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PubMed2005

Detection of ketamine and norketamine in urine of nonhuman primates after a single dose of ketamine using microplate enzyme-linked immunosorbent assay (ELISA) and NCI-GC-MS.

The general anesthetic ketamine (Ketalar, Ketaject, Vetalar) (KET) is used in human and veterinary medicine for induction of anesthesia for short surgical procedures and routine veterinary examination. Its illicit use by teenagers in rave parties has been reported, and it has recently been identified as a substance associated with sexual assault. One aim of this paper was to study the elimination of KET and its major metabolite norketamine (NKET) in urine collected from five nonhuman primates that received a single dose (5 mg/kg, I.M.) of KET and to study elimination patterns to determine how long after drug administration KET and NKET can be detected. Another aim of this study was to develop and validate a highly sensitive negative ion chemical ionization-gas chromatography-mass spectrometry (NCI-GC-MS) method for the simultaneous quantitation of KET and its major metabolite NKET in urine and to analyze urine samples collected from the animals. The last aim of this study was to apply and evaluate a newly developed ELISA screening methodology for detection of KET and its metabolites in the same urine samples collected from primates which received a single dose of KET. In two monkeys, KET was detected in urine up to 3 days after drug administration (32-7070 ng/mL); in one monkey, it was detected up to 4 days (65-13,500 ng/mL); in one monkey, it was detected only on days 1 and 2 (4000 and 70 ng/mL, respectively); and in one monkey, it was detected 10 days after KET injection (22-35,000 ng/mL). NKET concentrations ranged from 63 pg/mL to 1.75 microg/mL, and it remained in the urine throughout the entire 35-day study period in 4 out of 5 animals. In one monkey, NKET was detected up to 31 days after KET administration. Urine analysis using ELISA revealed that KET and NKET can be easily detectable at 25 ng/mL. In one monkey, KET and its metabolites were detected in urine up to 4 days after drug administration, up to 7 days in two monkeys, up to 11 days in one monkey, and 16 days after KET injection in one monkey. Urine extraction followed by screening using ELISA methodology allowed for significant extension of the detection period in all animals from the study. It is believed that the KET elimination in urine of nonhuman primates is slightly faster than in humans. We propose that NCI-GC-MS be employed to detect NKET as a target compound in urine in toxicological investigations of drug-facilitated sexual assault when KET use by the perpetrator is suspected.

Animals↗
PubMed1994

Abolition of cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates with a peptide fragment (VCL) derived from human plasma von Willebrand factor-glycoprotein Ib binding domain.

BACKGROUND: Platelets play an important role in the pathophysiology of acute coronary syndromes. The interaction between the platelet glycoprotein Ib receptor and von Willebrand factor is a critical event allowing platelet adhesion and aggregation and subsequent thrombus formation in vessels with high shear rates and damaged endothelium. Therefore, we tested the hypotheses that VCL, an antagonist of von Willebrand-glycoprotein Ib binding domain, (1) attenuates/abolishes cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates and (2) reduces botrocetin-induced platelet aggregation in vitro after intravenous in vivo administration. METHODS AND RESULTS: Cyclic flow variations were established in anesthetized, open-chest baboons (n = 18). The baboons were divided into three groups. One group (n = 8) received a bolus of VCL (4 mg/kg IV) followed by an infusion (6 mg.kg-1.h-1) for 90 minutes (schedule A). Another group (n = 6) received a 2-mg/kg bolus followed by an infusion of 3 mg.kg-1.h-1 for 90 minutes (schedule B). The third group received a placebo infusion of normal saline. Under dosing schedule A, cyclic flow variations were abolished in 7 of 8 baboons after 33 +/- 18 minutes and markedly attenuated in 1. The frequency of cyclic flow variations fell from 18 +/- 9.4 per hour during the control period to 1 +/- 2.5 per hour after VCL infusion, P < .002. After cessation of infusion, cyclic flow variations remained abolished in 5 of 7 animals for > 3 hours and returned in 2 of 7 after 2 to 2.5 hours. Under schedule B, cyclic flow variations were abolished in 3 of 6 baboons and markedly reduced in the remainder. The number of cyclic flow variations fell from 17 +/- 4.8 per hour during the control period to 5 +/- 4.9 per hour after the VCL infusion, P < .001. The cyclic flow variations returned spontaneously at 38 +/- 40 minutes under this dosing schedule. Placebo infusion of saline had no effect on cyclic flow frequency or severity. VCL administration was associated with slight prolongation in bleeding time and a reduction in botrocetin-induced platelet aggregation. The bleeding time increased from a control time of 88 +/- 32 to 276 +/- 204 seconds, P < .03, and from 142 +/- 28 to 176 +/- 36 seconds, P = .056, for schedules A and B, respectively. VCL decreased platelet aggregation in response to botrocetin (20 micrograms/mL), from a control value of 66 +/- 30.3 to 33 +/- 31.3 omega, P < .05, and from 64 +/- 23.5 to 46 +/- 15.8 omega, P = .006, for dosing schedules A and B, respectively. CONCLUSIONS: Therefore, administration of a peptide fragment corresponding to von Willebrand-glycoprotein Ib binding domain (1) is effective in abolishing cyclic flow variations in stenosed, endothelium-injured coronary arteries and (2) reduces platelet aggregation in vivo in response to botrocetin in nonhuman primates.

