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An analysis of the Bateson Review of research using nonhuman primates
Greek R, Hansen LA, Menache A
Medicolegal and Bioethics , 2011, DOI: http://dx.doi.org/10.2147/MB.S25938
Abstract: n analysis of the Bateson Review of research using nonhuman primates Commentary (6056) Total Article Views Authors: Greek R, Hansen LA, Menache A Published Date December 2011 Volume 2011:1 Pages 3 - 22 DOI: http://dx.doi.org/10.2147/MB.S25938 Ray Greek1, Lawrence A Hansen2, Andre Menache1 1Americans for Medical Advancement, Goleta, 2Department of Neurosciences, University of California, San Diego, CA, USA Abstract: An analysis of the use of nonhuman primates in biomedical research in the UK, the Review of Research Using Non-Human Primates (the "Bateson Review") was released in 2011. The review was applauded, to varying degrees, by most of the stakeholders in the controversy over using nonhuman primates in biomedical research. However, there has not been a scientific analysis of the review. In this paper, the Bateson Review is examined for both methodology and the science relevant to the use of nonhuman primates in biomedical research. The relevant science includes complexity theory, evolutionary biology, genetics, empirical evidence regarding the reliability of interspecies extrapolation, and the value of basic biomedical research in general in making discoveries that lead to human treatments. The authors of this paper conclude that the Bateson Review does not meet the criteria for a scientific assessment, in part, because it fails to consider the current science that impacts on the practice of using animals, in general, and nonhuman primates, specifically, in biomedical research. This lack of scientific consideration has legal and ethical ramifications. Since the Bateson Review fails as a scientific evaluation, the ethical and legal recommendations that are based on science are also suspect.
ARTs in action in nonhuman primates: Symposium summary – advances and remaining issues
Barry D Bavister
Reproductive Biology and Endocrinology , 2004, DOI: 10.1186/1477-7827-2-43
Abstract: Until recently, the primary rationale for ARTs research with nonhuman primates has been to provide information and new technologies that could assist human ARTs. Because basic research, and to some extent the development of new technologies, cannot or should not be done on humans, the nonhuman primate model ought to play a central role in these efforts. Paradoxically, this role to date has been minimal, for several reasons. First, human ART (IVF/IVP/ET) was established before ART in nonhuman primates. Human ART has been developing since 1969, when the first IVF was reported [3], culminating in the birth of Louise Brown in 1978, five years before the first nonhuman primate IVF births. Because of the social importance and commercialization of human ART, it has progressed much faster than nonhuman primate ART. This has made it difficult to present the case for nonhuman primate ART as a model for human ART, because the former is usually perceived as playing "catch-up" to the latter. Second, nonhuman primate ART presently owes more to human ART than vice-versa, e.g., the development and availability of human recombinant gonadotropins, without which monkey ART would be very difficult and perhaps prohibitively expensive. As a result, there has been very little technology transfer from basic research with nonhuman primates to the human clinical arena. Nevertheless, there are several key areas in which progress in human ART has virtually stalled, and quantum improvements in ART success will need new information and technology that can only be obtained using suitable experimental animal models, i.e., nonhuman primates. The efficiency of human ART is rather low – on average, about 12% per embryo transferred, and <5% per embryo produced [4,5]. Improvements could be made, for example, by devising even better culture media for IVP and objective methods for selecting the most viable embryos for transfer. Moreover, as this symposium demonstrates, there is great potential for nonhum
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates  [PDF]
Joana de Fátima Ferreira Borges da Costa,Mariana Ferreira Leal,Tanielly Cristina Raiol Silva,Edilson Ferreira Andrade Junior,Alexandre Pingarilho Rezende,José Augusto Pereira Carneiro Muniz,Antonio Carlos Cunha Lacreta Junior,Paulo Pimentel Assump??o,Danielle Queiroz Calcagno,Samia Demachki,Silvia Helena Barem Rabenhorst,Marília de Arruda Cardoso Smith,Rommel Rodriguez Burbano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0021988
Abstract: The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments.
