eighty per cent of faecal oestradiol and progesterone metabolites were excreted as free (rather than conjugated) steroids. Simply boiling (20 min) the dried faecal sample in 90% ethanol proved to be the most rapid and efficient means of extracting these steroid metabolites. High pressure liquid chromatography and immunoreactivity studies revealed that oestradiol was excreted in faeces as oestradiol (36%), oestrone (44%) and a conjugated metabolite that co-eluted with oestrone sulfate (20%). Progesterone was excreted as eight different free forms, only a minor portion of which was progesterone, and what appeared to be a conjugated metabolite that co-eluted with pregnanediol-glucuronide (20%). The free progesterone metabolites were identified by gas-chromatography-mass-spectrometry as epimers of 5-pregnane-3-diol and 5-pregnane-3-ol-one. These data suggest that currently available immunoassays for free oestradiol and oestrone should adequately characterize faecal oestrogen profiles in baboons. However, high variability in crossreactivities of various progesterone antisera to progesterone metabolites in baboons makes antiserum selection a more serious concern in attempts to quantify faecal progestogen dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

A study was conducted in captive baboons to determine (i) the impact of cereal dietary fibre on faecal progestogen excretion, and (ii) whether means of controlling dietary effects could be identified. Blood was collected on 3 days per week and faeces on 5 days per week from four unanesthetized cyclic female baboons, consecutively fed three diets of 5, 10 and 20% fibre for 90 days per diet. A 2 day lag time was detected before progesterone in the blood appeared in the faeces, regardless of diet (mean correlation was 0.62, P = 0.002). Increased dietary fibre had a negative effect on progestogen excretion (P < 0.004). Correspondence between blood and faecal progestogens was consistently greatest and the effect of dietary fibre least when faecal progestogens were expressed g-1 dry faeces. Several means of indexing faecal steroid excretion rates were examined including dehydroepiandrosterone (DHEA) and a number of byproducts of cholesterol metabolism. The cholesterol metabolite, cholestanone, was positively correlated with dietary fibre (r = 0.27; P < 0.04). Multiplying faecal progestogen concentration by the cholestanone g-1 dry faeces concentration increased the correlation between serum and cholestanone-indexed faecal progestogens (r = 0.78, P = 0.0001) compared with nonindexed progestogens (r = 0.71, P = 0.0001). We conclude that expressing faecal progestogens g-1 dry faeces may be sufficient and the most cost-effective method for controlling for most dietary effects when the objective is monitoring longitudinal endocrine status in baboons. However, it may be appropriate to express faecal progestogens by cholestanone concentrations when increased precision is needed to overcome the effects of profound variations in dietary fibre.

The metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was examined in the patas monkey, in order to provide further information about NNK metabolic pathways in primates. Female patas monkeys were given i.v. injections of [5-3H]NNK, and metabolites in serum and urine were analyzed by HPLC. Metabolism by alpha-hydroxylation of NNK was rapid and extensive, and the products of this pathway, 4-hydroxy-4-(3-pyridyl)butyric acid and 4-oxo-4-(3-pyridyl) butyric acid, accounted for a relatively large proportion of serum and urinary metabolites at all time points. This is significant because the formation of these products is associated with modification of DNA by NNK. The other major metabolic pathway was carbonyl reduction to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which detected both unconjugated and diastereomeric O-glucuronides. One of these glucuronides had been previously identified in rat urine, but the other diastereomer, which was the more prevalent of the two in serum and urine, had not been observed in studies of NNK metabolism in rodents. It was characterized by its spectral properties, by enzymatic hydrolysis to NNAL, and by derivatization of the released NNAL enantiomer with (R)-(+)-alpha-methylbenzylisocyanate. The two NNAL glucuronides accounted for 15-20% of the urinary metabolites in monkeys given 0.1 micrograms/kg NNK, which is similar to a smoker's dose, suggesting their use as dosimeters of NNK exposure in humans. Pharmacokinetic parameters were consistent with those observed in previous studies of nitrosamines, and varied predictably with body weight of five species. The results of this study have provided new insights relevant to assessing human metabolism of NNK.

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Herpes B virus (BV) is a common cause of recurring mucocutaneous infections in monkeys of the genus Macaca. Like its human counterpart, herpes simplex virus (HSV), BV establishes lifelong latency and can be reactivated from infected monkeys symptomatically or asymptomatically. Incidental infection of humans handling BV-shedding monkeys can result in fatal meningoencephalitis. To determine whether humans exposed to infected monkeys can acquire asymptomatic BV infections, 480 subjects were evaluated in a controlled seroprevalence study. Sera from 321 primate handlers, including many with repeated injuries inflicted by Macaca monkeys, and 159 people never exposed to monkeys were tested in blinded fashion by both competition ELISA and Western blot to determine the prevalence of BV and HSV seropositivity. Although 293 persons proved positive for HSV antibodies, no primate handlers or control subjects showed BV-specific antibody responses. There is no serologic evidence that BV causes asymptomatic infections in humans.