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PubMed1975

Induction of physical dependence upon alcohol in nonhuman primates.

Following the description of the alcohol withdrawal syndrome in man, efforts have been made to use the nonhuman primate as an animal model for studying the development of physical dependence upon alcohol. There is now general agreement regarding the qualitative description of the withdrawal reaction in the rhesus monkey, and various approaches, including intravenous infusion, intragastric intubation, and nonvolitional oral intake of ethanol have been successful in producing withdrawal in these animals. There still remain the major problems of developing objective procedures for quantitatively assessing the severity of the withdrawal syndrome and establishing the dose dependent and time dependent relationships between ethanol intake and the development of physical dependence. Until these basic issues are empirically resolved, little progress can be expected in our understanding of the critical determinants of the addictive process.

Administration, Oral↗
PubMed1997

Structural determinants of lumen narrowing after angioplasty in atherosclerotic nonhuman primates.

PURPOSE: The relationship between lumen narrowing, intimal hyperplasia, and wall remodeling after angioplasty was explored in a nonhuman primate model of atherosclerosis. METHODS: Cynomolgus monkeys (n = 37) used in long-term atherosclerosis studies underwent left iliac artery balloon injury. The uninjured right iliac artery served as a reference segment for intraanimal comparisons. One month later iliac arteries were fixed by perfusion (100 mm Hg) and removed for cross-sectional analysis to determine mean values for lumen area (LA), intimal area (IA), internal elastic lamina area (IELA), plaque burden (IA/IELA), and depth of wall injury. Values for each balloon-injured iliac artery were normalized to the contralateral uninjured iliac artery (percent of control), and linear regression analysis was performed comparing LA with IA, with IELA, and with depth of injury. Comparisons were also made between those arteries that remained dilated 1 month after balloon injury (LA > or = 140%; n = 13) and those that renarrowed (LA < or = 100%; n = 14). RESULTS: For all 37 animals, LA 1 month after balloon injury correlated well with IELA (r = 0.72; p < 0.001) but not with IA (r = 0.10; p = 0.54), suggesting that changes in artery size rather than neointimal mass determined lumen caliber. When comparing arteries that remained dilated (n = 13) with those that renarrowed (n = 14), there were no differences in depth of wall injury (injury depth: 0, no injury; 1, intima; 2, IEL; 3, media; 4, EEL; 2.1 +/- 0.3 vs 1.6 +/- 0.3; p = 0.12), neointimal accumulation (IA, 507% +/- 118% vs. 421% +/- 81% of control; p = 0.55), or plaque burden (IA/IELA, 0.39 +/- 0.04 vs 0.37 +/- 0.06; p = 0.71), respectively. However, wall size defined as IELA was significantly smaller in arteries that renarrowed than in those that remained dilated (IELA, 115% +/- 14% vs 230% +/- 19% of control; p < 0.001). CONCLUSIONS: Restenosis after angioplasty has been attributed to intimal hyperplasia, equating loss of lumen caliber with neointimal mass. The data presented herein suggest that lumen narrowing after arterial wall injury may have little to do with intimal mass per se, but rather that a change in wall caliber or wall narrowing is the cause of restenosis.

Angioplasty, Balloon↗
PubMed2004

Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its prophylaxis in nonhuman primates.

BACKGROUND: The authors previously reported thromboembolic complications associated with anti-CD154 monoclonal antibody (mAb) treatment in nonhuman primates. The underlying mechanisms of this complication and its management have not been established. METHODS: Eighty cynomolgus monkey renal allograft recipients treated with anti-CD154 mAb were studied for the incidence of thrombosis and its prophylaxis. RESULTS: Without anticoagulation prophylaxis, thromboembolic complications were seen in 5 of 11 recipients. With addition of perioperative heparin, the incidence was decreased to 2 of 10. No further improvement was observed by adding intraoperative prostaglandin (PG) E1. However, addition of ketorolac tromethamine to PGE1 and heparin decreased the incidence of thrombosis (one of eight). Most recently, the authors have found that ketorolac administration alone resulted in no thrombosis in 25 consecutive recipients. CONCLUSIONS: Ketorolac is remarkably effective in preventing thromboembolism associated with anti-CD154 mAb treatment, suggesting the mechanism underlying this complication may be related to platelet activation leading to enhanced aggregation.