Modeling human arthritic diseases in nonhuman primates
Michel PM Vierboom, Margreet Jonker, Ronald E Bontrop, Bert 't Hart
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1773
Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology [1,2]. Once established, immune reactions against joint components contribute significantly to the pathological hallmarks of the disease, being synovial hyperplasia (pannus formation) and a variable degree of destruction and remodeling of joint cartilage and bone. RA affects approximately 1% of people in Western countries, with a 2:1 prevalence in females over males. The ageing societies in the developed countries create a growing need for safer and more effective therapies to treat chronic diseases such as RA. The advent of biotechnology has fuelled the search for drugs that act more specifically to overcome the considerable side effects of nonspecific anti-inflammatory and immunosuppressive drugs. Especially for immune-mediated diseases, biotechnology-based therapies have a great therapeutic potential. The preclinical development of immunomodulatory compounds often begins with an observation in vitro, after which proof of therapeutic principle is obtained in animal models, usually in inbred strains of rats or mice.Unfortunately, the promising effects of new therapeutics observed in rodents are often not reproduced on testing in patients. There is a growing awareness that the evolutionary gap between inbred rodent strains and the human population is too wide for direct translation of data from rodents to humans [3]. Because of the closer evolutionary and immunological proximity to humans, nonhuman primates may help to bridge this gap [4-6]. Trans-species antigen presentation of human antigen-presenting cells to rhesus T cells and vice versa [7,8] nicely illustrates the immunological proximity of rhesus monkeys and humans [9-11].It is of critical importance for preclinical safety testing that the selected animal model is sensitive to the pharmacological action of the tested drug and that the tissue distribution and pharmacological properties of the molecules targeted by the treatment are
Use of live nonhuman primates in research in Asia  [cached]
Hagelin J
Journal of Postgraduate Medicine , 2004,
Abstract: Background: Use of live non-human primates (NHPs) in biomedical research is a controversial issue in many parts of the world. Recent use of NHPs in research in Asian countries was surveyed. Aim: To elucidate the use of NHPs in research in Asian countries. Settings and design: The peer-reviewed literature was sampled according to the species used, area of research, research class and geographic location. Articles derived from database searches were scrutinised. Methods and Material: Studies were identified from the PrimateLit database. Results and Conclusion: Results suggested that NHP research was conducted in 16 countries, of which Japan accounted for two-thirds. About 55% of studies involved use of live animals, whereas the remaining 45% used some lower level of biological material. More than 70% of the studies using live NHPs included use of Old World monkeys. M. fuscata (18%), M. mulatta (17%) and M. fascicularis (10%) were the three most commonly used species. The most common research areas were neuroscience (44%), conservation (14%) and behaviour (11%). Due to high demand for NHPs, there is room for increased breeding of NHPs to be used for research in Asian countries.
