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PubMed1980

The incidence of coccidioidomycosis among nonhuman primates housed outdoors at the California Primate Research Center.

Serum from 191 nonhuman primates housed outdoors from October 1977 to October 1978 at the California Primate Research Center was assayed for the presence of antibody specific for coccidioidin. One Macaca mulatta had coccidioidal antibody which was found to be associated with disseminated coccidioidomycosis. One Macaca radiata had complement-fixing antibody specific for coccidioidin and a pulmonary lesion. Additionally, two other animals had coccidioidal antibody but lacked clinical evidence of disease. The source of infection is suspected to be a severe dust storm originating in southern California.

Animals↗
PubMed2003

Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates.

To seek evidence that the nonhuman primate arterial wall, as it ages in the absence of atherosclerosis, exhibits alterations in pathways that are involved in the pathogenesis of experimental atherosclerosis, we assessed aortic matrix metalloproteinase-2 (MMP-2) and its regulators, ie, membrane type-1 of matrix metalloproteinase (MT1-MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and the expression of angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and chymase in young (6.4+/-0.7 years) and old (20.0+/-1.9 years) male monkeys. With advancing age, (1) the intimal thickness increased 3-fold and contained numerous vascular smooth muscle cells and matrix, but no inflammatory cells; (2) the intimal MMP-2 antibody-staining fraction increased by 80% (P<0.01); (3) in situ zymography showed that MMP-2 activity, mainly confined to the intima, increased 3-fold (P<0.01); (4) the MT1-MMP antibody-staining fraction increased by 150% (P<0.001), but the TIMP-2 antibody-staining fraction did not significantly change; (5) steady levels of the mRNA-staining fraction (via in situ hybridization) for MMP-2 increased 7-fold, for MT1-MMP increased 9-fold, and for TIMP-2 increased 2-fold (all P<0.001); and (6) intimal Ang II and ACE immunofluorescence were increased 5-fold and 5.6-fold, respectively, and colocalized with MMP-2. Thus, age-associated arterial remodeling and the development and progression of experimental atherosclerosis in young animals share common mechanisms, ie, MMP-2 activation and increased Ang II signaling. This might explain, in part, the dramatically exaggerated prevalence and severity of vascular diseases with aging.

Aging↗
PubMed1976

Nonhuman primate models of toxemia of pregnancy.

Hypertension in the nonpregnant and pregnant nonhuman primate is not found frequently by research investigators. Its incidence is probably infrequent. No well-defined clinical syndrome analogous to toxemia of human pregnancy has been described. The experimental induction of the disease in pregnant nonhuman primates has been difficult. Although there would be an important role for such an animal model, its discovery does not appear imminent.

Animals↗
PubMed1997

Characteristics of systemic antibody responses of nonhuman primates to cell envelope and cell wall antigens from periodontal pathogens.

The immune response of the primate, Macaca fascicularis, to cell envelope (CEA) or cell wall (CWA) antigens of several periodontal pathogens was examined to develop a strategy to interfere with ligature-induced periodontitis. Animals were parenterally immunized with CEA of either Porphyromonas gingivalis, Prevotella intermedia or a combination of CEA/CWA of Campylobacter rectus, Fusobacterium nucleatum and Actinomyces viscosus. Serum samples were taken every 2-4 weeks over a 4-month period, which included a 13-week interval with molar teeth ligated. All of the nonhuman primates in the study exhibited baseline levels of IgG, IgM and IgA antibody to formalinized whole cells of the bacteria. These levels increased significantly following immunization and were elevated above baseline throughout the remainder of the experiment. The largest change in antibody responses was seen in IgA antibody levels of P. gingivalis and C. rectus (42-fold above baseline), IgM antibody to P. intermedia, (41-fold increase) and IgG antibody to F. nucleatum and A. viscosus (32 and 63-fold increases). Moreover, the nonhuman primates exhibited differences in isotype response levels to whole microorganisms compared with the cell envelope antigens. These findings demonstrate the capacity of these nonhuman primates to produce an active immune response to microorganisms chronically colonizing the subgingival microbiota. Additionally, it appears that the bacteria may exhibit some unique differences in their immunogenicity as detected by the nonhuman primate and may contribute to the ability of the immune responses to effectively interact with these pathogens.

Actinomyces viscosus↗
PubMed1982

The pathoparasitology of the alimentary tract and pancreas of nonhuman primates: a review.