Animals↗
PubMed1999

Transplantation tolerance: a look at the nonhuman primate literature in the light of modern tolerance theories.

Ever since the beginning of clinical transplantation, investigators have searched for a way to transplant tissues from one person to another without chronic immunosuppression. That goal, known as allograft tolerance, has remained clinically elusive. In the past decade, however, many of the fundamental principles of tolerance have been redefined, and biological agents capable of exploiting them in vivo have been developed. Accordingly, experimental methods for tolerance induction have rapidly evolved in concert with a growing understanding of physiological tolerance to self and the development of novel immunoreactive reagents. In general, old world monkeys have become the pre-clinical testing ground for methods that have shown reasonable promise for clinical application, particularly antibodies or other biological agents with limited cross-species reactivity. As such, a survey of the nonhuman primate experience in transplantation is representative of all reasonably successful experimental attempts to develop clinically applicable tolerance regimens. This article summarizes many of the concepts currently unfolding in the tolerance literature. It also reviews the techniques for tolerance induction that have been and are currently being investigated in nonhuman primates. The validity of these models is summarized, and the older literature is reinterpreted in light of recent changes in our understanding of tolerance.

ABO Blood-Group System↗
PubMed1999

Lentiviral gene transfer to the nonhuman primate brain.

Lentiviral vectors infect quiescent cells and allow for the delivery of genes to discrete brain regions. The present study assessed whether stable lentiviral gene transduction can be achieved in the monkey nigrostriatal system. Three young adult Rhesus monkeys received injections of a lentiviral vector encoding for the marker gene beta galatosidase (beta Gal). On one side of the brain, each monkey received multiple lentivirus injections into the caudate and putamen. On the opposite side, each animal received a single injection aimed at the substantia nigra. The first two monkeys were sacrificed 1 month postinjection, while the third monkey was sacrificed 3 months postinjection. Robust incorporation of the beta Gal gene was seen in the striatum of all three monkeys. Stereological counts revealed that 930,218; 1,192,359; and 1,501,217 cells in the striatum were beta Gal positive in monkeys 1 (n = 2) and 3 (n = 1) months later, respectively. Only the third monkey had an injection placed directly into the substantia nigra and 187,308 beta Gal-positive cells were identified in this animal. The injections induced only minor perivascular cuffing and there was no apparent inflammatory response resulting from the lentivirus injections. Double label experiments revealed that between 80 and 87% of the beta Gal-positive cells were neurons. These data indicate that robust transduction of striatal and nigral cells can occur in the nonhuman primate brain for up to 3 months. Studies are now ongoing testing the ability of lentivirus encoding for dopaminergic trophic factors to augment the nigrostriatal system in nonhuman primate models of Parkinson's disease.