Alprostadil↗
PubMed2001

Prevalence of hepatitis B virus infections in nonhuman primates.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in nonhuman primates. Serum samples from Europe, Thailand and Vietnam were analyzed. Sera obtained from 262 apes and 454 monkeys were tested for HBV infection serologically and for HBV DNA using nested PCR (nPCR). A total number of 198 ape sera and all but one (Cercopithecus aethiops) of the 4543 monkey sera had no serological signs of HBV infection. Among the 64 of 262 (24.4%) seropositive ape sera, we found, as in humans, different stages of HBV infection: very early HBV infection, active infection with high level of infectivity, virus carriers with low infectivity, and passed HBV infection. In the cases with passed infection, 47.8% harbored HBV DNA in the presence of protective antibodies to the HBV surface antigen (HBsAb). This indicates HBV persistence in apes despite immune control. In contrast to apes, in monkeys HBV infection is a very rare event.

Animals↗
PubMed2005

Chronic drug exposures during development in nonhuman primates: models of brain dysfunction in humans.

This review of our work presents three specific examples of how nonhuman primates (rhesus monkeys, Macaca mulatta) have been used to study the effects of chronic drug exposures on brain function during different stages of development. In all cases, exposure levels similar to those experienced by humans were employed and the focus was on long-term--not acute--effects. In the case of the marijuana studies, exposures occurred during the adolescent period; for the cocaine studies, exposures occurred in binge-like fashion entirely before birth (in utero); and for the remacemide studies, exposures occurred daily in juveniles, prior to adolescence. An automated battery of behavioral tasks, the National Center for Toxicological Research Operant Test Battery (NCTR OTB), designed to assess aspects of motivation, visual discrimination, time perception, short-term memory, and learning, was used to monitor treatment effects. Chronic marijuana smoke exposure resulted in an 'amotivational' syndrome--even in weekend-only smokers--that resolved within three months of exposure cessation. In utero cocaine exposure was shown to cause behavioral rigidity or lack of plasticity as evidenced by the difficulty of subjects to adjust to rules changes for some OTB tasks. These effects were seen in adult subjects suggesting that the effects of gestational cocaine exposure are long-term or permanent. In addition, animals exposed to cocaine in utero were less sensitive to the behaviorally-disrupting effects of cocaine as adults. Remacemide caused profound and long-lasting, perhaps permanent, changes in learning task performance and because performance of this same task by children is significantly correlated with traditional measures of intelligence (IQ), these data suggest that such treatment may provide a valuable model of chemically-induced mental retardation.

Animals↗
PubMed2006

Perceptual considerations in the use of colored photographic and video stimuli to study nonhuman primate behavior.

The use of photographs, slides, computerized images, and video to study behavior is increasingly being employed in nonhuman primates. However, since these mediums have been designed to simulate natural coloration for normal trichromatic human vision, they can fail to reproduce color in meaningful and accurate ways for viewers with different visual systems. Given the range of color perception that exists both across and within different species, it is necessary to consider this variation in order to discern the suitability of these mediums for experimental use. Because of the high degree of visual similarity among humans, Old World monkeys, and apes, the use of photographic and video stimuli should be acceptable in terms of replicating naturalistic coloration and making noticeable color manipulations. However, among New World primates and prosimians, there exists a considerable degree of variation in color perceptual abilities depending on the species, sex, and allelic combination of the animals involved. Therefore, the use of these mediums to study behavior is problematic for these species, and should be done with caution.

Animals↗
PubMed1976

A model for therapeutic interventins on established coronary atherosclerosis in a nonhuman primate.

