Biosafety in acquired immunodeficiency syndrome (AIDS) studies using nonhuman primates

The safety recommendations for studies on acquired immunodeficiency syndrome (AIDS) using nonhuman primates are based on knowledge about the epidemiology of the disease in humans, characteristics of the virus, and standard methods for handling nonhuman primates in the laboratory. Appropriate procedures avoid exposure to potentially infectious materials by skin puncture or to mucous membranes by using appropriate disinfecting agents, physical containment, protective clothing, and animal handling techniques.     

Detection of anti-Leptospira antibodies in captive nonhuman primates from Salvador, Brazil

Leptospirosis is a widely distributed zoonosis that affects several species of domestic and wild animals. Under captive conditions, Leptospirosis is a potential problem because the physical conditions in most zoos and research centers cannot prevent the captive animals from being exposed to rodents, raccoons, opossums, and other local wildlife that are known carriers. Yet, despite the potential risk, animals that are destined for reintroduction into the wild are not routinely tested for anti-Leptospira antibodies before their release. The purpose of this study was to determine the occurrence of anti-Leptospira antibodies in captive New World monkeys that were housed in the Wild Animals Screening Center in Salvador, Brazil. Blood samples were collected from 44 monkeys (28 Callithrix jacchus, eight Callithrix pennicilata, and eight Cebus sp.). The animals were screened for antibodies with the microscopic agglutination test. Twenty-five (56.8%) primates were seroreactive, with Icterohaemorrhagiae being the most frequent serogroup. None of the monkeys, however, presented clinical signs of leptospirosis. Thus, seroreactivity with low titers in asymptomatic animals, as observed in this study, suggests exposure to the agent. The unexpected predominance of the serogroup Icterohaemorrhagiae further suggests that exposure to this serogroup occurred in captivity. Therefore, the dangerous possibility cannot be ignored that reintroduced monkeys will carry the leptospiral serovars into wild populations. In conclusion, primates exposed to urban serovars before their release from captivity represent a potentially significant health risk to wild populations.     

The use of nonhuman primates in the study of bilirubin metabolism and bile secretion

Close similarities exist in the chemical structure of fetal and adult bile pigments and mechanisms for hepatic bilirubin conjugation and transport in human and nonhuman primates. Newborn monkeys, unlike other animals, develop physiologic hyperbilirubinemia and are ideal animal models in which to investigate this developmental human disorder. Aberrations in bile pigment metabolism and compartmentalization which occur in hemolytic, hepatocellular, and obstructive diseases, closely resemble those reported in counterpart syndromes in man. Similarities also exist in the mechanisms responsible for the secretion of canalicular and ductular/ductal bile and the composition of bile. Nonhuman primates offer distinct advantages for comparative studies concerning bile pigment metabolism and the secretion of bile.     

Tumors of the respiratory tract observed at the German Primate Center, 1978–1994

Abstract: Eight spontaneous pulmonary tumors (four bronchiolar tubular adenomas, two bronchiolar adenocarcinomas, two squamous-cell carcinomas) occurred in a total of 54 adult tree shrews (Tupaia belangeri) of the GPC colonies between 1978 and 1994. The adenomas and adenocarcinomas consisted of tubularly or trabecularly arranged cuboidal to cylindrical cells interspersed with some PAS-positive goblet cells, thus resembling the epithelial lining of respiratory bronchioles of tree shrews. The two squamous-cell carcinomas probably originated from the pulmonary alveoles. Three more pulmonary tumors (one small-cell carcinoma, one bronchial adenoma, one squamous-cell carcinoma) developed in 409 adult callitrichids of the GPC colonies during the same period, and one more bronchial adenoma was observed in a common marmoset (Callithrix jacchus) of another colony located in Göttingen. With regard to the adenomas and squamous-cell carcinomas, a similar cellular origin with the tree shrews is assumed. The small-cell carcinoma possibly developed from the bronchial epithelium, provided a pathogenesis parallel to that of human small-cell carcinoma is suggested. Four of the tree shrew pulmonary adenomas/adenocarcinomas and the small-cell Ca were macroscopically visible as yellowish-grey nodules of 1 mm × 1 mm to 15 mm × 15 mm diameter, predominantly involving the main lobes (2 × right main lobes, 2 × left main lobes, 1 × all lobes). The pulmonary tumors of the other animals were below macroscopical detectability.     