Animals↗
PubMed1996

Characteristics of systemic antibody responses of nonhuman primates following active immunization with Porphyromonas gingivalis, Prevotella intermedia and Bacteroides fragilis.

Periodontal disease is an infectious disease manifested by the progressive change of a healthy resident commensal microbiota to a pathogenic one characterized by a specific microbiota. Thus, the prospect for the use of selected bacteria or their antigens as a vaccine to interfere with the microbial changes and resulting progression of periodontal tissue destruction has been proposed. As a first step in examining the use of bacterial antigens as immunogens in periodontitis, this study characterized the humoral immune response in Macaca fascicularis after systemic immunization with intact Porphyromonas gingivalis, Prevotella intermedia and Bacteroides fragilis. Parental immunization of the nonhuman primate with the intact bacteria resulted in the production of specific and significantly elevated levels of antibodies to P. gingivalis and P. intermedia, with the predominant isotype being immunoglobulin G (IgG). In contrast, the principal response to the nonoral, intestinal bacterium, B. fragilis, was of the IgM isotype. Immunization increased IgG, IgM, and IgA antibody by 14-227 fold to P. gingivalis and 8-108 fold to P. intermedia. The level of serum IgA antibody increased (77-227 fold). The kinetics of the antibody response post-immunization and post-ligation differed with respect to each of the bacteria tested. IgG antibody to P. gingivalis increased through week 16 of the experiment and remained elevated above baseline through week 32. The IgG antibody level to P. intermedia peaked at 4 weeks following the third immunization and decreased post-ligation to near baseline levels by week 16. Characterization of the immune response after active immunization in the nonhuman primate has demonstrated a substantial and specific increase in antibody response which was sustained for several weeks. The insights obtained from these studies should help optimize the potential for immunologic interference with progressing periodontitis.

Analysis of Variance↗
PubMed2005

Effects of ovarian hormones on cognitive function in nonhuman primates.

Several studies have suggested that estrogen benefits verbal memory and lowers the risk of Alzheimer's disease in women, and improves cognitive function in animal models. However, the negative outcome of the Women's Health Initiative Memory Study has challenged the rationale for using estrogen as a protective agent against age-related cognitive decline. In view of the limitations of the Women's Health Initiative Memory Study, it is clear that our understanding of estrogen effects would greatly benefit from further interactions between clinical and basic science. Animal models of menopause can provide crucial information regarding the consequences of estrogen loss and replacement on several systems, including cognition. In this paper, I review the evidence that nonhuman primates, who share numerous cognitive and physiological characteristics with humans, can substantially contribute to our understanding of estrogen influences on the brain and cognition. Studies in young adult females suggest that some aspects of cognition fluctuate with the menstrual cycle, but that ovariectomy and estrogen replacement have only modest effects on cognitive function. In contrast, data in aged, naturally or surgically menopausal monkeys indicate that estrogen modulates a broad range of cognitive domains. Neurobiological data are consistent with the cognitive findings and demonstrate an array of morphological and physiological changes in brain areas important for cognition following ovariectomy and/or estrogen replacement. It is concluded that nonhuman primates, by providing a bridge between rodent and human data, constitute invaluable models to further our understanding of hormonal actions on the brain and cognition and to develop effective hormonal interventions against brain and cognitive aging.

Adult↗
PubMed2006

Evolution of an intronic microsatellite polymorphism in Toll-like receptor 2 among primates.

Nonhuman primates express varying responses to Mycobacterium tuberculosis: New World monkeys appear to be resistant to tuberculosis (TB) while Old World monkeys seem to be particularly susceptible. The aim of this study was to elucidate the presence of the regulatory guanine-thymine (GT) repeat polymorphisms in intron 2 of Toll-like receptor 2 (TLR2) associated with the development of TB in humans and to determine any variations in these microsatellite polymorphisms in primates. We sequenced the region encompassing the regulatory GT repeat microsatellites in intron 2 of TLR2 in 12 different nonhuman primates using polymerase chain reaction amplification, TA cloning, and automatic sequencing. The nonhuman primates included for this study were as follows: chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), Celebes ape (Macaca nigra), rhesus monkey (Macaca mulatta), pigtail macaque (Macaca nemestrina), patas monkey (Erythrocebus patas), spider monkey (Ateles geoffroyi), Woolly monkey (Lagothrix lagotricha), tamarin (Saguinus labiatus), and ring-tailed lemur (Lemur catta). Nucleotide sequences encompassing the regulatory GT repeat region are similar across species and are completely conserved in great apes. However, Old World monkeys lack GT repeats altogether, while New World monkeys and ring-tailed lemurs have much more complex structures around the position of the repeats. In conclusion, the genetic structures encompassing the regulatory GT repeats in intron 2 of human TLR2 are similar among nonhuman primates. The sequence is most conserved in New World monkeys and less in Old World monkeys.

