Comparative lifespan and healthspan of nonhuman primate species common to biomedical research.

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHPs that survived to adulthood and died of natural/health-related causes.

The impact of housing on birth outcomes in breeding macaque groups across multiple research centers.

Demand for nonhuman primates in research has increased over the past several years, while nonhuman primate supply remains a challenge in the United States. Global nonhuman primate supply issues make it increasingly important to maximize domestic colony production. To explore how housing conditions across primate breeding colonies impact infant survival and animal production more broadly, we collected medical records from 7959 rhesus macaques (Macaca mulatta) and 492 pigtail macaques (Macaca nemestrina) across seven breeding facilities and used generalized mixed-effect modeling to determine prenatal and infant survival odds by housing type and group size.

Nonhuman primate genetic models for the study of rare diseases.

Pre-clinical research and development relies heavily upon translationally valid models of disease. A major difficulty in understanding the biology of, and developing treatments for, rare disease is the lack of animal models. It is important that these models not only recapitulate the presentation of the disease in humans, but also that they share functionally equivalent underlying genetic causes.

Use of Fluconazole-impregnated Beads to Treat Osteomyelitis Caused by in a Pigtailed Macaque ().

A 3-y-old male pigtailed macaque () presented for swelling of the left distal forearm and decreased use of the arm. The monkey had been raised at an indoor-outdoor facility in Arizona and transferred to an indoor facility in Washington 2 mo prior to presentation. A preliminary diagnosis of fungal osteomyelitis of the radius was made based on radiographs and titers.

Comparative Risk of Human Injury/Exposure While Collecting Blood from Sedated and Unsedated Nonhuman Primates.

Collection of blood samples for research or clinical evaluation is one of the most common procedures performed in non-human primates. Several possible methods can be used to obtain samples. In the early days of primate research, manual or physical restraint was used, which was stressful for the animal and risky for the human.

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation.

Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART.

Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.

Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection.

Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration.

Transmission of Chagas disease via blood transfusions in 2 immunosuppressed pigtailed macaques (Macaca nemestrina).

A 2.25-y-old male pigtailed macaque (Macaca nemestrina) was experimentally irradiated and received a bone marrow transplant. After transplantation and engraftment, the macaque had unexpected recurring pancytopenia and dependent edema of the prepuce, scrotum, and legs.

Thromboelastography values from pigtail macaques ( Macaca nemestrina): effects of age and sex.

Thromboelastography is a clinical laboratory test used to assess global hemostasis. With technologic advances and the test's reemergence in human medicine, its utility in veterinary medicine is being explored. Because assays for PT, aPTT, and d-dimers require platelet-poor plasma, whereas thromboelastography is performed on whole blood, thromboelastography provides a more accurate representation of coagulation and allows the identification of hypocoagulable, hypercoagulable, and hyperfibrinolytic states.

Pubertal delay in male nonhuman primates (Macaca mulatta) treated with methylphenidate.

Juvenile male rhesus monkeys treated with methylphenidate hydrochloride (MPH) to evaluate genetic and behavioral toxicity were observed after 14 mo of treatment to have delayed pubertal progression with impaired testicular descent and reduced testicular volume. Further evaluation of animals dosed orally twice a day with (i) 0.5 mL/kg of vehicle (n = 10), (ii) 0.

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies.

Risk factors for dystocia in pigtailed macaques (Macaca nemestrina).

Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not.

Primary hepatic Mycobacterium tuberculosis complex infection with terminal dissemination in a pig-tailed macaque (Macaca nemestrina).

An adult, female, pig-tailed macaque (Macaca nemestrina) of Indonesian origin presented with profound weight loss, anemia (PCV, 29%; normal, 36% to 45%), hypoalbuminemia (1.0 g/dL; normal, 3.5 to 5.

Toxicity assessment of pramipexole in juvenile rhesus monkeys.

Pramipexole (PPX) is a dopamine agonist approved for the treatment of the signs and symptoms of idiopathic Parkinson's disease as well as restless leg syndrome. The objective of this study was to investigate the toxicity of PPX when administered orally to juvenile rhesus monkeys once daily for 30 weeks, and to assess the reversibility of toxicity during a 12-week recovery. Rhesus monkeys (N=4 males and 4 females/group; 22-24 months of age) were orally treated daily for 30 weeks with 0.

