Onchocerca sp. in an imported Zangersheide gelding causing suspensory ligament desmitis.

A 5-year-old imported Zangersheide gelding was evaluated for SC swellings over both forelimbs and lameness localized to the distal metacarpus. Ultrasound examination of the SC masses was compatible with verminous granulomas. Linear hyperechoic foci were present within the suspensory ligament branches of both forelimbs, suggestive of ligamentous parasitic infiltrates. A diagnosis of onchocerciasis was confirmed on biopsy of a SC mass. The gelding was treated with ivermectin and a tapering course of PO dexamethasone but was eventually euthanized. Necropsy confirmed the presence of SC eosinophilic granulomas and degenerative suspensory ligament desmitis, both with intralesional nematodes. Given the location and appearance of the nematode, a diagnosis of Onchocerca sp., most likely O. reticulata, was made. Onchocerciasis should be included as a differential diagnosis for multifocal suspensory ligament desmitis with these sonographic characteristics when paired with SC masses in imported European Warmbloods.

RETROSPECTIVE REVIEW OF MORBIDITY AND MORTALITY IN A POPULATION OF CAPTIVE BUDGERIGARS (MELOPSITTACUS UNDULATES).

This retrospective study reviews the diseases associated with morbidity and mortality in 221 budgerigars (Melopsittacus undulates) from a captive population from 2013 to 2019. The study aimed to evaluate the health status of a flock of budgerigars typical of today's zoologic collections. Based on previous literature, it was hypothesized that age-related conditions such as neoplasia would be common, whereas metabolic and nutritional disorders would be less common. Neoplasia was widespread among the population, affecting 34% of birds (75/221). Carcinomas made up most neoplastic processes and most commonly affected the renal system (n = 22), followed by the proventriculus (n = 7). Pituitary, adrenal, and hepatocellular carcinomas were less commonly diagnosed. Sarcomas affected the population less often than carcinomas and were found within the coelom (undifferentiated four cases), within the spleen (three cases), within the kidney (two cases), and one subcutaneous soft tissue sarcoma. There were five cases of multicentric lymphoma found most commonly affecting the spleen and liver. Benign neoplasms affected the pituitary most commonly (nine cases), followed by the reproductive system, with seminomas (seven cases) being most common. Macrorhabdus ornithogaster (MO) was found in 56 cases. The majority (38 cases) were found in conjunction with a range of comorbidities, but several birds experienced MO infections alone, and it was thought to have been the cause of death in these birds (22 cases). In contrast to our hypothesis, disease associated with nutritional or metabolic disorders impacted a substantial portion of the population; hepatic lipidosis (26 cases) was the most common along with obesity (26 cases), followed by atherosclerosis, xanthomas, and gout (8, 7, and 4 cases, respectively). Traumatic lesions were noted in 41 cases and were most commonly characterized by head trauma and cerebral hemorrhage. Toxicity was rare; five total cases caused by a single carbon monoxide event were identified.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Pulmonary silicosis in 2 rock hyraxes, and literature review.

Two rock hyraxes (Procavia capensis), from the Chattanooga Zoo, were submitted separately for autopsy at the University of Tennessee Veterinary Medical Center. The first was a 4-y-old intact female that died without premonitory signs and the second was a 10-y-old intact male that was euthanized because of severe renal disease. Microscopically, the lungs of both hyraxes had multifocal-to-coalescing, <1-mm diameter aggregates of epithelioid macrophages separated by streams of fibrous tissue. Macrophages contained intracytoplasmic, clear, acicular, birefringent crystals. Transmission electron microscopy and energy-dispersive x-ray spectroscopy findings on the lung samples were consistent with silica crystal deposition. The hyraxes had been housed together on commercially sourced play sand composed of 99-99.5% quartz, a crystalline silica polymorph. The microscopic findings, transmission electron microscopy, and energy-dispersive x-ray spectroscopy of the intrahistiocytic crystals, in addition to the history of exposure to crystalline silica, were consistent with pulmonary silicosis. Pulmonary silicosis has not been reported previously in rock hyraxes, to our knowledge.

Formulation of a triple combination gemcitabine plus romidepsin + cisplatin regimen to efficaciously and safely control triple-negative breast cancer tumor development.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive, lethal, and heterogeneous subtype of breast cancers, tending to have lower 5-year survival rates than other BC subtypes in response to conventional chemotherapies. This study's aim was to identify advanced regimens to effectively control TNBC tumor development. METHODS: We investigated the combination of the DNA synthesis inhibitor gemcitabine, the DNA-damaging agent cisplatin, and the histone deacetylase inhibitor romidepsin to control a variety of breast cells in vitro. We studied the toxicity of drug doses and administration schedules to determine tolerable combination regimens in immune-deficient nude and -competent BALB/c mice. We then studied the efficacy of tolerable regimens in controlling TNBC cell-derived xenograft development in nude mice. By reducing clinically equivalent doses of each agent in combination, we formulated tolerable regimens in animals. We verified that the tolerable triple combination gemcitabine plus romidepsin + cisplatin regimen more efficacious than double combination regimens in controlling xenograft tumor development in nude mice. RESULTS: A triple combination of gemcitabine + romidepsin + cisplatin synergistically induced death of the TNBC M.D. Anderson-Metastatic Breast cancer (MDA-MB) 231 and MDA-MB468, as well as Michigan Cancer Foundation (MCF) 7, MCF10A, and MCF10A-Ras cells. Cell death induced by gemcitabine + romidepsin + cisplatin was in a reactive oxygen species-dependent manner. CONCLUSION: Considering the high costs for developing a new anticancer agent, we used the FDA-approved drugs gemcitabine, romidepsin (is approved for T-cell lymphoma and is under clinical trial for TNBC), and cisplatin to economically formulate an efficacious and safe combination regimen. The highly efficacious gemcitabine plus romidepsin + cisplatin regimen should be poised for efficient translation into clinical trials, ultimately contributing to reduced mortality and improved quality of life for TNBC patients.

Microbial translocation and skeletal muscle in young and old vervet monkeys.

Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6-27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.