Absence of intestinal colonization by vancomycin-resistant enterococci in nonhuman primates
Xavier, Diego Batista;Rosa, Adriana Helena;Sena, Hilana dos Santos;Teixeira, Danillo Simonini;Tomaz, Carlos;Titze-de-Almeida, Ricardo;
Pesquisa Veterinária Brasileira , 2010, DOI: 10.1590/S0100-736X2010000600004
Abstract: the animal reservoirs of vancomycin-resistant enterococci (vre) have important role in the epidemiology of the bacteria and resistant genes. the present work searched fecal samples taken off nonhuman primates for the presence of vre. resistance profiles, virulence traits, and genetic variability among enterococci isolates were also analyzed. the samples included capuchin monkeys (cebus apella, n=28) and common marmoset (callithrix penicillata, n=37) housed in the primate center of the university of brasília, brazil. most individuals were captive monkeys from the central-west and south-east regions of brazil (n=48). we collected rectal swabs and carried out selective isolation followed by multiplex polymerase chain reaction (pcr) to identify species and resistance genes. no vana or vanb-containing enterococci were found. the carriage rates ranged from 1.5% for the vanc-type e. casseliflavus and e. gallinarum until 12.3% (n=8) for enterococcus faecalis. all e. faecalis isolates showed susceptibility to vancomycin, teicoplanin, ampicillin, gentamicin, and streptomycin. the virulence genes ace and esp were prevalent (100.0%, 87.5%). multilocus variable number of tandem repeats (mlva) revealed diversity in the number of repeats among e. faecalis isolates and targets, which was higher for espc, efa5, and efa6. we identified six different mlva genotypes that were divergent from those described in human beings. also, they were clustered into two genogroups that showed host-specificity for the species cebus apella or callithrix penicillata. in conclusion, no vana- or vanb-containing enterococci were found colonizing those primate individuals. this finding suggested that the primate individuals investigated in our study are not directly involved in the epidemiological chain of high-level vancomycin-resistant genes vana or vanb in brazil. our study also showed that e. faecalis isolated from nonhuman primates carry virulence traits and have ability to spread their lineages amon
Nocturnal thoracoabdominal asynchrony in house dust mite-sensitive nonhuman primates
XiaoJia Wang, Shaun Reece, Stephen Olmstead, et al
Journal of Asthma and Allergy , 2010, DOI: http://dx.doi.org/10.2147/JAA.S11781
Abstract: cturnal thoracoabdominal asynchrony in house dust mite-sensitive nonhuman primates Methodology (2240) Total Article Views Authors: XiaoJia Wang, Shaun Reece, Stephen Olmstead, et al Published Date July 2010 Volume 2010:3 Pages 75 - 86 DOI: http://dx.doi.org/10.2147/JAA.S11781 XiaoJia Wang, Shaun Reece, Stephen Olmstead, Robert L Wardle, Michael R Van Scott Department of Physiology, East Carolina University, Greenville, North Carolina, USA Abstract: Nocturnal bronchoconstriction is a common symptom of asthma in humans, but is poorly documented in animal models. Thoracoabdominal asynchrony (TAA) is a noninvasive clinical indication of airway obstruction. In this study, respiratory inductive plethysmography (RIP) was used to document nocturnal TAA in house dust mite (HDM)-sensitive Cynomolgus macaques. Dynamic compliance (Cdyn) and lung resistance (RL) measured in anesthetized -animals at rest and following exposure to HDM allergen, methacholine, and albuterol were highly -correlated with three RIP parameters associated with TAA, ie, phase angle of the rib cage and abdomen waveforms (PhAng), baseline effort phase relation (eBPRL) and effort phase relation (ePhRL). Twenty-one allergic subjects were challenged with HDM early in the morning, and eBPRL and ePhRL were monitored for 20 hours after provocation. Fifteen of the allergic subjects exhibited gradual increases in eBPRL and ePhRL between midnight and 6 am, with peak activity at 4 am. However, as in humans, this nocturnal response was highly variable both between subjects and within subjects over time. The results document that TAA in this nonhuman primate model of asthma is highly correlated with Cdyn and RL, and demonstrate that animals exhibiting acute responses to allergen exposure during the day also exhibit nocturnal TAA.
