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After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant in dogs, cats and horses, with ratios of 30.3, 5.3 and 1.5, respectively, while R(-) is the predominant enantiomer in sheep. The interpretation of these inter-species differences can be supported by experimental evidence, however some informations are lacking and additional investigation is required. In the case of ketoprofen where S(+) is predominant in rats, dogs and horses, the metabolic chiral inversion from R(-) to S(+), which has been demonstrated in rats, may also take place in the latter two species. In addition, the well documented stereoselective clearance of the glucuronides, possibly in favour of the enantiomer S(+), may explain the lower body clearance of the R(-) enantiomer in sheep. For carprofen, no metabolic chiral inversion was shown in rats and dogs after administration of each enantiomer individually, but for this compound, stereoselective clearance of glucuronides has been demonstrated which may support the idea of a plasma concentration shift of the enantiomeric proportions vs time in favour of the R(-) enantiomer. Regardless of the possible biological mechanisms which are responsible for these inter-species differences, the existence of these differences gives rise to at least two important issues: The choice of animal species which can be used in the research of drugs destined for human therapeutics: the most pertinent animal species will be the one which demonstrates an enantiomeric plasma profile closest to that observed in man. The present data show that the ideal animal species from this respect has still to be identified. For application in veterinary therapeutics, a careful balance must be established between the requirement of favourable bioavailability of the active S(+) enantiomer and the potential of any possible chiral inversion of R(-) to generate hybrid molecules in meat and milk which in turn may lead to residues, the toxicity of which to the human consumer is still unknown.

This study of the distribution of C. solatus was mainly carried out by interviewing 330 local hunters at 102 locations. The species was found to occur in a 9 500-10 300 km2 area. Its distribution is limited to the north and east by the Ogooué, Lolo, and Bouenguidi rivers, and to the west by the Ofifoué river in its lower course. In the southwest, its distribution follows the limit of a specific forest type. The southern limit seems to coincide at least in part with increased elevation. Anthropic factors cannot account f or such a restricted distribution, as C. solatus is also found in the degraded vegetation of the settled areas, where its abundance is apparently similar to that found in the primary lowland forest which covers most of its range. Historical factors which may explain the radiation of the Ihoesti superspecies are discussed. The status of mountain species commonly attributed to the Ihoesti group is questioned., Cette étude sur la distribution de C. solatus repose principalement sur une série d’interviews. L’aire de distribution de cette espèce endémique est particulièrement limitée (variant entre 9 500 et 10 300 km2). Au Nord, à l’Est et au N. -O., l’Ogooué ou ses affluents en constituent les limites. Par contre, au S.-O., C. solatus n’atteint pas la rivière mais sa limite suit celle des forêts de plaine qui couvrent l’essentiel de son aire de distribution. Au Sud, l’augmentation de l’altitude rend compte pro parte de sa distribution irrégulière. Les facteurs anthropiques ne peuvent rendre compte de l’aire de distribution réduite de C. solatus, puisque l’espèce colonise les forêts secondaires dans lesquelles elle atteint une abondance comparable à celle observée en forêt primaire. Les facteurs historiques qui ont été proposés pour expliquer la distribution disjointe des trois espèces de Ihoesti sont discutés. Le statut d’espèces de montagne qui leur est attribué couramment est notamment débattu., Gautier Jean-Pierre,Moysan F.,Feistner Anna T. C.,Loireau Jean-Noël,Cooper Robert W. The distribution of Cercopithecus (Ihoesti) solatus, an endemic guenon of Gabon. In: Revue d'Écologie (La Terre et La Vie), tome 47, n°4, 1992. pp. 367-381.

WOS:A1988P968300003; International audience; The banded chromosomes of Harrison’s monkey, Cercopithecus (lhoesti) solarus, and Preuss’ monkey, Cercopithecus (Ihoesti)preussi, were studied for the first time and compared with those of l’Hoest’s monkey, Cercopithecus (lhoesti] Ihoesti; the savannah guenons, Cercopithecus aethiops ssp. and the patas monkey, Cercopithecus (Erythrocebus)patas. The karyotype of C. preussi was identical to that previously reported for C. Ihoesti, and differed by three chromosomal rearrangements from C. solatus. The latter’s next closest cytogenetic affinities were to the savannah guenons and then to C. patas. These data were consistent with the designation of C. solatus as a new species.