A review of the literature concerning the gross and histologic lesions associated with protozoal and metazoal parasitism in the alimentary tract and pancreas of nonhuman primates is presented. In addition, the natural history, morphology, life cycle, methods for diagnosis, and potential for zoonotic disease are reviewed briefly for each parasite discussed. The parasite species reviewed in detail are those most common or most likely to produce lesions in the alimentary tract and pancreas of the nonhuman primate host. All parasites, both pathogenic and nonpathogenic, in each major group (protozoa: flagellates, sarcodines, sporozoans, neosporans, and ciliates; and metazoa: trematodes, cestodes, nematodes, acanthocephalans, and pentastomids) that have been reported in the nonhuman primate alimentary tract and pancreas are presented in tables.

Amebiasis↗
PubMed1982

The pathoparasitology of the alimentary tract and pancreas of nonhuman primates: a review.

A review of the literature concerning the gross and histologic lesions associated with protozoal and metazoal parasitism in the alimentary tract and pancreas of nonhuman primates is presented. In addition, the natural history, morphology, life cycle, methods for diagnosis, and potential for zoonotic disease are reviewed briefly for each parasite discussed. The parasite species reviewed in detail are those most common or most likely to produce lesions in the alimentary tract and pancreas of the nonhuman primate host. All parasites, both pathogenic and nonpathogenic, in each major group (protozoa: flagellates, sarcodines, sporozoans, neosporans, and ciliates; and metazoa: trematodes, cestodes, nematodes, acanthocephalans, and pentastomids) that have been reported in the nonhuman primate alimentary tract and pancreas are presented in tables.

Acanthocephala↗
PubMed1988

Microscopic investigations of areolar brow structure in nonhuman primates and of vermiculate brow structure in hominids.

The microscopic structure of bone of the brow region was studied in adult human crania showing the vermiculate surface pattern, and in immature nonhuman primates with an areolar surface. Serial sections from different parts of each brow sampled regional comparability. The human brow regions are basically similar, and differ from those of the other primates. The elevations and depressions of vermiculate surfaces are lamellar bone, usually covered by layers featuring Sharpey's fibers. In contrast, the immature nonhuman primates do not have continuous brow surface layers. Passageways to the interior are closely spaced and separated by irregular projections. These findings indicate that fossil and modern human vermiculate surfaces are not structurally equivalent to areolar brow surfaces observed in some immature nonhuman primates. Reports describing fossil hominid brow regions as composed of 'fine cancellous bone' are probably erroneous and give misleading interpretations of their development and function.

Adult↗
PubMed1996

Cysteine conjugate beta-lyase-dependent biotransformation of the cysteine S-conjugates of the sevoflurane degradation product compound A in human, nonhuman primate, and rat kidney cytosol and mitochondria.

BACKGROUND: 2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A) is a fluorinated alkene formed by the degradation of sevoflurane in the anesthesia circuit. Compound A is toxic to the kidneys in rats and undergoes glutathione-dependent metabolism in vivo. Several nephrotoxic halogenated alkenes also undergo cysteine conjugate beta-lyase-dependent biotransformation. These experiments were designed to test the hypothesis that cysteine S-conjugates of compound A undergo beta-lyase-dependent biotransformation. METHODS: S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine 4, S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-L-cysteine 5, and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine 11 were incubated with rat, human, and nonhuman primate (cynomolgus, rhesus, and marmoset) kidney cytosol and mitochondria. beta-Lyase activity was determined by measuring pyruvate formation. RESULTS: Compound A-derived conjugates 4 and 5 as well as conjugate 11, a positive control, were substrates for cytosolic and mitochondrial beta-lyase from human, nonhuman primate, and rat kidney. For all substrates, beta-lyase activity was highest in the rat and lowest in the human and was higher in cytosol than in mitochondria. Conjugate 11 was a much better substrate than conjugates 4 or 5. The biotransformation of conjugates 4, 5, and 11 was inhibited by the beta-lyase inhibitor (aminooxy)acetic acid and was stimulated by the amino group acceptor 2-keto-4-methylthiolbutyric acid, indicating a role for beta-lyase. CONCLUSIONS: These data confirm the presence of beta-lyase activity in human and rat kidney and show that activity is also present in kidney tissue from nonhuman primates. The data also show that compound A-derived conjugates 4 and 5 undergo beta-lyase-catalyzed biotransformation. beta-Lyase activity in rat and nonhuman primate kidney tissue was 8 to 30 times and one- to three times, respectively, higher than in human kidney tissue.

Anesthetics, Inhalation↗
PubMed1995

Intrathecal administration of topotecan in nonhuman primates.

