Parturition in baboons (PAPIO SPP.).

The Old World non-human primates (NHP) - baboons (Papio spp.) share similarities with humans regarding fetal and placental development and some pregnancy-related complications. Information about the mechanism of birth and complications arising during parturition in these species is relatively sparse. In this manuscript, we add information from a series of pathological and observational cases to highlight insights and selected complications of birth in Papio spp, based on video-recording of the delivery process, X-ray, MRI, and ultrasound evaluations in pregnant baboons. Additionally, we abstracted pathology records obtained from perinatal loss in a large baboon colony during a 17 year period. The presented cases provide important information for the management of pregnancy and delivery in Papio spp.

Reovirus-associated meningoencephalomyelitis in baboons.

Baboon orthoreovirus (BRV) is associated with meningoencephalomyelitis (MEM) among captive baboons. Sporadic cases of suspected BRV-induced MEM have been observed at Southwest National Primate Research Center (SNPRC) for the past 20 years but could not be confirmed due to lack of diagnostic assays. An immunohistochemistry (IHC)-based assay using an antibody against BRV fusion-associated small transmembrane protein p15 and a conventional polymerase chain reaction (PCR)-based assay using primers specific for BRV were developed to detect BRV in archived tissues. Sixty-eight cases of suspected BRV-induced MEM from 1989 through 2010 were tested for BRV, alphavirus, and flavivirus by IHC. Fifty-nine of 68 cases (87%) were positive for BRV by immunohistochemistry; 1 tested positive for flavivirus (but was negative for West Nile virus and St Louis encephalitis virus by real-time PCR), and 1 virus isolation (VI) positive control tested negative for BRV. Sixteen cases (9 BRV-negative and 7 BRV-positive cases, by IHC), along with VI-positive and VI-negative controls, were tested by PCR for BRV. Three (of 9) IHC-negative cases tested positive, and 3 (of 7) IHC-positive cases tested negative by PCR for BRV. Both IHC and PCR assays tested 1 VI-positive control as negative (sensitivity: 75%). This study shows that most cases of viral MEM among baboons at SNPRC are associated with BRV infection, and the BRV should be considered a differential diagnosis for nonsuppurative MEM in baboons.

Endocannabinoid crosstalk between placenta and maternal fat in a baboon model (Papio spp.) of obesity.

INTRODUCTION: Maternal obesity (MO) remains a serious obstetric problem with acute and chronic morbidities for both mothers and offspring. The mechanisms underlying these adverse consequences of MO remain unknown. Endocannabinoids (ECB) are neuromodulatory lipids released from adipocytes and other tissues. Metabolic crosstalk between placenta and adipocytes may mediate sequelae of MO. The goal of this study was to elucidate placental and systemic ECB in MO. MATERIAL AND METHODS: Placentas, sera, and subcutaneous fat were collected at Cesarean sections performed near term (0.9 G) in four non-obese (nOB) and four obese (OB) baboons (Papio spp.). Concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured by liquid chromatography coupled to tandem mass spectrometry. AEA and 2-AG pathways were characterized in placentas by Q-RT-PCR, Western blot and immunohistochemistry. RESULTS: Placental 2-AG levels were lower and maternal fat AEA levels were higher in OB (1254.1 ± 401.3 nmol/kg and 17.3 ± 4 nmol/kg) vs. nOB (3124.2 ± 557.3 nmol/kg and 3.1 ± 0.6 nmol/kg) animals. Concentrations of 2-AG correlated positively between maternal fat and placenta (r = 0.82, p = 0.013), but correlated negatively with maternal leptin concentrations (r = -0.72, p = 0.04 and r = -0.83, p = 0.01, respectively). CONCLUSION: This is the first study to demonstrate differential ECB pathway regulation in maternal fat and placenta in MO. Differential regulation and function exist for AEA and 2-AG as the major ECB pathways in placenta.

Abruptio placentae in the baboon (Papio spp.).