The observations so far conducted in cynomologus monkeys on semipurified diets containing butter and cholesterol suggest that this nonhuman primate is an excellent model for studying the therapy of established coronary atherosclerosis. (1) This species is available at a reasonable cost and can be kept in captivity in good health for prolonged periods of time. (2) It readily accepts semipurified diets with a percentage composition similar to that of human diets in the U.S. (3) Ingestion of these diets leads quite rapidly (around 6 months) to moderate coronary atherosclerosis. More prolonged feeding leads to lesions which are histologically very similar to those in man. (4) The distribution of lesions in the main coronary arteries is similar to that in man. (5) Methods to quantify the coronary lesions are available. (6) The diets can be so modified that cholesterol levels closely resemble those in hypercholesterolemic man. (7) The monkeys are amenable to several therapeutic regimens which show promise of arresting the progress or inducing the regression of the coronary lesions.

Animals↗
PubMed1976

Carcinogen-induced cutaneous neoplasms in nonhuman primates.

Dimethylbenzanthracene (DMBA) combined with UV light, dodecylbenzene (DDB), or both was oncogenic when applied to the skin of nonhuman primates. Ten years after the cutaneous application of DMBA and a cocarcinogen, 2 groups of rhesus monkeys (Macaca mulatta) displayed dermal melanosis, papillomas, basal cell tumors, and mesodermal sarcomas (accompanied in one case by hepatic metastasis). One group had been painted for 15 months; the other, for 6 1/2 years. Eight years after the initiation of a 4-year regimen of biweekly applications of DMBA plus a cocarcinogen, papillomas, basal cell tumors, and basosquamous cell epidermal tumors with satellite lipomas were observed in galagos (Galago crossicaudatus). The same carcinogen applied to the skin of pottos (Perodicticus potto) caused death in 6 of the 7 animals within 9 weeks. Neoplasms occurred in 17 of the 19 primates that lived longer than 9 weeks after the cutaneous application of DMBA combined with either UV light or DDB.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Renal mechanoreceptors in nonhuman primates.

The present experiments provide the first description of the afferent discharge characteristics of renal mechanosensitive receptors in the nonhuman primate. Twenty-seven single units with mechano-sensitive receptor activity were obtained. Afferent discharge occurred regularly (pulse synchronous) or irregularly (pulse asynchronous) under spontaneous respiration. The activity of pulse synchronous units was increased by partial occlusion of the renal vein and elevation of arterial pressure. Impulse activity decreased or disappeared during bleeding or renal arterial occlusion. The impulse activity of pulse asynchronous units was increased by partial occlusion of the renal vein. The impulse activity of silent units was induced only by partial occlusion of the renal vein. An increase in ureteral pressure (50 mmHg) produced an increase or induced impulse activity in only three of the 27 fibers tested. Compression of the kidney or renal venous occlusion was associated with a decrease in systemic arterial pressure, whereas renal arterial occlusion produced a rise in systemic arterial pressure. An increase in ureteral pressure (50 mmHg) did not produce a change in arterial pressure.

Afferent Pathways↗
PubMed1980

Normal erythrocytic delta-aminolevulinic acid dehydratase activity in ten nonhuman primate species.

Normal data on erythrocytic delta-aminolevulinic acid dehydratase (ALAD) activity were obtained from ten species of nonhuman primates: Tupaia glis, Galago crassicaudatus, Saimiri sciureus, Papio spp., Theropithecus gelada, Macaca mulatta, Macaca fascicularis, Macaca nigra, Hylobates lar entelloides and Pan troglodytes. Significant differences between species were observed with M. mulatta having the lowest activity and G. crassicaudatus the highest. Pan troglodytes and Papio spp. have levels of erythrocytic ALAD activity most closely approximating that of man.

Animals↗
PubMed1994

Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates.

