Mitochondrial divergence between 2 populations of the hooded capuchin, Cebus (Sapajus) cay (Platyrrhini, Primates).

We analyzed the molecular divergence of 2 separate populations of Cebus apella paraguayanus, recently considered a junior synonym of Cebus cay, and estimated its time of separation from C. apella. Cytochrome b DNA from 23 C. cay from Brazil and 9 from Paraguay showed 24 haplotypes (20 and 4, respectively), accounting for 29 variable sites (19 transitions and 10 transversions), with 40.0%, 26.7%, and 33.0% replacements at first, second, and third codon positions, respectively. Genetic distance between haplotypes averaged 0.5%, with 1.1% between C. cay populations. Phylogenetic reconstructions and median joining separated C. cay from Brazil and Paraguay. Neighbor joining showed C. cay and C. apella as sister groups, although C. cay and C. apella collapsed in maximum parsimony and maximum likelihood topologies. Analysis of molecular variance showed the highest variance component between C. cay populations, and mismatch distribution indicated that this species suffered a recent demographic expansion. Divergence time estimates suggested that the 2 populations of C. cay split in the Pleistocene, a period of repeated glaciation events leading to drastic changes in the vegetation composition of different biomes.

Suppression of ovulation by a synthetic progestin in the capuchin monkey.

BACKGROUND: From the limited research in New World monkeys it is not clear whether they are as sensitive to the antiovulatory effects of synthetic progestins as noted in human beings. We examined whether levonorgestrel prevented ovulation in the capuchin monkey. METHODS: Cebus apella monkeys were treated orally with two doses of 2 mg of levonorgestrel, 8-9 hours apart, in four periovulatory stages assessed by laparoscopy. RESULTS: Levonorgestrel-induced luteinization of the follicle prevented oocyte release up to 8 hours before ovulation. Unhealthy oocytes were recovered from 46% of unruptured follicles. Luteal progesterone was reduced by 55%, 35%, and 25% according to when levonorgestrel was given -2, -1, and 0 day from estradiol peak respectively. CONCLUSION: The capuchin monkey, a neotropical primate in which progesterone circulates at levels much higher than in Old World primates and human beings, is sensitive to the antiovulatory effects of synthetic progestins.

Pharmacokinetics and pharmacodynamics of interferon beta 1a in Cebus apella.

BACKGROUND: Recombinant human interferon (hIFN beta) is indicated for the treatment of multiple sclerosis. Its effect presents species restriction, thus lacking biological activity on most mammals. Although there have been previous studies of the pharmacology of INF beta in Old World primates, no data exists on New World primates. Therefore, we explored its effect on Cebus apella, a New World monkey, describing the pharmacology of this molecule when injected by subcutaneous route in this species. METHODS: Safety, pharmacokinetics and pharmacodynamics of IFN beta were evaluated in nine Cebus apella individuals. RESULTS: A single subcutaneous injection of 12 x 10(6) IU of hIFN beta 1a resulted in a median AUC((0-48)) (area under the curve) of 14.82 ng/ml, a C(max) (maximum plasma concentrations) of 1.51 ng/ml and a T(max) (time to achieve maximum plasma concentrations) of 3 h. IFN beta was biologically active as demonstrated by an increase in neopterin levels. There were no safety concerns. CONCLUSIONS: New World non-human primates are a suitable animal model for the study of IFN beta pharmacology.

Cortisol response and ovarian hormones in juvenile and cycling female Cebus monkeys: effect of stress and dexamethasone.

We examined cortisol profiles in relation to ovarian hormones and their response to a repeated composite stressor with and without dexamethasone suppression. To evaluate the day-to-day changes in circulating cortisol relative to ovarian hormones, we subjected five adult female Cebus apella monkeys daily to restraint, sedation, transport to a neighboring room for femoral venipuncture, and return to the cage throughout the menstrual cycle. The cortisol response to the repeated stressor for blood collection, its relationship with the ovarian function, and the effects of dexamethasone were evaluated in six juveniles (18-24 months old) and five adult females in the luteal phase. Blood was sampled at time 0; then the monkeys received the vehicle and their blood was sampled again at 1, 2, 4, and 24 hr. This experiment was repeated 3 weeks later, with dexamethasone (i.m. 2 mg/Kg) injected instead of vehicle. Plasma aliquots were assayed for cortisol, progesterone, and estradiol. The results revealed that from middle infancy and throughout adulthood, hypercortisolism is the norm in female Cebus monkeys. The high cortisol values remained unchanged across the cycle despite the cyclic changes in estradiol and progesterone levels. Juvenile monkeys exhibited a higher cortisol response to stress than adults, and both juvenile and adult monkeys exhibited the typical suppression by dexamethasone. A rapid suppression of progesterone co-occurred in parallel with cortisol after dexamethasone injection in juvenile monkeys, suggesting that most circulating progesterone originates in the adrenals. In contrast, adult females exhibited an overincrement of progesterone levels, in parallel with a rise in cortisol, in response to the stressor, and this effect was exacerbated by dexamethasone. The findings suggest that hypercortisolism is insufficient to disrupt ovarian development toward a normal cyclical function, and that ovarian steroids have no influence on day-to-day circulating cortisol levels. On the other hand, the overincrement of progesterone levels induced by stress and/or glucocorticoids during the early luteal phase is unlikely to interfere with the development of this phase and implantation in this monkey species.

Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus apella).

The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.

PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant hepatitis B vaccine that enhances the Th1 response.

PyNTTTTGT oligodeoxinucleotides (ODNs) cause activation, proliferation and immunoglobulin secretion on B cells, and the expression of co-stimulatory molecules on plasmacytoid dendritic cells of primates. It has now been discovered that these ODNs are also active on rat cells. This fact allowed us to investigate the adjuvant properties of PyNTTTTGT ODNs in a human Hepatitis B vaccine using this animal model. A very significant increment, as compared with the antigen alone, was observed in the antibody production induced by vaccination with the recombinant Hepatitis B surface antigen adjuvated with the PyNTTTTGT prototype IMT504 ODN. Analysis of the IgG subclass distribution in the sera of vaccinated animals indicated that, although an increase was observed in the titer of all the IgG subclasses, the increase on the Th1-associated IgG2b subclass was clearly more pronounced. Remarkably, this effect on the IgG2b titer was observed even if alum, a Th2 promoting adjuvant, was present together with IMT504 in the vaccine formulation. The increase in the Th1 response induced by IMT504 was also suggested by in vitro gamma interferon secretion assays. Monkeys of the species Cebus apella immunized with the recombinant Hepatitis B surface antigen plus alum and IMT504 also showed titers of antibodies against the antigen several times superior to the titers observed in control animals immunized with the antigen plus alum without ODN. Since rat and monkey cells are significantly less immunostimulated "in vitro" by PyNTTTTGT ODNs than human cells, the present results reasonably predict a very good performance of these ODNs as adjuvants in human vaccination.