The cerebrospinal fluid (CSF) pharmacokinetics of topotecan were studied in a nonhuman primate model following intraventricular administration of 0.1 mg. Lactone and total drug concentrations were measured using a reverse-phase HPLC method with fluorescence detection. The mean peak concentrations of lactone and total drug in ventricular CSF were 83 +/- 18 microM and 88 +/- 25 microM, respectively. CSF drug elimination of the lactone was bi-exponential with a terminal half-life of 1.3h. The mean clearance from ventricular CSF was 0.075 ml/min for the lactone and 0.043 ml/min for total drug. The ventricular CSF drug exposure (AUC) to lactone was 450-fold greater following intraventricular administration of 0.1 mg topotecan than after systemic intravenous administration of a 40-fold higher dose (10 mg/m2). Peak lumbar concentrations (n = 1), which occurred 2 h after intraventricular drug administration, were 0.98 microM and 2.95 microM for the lactone and total drug, respectively. A transient CSF pleocytosis was observed in one animal following intralumbar topotecan administration and in one animal following intralumbar topotecan administration. No other acute or chronic neurologic or systemic toxicities were observed following a single intraventricular dose or weekly (x4) intralumbar topotecan. Compared with systemic topotecan, intrathecal administration provided a significant pharmacokinetic advantage in terms of CSF drug exposure and did not produce any significant neurotoxicity in a nonhuman primate model. Intrathecal topotecan should be evaluated clinically as a potential alternative therapy for refractory meningeal tumors.

Animals↗
PubMed2004

Induction of diabetes in nonhuman primates by means of temporary arterial embolization and selective arterial injection of streptozotocin.

PURPOSE: To develop and assess a technique for induction of C peptide-negative diabetes in adult nonhuman primates in preparation for preclinical investigation of type 1 diabetes treatments. MATERIALS AND METHODS: First, temporary embolization of the hepatic and gastric arteries was performed in 14 adult nonhuman primates (six cynomolgus, five rhesus, and three pigtail macaques). After embolization was confirmed with angiography, streptozotocin was injected at a dose of 50-70 mg/kg into the celiac artery and branches supplying the pancreas. The macaques then were given intravenous injections of arginine and glucose, and blood levels of insulin and C peptide were measured with an enzyme-linked immunosorbent assay to determine whether diabetes had been induced. RESULTS: All but one of the macaques developed persistent long-term C peptide-negative diabetes after the streptozotocin injection. One macaque did not develop diabetes after the initial injection and was given a second dose of streoptozotocin, which did induce diabetes. None of the macaques showed any symptoms of hepatic or renal injury, and only one died (of gastric dilatation 5 days after the procedure). CONCLUSION: Streptozotocin injection after temporary embolization of the hepatic and gastric arteries is a safe and reproducible method for inducing C peptide-negative diabetes in adult nonhuman primates in preparation for preclinical investigation of type 1 diabetes treatments.

Animals↗
PubMedDate not supplied

Evaluation of transit-time and electromagnetic flow measurement in a chronically instrumented nonhuman primate model.

The Physiology Research Branch at Brooks AFB conducts both human and nonhuman primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to identify the particular mechanisms that invoke these responses. Primary investigative efforts in our nonhuman primate model require the determination of total peripheral resistance, systemic arterial compliance, and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. This study evaluated accuracy, linearity, biocompatability, and anatomical features of commercially available electromagnetic (EMF) and transit-time flow measurement techniques. Five rhesus monkeys were instrumented with either EMF (3 subjects) or transit-time (2 subjects) flow sensors encircling the proximal ascending aorta. Cardiac outputs computed from these transducers taken over ranges of 0.5 to 2.0 L/min were compared to values obtained using thermodilution. In vivo experiments demonstrated that the EMF probe produced an average error of 15% (r = .896) and 8.6% average linearity per reading, and the transit-time flow probe produced an average error of 6% (r = .955) and 5.3% average linearity per reading. Postoperative performance and biocompatability of the probes were maintained throughout the study. The transit-time sensors provided the advantages of greater accuracy, smaller size, and lighter weight than the EMF probes. In conclusion, the characteristic features and performance of the transit-time sensors were superior to those of the EMF sensors in this study.

Animals↗
PubMed1990

Metabolic processing and carcinogenicity of heterocyclic amines in nonhuman primates.