INTRODUCTION: Placental abruption is a serious condition that increases perinatal morbidity and mortality. Clinical prevention and treatment options are limited, especially in human preterm deliveries. Knowledge of the mechanisms that keep the placenta in place during pregnancy is critical for developing strategies for the prevention of abruption. Failure of physiological transformation of spiral arteries has been described as a major contributing factor of the placental abruption development. Baboons (Papio spp.) share striking similarities with humans in regard to placental structure, utero-placental blood flow, and fetal development; however, the mode of trophoblast invasion is shallow in baboons. This fact prompted the hypothesis that the incidence of placental abruption will be increased in baboons compared to humans. MATERIAL AND METHODS: Baboon placentas were collected between 2002 and 2008. Two independent veterinary pathologists evaluated the slides. A certified physician pathologist performed additional histology. RESULTS: Placental abruption was diagnosed in 22 baboons among 2423 live births during the study period (0.9% prevalence). The most common clinical presentations were fetal demise and vaginal bleeding. The most common pathological findings were intraplacental hemorrhages with or without hematoma formation (86.4%). Other findings consisted of neutrophil infiltration (50%), decidual necrosis (22.7%), decidual vascular congestion and inflammation, villous congestion and retroplacental hemorrhage/hematoma (each 18.2%). These pathologic findings were the same for term and preterm deliveries. CONCLUSION: This is the first systematic study of placental abruption in non-human primates, analyzing a large colony of baboons. Despite differences in trophoblast invasion, the clinical features observed in placental abruption affecting baboons resembled those reported in humans. The cluster of placental pathological findings in baboons also agreed with clinical reports, but the prevalence of these findings differed between baboons and humans. We discuss a mechanism of anti-abruption forces that offset shallow trophoblast invasion observed in baboons.

Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans.

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.

The morphometry of materno-fetal oxygen exchange barrier in a baboon model of obesity.

INTRODUCTION: More than one-fourth of U.S. women are overweight; more than one-third are obese. Maternal obesity has been linked to an increased incidence of stillbirths, fetal macrosomia, fetal intrauterine growth restriction and pre-eclampsia. The placenta plays a key role in the nutrients and oxygen supply to the fetus. The data about structural changes in the placental villous membrane (VM), a major component of the feto-maternal nutrient and oxygen exchange barrier, during obesity are sparse and inconsistent. Our objective was to evaluate the morphometric changes in the placental exchange barrier in a baboon model of obesity. MATERIALS AND METHODS: The previously described baboon model of maternal obesity was studied. We compared 4 obese to 4 non-obese baboons. Placental stereology with the use of transmission electron microscopy was performed to estimate VM oxygen diffusing capacities and morphometry. RESULTS: The specific placental oxygen diffusing capacities per unit of fetal weight were similar in baboons and humans. Maternal leptin concentrations correlated negatively with placental basement membrane thickness (r = -0.78, p < 0.05), while fetal leptin levels correlated negatively with endothelial thickness of fetal capillaries (r = -0.78, p < 0.05). The total and specific villous membrane oxygen diffusing capacities were not different between the two groups. CONCLUSION: To the best of our knowledge this is the first report of placental oxygen diffusing capacities and placental ultrastructural changes in a baboon model of obesity. Previously reported placental inflammation in maternal obesity is not associated with changes in the VM diffusing capacities and ultrastructure.

Intracranial meningioma in a baboon (Papio spp.).

Meningioma is the most common intracranial non-glial tumour of cats, dogs and man. Few spontaneously arising brain tumours have been reported in non-human primates. This report describes a meningioma in a captive baboon. Clinical signs exhibited by the animal included head pressing, visual impairment and vestibular disease. The tumour arose from the ventral aspect of the cranial cavity and compressed the overlying left side of the cerebellum and brainstem. Microscopically, the mass was characterized by pleomorphic spindle-shaped to polygonal cells arranged in sheaths, vague whorls and occasional papillary structures on vascular cores. Nuclear cytoplasmic invagination, syncytial-like cells and areas of mineralization were also evident. Immunohistochemically, the neoplastic cells expressed vimentin and S-100 protein, but not pancytokeratin, glial fibrillary acidic protein or epithelial membrane antigen. The features of this tumour are similar to those of meningiomas in other species.

[Diffuse anterior retinoblastoma]. / Diffuses anteriores Retinoblastom.

