Search

Sustained activation of the aryl hydrocarbon receptor (AHR) is believed to be the initial key event in AHR receptor-mediated tumorigenesis in the rat liver. The role of AHR in mediating pathological changes in the liver prior to tumor formation was investigated in a 4-week, repeated-dose study using adult female wild-type (WT) and AHR knockout (AHR-KO) rats treated with 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). Beginning at 8 weeks of age, AHR-KO and WT rats were dosed by oral gavage with varying concentrations of TCDD (0, 3, 22, 100, 300 and 1000 ng kg−1 day−1). Lung, liver and thymus histopathology, hematology, serum chemistry and the distribution of TCDD in liver and adipose tissue were examined. Treatment-related increases in the severity of liver and thymus pathology were observed in WT, but not AHR-KO rats. In the liver, these included hepatocellular hypertrophy, bile duct hyperplasia, multinucleated hepatocytes and inflammatory cell foci. A loss of cellularity in the thymic cortex and thymic atrophy was observed. Treatment-related changes in serum chemistry parameters were also observed in WT, but not AHR-KO rats. Finally, dose-dependent accumulation of TCDD was observed primarily in the liver of WT rats and primarily in the adipose tissue of AHR-KO rats. The results suggest that AHR activation is the initial key event underlying the progression of histological effects leading to liver tumorigenesis following TCDD treatment. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources.

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. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

Secondary amyloidosis is a progressive systemic disease for which there is no reliable diagnostic assay, preventive measure, or treatment. In an attempt to elucidate an antemortem diagnosis, 30 female pig-tailed macaques (Macaca nemestrina) at the Washington National Primate Research Center were surveyed for amyloidosis. Amyloid was demonstrated histologically in 47% (14 of 30) of the animals. The distribution and severity of amyloid deposition was variable. Affected animals had a mean age (+/-1 standard deviation) of 13.2 +/- 4.9 y, which was significantly greater than the mean age of unaffected animals (9.3 +/- 4.1) y. Twelve tests were evaluated for detection of amyloidosis; the diagnostic value of each was determined through comparison of histologically positive and histologically negative animals. Diagnostic tests evaluated were endoscopic examination and biopsy of the stomach and colon, abdominal ultrasonography, hepatic radiology, serum amyloid A (SAA), endothelin 1, alpha-fetal protein, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyltransferase (GGT), alkaline phosphatase, cholesterol, blood urea nitrogen, total bilirubin, C-reactive proteins, and erythrocyte sedimentation rate. Amyloidotic animals demonstrated a distinctive serologic profile: elevated SAA, GGT, and AST in combination with decreased total protein and albumin. Radiology demonstrated hepatomegaly in animals with hepatic amyloid deposition. In the absence of known infection or trauma, an amyloidotic serologic profile and radiologic hepatomegaly are consistent with systemic amyloidosis in M. nemestrina.

We report the assessment and validation of an NS1 epitope-blocking enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to West Nile virus (WNV) in macaques. Sera from naturally infected Macaca nemestrina were tested by ELISA and plaque reduction neutralization test (PRNT). Results were correlated with hemagglutination inhibition (HAI) data. Our results demonstrate that the blocking ELISA rapidly and specifically detects WNV infection in M. nemestrina. In addition, the diagnostic value of 7 commercially available immunoassays (PanBio immunoglobulin [Ig] M ELISA, PanBio IgG ELISA, PanBio immunofluorescence assay (IFA), InBios IgG ELISA, InBios IgM ELISA, Focus Diagnostics IgG ELISA, and Focus Diagnostics IgM ELISA) in M. nemestrina was evaluated and compared with that of the epitope-blocking ELISA. The PanBio IgG ELISA was found to effectively diagnose WNV exposure in M. nemestrina. Further, PanBio IFA slides are fast and reliable screening tools for diagnosing flaviviral exposure in M. nemestrina.

Members of a wild-caught colony of 16 gray-crowned rosy finches (Leucosticte tephrocotis) were presented with dermal and mucosal lesions, anorexia, emaciation, lethargy, and sudden death. Lesions included dermatitis, conjunctivitis, and glossitis. Skin scrapings from and bacterial culture of dermal lesions yielded Staphylococcus aureus and Candida albicans. Necropsy and histologic examination revealed characteristic epidermal and mucosal pox lesions, with the presence of characteristic Bollinger body intracellular inclusions. Electron microscopy (EM) provided confirmation of pox virus infection. This epornitic resulted in the death or euthanasia of 12 birds (75% morbidity and associated mortality) and was brought to conclusion through culling of affected birds. The source of infection remains unknown, although multiple modes of introduction exist. Similar epornitics may be prevented through indoor, species-specific housing, and quarantine. Vaccination and antiparasitic treatment may reduce the risk of disease spread.