Animals↗
PubMed1997

Behavioral and physiological effects of xanthines in nonhuman primates.

Caffeine and related xanthines can have significant behavioral effects on measures of locomotor activity, schedule-controlled behavior, drug self-administration, and learning and memory. Xanthines also produce numerous physiological effects including positive inotropic and chronotropic effects on the heart, decreased airway resistance in the lung, and respiratory stimulation. Due to the widespread use of xanthines as constituents of food and beverages and as therapeutic drugs, identification of mechanisms that mediate their pharmacological effects has considerable relevance for drug development and therapeutics. Two primary mechanisms involving the cyclic nucleotide system have been implicated as the bases for the effects of xanthines in the CNS. Many xanthines bind to specific adenosine recognition sites and block the actions of adenosine. Xanthines also inhibit cyclic nucleotide phosphodiesterases, the enzymes responsible for the hydrolytic inactivation of cyclic AMP and cyclic GMP. Recent research in nonhuman primates has characterized the behavioral, respiratory and cardiovascular effects of a number of xanthines and related drugs differing in affinity at different subtypes of adenosine receptors and in capacity to inhibit different molecular forms of PDE. The behavioral-stimulant effects of xanthines appear to be mediated principally by their adenosine-antagonist actions and may be limited by PDE inhibition. The respiratory-stimulant and cardiac effects of xanthines, on the other hand, appear to be linked more closely to their PDE-inhibiting actions than to adenosine antagonism. Converging lines of evidence suggest that adenosine A2 and cAMP-specific (possibly type IV) PDE mechanisms play especially prominent roles in mediating the behavioral and physiological effects of xanthines in nonhuman primates.

Animals↗
PubMed2003

Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates.

OBJECT: Leukocyte-endothelial cell interactions occurring in the first hours after subarachnoid hemorrhage (SAH) initiate changes in the endothelium and vessel wall that lead to an influx of leukocytes and the development of chronic vasospasm days later. Upregulation of intercellular adhesion molecule-1 (ICAM-1), also called CD54, appears to be a crucial step in this process. There is increasing experimental evidence that blocking the interaction between ICAM-1, which is expressed on endothelium, and integrins such as lymphocyte function-associated antigen-1 (CD11a/CD18) and macrophage antigen-1 (complement receptor 3, CD11b/CD18), which are expressed on the surface of leukocytes,prevents not only inflammation of vessel walls but also chronic vasospasm. The authors extend their previous work with monoclonal antibody (mAb) blockade of leukocyte migration to a nonhuman primate model of chronic, posthemorrhagic cerebral vasospasm. METHODS: Before surgery was performed, six young adult male cynomolgus monkeys underwent baseline selective biplane common carotid and vertebrobasilar artery cerebral angiography via a transfemoral route. On Day 0, a right frontosphenotemporal craniectomy was performed with arachnoid microdissection and placement of 2 to 3 ml of clotted autologous blood in the ipsilateral basal cisterns. The animals were given daily intravenous infusions of 2 mg/kg of either a humanized anti-CD11/CD18 or a placebo mAb beginning 30 to 60 minutes postoperatively. The monkeys were killed on Day 7 after a repeated selective cerebral angiogram was obtained. The area of contrast-containing vessels observed in each hemisphere on anteroposterior angiographic views was calculated for the angiograms obtained on Day 7 and expressed as a percentage of the area on baseline angiograms (percent control areal fraction). Review of flow cytometry and enzyme immunoassay data confirmed the presence of the anti-CD11/CD18 antibody in the serum and bound to leukocytes in the peripheral blood of treated animals. Comparisons of the groups revealed 53 +/- 4.8% control vascular areal fraction in the placebo group (two animals) and 95.8 +/- 9.4% in the anti-CD11/CD18-treated group (three animals), a statistically significant difference (p = 0.043, t-test). CONCLUSIONS: These results show that blockade of leukocyte migration into the subarachnoid space by an anti-CD11/CD18 mAb is effective in preventing experimental cerebral vasospasm in nonhuman primates, despite the unaltered presence of hemoglobin in the subarachnoid space. These experimental data support the hypothesis that inflammation plays a role in cerebral vasospasm after SAH.