OBJECTIVE: The purpose of this study was to examine the relationship between behavior and serotonin by using a nonhuman primate model of aggression and impulse control. METHOD: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Physiological data were obtained from 22-23 of the subjects. Blood and CSF samples were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. RESULTS: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were inversely correlated with "escalated" aggression, i.e., a measure of more intense or severe aggression as defined by the ratio of chases and physical assaults to all aggressive acts. CSF 5-HIAA concentrations were significantly lower in those subjects who showed evidence of physical wounding than in subjects with no wounds. Low CSF 5-HIAA concentrations were also correlated with greater risk-taking as determined by an analysis of leaping behaviors in the forest canopy. The ratio of long leaps (leaps that traversed the longest distances at dangerous heights) to all leaps was negatively correlated with CSF 5-HIAA concentrations. CONCLUSIONS: Adolescent male rhesus macaques with low CSF 5-HIAA concentrations are at risk for 1) exhibiting more violent forms of aggressive behavior and 2) loss of impulse control as evidenced by greater risk taking during movement through the forest canopy.

Aggression↗
PubMedDate not supplied

Haptic breakage following neonatal IOL implantation in a nonhuman primate model.

To evaluate the long-term safety of implanting intraocular lenses (IOLs) in neonatal eyes using a nonhuman primate model, a one-piece all-polymethylmethacrylate (PMMA) IOL was implanted into the posterior chamber of 21 neonatal Rhesus monkey eyes following a lensectomy and anterior vitrectomy. These monkeys then were monitored for 26 to 40 months for complications. The eyes from seven monkeys were studied histopathologically. One or both haptics broke on 7 of the 21 (33%) IOLs in a mean of 21 months (range 6 to 31 months) after their implantation. Only one of the haptics from these seven eyes was found to be in the capsular bag when these eyes were studied histopathologically. Nine haptics had eroded into the iris leaflets, two into the ciliary body, and one into the anterior chamber. One additional haptic was in the sulcus. The haptics of one-piece all-PMMA IOLs may break if implanted in neonatal eyes. A number of factors likely contributed to haptic breakage in these eyes, including an increased number of reoperations, malpositioning of IOL haptics, rapid circumferential and axial growth, and the formation of large Soemmerring's rings.

Animals↗
PubMed1989

An overview of the world literature on spontaneous tumors in nonhuman primates.

A review of the world literature has revealed a total of 783 spontaneous neoplasms that have occurred in nonhuman primates, all similar to tumors in human beings. Carcinomas were the most frequently reported. Neoplasms occurred most frequently in older animals as they generally do in man. There were more reports on neoplasms in baboons and macaques than in other species. The digestive system was more commonly affected than were other organ systems.

Age Factors↗
PubMed1980

Susceptibility of nonhuman primate species to infection by simian rotavirus SA-11.

Enzyme-linked immunosorbent assay examination of sera from three nonhuman primate species demonstrated the presence of antibody reacting with simian rotavirus SA-11 and calf rotavirus C486. The occurrence of this antibody in sera from adult, wild-caught animals suggests natural rotovirus infection. The occurrence of antibody was highest in the chimpanzee and declined, respectively, in the rhesus macaque and in the squirrel monkey. Inoculation of three infant rhesus macaques, a nursery-reared chimpanzee, and a cesarian-derived nursery-reared baboon with SA-11 virus resulted in enteric infection, with virus excretion beginning 48 to 72 hours after oral administration of the virus. Clinical disease, as manifested by diarrhea, was observed only in the chimpanzee. Inoculation of ten squirrel monkeys, from 30 to 191 days old, induced infection only in the monkey inoculated at 30 days of age. This monkey became ill within 48 hours after viral administration and was euthanatized. Necropsy demonstrated a generalized infection, with virus recovered from lung, liver, kidney, spleen, and intestine. The remaining nine inoculated squirrel monkeys failed to develop enteric infection and did not respond with antibody to SA-11 virus.

Animals↗
PubMed1981

[Tumor viruses of nonhuman primates (author's transl)].

