Pancreas anatomy and surgical procedure for pancreatectomy in rhesus monkeys

Background The aim of this study was to investigate the pancreas anatomy and surgical procedure for harvesting pancreas for islet isolation while performing pancreatectomy to induce diabetes in rhesus monkeys. Methods The necropsy was performed in three cadaveric monkeys. Two monkeys underwent the total pancreatectomy and four underwent partial pancreatectomy (70–75%). Results The greater omentum without ligament to transverse colon, the cystic artery arising from the proper hepatic artery and the branches supplying the paries posterior gastricus from the splenic artery were observed. For pancreatectomy, resected pancreas can be used for islet isolation. Diabetes was not induced in the monkeys undergoing partial pancreatectomy (70–75%). Conclusions Pancreas anatomy in rhesus monkeys is not the same as in human. Diabetes can be induced in rhesus monkeys by total but not partial pancreatectomy (70–75%). Resected pancreas can be used for islet isolation while performing pancreatectomy to induce diabetes.     

Long-term effect of a simple nest-box on the reproductive efficiency and other life traits of an Aotus lemurinus lemurinus monkey colony: an animal model for malaria research

Background The long‐term effect of a PVC pipe nest‐box on the reproductive efficiency and other life traits of an Aotus monkey‐breeding colony have not been characterized. Methods and Results We analyzed laboratory records of the Gorgas Memorial Institute (GMI) Aotus monkey colony in Panama for the period 1999–2010 and found a 273% increase in the annual mean life births in the following 7 years after the introduction of a PVC pipe nest‐box in 2002, as well as increases in the mean body mass and survival of laboratory‐bred monkeys. Other life traits such as inter‐birth interval, parity, birth sex distribution, mortality, and longevity were also determined. Conclusions The use of a PVC pipe nest‐box significantly improved the reproductive efficiency and other life traits of the GMI Aotus breeding colony.     

25‐Hydroxy‐vitamin D levels among Callithrix penicillata primate species raised in captivity

Background Animals in captivity should receive adequate sunlight exposure for sufficient generation of vitamin D [25(OH)D]. In the present study, 25(OH)D serum levels of 84 Callithrix penicillata primates were evaluated. Objectives To determine 25(OH)D levels of those animals; to evaluate the influence of gender and period of sunlight exposure on their 25(OH)D levels. Methods Three groups were evaluated: group 1 (n = 29) on free sunlight exposure; group 2 (n = 34) on partial sunlight exposure; group 3 (n = 21) without sunlight exposure. Results The obtained 25(OH)D values were: group 1, 121.2 ± 33.3 ng/ml; group 2, 115.2 ± 32.2 ng/ml; group 3, 53.3 ± 10.4 ng/ml. Significant statistical differences were obtained between groups 1 and 3 (p < 0.001) and groups 2 and 3 (p < 0.001); no statistical difference was found between genders. Conclusion Direct sunlight exposure is essential for 25(OH)D sufficiency and it is proposed that the 25(OH)D normal range for captive Callithrix penicillata would be from 104.8 to 137.1 ng/ml (CI = 95%).     

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations

Background Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. Methods Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non‐uniform group of monkeys. Results Sham injury and cord compression by canal invasion of 50–75% produced minimal morpho‐functional alterations, if at all. Canal invasion of 90–100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12‐week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. Conclusions Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates.     

Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIV(SF162P3)

Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIV_SF162P3. Methods Seven SHIV_SF162P3‐infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. Results Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7–10 post‐infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. Conclusions These pilot studies demonstrate the first successful STI‐SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.     

Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow

The regeneration potential of mesenchymal stem cells (MSCs) diminishes with advanced age and this diminished potential is associated with changes in cellular functions. This study compared MSCs isolated from the bone marrow of rhesus monkeys (rBMSCs) in three age groups: young (< 5 years), middle (8-10 years), and old (> 12 years). The effects of aging on stem cell properties and indicators of stem cell fitness such as proliferation, differentiation, circadian rhythms, stress response proteins, miRNA expression, and global histone modifications in rBMSCs were analyzed. rBMSCs demonstrated decreased capacities for proliferation and differentiation as a function of age. The production of heat shock protein 70 (HSP70) and heat shock factor 1 (HSF1) were also reduced with increasing age. The level of a core circadian protein, Rev-erb α, was significantly increased in rBMSCs from old animals. Furthermore, analysis of miRNA expression profiles revealed an up-regulation of mir-766 and mir-558 and a down-regulation of mir-let-7f, mir-125b, mir-222, mir-199-3p, mir-23a, and mir-221 in old rBMSCs compare to young rBMSCs. However, there were no significant age-related changes in the global histone modification profiles of the four histone core proteins: H2A, H2B, H3, and H4 on rBMSCs. These changes represent novel insights into the aging process and could have implications regarding the potential for autologous stem cells therapy in older patients.     

