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Ely J.J.,Alamogordo Primate Facility | Bishop M.A.,Texas A&M University | Lammey M.L.,Alamogordo Primate Facility | Sleeper M.M.,University of Pennsylvania | And 2 more authors.
Comparative Medicine | Year: 2010

Cardiovascular disease is the leading cause of morbidity and mortality among captive chimpanzees. The most prevalent form of cardiovascular disease among chimpanzees is sudden cardiac death. Myocardial fibrosis was the only significant pathologic lesion observed in affected animals at necropsy. We previously showed an association between myocardial fibrosis and sudden cardiac death. The presumed pathogenesis was interstitial myocardial fibrosis that led to decreased myocardial contractility and interrupted signal propagation in the heart, leading to fibrillation and resulting in sudden cardiac death. In this pilot study, we assayed 5 biomarkers of collagen types I and HI metabolism and fibrogenesis and studied their association with CVD in chimpanzees. The biomarker MMP1 did not crossreact in chimpanzee sera and could not be studied further. Two biomarkers (TIMP1 and PINP) and their difference showed no significant association with CVD in chimpanzees. The biomarkers ICTP and PIIINP were significantly increased in cases of CVD with concurrent renal disease. Furthermore, both biomarkers showed a significant trend to increase with disease severity. We conclude that ICTP and PIIINP warrant further study for antemortem detection of renal and myocardial fibrosis in chimpanzees. Copyright 2010 by the American Association for Laboratory Animal Science.


Bozek K.,Chinese Academy of Sciences | Bozek K.,Max Planck Institute for Evolutionary Anthropology | Wei Y.,Chinese Academy of Sciences | Wei Y.,University of Chinese Academy of Sciences | And 19 more authors.
PLoS Biology | Year: 2014

Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys. © 2014 Bozek et al.


PubMed | Southwest Research Institute, University of Texas M. D. Anderson Cancer Center, Alamogordo Primate Facility and U.S. Department of Agriculture
Type: Journal Article | Journal: Veterinary pathology | Year: 2016

Chimpanzees (Pan troglodytes) have served as an important model for studies of reproductive diseases and aging-related disorders in humans. However, limited information is available about spontaneously occurring reproductive tract lesions in aging chimpanzees. In this article, the authors present histopathologic descriptions of lesions identified in the reproductive tract, including the mammary gland, of 33 female and 34 male aged chimpanzees from 3 captive populations. The most common findings in female chimpanzees were ovarian atrophy, uterine leiomyoma, adenomyosis, and endometrial atrophy. The most common findings in male chimpanzees were seminiferous tubule degeneration and lymphocytic infiltrates in the prostate gland. Other less common lesions included an ovarian granulosa cell tumor, cystic endometrial hyperplasia, an endometrial polyp, uterine artery hypertrophy and mineralization, atrophic vaginitis, mammary gland inflammation, prostatic epithelial hyperplasia, dilated seminal vesicles, a sperm granuloma, and lymphocytic infiltrates in the epididymis. The findings in this study closely mimic changes described in the reproductive tract of aged humans, with the exception of a lack of malignant changes observed in the mammary gland and prostate gland.


Bozek K.,Chinese Academy of Sciences | Bozek K.,Max Planck Institute for Evolutionary Anthropology | Wei Y.,Chinese Academy of Sciences | Yan Z.,Chinese Academy of Sciences | And 15 more authors.
Neuron | Year: 2015

Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution. © 2015 Elsevier Inc.


Videan E.N.,Alamogordo Primate Facility | Videan E.N.,University of Michigan | Satterfield W.C.,Michale eling Center for Comparative Medicine and Research | Buchl S.,Michale eling Center for Comparative Medicine and Research | Lammey M.L.,Alamogordo Primate Facility
American Journal of Primatology | Year: 2011

Uterine leiomyomata are common, affecting 70-80% of women between 30 and 50 years of age. Leiomyomata have been reported for a variety of primate species, although prevalence rates and treatments have not been widely reported. The prevalence, diagnosis, and treatment of uterine leiomyomata in the Alamogordo Primate Facility and the Keeling Center for Comparative Medicine and Research were examined. Uterine leiomyomata were diagnosed in 28.4% of chimpanzees with an average age at diagnosis of 30.4±8.0 years. Advanced age (>30 years) was related to an increase in leiomyomata and use of hormonal contraception was related to a decrease in leiomyomata. As the captive chimpanzee population ages, the incidence of leiomyomata among female chimpanzees will likely increase. The introduction of progesterone-based contraception for nonbreeding research and zoological chimpanzees may reduce the development of leiomyomata. Finally, all chimpanzee facilities should institute aggressive screening programs and carefully consider treatment plans. © 2011 Wiley-Liss, Inc.


Nunamaker E.A.,Purdue University | Nunamaker E.A.,University of Illinois at Chicago | Lee D.R.,Alamogordo Primate Facility | Lee D.R.,Washington Regional Primate Center | Lammey M.L.,Alamogordo Primate Facility
Comparative Medicine | Year: 2012

The current aging population of captive chimpanzees is expected to develop age-related diseases and present new challenges to providing their veterinary care. Spontaneous heart disease and sudden cardiac death are the main causes of death in chimpanzees (especially of male animals), but little is known about the relative frequency of other chronic diseases. Furthermore, female chimpanzees appear to outlive the males and scant literature addresses clinical conditions that affect female chimpanzees. Here we characterize the types and prevalence of chronic disease seen in geriatric (older than 35 y) female chimpanzees in the colony at Alamogordo Primate Facility. Of the 16 female chimpanzees that fit the age category, 87.5% had some form of chronic age-related disease. Cardiovascular-related disease was the most common (81.25%) followed by metabolic syndrome (43.75%) and renal disease (31.25%). These data show the incidence of disease in geriatric female chimpanzees and predict likely medical management challenges associated with maintaining an aging chimpanzee population. Copyright 2012 by the American Association for Laboratory Animal Science.