The potential for human exposure to heterocyclic amine (HAA) mutagens derived from cooking food prompted an evaluation of the disposition and carcinogenicity of three of the HAAs in nonhuman primates, especially cynomolgus monkeys. The three HAAs currently under study are 2-amino-3-methylimidazo [4, 5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo [4,5,b]pyridine (PhIP). These three HAAs were selected on the basis of several factors including structure, mutagenic activity in vitro, concentration in cooked meat, activity in rodent carcinogenicity tests and availability. Studies on the disposition of IQ demonstrated that it was extensively metabolized in monkeys and excreted in urine and feces as metabolites. These metabolites represent predominantly detoxification products of IQ. The extent of in vivo activation of IQ and PhIP was assessed by measuring DNA adducts in various tissues and white blood cells of monkeys following administration of the compounds. Both compounds form high levels of DNA adducts in a number of organs, particularly the liver, kidney, and heart. The carcinogenicity of IQ, 8-MeIQx and PhIP in nonhuman primates has been under study for 5 years, 24 months, and 7 months, respectively. Thus far, IQ has induced hepatocellular carcinoma in 3 of 20 monkeys at doses of 10 mg/kg daily, 5 days/week and in 10 of 20 monkeys at 20 mg/kg on the same schedule. Thus, IQ is a potent liver carcinogen in nonhuman primates and a potential carcinogen for humans.

Animals↗
PubMed2003

In utero hematopoietic stem cell transplantation in nonhuman primates: the role of T cells.

In utero transplantation of hematopoietic stem cells is a promising treatment for immune and hematologic diseases of fetuses and newborns. Unfortunately, there are limited data from nonhuman primates and humans describing optimal transplantation conditions. The purpose of this investigation was to determine the effect of T-cell number on engraftment and the level of chimerism after in utero transplantation in nonhuman primates. CD34(+) allogeneic adult bone marrow cells, obtained from the sire after G-CSF and stem cell factor administration, were transplanted into female fetal recipients. The average CD34(+) cell dose was 3.0 x 10(9)/kg (range, 9.9 x 10(8) to 4.4 x 10(9)) and the T-cell dose ranged from 2.6 x 10(5) to 1.1 x 10(8)/kg. Chimerism was determined in peripheral blood subsets (CD2, CD13, and CD20) and in progenitor cell populations by using polymerase chain reaction. Chimerism was noted in seven of eight live-born animals. The level of chimerism in the progenitor population was related to the fetal T-cell dose (r = 0.64, p < 0.02). At the lowest T-cell dose (2.6 x 10(5)/kg), no chimerism was detected. As the T-cell dose increased to 10(6-7)/kg, the level of chimerism increased. Adjusting the T-cell dose to 1.1 x 10(8)/kg resulted in fatal graft-versus-host disease (GVHD). The results of this study emphasize the importance of T cells in facilitating donor cell engraftment and in producing GVHD in fetal nonhuman primates. Some animals achieved levels of chimerism in the marrow hematopoietic progenitor cell population that would likely have clinical relevance. However, the levels of chimerism in peripheral blood were too low for therapeutic benefit. Further studies are needed to test methods that are likely to enhance donor cell engraftment and peripheral blood levels of donor cells.

Animals↗
PubMed2003

Advances in nonhuman primate alcohol abuse and alcoholism research.

Advances in our understanding of the biological basis of alcohol abuse and alcoholism and the development of prevention and therapeutic intervention require appropriate animal models. Nonhuman primates are important to the study of complex biomedical disease processes. Genetic, anatomical, physiological, and behavioral similarities to humans offer unique opportunities for translational research along with the advantage of a degree of experimental control that is not possible in human studies. The purpose of this review is to outline the approaches taken with nonhuman primates as subjects in alcohol research and to highlight our current understanding of data on organismal variables that can be uniquely studied in these complex organisms. We review literature on alcohol self-administration to provide an integrative framework for discussion of progress in 2 important areas of research. Designs that incorporate self-administration provide a context for studying excessive alcohol consumption, including the organismal and environmental factors that influence risk for heavy drinking. We then review the use of monkeys to identify aspects of adverse biomedical consequences that follow excessive alcohol consumption. One of the primary conclusions to be drawn from this review is that nonhuman primates are a central part of the translational bridge in alcohol research, providing powerful and unique opportunities for experimental work that can address the biomedical complexities of alcohol abuse and alcoholism.

Alcoholism↗
PubMed2003

West Nile virus infection in nonhuman primate breeding colony, concurrent with human epidemic, southern Louisiana.