An overview of biohazards associated with nonhuman primates

Because of their close phylogenetic relationship, human and nonhuman primates share susceptibility to many pathogens which do not affect lower animals. This similarity, which makes them invaluable models for studying human infectious diseases, also makes primate animals potentially dangerous to work with. The biohazards inherent in the use of nonhuman primates in biomedical research are zoonoses, injuries, and infectious agents introduced by study protocols. This review addresses the various kinds of parasites, fungi, rickettsiae, spirochetes, and viral agents found naturally occurring, or experimentally induced, in nonhuman primates with reference to measures for preventing spread among the animals or to personnel.     

Polymorphism of glycophorins in nonhuman primate erythrocytes

Using immunoblotting techniques and polyclonal antisera to human erythrocyte glycophorin, we show that erythrocytes of several species of nonhuman primates, including representatives of anthropoid apes (19 chimpanzees, 3 gorillas, 6 orangutans, and 3 gibbons) and Old World monkeys (3 baboons, 5 rhesus monkeys, and 6 cynomologus macaques), contain human glycophorin-like molecules. Each species displays a unique glycophorin profile; in anthropoid apes the profile is more complex than in Old World monkeys and more similar to that seen in humans. The chimpanzee was the only species in which human -like glycophorin was detected but it differed from its human counterpart in electrophoretic mobility and reaction with M-specific monoclonal antibody. In contrast to humans, highly polymorphic glycophorin profiles were observed in each species of anthropoid apes and three distinct patterns were defined in each. No such polymorphism has been found so far among the Old World monkeys in the limited number of animals studied. The major glycophorins in all species but the chimpanzees failed to react with M- or N-specific monoclonal antibodies, suggesting structural differences from the human within the amino terminal regions. The reaction with the minor glycophorins showed inter- and intraspecies variability. All glycophorins, except -like glycophorin in the chimpanzee, reacted with the antiserum to the carboxyl terminal fragment of human glycophorin, indicating a structural relation to the human in this region. An unexpected correlation was observed, in the chimpanzee, between the patterns of electrophoretically resolved glycophorins and the V-A-B-D blood-group phenotypes, allowing the assignment of each determinant to specific glycophorin bands. The basis for the differences observed between human and nonhuman primate glycophorins is not clear but the possibilities include a common nonpolymorphic ancestor and differences in selective pressures.This research was supported by National Institutes of Health Grant 5 RO1 GM16389.     

Trends of plant use by humans and nonhuman primates in Amazonia

Analyses of plant use in Amazonia by three species of nonhuman primates reveal a common trend: more primitive plant species are used as food. An identical situation prevails for three indigenous human societies which additionally selected more recently evolved plant species as medicine. One hypothesis to explain the observations is related to the presence of toxic constituents in the more advanced species, in contrast to astringent polyphenols in the more primitive ones. Thus a certain degree of astringency might indicate absence of harmful chemicals, and even stimulate ingestion. © 1996 Wiley-Liss, Inc.     

Olfactory responsiveness to two odorous steroids in three species of nonhuman primates

Social communication by means of odor signals is widespread among mammals. In pigs, for example, the C19-steroids 5-alpha-androst-16-en-3-one and 5-alpha-androst-16-en-3-ol are secreted by the boar and induce the mating stance in the sow. In humans, the same substances have been shown to be compounds of body odor and are presumed to affect human behavior. Using an instrumental conditioning paradigm, we here show that squirrel monkeys, spider monkeys and pigtail macaques are able to detect androstenone at concentrations in the micromolar range and thus at concentrations at least as low as those reported in pigs and humans. All three species of nonhuman primates were considerably less sensitive to androstenol, which was detected at concentrations in the millimolar range. Additional tests, using a habituation-dishabituation paradigm, showed that none of the 10 animals tested per species was anosmic to the two odorous steroids. These results suggest that androstenone and androstenol may be involved in olfactory communication in the primate species tested and that the specific anosmia to these odorants found in approximately 30% of human subjects may be due to their reduced number of functional olfactory receptor genes compared with nonhuman primates.     