Animals↗
PubMed2006

Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans.

This study focused on the in vivo effects of the kappa-opioid hallucinogen salvinorin A, derived from the plant Salvia divinorum. The effects of salvinorin A (0.0032-0.056 mg/kg i.v.) were studied in a neuroendocrine biomarker assay of the anterior pituitary hormone prolactin in gonadally intact, adult male and female rhesus monkeys (n = 4 each). Salvinorin A produced dose- and time-dependent neuroendocrine effects, similar to the synthetic high-efficacy kappa-agonist U69,593 ((+)-(5alpha,7 alpha,8beta)-N-methyl-N-[7-(1-pyrrolidiniyl)-1-oxaspiro[4.5]dec-8yl]-benzeneacetamide), but of shorter duration than the latter. Salvinorin A was approximately equipotent to U69,593 in this endpoint (salvinorin A ED50, 0.015 mg/kg; U69,593 ED(50), 0.0098 mg/kg). The effects of i.v. salvinorin A were not prevented by a small dose of the opioid antagonist nalmefene (0.01 mg/kg s.c.) but were prevented by a larger dose of nalmefene (0.1 mg/kg); the latter nalmefene dose is sufficient to produce kappa-antagonist effects in this species. In contrast, the 5HT2 receptor antagonist ketanserin (0.1 mg/kg i.m.) did not prevent the effects of salvinorin A. As expected, the neuroendocrine effects of salvinorin A (0.0032 mg/kg i.v.) were more robust in female than in male subjects. Related studies focused on full-length cloning of the coding region of the rhesus monkey kappa-opioid receptor (OPRK1) gene and revealed a high homology of the nonhuman primate OPRK1 gene compared with the human OPRK1 gene, including particular C-terminal residues thought to be involved in receptor desensitization and internalization. The present studies indicate that the hallucinogen salvinorin A acts as a high-efficacy kappa-agonist in nonhuman primates in a translationally viable neuroendocrine biomarker assay.

Amino Acid Sequence↗
PubMed2002

Efficacy of myoblast transplantation in nonhuman primates following simple intramuscular cell injections: toward defining strategies applicable to humans.

Nonhuman primates were used to define myoblast transplantation strategies applicable to humans. Nevertheless, previous experiments were based on the use of myotoxins concomitant with the myoblast injections. Since myotoxins must be avoided for clinical applications, we analyzed the efficacy of simple myoblast injections (i.e., myoblasts resuspended only in saline) into monkey muscles. We also evaluated different FK506 dosages (in combination or not with mycophenolate mofetil) for immunosuppression. Allogeneic myoblasts transduced with the beta-galactosidase (beta-Gal) gene were implanted in the muscles of 19 monkeys by injections placed 1 to 2 mm from each other. A biopsy was performed at the implanted sites 1 month later, and histologically studied for demonstration of beta-Gal+ myofibers, lymphocyte infiltration, and CD8+ cells. The presence of antibodies against the donor myoblasts and the blood levels of FK506 were analyzed. Our results show that: (1) If myoblast injections are sufficiently close to each other, high percentages of hybrid myofibers can be obtained following myoblast transplantation in primates (25 to 67% with an interinjection distance of 1 mm). (2) Efficient immunosuppression can be reached by increasing FK506 dosages, but also by combining this drug with mycophenolate mofetil, a combination that reduces toxic effects. The present results represent a step towards a better designing of myoblast transplantation strategies in humans.