The genetic toxicology of methylphenidate hydrochloride in non-human primates.

The studies presented in this work were designed to evaluate the genetic toxicity of methylphenidate hydrochloride (MPH) in non-human primates (NHP) using a long-term, chronic dosing regimen. Thus, approximately two-year old, male rhesus monkeys of Indian origin were orally exposed to MPH diluted in the electrolyte replenisher, Prang, five days per week over a 20-month period. There were 10 animals per dose group and the doses were (1) control, Prang only, (2) low, 0.

Multigenerational exposure to ethinyl estradiol affects bone geometry, but not bone mineral density in rats.

Estrogenic compounds are known to prevent bone loss in ovariectomized adult rats; however, their effects on bone in developing and reproductively-intact rats are less well-understood. In a large multigenerational experiment 0, 2, 10, or 50 ppb ethinyl estradiol (EE) in the diet was fed to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) and femurs were collected from subsets of these animals at necropsy at 48 days, 70 days, 140 days, or 2 years of age and subjected to dual-energy X-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area.

Relationships between densitometric and morphological parameters as measured by peripheral computed tomography and the compressive behavior of lumbar vertebral bodies from macaques (Macaca fascicularis).

Study Design: The measured maximum compressive force and stress of lumbar vertebral bodies from cynomolgus monkeys were compared with peripheral quantitative computed tomography (pQCT) derived densitometric and morphologic vertebral parameters.

Objectives: To determine, which pQCT parameters were predictive of vertebral mechanical behavior, and of these, identify those that were the best predictors of vertebral load capacity. A secondary objective was to test the suitability of a multiple parameter-based approach for predicting vertebral mechanical load response.

Flow cytometric analysis of micronuclei in peripheral blood reticulocytes IV: an index of chromosomal damage in the rhesus monkey (Macaca mulatta).

We report evaluation in rhesus monkeys of a flow cytometric procedure (MicroFlow) that has previously been shown to allow assessment of micronucleated reticulocytes (MN-RETs) in the peripheral blood of rats and dogs. Reticulocytes (RETs) were labeled with anti-CD71-fluorescein isothiocyanate, DNA was stained with propidium iodide using RNase treatment, and anti-CD61-phycoerythrin was used to reduce interference from platelets. Flow cytometric data were compared with microscopic scores of peripheral blood and bone marrow using standard acridine orange staining.

Effect of prolonged ketamine exposure on cardiovascular physiology in pregnant and infant rhesus monkeys (Macaca mulatta).

Physiologic measurements in nonhuman primates usually are collected from animals that are chemically or physically restrained. Both types of restraint may affect the parameters measured, and those effects can vary with age. Heart rate, respiratory rate, oxygen saturation, expired CO2, blood pressure, temperature, blood glucose, hematocrit, and venous blood gasses were measured in rhesus monkeys that were either infused intravenously with ketamine for 24 h or were cage-housed and physically restrained for sample collection.

Ketamine-induced neuronal cell death in the perinatal rhesus monkey.

Ketamine is widely used as a pediatric anesthetic. Studies in developing rodents have indicated that ketamine-induced anesthesia results in brain cell death. Additional studies are needed to determine if ketamine anesthesia results in brain cell death in the nonhuman primate and if so, to begin to define the stage of development and the duration of ketamine anesthesia necessary to produce brain cell death.

Oral treatment with retinoic acid decreases bone mass in rats.

13-cis-retinoic acid (13-cis-RA, isotretinoin) is used to treat severe recalcitrant acne. Other retinoids have adverse effects on bone. Recent studies of human patients treated with 13-cis-RA have had varying results, perhaps because of variability among patients and the lack of control groups.

Multigenerational exposure to genistein does not increase bone mineral density in rats.

Genistein has been shown to prevent bone loss in ovariectomized adult rats. However, the effects of genistein on bone in developing and reproductively-intact rats have not been examined. A large multigenerational experiment involved feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years.