Comparative analysis of natural killer cell activity, lymphoproliferation and lymphocyte surface antigen expression in nonhuman primates housed at the CIRMF Primate Center, Gabon

Six different species of nonhuman primates housed at the CIRMF Primate Center, cynomolgus monkeys (Macaca fascicularis), rhesus monkeys (Macaca mulatta), mandrills (Mandrillus sphinx), vervets (Cercopithecus aethiops pygerythrus), chimpanzees (Pan troglodyte) and baboons (Papio hamadryas), were evaluated for their natural killer cell activity and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin and staphylococcal enterotoxin A) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens. Basic information on normal immune functions in these primates is important because of their use as experimental animal models for the study of human diseases such as acquired immunodeficiency syndrome (AIDS), hepatitis, loiasis and malaria.     

Development of Y-chromosomal microsatellite markers for nonhuman primates

We have analysed 136 newly identified human Y-chromosomal microsatellites in five (sub)species of nonhuman primates. We identified 83 male-specific loci for central chimpanzees, 82 for western chimpanzees, 67 for gorillas, 45 for orangutans and 19 loci for mandrills. Polymorphism was detected at 56 loci in central chimpanzees, 29 in western chimpanzees, 24 in western gorillas, 17 in orangutans and at three in mandrills. Success in male-specific amplification of human Y-chromosomal microsatellites in nonhuman primates was significantly negatively correlated with divergence time from the human lineage. We observed significantly more Y-chromosomal microsatellite diversity in central chimpanzees than in western chimpanzees. There were significantly more male-specific loci with longer alleles in humans than with longer alleles in the nonhuman primates; however, this significant difference disappeared when only the loci which are polymorphic in nonhuman primates were analysed, suggesting that ascertainment bias is responsible. This study provides primatologists with a large number of polymorphic, male-specific microsatellite markers that will be valuable for investigating relevant questions in behavioural ecology such as male reproductive strategies, kin-based cooperation among males and male-specific dispersal patterns in wild groups of nonhuman primates.     

Use of primates in research: a global overview

We assessed the use of nonhuman primates and nonhuman primate biological material in research by reviewing studies published in 2001 in peer-reviewed journals. The number and species of primates used, the origin of the animals, the type of study, the area of research of the investigation, and the location at which the research was performed were tabulated. Additionally, factors related to the animals that may have affected the outcome of the experiments were recorded. A total of 2,937 articles involving 4,411 studies that employed nonhuman primates or nonhuman primate biological material were identified and analyzed. More than 41,000 animals were represented in the studies published in 2001. In the 14% of studies for which re-use could be determined, 69% involved animals that had been used in previous experiments. Published studies most commonly used nonhuman primates or nonhuman primate biological material from the species Chlorocebus aethiops (19%), Macaca mulatta (18%), M. fascicularis (9%), and Papio spp. (6%). Of these studies, 54% were classified as in vitro studies, 14% as noninvasive, 30% as chronic, and 1% were considered acute. Nonhuman primates were primarily used in research areas in which they appear to be the most appropriate models for humans. The most common areas of research were microbiology (including HIV/AIDS (26%)), neuroscience (19%), and biochemistry/chemistry (12%). Most (84%) of the primate research published in 2001 was conducted in North America, Europe, and Japan. The animals and conditions under which they were housed and used were rarely described. Although it is estimated that nonhuman primates account for an extremely small fraction of all animals used in research, their special status makes it important to report the many husbandry and environmental factors that influence the research results generated. This analysis has identified that editors rarely require authors to provide comprehensive information concerning the subjects (e.g., their origin), treatment conditions, and experimental procedures utilized in the studies they publish. The present analysis addresses the use of primates for research, including the effects of a shortage of suitable nonhuman primate subjects in many research areas.     