Forty-seven patients were diagnosed as having systemic lupus erythematosus (SLE) and 34 patients primary Sjögren's syndrome (SS); 30 controls were also studied. Anti cardiolipin (CL), anti double-stranded DNA (ds DNA) and anti single-stranded DNA (ss DNA) antibodies were determined by the enzyme-linked immunosorbent assay. Elevated anti-CL antibody levels were detected in 47.8 p. 100 (n = 46) of patients with SLE and in 85.3 p. 100 (n = 34) of patients with SS, but only once in controls. Elevated ss DNA were detected in 91.5 p. 100 (n = 47) of patients with SLE and in 18.3 p. 100 of patients with SS but never in controls. Elevated anti-ss DNA were detected in 93.3 p. 100 and 97.1 p. 100 respectively of patients with SLE and SS and in 3.3 p. 100 of controls. There was no correlation between anti-CL and thrombosis, circulating lupus anti coagulant or VDRL. The most striking association, however, was between anti-CL and anti ss-DNA antibodies in SLE. There was no correlation between anti-CL and anti ds-DNA antibodies in SLE patients. Anti CL antibodies were correlated both to ss-DNA and anti ds-DNA in SS patients. Absorption of positive anti-CL antibodies sera were done on DNA (ss-DNA and ds-DNA) affinity column chromatography: anti-CL antibodies were absorbed only by ss DNA in SLE and by both ss DNA and ds DNA in SS.

Semen characteristics were studied in 6 wild-born chimpanzees with dental ages ranging approximately from 6 to 12 years. The animals formed 2 groups, early pubertal (EP, N = 3, 6-9 years) and late pubertal (LP, N = 3, 11-12 years). Mean body weight, testicular volume and serum androgen concentration were significantly lower in Group EP (32.2 +/- 1.6 kg, 34.0 +/- 7.7 cm3, 2.1 +/- 0.1 ng/ml) than in Group LP (55.7 +/- 5.7 kg, P less than 0.01; 100.5 +/- 11.9 cm3, P less than 0.01; 3.6 +/- 0.7 ng/ml, P less than 0.05). Ejaculates were obtained by masturbation in all subjects. The mean ejaculate volume was lower in Group EP (0.56 +/- 0.20 ml) than in Group LP (3.77 +/- 0.73 ml, P less than 0.01). In Group EP, 2 animals were azoospermic while the third produced semen with means of 57.1 x 10(6) spermatozoa per ml, 20% motility and 40% vitality. These values were low when compared with the mean values of Group LP (376 x 10(6) spermatozoa per ml, 67% motility and 78% vitality). Mean total sperm count was correlated with testicular volume (r = 0.84) and serum androgen concentration (r = 0.96). The mean concentrations of L-carnitine, fructose, citrate and acid phosphatase for the two groups were not significantly different; but, related to the differences in ejaculate volumes, their total amounts in total ejaculate were lower in Group EP than in Group LP. These results suggest that, in chimpanzees, mechanisms of seminal plasma production and ejaculation are functional early in the reproductive life and that the emission of spermatozoa occurs later.

CGP 20,376, a benzthiazole and new antifilarial agent, was investigated at CIRMF in eight wild born chimpanzees naturally infected with Dipetalonema vanhoofi. Single oral doses (3.75, 7.5, 11 and 15 mg/kg) were administered. Drug levels during the first hour after administration were assessed in seven chimpanzees at 10 minute intervals in the blood. Levels of unchanged drug (CGP 20,376) were higher than those of its metabolite (CGP 20,308). However, there was considerable variation between individuals, although the results for each animal were consistent. Because of investigational limitations a complete drug profile could not be established. Unsheathed microfilariae of D. vanhoofi were monitored during the first hour following drug administration in seven chimpanzees. In five the microfilaraemia dropped to low counts within 10 minutes and remained below the initial values for the next 50 minutes while in two other chimpanzees it showed a more irregular reduction. Periodic microfilarial counts over the next 20 months, at roughly 30 day intervals, showed that three chimpanzees, treated with 7.5, 11 and 15 mg/kg respectively, remained free of circulating microfilariae from Day 1 to Day 600, the chimpanzee treated with 3.75 mg/kg remained microfilaremic and, in three chimpanzees low numbers of microfilariae reappeared within one year, whereas in the remaining ape they reappeared after one year. No major clinical adverse effects were observed, but liver function tests showed mild reversible changes at the 11 and 15 mg/kg doses. CGP 20,376 was therefore microfilaricidal, except for the lowest dose, and it was possibly macrofilaricidal in those chimpanzees which remained free of microfilariae for 600 days. Clinically CGP 20,376 was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic polymorphisms of drug oxidation are major determinants of interindividual variations in drug response and toxicity. Many animal models, including rats, have been used for clinical investigations of pharmacogenetics. However, because of large interspecies differences, these data are difficult to extrapolate to humans. We therefore phenotyped 64 non-human primates for debrisoquine and mephenytoin polymorphisms and identified poor metabolizers of both drugs. The frequency of poor metabolizers was 14% for debrisoquine (95% confidence limits, 6.5-25%) and 3% for mephenytoin (95% confidence limits, 0.5-10%). If family studies demonstrate a genetic basis for the two independent defects, this animal species could be used for in vivo and in vitro pharmacogenetic investigations.