Animals↗
PubMed2001

Characterization of the MHC class I-related MR1 locus in nonhuman primates.

We characterized the MHC-related 1 ( MR1) locus in two nonhuman primates species, Pongo pygmaeus and Pan troglodytes. MR1 cDNA sequences encoding several isoforms generated through alternative splicing were observed in both species. Amino acid alignment between the five species in which MR1 has been characterized to date - human, chimpanzee, orangutan, mouse, and rat - reveals a very high degree of conservation specially in the alpha1 and alpha2 domains of the molecule. The main differences concentrate in the transmembrane and cytoplasmic domains. In the three primates species there is a lysine residue inside the putative transmembrane domain which is not present in rodents. Furthermore, the MR1 cytoplasmic region is longer in rodents, with a conserved serine-containing motif that could be involved in endocytosis; remarkably, this motif is absent in the three primate species. We also describe the presence in the chimpanzee of a sequence homologous to the MR1P1 pseudogene previously found in humans.

Amino Acid Sequence↗
PubMed1991

Rice bran oil lowers serum total and low density lipoprotein cholesterol and apo B levels in nonhuman primates.

The hypolipidemic response of rice bran oil (RBO) was investigated in nonhuman primates fed semi-purified diets containing blends of oils which included RBO at 0-35% Kcals as dietary fat. The studies demonstrated the following: (a) the degree of reduction of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) was highly correlated with initial serum cholesterol levels of the monkey on the stabilization diet; (b) the content of rice bran oil in the diet was the predominant factor influencing serum TC, LDLC and apoB causing up to a 40% reduction in LDLC without affecting high density lipoprotein cholesterol (HDLC) when RBO was the sole dietary oil fed; (c) the cholesterol-lowering capabilities of RBO were not explained by its fatty acid composition. These studies suggest that RBO may be an additional vegetable oil which lowers serum cholesterol levels by unique mechanisms which will require further study.

Animals↗
PubMed1997

Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior. A nonhuman primate model investigating genetic and environmental influences on neurotransmission.

We have used nonhuman primates to examine developmental and behavioral correlates of CNS serotonergic activity, as measured by concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). These studies show that interindividual differences in CNS serotonin turnover rate exhibit traitlike qualities and are stable across time and settings, with interindividual differences in CSF 5-HIAA concentrations showing positive correlations across repeated sampling. Primates with low CNS serotonergic activity exhibit behaviors indicative of impaired impulse control, unrestrained aggression, social isolation, and low social dominance. Maternal and paternal genetic influences play major roles in producing low CNS serotonin functioning, beginning early in life. These genetic influences on serotonin functioning are further influenced by early rearing experiences, particularly parental deprivation.

Animals↗
PubMed1991

Human follicle-stimulating hormone exerts a stimulatory effect on spermatogenesis, testicular size, and serum inhibin levels in the gonadotropin-releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis).