Use of florfenicol in non-human primates

Studies were undertaken to determine if florfenicol, an antimicrobial agent structurally similar to chloramphenicol, could be used as an effective broad spectrum antibiotic for the treatment of bacterial infections in primates. Florfenicol was developed as an injectable antibiotic for use in cattle on an every other day dosing schedule. Its broad spectrum activity, long duration of action following i.m. administration, and its safety as compared with chloramphenicol made it an attractive antibiotic for use in non-human primates. Previous studies had shown that florfenicol is effective against common primate pathogens such as Salmonella, Klebsiella, Escherichia coli, Bordetella bronchiseptica, Streptococcus pneumoniae, Staphylococcus spp., and Yersinia pseudotuberculosis. We performed experiments on a total of 15 macaques. The animals were given florfenicol at 50 mg/kg i.m. and blood samples taken at various time points. Serum was evaluated for florfenicol absorption. Necropsies were also performed to determine if major organs were affected and to determine the effects of i.m. injection of florfenicol. We determined that florfenicol given every 48 hours in rhesus macaques results in blood levels that were acceptable for therapeutic use. The effect on muscle tissue of i.m. injection was similar to ketamine and normal saline. There were no gross lesions observed and no changes with tissues submitted for histology. Our work shows that with further studies, florfenicol may be useful when injectable antibiotic therapy is required in non-human primates.     

非人灵长类的亲缘选择

亲缘选择是动物进化的重要研究领域之一,非人灵长类因具有丰富的社会网络,是亲缘选择研究领域的重要类群。动物进行亲缘选择的前提是亲缘识别,并常通过社会行为的亲缘偏向表现。因此,本文从非人灵长类的亲缘识别机制和亲缘关系对其社会行为的影响两方面进行了综述:熟悉性和表现型匹配是目前普遍认同的非人灵长类亲缘识别机制,同时这两种机制并不相互排斥,它们可能共同在灵长类的亲缘识别中起作用;在非人灵长类中,亲缘关系是影响社会行为模式的主导因子,它影响着多种灵长类个体的友好行为、攻击行为和性行为的选择,同时亲缘偏向行为在不同物种中表现不尽相同,说明亲缘选择理论可以部分解释灵长类的行为,但存在一定的局限性。本文分析了两种亲缘识别机制的异同以及在实际研究中利用亲缘选择理论解释非人灵长
类社会行为的局限及可能原因。目前,对非人灵长类社会中的亲缘选择研究正逐步深入,其中分子遗传学技术的应用是重要的推动力量。同时,依然存在诸如汉密尔顿规则参数估计和新大陆猴的亲缘选择研究案例的难点,有待研究者进一步探究。     

Government regulation of nonhuman primate facilities

Myriad international, federal, and state laws, regulations, rules, guidelines, and standards directly affect the activities of all nonhuman primate research facilities. Federal regulations alone encompass every aspect of facility operations. They govern the procurement, possession, handling, care, and utilization of nonhuman primates, the design, construction, maintenance, and operation of the facility, and the occupational and environmental protection afforded not only facility personnel, but also the general public. Proper management of a nonhuman primate facility depends on continual monitoring of constantly changing laws and regulations applicable to the type of facility operated and research conducted. An in-house compliance assurance program is necessary to assure conformance with pertinent regulations.     

非人灵长类糖尿病动物模型研究进展

糖尿病是继心血管疾病和肿瘤之后的另一种严重危害人类健康的重要慢性疾病,据世界卫生组织(WHO)报道,2009年全世界约有2.2亿糖尿病患者。对糖尿病发病机理的研究、预防和诊断、治疗药物的筛选和评价都需要合适的动物模型。在已报道的糖尿病动物模型中,非人灵长类动物糖尿病病程、病症与人类的糖尿病最为相似。该文从糖尿病动物模型的来源归纳了目前报道的主要的非人灵长类糖尿病模型,重点介绍了猕猴、食蟹猴和树鼩糖尿病模型及其特征,并对该领域的发展提出了一些思考。