During the summer of 2002, an epidemic of West Nile meningoencephalitis occurred in southern Louisiana. Following the outbreak, blood samples were collected from 1,692 captive rhesus monkeys (Macaca mulatta), pigtail macaques (M. nemestrina), and baboons (Papio spp.) that were permanently housed outdoors at a nonhuman primate breeding facility in St. Tammany Parish, Louisiana. The serum samples were examined for antibodies to West Nile virus (WNV). Overall, 36% of the captive nonhuman primates had WNV antibodies; comparison of these samples with banked serum samples from previous blood collections indicated that the animals were infected subclinically from February to August 2002. WNV activity was demonstrated in surveillance at the nonhuman primate-breeding colony and in the neighboring community during this same period. The high infection rate in this captive nonhuman primate population illustrates the intensity of WNV transmission that can occur silently in nature among other susceptible vertebrates during epidemic periods.

Animal Husbandry↗
PubMed1996

Strategies for using nonhuman primates in genetic research on multifactorial diseases.

Multifactorial diseases such as coronary heart disease, cancer, and osteoporosis are of increasing public health concern. Such diseases have a complex etiopathogenesis involving genetic and environmental factors and interactions between these factors. Nonhuman primates are uniquely suited as animal models for complex human diseases because of their close evolutionary relationship to humans. We present the rationale for using nonhuman primates as animal models in research designed to assess the genetic determinants of multifactorial diseases. Strategies and current approaches for the use of nonhuman primate models in genetic research on complex diseases are reviewed.

Animals↗
PubMed2005

The effect of pinealectomy on scoliosis development in young nonhuman primates.

STUDY DESIGN: Prospective study on pinealectomy in primates. OBJECTIVE: To evaluate whether pinealectomy in a bipedal nonhuman primate model will result in the development of scoliosis. SUMMARY OF BACKGROUND DATA: Pinealectomy in newborn chickens consistently resulted in scoliosis development. Published data suggest that the surgical removal of the pineal, loss of melatonin secretion, and a bipedal posture are important elements in the development of scoliosis in lower animal models. METHOD: There were 18 rhesus monkeys between 8 and 11 months old that underwent pineal excision. All monkeys were kept in a regulated 12-hour light-dark cycle. Monthly radiographs assessed scoliosis development. Completeness of pineal excision was assessed by measurement of a major metabolite of melatonin in the urine, 6-sulfatoxymelatonin, using an enzyme-linked immunosorbent assay assessed. RESULTS: Mean follow-up was 28 months (range 10-41). Seven monkeys died prematurely, and 11 survived to date; the data from those that died could still be used, although follow-up was shortened. At the latest follow-up or death, scoliosis did not develop in any of the monkeys. Urinary 6-sulfatoxymelatonin measurements revealed 3 patterns. Group 1 consisted of 10 monkeys, which showed definite evidence of complete pineal excision. Group 2 consisted of an uncertain group of 2 monkeys in which the nighttime melatonin level is slightly high. Group 3 consisted of 6 monkeys that had incomplete pineal excision or ectopic melatonin production. CONCLUSIONS: To our knowledge, this is the first report of pinealectomy in nonhuman primates. Of the 18 monkeys, 10 had a loss of melatonin secretion, for a mean of 29 months after surgery. Because none of the monkeys had scoliosis develop, this study strongly suggests that the possible etiologic factors producing idiopathic scoliosis in lower animals are different from primates, and findings in lower animals cannot necessarily be extrapolated to human beings.

Animals↗
PubMed1993

Research-oriented genetic management of nonhuman primate colonies.

Genetic management is an important component of the general management of nonhuman primate colonies. However, standard genetic management techniques were developed primarily to address the goals of population conservation, particularly in zoo situations. The special needs of colonies that produce animals for biomedical research have not previously been fully addressed and the great potential of genetic management in the research environment remains to be realized. A research-oriented genetic management approach balances long-term breeding goals and current and future experimental needs, yielding a comprehensive overall colony management program. Pedigree information, genetic markers (e.g., serum proteins, red blood cell enzymes, restriction fragment length polymorphisms, and single-locus microsatellites), and quantitative traits (e.g., routinely gathered clinical chemical values, weights, and blood pressures) can be used alone or in combination to estimate genetic variability in the colony and to characterize animals for experimentally relevant traits. The statistical power of experiments using nonhuman primates can be improved when animals are selected on the basis of their genetic values or genotypes for experimentally relevant traits because the quantified genetic variation among subjects can then be minimized. The incorporation of experimental needs into the overall genetic management plans for captive breeding colonies helps ensure the long-term viability of colonies for meeting the demands of both breeding and research.

Animals↗