The role of FSH in spermatogenesis was investigated in nonhuman primates depleted of testosterone by GnRH antagonist treatment. The GnRH antagonist antide (Nal-Lys; [N-acetyl-D-2-naphthyl-Ala1,D-4-chloro-Phe2,D-pyridyl-Ala3, nicotinyl-Lys5,D-nicotinyl-Lys6,isopropyl-Lys8,D-Ala10 ]-GnRH) was used at a daily dose of 450 micrograms/kg to suppress endogeneous gonadotropin and androgen production. Four groups of five cynomolgus monkeys (Macaca fascicularis) were subjected to the following treatment throughout a 16-week period: vehicle (group 1), GnRH antagonist (group 2), and GnRH antagonist plus human FSH (Fertinorm; 2 x 15 IU/day.animal; hFSH) during weeks 0-8 (group 3) or 8-16 (group 4). Testicular biopsies were performed before and after 4, 8, and 16 weeks of treatment. The tissue was analyzed by light microscopy and flow cytometry. Serum testosterone levels were suppressed into the range of orchidectomized animals in all GnRH antagonist-treated groups. In the absence of hFSH, serum inhibin levels were also markedly lowered. Concomitant administration of hFSH attenuated the GnRH antagonist-induced reduction of testicular size, while delayed treatment with hFSH failed to restimulate testicular volume. Numbers of A-dark spermatogonia, the reserve stem cells, were not altered by any of the treatments. hFSH either fully maintained or increased the counts for A-pale spermatogonia (renewing stem cells). The development of pachytene spermatocytes and round and elongated spermatids was markedly reduced or inhibited by the GnRH antagonist within 6-18 weeks. In contrasts, hFSH maintained these cell types at about 50% of baseline for 8 weeks. After 8 weeks of GnRH antagonist administration, hFSH stimulated A-pale spermatogonia and spermatocytes 2- to 3-fold with only minor effects on spermatid numbers. By means of flow cytometry, testicular cells were quantified according to DNA content. Within 8-16 weeks of GnRH antagonist treatment the percentage of 4C (mainly primary spermatocytes), 1C (round spermatids), and 1CC cells (elongated spermatids) had fallen from 65-75% to 5-25%. hFSH completely maintained the relative number of these cells, but failed to significantly restimulate the formation of 1CC cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

The roles of nonhuman primates in the preclinical evaluation of candidate AIDS vaccines.

Preclinical studies in nonhuman primates (NHP) play key roles in AIDS vaccine development efforts. In addition to their traditional utilization to gauge vaccine safety and immunogenicity, NHP models are currently employed to an unprecedented extent and in unprecedented ways in contemporary basic and applied vaccine development efforts. Current studies employ NHP models to probe fundamental mechanisms of primate immune system regulation, to investigate pathogenic mechanisms of AIDS, and to optimize immunization strategies involving novel vaccine vectors. The use of experimental challenges of immunized NHPs with either simian immunodeficiency virus or chimeric simian/human immunodeficiency virus to generate preclinical vaccine efficacy data has emerged as an important criterion for facilitating entry of a given vaccine candidate into early phase clinical evaluation in humans. However, for studies of the biology of AIDS virus transmission, AIDS virus disease pathogenesis and AIDS virus vaccine efficacy that are predicated on experimental viral challenge to be most valuable, additional efforts need to be devoted to generating challenge models that more closely recapitulate HIV-1 infection in humans. Towards this end, improved communication between clinical and preclinical investigators, to promote a bidirectional flow of information focusing on individual research needs and shared goals should enable the NHP models to most effectively expedite progress toward the development of a safe and effective AIDS vaccine.

AIDS Vaccines↗
PubMed1975

Pneumoperitoneography: a special radiological technic used in nonhuman primate medicine.

Visualization of abdominal structures was difficult in survey radiographs of nonhuman primates due to the paucity of intra-abdominal fat and the presence of gastrointestinal contents. Simple pneuoperitoneography combined with contrast gastrointestinal studies provided valuable information, ie, size, shape, and position, of abdominal structures. After ip injection of carbon dioxide, a series of positional radiographs were exposed to delineate the various abdominal organs. The positioning device used in the examination was illustrated and described and the clinical indications and diagnostic value of pneumoperitoneography discussed.

Animals↗
PubMed1982

Carcinoembryonic antigen in nonhuman primates.

Blood levels of carcinoembryonic antigen (CEA) have been measured in several nonhuman primate species. Only gorillas and chimpanzees were found to have significant elevations of CEA-like activity in their blood compared to the normal values of less than 2.5 ng/ml in humans. The average CEA level in 134 chimpanzees was 25.2 ng/ml (range, 4.2--95 ng/ml) and in 13 gorillas it was 32 ng/ml (range, 12.4--61.9 ng/ml). These levels were not related to sex. Blood levels repeatedly taken over a 1 1/2-year period remained relatively stable in both species. Analysis of parallelism of immunologic reactivity showed chimpanzee CEA to be similar to but not identical with human CEA. The molecular size of chimpanzee CEA was also similar to that of human CEA.

Animals↗