Ely J.J.,Alamogordo Primate Facility | Zavaskis T.,Alamogordo Primate Facility | Lammey M.L.,Alamogordo Primate Facility
Zoo Biology | Year: 2013

Cardiovascular disease is a primary cause of morbidity and mortality in captive chimpanzees. Four years of blood pressure (BP) data were analyzed from a captive former laboratory population of 201 healthy adult chimpanzees with assessment of age and obesity on elevated BP. Five different measures of obesity were compared: abdominal girth, basal metabolic rate, body-mass index (BMI), body weight, and surface area. Systolic BP varied by sex. Obesity did not influence male BP. For females, obesity was a significant determinant of BP. The best measure of female obesity was basal metabolic rate and the worst was BMI. Median systolic BP of healthy weight females (<54.5 kg) was significantly lower (128 mmHg) than overweight or obese females (140 mmHg), but both were lower than all males (147 mmHg). For diastolic BP, neither sex nor any of the five obesity measures was significant. But age was highly significant, with geriatric chimpanzees (>30 years) having higher median diastolic BP (74 mmHg) than young adults of 10-29 years of age (65 mmHg). By these criteria, 80% of this population is normotensive, 7% prehypertensive, and 13% hypertensive. In summary, systolic BP intervals required adjustment for obesity among females but not males. Diastolic BP required adjustment for advanced age (≥30 years). Use of these reference intervals can facilitate timely clinical care of captive chimpanzees. © 2012 Wiley Periodicals, Inc.


Videan E.N.,Alamogordo Primate Facility | Lammey M.L.,Alamogordo Primate Facility | Lee D.R.,Alamogordo Primate Facility
Journal of the American Association for Laboratory Animal Science | Year: 2011

Degenerative joint disease (DJD), also known as osteoarthritis, has been well documented in aging populations of captive and free-ranging macaques; however, successful treatments for DJD in nonhuman primates have not been published. Published data on chimpanzees show little to no DJD present in the wild, and there are no published reports of DJD in captive chimpanzees. We report here the first documented case of DJD of both the right and left femorotibial joints in a captive male chimpanzee. Progression from minimal to moderate to severe osteoarthritis occurred in this animal over the course of 1 y. Treatment with chondroprotective supplements (that is, glucosamine chondroitin, polysulfated glycosaminoglycan) and intraarticular corticosteroid injections (that is, methylprednisolone, ketorolac), together with pain management (that is, celecoxib, tramadol, carprofen), resulted in increased activity levels and decreased clinical signs of disease. DJD has a considerable negative effect on quality of life among the human geriatric population and therefore is likely to be one of the most significant diseases that will affect the increasingly aged captive chimpanzee population. As this case study demonstrates, appropriate treatment can improve and extend quality of life dramatically in these animals. However, in cases of severe osteoarthritis cases, medication alone may be insufficient to increase stability, and surgical options should be explored. Copyright 2011 by the American Association for Laboratory Animal Science.


C-reactive protein, a conserved acute-phase protein synthesized in the liver and involved in inflammation, infection, and tissue damage, is an informative biomarker for human cardiovascular disease. Out of 258 captive adult common chimpanzees (Pan troglodytes) assayed for CRP, 27.9% of the data were below the quantitation limit. Data were analyzed by the Kaplan-Meier method and results compared to other methods for handling censored data (including deletion, replacement, and imputation). Kaplan-Meier results demonstrated a modest age effect and a strong effect of HCV infection in reducing CRP but did not allow inference of reference intervals. Results of other methods varied considerably. Substitution schemes differed widely in statistical significance, with estimated group means biased by the size of the substitution constant, while inference of unbiased reference intervals was impossible. Single imputation gave reasonable statistical inferences but unreliable reference intervals. Multiple imputation gave reliable results, for both statistical inference and reference intervals, and was comparable to the Kaplan-Meier standard. Other methods should be avoided. CRP did not predict cardiovascular disease, but CRP levels were reduced by 50% in animals with hepatitis C infection and showed inverse relationships with 2 liver function enzymes. Results suggested that hsCRP can be an informative biomarker of chronic hepatic dysfunction.


PubMed | Charles River Associates and Alamogordo Primate Facility
Type: Journal Article | Journal: Veterinary pathology | Year: 2016

Cardiorenal syndrome involves disease and dysfunction of the heart that leads to progressive renal dysfunction. This study investigated the relationship between cardiac and renal disease in 91 aged chimpanzees at the Alamogordo Primate Facility by evaluation of the medical histories, metabolic parameters, functional measurements of the cardiovascular system, clinical pathology, and histopathology focused on the heart and kidney. Cardiac fibrosis was the most frequent microscopic finding in 82 of 91 animals (90%), followed by glomerulosclerosis with tubulointerstitial fibrosis in 63 of 91 (69%). Cardiac fibrosis with attendant glomerulosclerosis and tubulointerstitial fibrosis was observed in 58 of 91 animals (63%); there was a statistically significant association between the 2 conditions. As the severity of cardiac fibrosis increased, there was corresponding increase in severity of glomerulosclerosis with tubulointerstitial fibrosis. Altered metabolic, cardiovascular, and clinical pathology parameters indicative of heart and kidney failure were commonly associated with the moderate to severe microscopic changes, and concurrent heart and kidney failure were considered the cause of death. The constellation of findings in the chimpanzees were similar to cardiorenal syndrome in humans.

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