Retinoblastoma is the most common primary intraocular tumor in childhood. Diffuse anterior retinoblastoma is an uncommon variant and usually occurs in comparatively older children. Typically, there is an extensive infiltration of the anterior segment by tumor cells clinically mimicking anterior uveitis with pseudohypopyon. The actual retinal focus is often very small and may not be detected despite a thorough histological examination. In this case report the clinical and histological findings of a diffuse anterior retinoblastoma are described.

Lacrimal gland choristoma in a preterm infant, presenting with spontaneous hyphema and increased intraocular pressure.

We report a case of intraocular lacrimal gland choristoma presenting very early in a preterm infant with hyphema, a mass lesion and raised intraocular pressure. Enucleation of the involved eye, which is the treatment in most cases, was performed and prosthesis was fitted successfully. An interesting additional finding in our patient was a choroidal defect, not reported to date with other cases in the literature.

Spontaneous gallbladder pathology in baboons.

BACKGROUND: Gallbladder pathology (GBP) is a relatively uncommon, naturally occurring morbidity in both baboons and humans. METHODS: A retrospective analysis was performed on 7776 necropsy reports over a 20 year period to determine the prevalence of baboon GBP. RESULTS: Ninety-seven cases of GBP were identified, yielding a 20 year population prevalence of 1.25%. GBP is more common in adult female baboons, occurring with a female to male ratio of nearly 2:1. Among gallbladder pathologies, cholecystitis (35.1%) and cholelithiasis (29.9%) were the most prevalent abnormalities, followed by hyperplasia (16.5%), edema (15.5%), amyloidosis (5.2%), fibrosis (4.1%), necrosis (4.1%), and hemorrhage (1.0%). CONCLUSION: Many epidemiologic similarities exist between GBP in baboons and humans suggesting that the baboon may serve as a reliable animal model system for investigating GBP in humans.

Further studies on the frequency and length of the glandulo-metaplastic esophageal mucosa in baboons.

BACKGROUND: In previous studies, the length of the glandulo-metaplastic esophageal mucosa (GMEM) at the gastroesophageal junction was assessed in a selected group of baboons. In this study, the length of the GMEM was measured in the entire esophagus in a cohort of unselected adult baboons. MATERIALS AND METHODS: In 15 female baboons, the entire esophagus was removed en bloc at autopsy, from the tongue to the angle of His. No part of the stomach was included. The length of GMEM was measured using a calibrated ocular microscale. RESULTS: GMEM was found in 11 out of the 15 esophagi. The total length of GMEM recorded in the 11 cases was 115 mm (mean 10.5 mm, range 1-45 mm). The mean age for animals with GMEM was 15.5 years (range 7-32 years) and for animals without GMEM was 14.0 years (range 7-20 years); the difference was non-significant (p<0.6). No significant association was found between the length of the GMEM and the age of the animals (p<0.6). CONCLUSION: This study substantiates the notion that GMEM in baboons is a postnatal physiological adaptative process of the esophageal mucosa to daily regurgitation with rumination of gastric juices of low pH. The GMEM apparently progresses upwards, along the esophageal mucosa. The baboon might be an excellent animal model to study the series of histological events that take place in the distal esophagus under the influence of protracted gastroesophageal reflux.

Evaluation of four hematology and a chemistry portable benchtop analyzers using non-human primate blood.

BACKGROUND: Near patient testing (NPT) and point-of-care testing (POCT) using portable benchtop analyzers has become necessary in many areas of the medical community, including biocontainment. METHODS: We evaluated the Beckman AcT diff, Abaxis Vetscan HMII (two instruments), Abbott Cell-Dyn 1800, and Abaxis Vetscan VS2 for within-run precision and correlation to central laboratory instruments using non-human primates blood. RESULTS: Compared with the central laboratory instruments, the Beckman AcT diff correlated on 80%; the HMII instruments on 31% and 44%, the CD1800 on 31%, and the VS2 on 71% of assays. For assays with published manufacturers precision guidelines, the AcT diff met all nine, the HMII instruments met one and six of six, and the CD 1800 met one of six. CONCLUSIONS: Laboratories using NPT/POCT must test their individual instruments for precision and correlation, identify assays that are reliable, and exclude or develop supplemental procedures for assays that are not.

Spontaneous pathology of the baboon endocrine system.