Correlations between Hippocampal Neurogenesis and Metabolic Indices in Adult Nonhuman Primates  [PDF]
Tarique D. Perera,Dunyue Lu,Lakshmi Thirumangalakudi,Eric L. P. Smith,Arkadiy Yaretskiy,Leonard A. Rosenblum,John G. Kral,Jeremy D. Coplan
Neural Plasticity , 2011, DOI: 10.1155/2011/875307
Abstract: Increased neurogenesis in feeding centers of the murine hypothalamus is associated with weight loss in diet-induced obese rodents (Kokoeva et al., 2005 and Matrisciano et al., 2010), but this relationship has not been examined in other species. Postmortem hippocampal neurogenesis rates and premortem metabolic parameters were statistically analyzed in 8 chow-fed colony-reared adult bonnet macaques. Dentate gyrus neurogenesis, reflected by the immature neuronal marker, doublecortin (DCX), and expression of the antiapoptotic gene factor, B-cell lymphoma 2 (BCL-2), but not the precursor proliferation mitotic marker, Ki67, was inversely correlated with body weight and crown-rump length. DCX and BCL-2 each correlated positively with blood glucose level and lipid ratio (total cholesterol/high-density lipoprotein). This study demonstrates that markers of dentate gyrus neuroplasticity correlate with metabolic parameters in primates. 1. Introduction The hippocampus is receiving increasing attention for its potential role in energy regulation [1]. The hippocampus is part of a neural circuit involved with reward and energy regulation [2] and is sensitive to satiety signals associated with learning and memory [3]. Recent findings indicate that palatable high-fat diets promote excessive food intake and weight gain and interfere with hippocampal functioning. This is supported by epidemiological data linking diets high in saturated fat with weight gain and memory deficits [4–6]. Furthermore, rats and humans with diabetes mellitus show age-related performance impairments on memory tasks [7]. More recent studies demonstrate that high-fat diet-induced maternal obesity impairs offspring hippocampal BDNF production [8], alters fetal hippocampal development [9], and reduces hippocampal neurogenesis during the early life of their offspring [10]. Moreover, adult male rats fed with a high-fat diet show impaired hippocampal neurogenesis [11]. Neurogenesis induced by ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) in feeding centers of the murine hypothalamus is associated with weight loss in obese rodents [12, 13]. Because both hippocampal neurogenesis and proxy metabolic parameters are connected with stress and mood disorders [14–16], the aforementioned hypothalamic data raise important questions regarding the relationship between hippocampal neurogenesis and the regulation of peripheral metabolic parameters. We present a pilot study of the relationship between hippocampal neurogenesis and metabolic parameters in adult nonhuman primates. 2.
Optimization of a Novel Non-invasive Oral Sampling Technique for Zoonotic Pathogen Surveillance in Nonhuman Primates  [PDF]
Tierra Smiley Evans?,Peter A. Barry?,Kirsten V. Gilardi?,Tracey Goldstein?,Jesse D. Deere?,Joseph Fike?,JoAnn Yee?,Benard J Ssebide?,Dibesh Karmacharya?,Michael R. Cranfield
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0003813
Abstract: Free-ranging nonhuman primates are frequent sources of zoonotic pathogens due to their physiologic similarity and in many tropical regions, close contact with humans. Many high-risk disease transmission interfaces have not been monitored for zoonotic pathogens due to difficulties inherent to invasive sampling of free-ranging wildlife. Non-invasive surveillance of nonhuman primates for pathogens with high potential for spillover into humans is therefore critical for understanding disease ecology of existing zoonotic pathogen burdens and identifying communities where zoonotic diseases are likely to emerge in the future. We developed a non-invasive oral sampling technique using ropes distributed to nonhuman primates to target viruses shed in the oral cavity, which through bite wounds and discarded food, could be transmitted to people. Optimization was performed by testing paired rope and oral swabs from laboratory colony rhesus macaques for rhesus cytomegalovirus (RhCMV) and simian foamy virus (SFV) and implementing the technique with free-ranging terrestrial and arboreal nonhuman primate species in Uganda and Nepal. Both ubiquitous DNA and RNA viruses, RhCMV and SFV, were detected in oral samples collected from ropes distributed to laboratory colony macaques and SFV was detected in free-ranging macaques and olive baboons. Our study describes a technique that can be used for disease surveillance in free-ranging nonhuman primates and, potentially, other wildlife species when invasive sampling techniques may not be feasible.
Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates  [PDF]
Tarique D. Perera,Andrew J. Dwork,Kathryn A. Keegan,Lakshmi Thirumangalakudi,Cecilia M. Lipira,Niamh Joyce,Christopher Lange,J. Dee Higley,Gorazd Rosoklija,Rene Hen,Harold A. Sackeim,Jeremy D. Coplan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017600
Abstract: Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs.
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