Tumor viruses which in the past few years have been increasingly isolated from tissues of nonhuman primates are of considerable interest for contemporary investigations on putative human tumor viruses. This review covers the presently known isolates belonging to the families of papova, adeno, (gamma) herpes, pox, and retro viruses and originating from New World and Old World monkeys as well as from apes. Some of the isolates exhibit oncogenic activity in different simian species and are, therefore, particularly suited for the analysis of viral oncogenesis is primates.

Adenoviridae↗
PubMed1987

Ontogenetic plasticity in nonhuman primates: I. Secular trends in the Cayo Santiago macaques.

Although secular trends toward increasing body size are apparent in many human populations, little is known about their occurrence in nonhuman primates. The Cayo Santiago skeletal collection of Macaca mulatta includes 101 adult animals (greater than or equal to 10 years of age) born at different times in the past 3 1/2 decades, so that variation in size may be examined relative to birth year. No secular trends in orbital height were observed in this sample, but in both sexes lengths of adult long bones increased significantly over time, while cranial dimensions and length of the second molar in female also showed significant variation with birth year. These changes were consistent with the history of provisioning of the animals and with fluctuations in population size. Low-order correlations were observed between birth year and body proportions, especially the crural index in males, a pattern that has also been observed in human populations. These findings argue that, in addition to biomechanics and heritage, diet may affect allometric relationships and that an inherent plasticity or malleability of the growth process may be characteristic of nonhuman as well as human primates.

Animals↗
PubMed2002

Humanized anti-CD154 antibody therapy for the treatment of allograft rejection in nonhuman primates.

The anti-CD154 antibody hu5C8 prevents acute allograft rejection and prolongs allograft survival after withdrawal of therapy in nonhuman primates. This study describes the use of hu5C8 as a rescue agent for rejection developing after the withdrawal of hu5C8. Twelve rhesus monkeys that had received renal allografts under hu5C8 induction and subsequently rejected were studied. Rescue with hu5C8 was analyzed based on the histological character of the rejection (acute versus chronic) and whether conventional therapy was received at the time of rescue or induction. The diagnosis of rejection and response to therapy was based on allograft function and histology. Four monkeys that had acute rejection associated with conventional immunosuppression and hu5C8 were not reversed by hu5C8 rescue. Four animals with isolated chronic rejection following prolonged rejection-free survival after the withdrawal of hu5C8 did not respond to hu5C8 rescue therapy. Hu5C8 rescue therapy effectively reversed acute rejection occurring in two monkeys after hu5C8 withdrawal. One of two animals with combined acute on chronic rejection responded to hu5C8 rescue therapy. Hu5C8 effectively reverses acute but not chronic allograft rejection and appears to have no synergistic effect with conventional rescue agents.

Acute Disease↗
PubMed2006

Chronic antibody mediated rejection of renal allografts: pathological, serological and immunologic features in nonhuman primates.

The pathogenesis of late renal allograft loss is heterogeneous and difficult to diagnose. We have analyzed renal allografts in nonhuman primates to determine the relationship between alloantibodies and the graft pathology of late graft loss. Seventeen Cynomolgus monkeys were chosen from among those on several protocols for renal allotransplantation with mixed chimerism induction so that animals with and without alloantibodies were included. All animals received transient CD154 blockade and short-term cyclosporine treatment until day 28. Serial blood samples were tested for alloantibodies. Protocol biopsies and autopsy kidneys were scored for pathology and C4d deposition. Group 1, defined by complete lack of C4d deposition (24 tissue samples; 8 recipients), had no detectable alloantibodies (33 serum samples; 1-7 samples per recipient) and no evidence of chronic rejection. Three survived greater than 2 years with normal function and histology. Group 2, defined as having C4d deposition in peritubular capillaries, all made alloantibodies (100%), and most grafts later showed chronic allograft glomerulopathy (89%), and/or arteriopathy (89%). All grafts in Group 2 failed (3-27 months). Pathologic lesions of typical of chronic rejection in humans develop in monkeys, correlate with antecedent alloantibodies/C4d deposition and predict chronic rejection rather than durable accommodation.

Animals↗