BACKGROUND: Study of endocrine pathology in animal models is critical to understanding endocrine pathology in humans. METHODS: We evaluated 434 endocrine-related diagnoses from 4619 baboon necropsies, established the incidence of spontaneous endocrine pathology, and analyzed the clinical and biochemical data associated with the individual cases. RESULTS: The most common diagnoses in descending order, were pancreatic islet cell amyloidosis (n = 259), ovarian cysts (n = 50), pituitary adenoma (n = 37), pancreatic islet cell adenoma (n = 20), granulosa cell tumor (n = 15), thyroid adenoma (n = 11), adrenal hyperplasia (n = 10), thyroid carcinoma (n = 8), and pheochromocytoma (n = 6). The incidence of pancreatic islet cell amyloidosis progressively increased with age. Pheochromocytomas were associated with renal and heart failure. The incidence of pancreatic islet cell amyloidosis and adrenal pathology was similar to humans; the incidence of pituitary adenoma and thyroid pathology was lower than in humans. CONCLUSIONS: Endocrine disease in baboons is common and shares clinical and biochemical characteristics with endocrine disease in humans.

Feto-placental adaptations to maternal obesity in the baboon.

Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were: 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals; and 3) maternal obesity in humans and baboons is similar in regard to increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses.

Neoplasia in the chimpanzee (Pan spp.).

BACKGROUND: Chimpanzees have over 98% genomic sequence homology with humans and may have a similar host response to malignancy. There is minimal information concerning cancer in the chimpanzee and such information would be valuable to individuals caring for and using them for research. METHODS: Spontaneous neoplasia that was documented in two chimpanzee colonies and in the literature were evaluated statistically. RESULTS: In all, 105 spontaneous and 12 experimental neoplasms were diagnosed. Seventy-four spontaneous tumors occurred in females, 24 in males,and seven in animals of undetermined sex. Of the spontaneous tumors 89 were benign, 14 were malignant, and two were undetermined. Neoplasia was most common in the urogenital system in females. CONCLUSIONS: Neoplasia is not uncommon in the chimpanzee, is generally benign, and occurs primarily in the urogenital system in females.

Gastrointestinal stromal tumors in a baboon, a spider monkey, and a chimpanzee and a review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are believed to originate from the intestinal pacemaker cells (interstitial cells of Cajal) or their progenitor cells. Spontaneous tumors have been reported in dogs, horses, rhesus, and a chimpanzee and they have been produced experimentally in mice and rats. GISTs represent a diagnostic challenge because they cannot be differentiated from non-lymphoid mesenchymal tumors without using human c-kit (CD117) immunohistochemistry. METHODS: Three neoplasms were incidental findings at necropsy in the stomachs of a baboon and a spider monkey and in the rectum of a chimpanzee. RESULTS: The GISTs were initially diagnosed grossly and histologically with hematoxylin and eosin as leiomyomas. Immunohistochemical analysis revealed that all three were c-kit (CD117) positive. CONCLUSIONS: These are the first reports of GISTs in the baboon and spider monkey and the second in a chimpanzee. The occurrence of GISTs in non-human primates may provide a unique opportunity to study these tumors.

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates.

BACKGROUND: Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. METHODS: One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. RESULTS: Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. CONCLUSIONS: When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a first case report.

BACKGROUND: Eosinophilic bronchitis is a recently described, relatively benign condition in humans that is characterized by a corticosteroid-responsive chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The exact cause of this condition is currently unknown, however has been associated with various occupational exposures in humans. It has also been reported to progress to irreversible airway obstruction. This disease has been reported in dogs and horses, but not in non-human primates. METHODS: Gross examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta, which died of severe non-responsive respiratory distress revealed that the lungs were markedly inflated and moist. RESULTS: Hematoxylin and eosin-stained sections from the lungs contained widespread accumulation of eosinophils, sloughed epithelial cells, and mucus centered around bronchioles and adjacent airways. There was no evidence of mast cell infiltration of peribronchiolar smooth muscle, goblet cell hyperplasia, or basement membrane thickening. CONCLUSIONS: This ruled out recurrent episodes as would be expected in asthma, favoring the diagnosis of an eosinophilic bronchitis-like lesion. We report a first case of eosinophilic bronchitis-like features in a M. mulatta.