Relationship between gastrointestinal transit time and anesthetic fasting protocols in the captive chimpanzee, Pan troglodytes

Background Lengthy social separation and prolonged fasting time contribute to increased risks associated with anesthesia in captive primates. This study is an initial attempt to identify a safe pre‐anesthetic fasting procedure by identifying gastric emptying time (GET) and gastrointestinal transit time (GTT) of captive chimpanzees, Pan troglodytes. Methods Seven adult chimpanzees at the North Carolina Zoo immobilized for annual physical examinations were fed barium‐impregnated polyethylene spheres to measure GET. Eleven animals were individually fed a color dye marker and fecal passage was observed to determine GTT. Results Gastric emptying time (GET) was approximated to be >3 hours but <16 hours. The mean GTT was 16.5 hours. Conclusions This study indicates that a fasting time of 3 hours would allow for complete gastric emptying and could potentially replace the current overnight fast (≥16 hour) to help minimize complications associated with pre‐anesthetic fasting in captive primates.     

Retrobulbar primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus)

Background A 2.8‐year‐old female captive‐bred common squirrel monkey (Saimiri sciureus) showed exophthalmos of the right eye, and the eye was surgically enucleated. A tumor mass was found in the eye. Methods Formalin‐fixed tumor samples were examined histopathologically and immunohistochemically for diagnosis. Results The retrobulbar tumor mass adhered to the sclera and infiltrated the choroid. Histopathologically, tumor cells were pleomorphic, arranged in a sheet pattern, and mimicked primitive neuroectodermal cells. The tumor cells were strongly positive for precursor neuronal cell markers (beta III tubulin, neuron‐specific enolase, vimentin, nestin, doublecortin, oligo2, and S‐100), but negative for mature cell markers (cytokeratin, neurofilament, and glial fibrillary acidic protein) and a retinoblastoma marker (rhodopsin). Conclusions This is the first reported case for the retrobulbar location of primitive neuroectodermal tumor in non‐human primates.     

Splenic angioleiomyoma in an owl monkey (Aotus nancymae)

Background An adult male owl monkey (Aotus nancymae) underwent a splenectomy. When the spleen was removed, a small, nodular mass slightly bulging over the splenic surface was noted. Methods The mass was examined by light and transmission electron microscopy and by immunohistochemistry. Results On light microscopy, the mass was well‐circumscribed, non‐encapsulated, and composed of haphazardly arranged smooth muscle bundles admixed with numerous small capillary‐like structures containing blood. Immunohistochemical (IHC) staining revealed the tumor was strongly positive for smooth muscle actin yielding vascular smooth muscle bundles, and for Factor VIII, staining endothelial cells within the smooth muscle bundles. Transmission electron microscopy (TEM) showed a large portion of the cells to be atypical appearing smooth muscle and a few cells had structures resembling Weibel–Palade bodies indicating endothelial cells. Conclusions Based on cell morphology, by light and TEM, and IHC a final diagnosis of splenic angioleiomyoma was made. This is, to our knowledge, the first report of an angioleiomyoma in a non‐human primate.     

Pathology of spontaneous air sacculitis in 37 baboons and seven chimpanzees and a brief review of the literature

Background Air sacculitis is an important clinical condition in non‐human primates. Methods We evaluated 37 baboons and seven chimpanzees with spontaneous air sacculitis submitted to pathology over a 20‐year period. Results Air sacculitis was observed almost exclusively in males. Common reported signs were halitosis, coughing, nasal discharges, depression, anorexia, and weight loss. Gross lesions included thickened air sacs and suppurative exudate lining the walls. Microscopic lesions included marked epithelial hyperplasia or hypertrophy, necrosis, fibrosis, cellular infiltrates, and bacterial colonies. Mixed bacterial infections were more common than infections by single species of bacteria. Streptococcus sp. was the most frequent bacteria isolated in both baboons and chimpanzees. Conclusions This is the first report describing the gross and microscopic lesions of air sacculitis in chimpanzees. The preponderance of males suggests a male sex predilection in baboons.     

Maternal parity affects neonatal survival rate in a colony of captive bred baboons (Papio hamadryas)

Background Non‐human primates, particularly baboons, are valuable as animal models for reproductive research, because of their similarity to humans. Knowledge of colony‐specific pregnancy and neonatal outcomes is essential for interpretation of such research. Methods A retrospective review of the reproductive records of the Australian National Baboon Colony (ANBC) from 1994 to 2006 was performed. Results The overall live birth rate was over 70% of recognized pregnancies. Pregnancy loss was due to equal proportions of spontaneous abortion and stillbirth, and was not affected by maternal age or parity. Stillbirth rates were increased by the use of animals in novel late pregnancy experimental protocols. Neonatal mortality rates were low overall, but significantly higher in primiparous compared with multiparous mothers (P < 0.05). There were no cases of maternal mortality. Conclusions The success of the ANBC breeding programme is demonstrated by the low rate of pregnancy loss, high neonatal survival rate and lack of maternal mortality.     

Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta)

Backgroud A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. Methods To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. Results Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin‐resistant Staphylococcus aureus infection. Vancomycin and ampicillin‐sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. Conclusions Simian noma associated with methicillin‐resistant Staphylococcus aureus (MRSA) had not previously been reported in non‐human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.