Background Intestinal absorption of bile acids is mediated by the apical sodium-dependent bile acid transporter (ASBT). Fecal bile acid dysmetabolism has been reported in dogs with chronic inflammatory enteropathy (CIE). Objective Characterization of ASBT distribution along the intestinal tract of control dogs and comparison to dogs with CIE. Animals Twenty-four dogs with CIE and 11 control dogs. Methods The ASBT mRNA and protein expression were assessed using RNA in situ hybridization and immunohistochemistry, respectively. The concentrations of fecal bile acids were measured by gas chromatography-mass spectrometry. The fecal microbiota dysbiosis index was assessed with a quantitative polymerase chain reaction panel. Results In control dogs, ASBT mRNA expression was observed in enterocytes in all analyzed intestinal segments, with highest expression in the ileum. The ASBT protein expression was restricted to enterocytes in the ileum, cecum, and colon. Dogs with CIE had significantly decreased expression of ASBT protein in the ileum (P = .001), which was negatively correlated with histopathological score (ρ = −0.40; P_corr = .049). Additionally, dogs with CIE had a significantly increased percentage of primary bile acids in feces compared to controls (P = .04). The fecal dysbiosis index was significantly higher in dogs with CIE than in control dogs (P = .01). Conclusions and Clinical Importance These findings indicate that ileal protein expression of ASBT is downregulated in dogs with CIE. This change may be linked to the inflammatory process, intestinal dysbiosis, and fecal bile acid dysmetabolism observed in these patients.

Immunohistochemistry using a commercial polyclonal antibody for lyssavirus was applied to 39 archival cases of rabies. Paraffin blocks from 13 different species were available, including 3 dogs, 4 cats, 1 pig, 6 cattle, 4 horses, 1 llama, 7 skunks (Mephitis mephitis), 7 raccoons (Procyon lotor), 1 bat (Myotis species), 1 white-tailed deer (Odocoileus virginianus), 1 bobcat (Lynx rufus), 2 gray foxes (Urocyon cinereoargenteus), and 1 red fox (Vulpes vulpes). All cases had previously been diagnosed as rabies using histopathology and/or fluorescent antibody testing. The immunohistochemistry technique successfully detected lyssavirus antigen in all cases. In species for which 3 or more samples were available, distributional trends were seen in 4 main brain regions: brainstem, cerebellum, hippocampus, and cerebrum. The best site for rabies virus detection in dogs and cats was the hippocampus. For cattle, viral antigen was most prominent in the brainstem, followed by the cerebellum. In horses, the cervical spinal cord and adjacent brainstem were the optimal sites for detecting rabies virus antigen. In raccoons and skunks, positive labeling was widely dispersed, so selection might be less important for these wildlife reservoir species. Immunohistochemistry should prove useful in enhancing the accuracy of rabies diagnosis through informed selection of brain sampling sites when composite sampling is not feasible. This immunohistochemical technique could provide reliable virus detection in formalin-fixed tissues in any potentially infected species.

Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial digital flexor tendon (SDFT) of 17 horses. Tendon lesions were treated 1 week later with an intralesional injection of miR29a or placebo. miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1. The relative lesion cross-sectional area was significantly lower in miR29a tendons compared to control tendons. Histology scores were significantly better for miR29a-treated tendons compared to control tendons. These data support the mechanism of microRNA-mediated modulation of early pathophysiologic events that facilitate tissue remodeling in the tendon after injury and provides a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing.

Clostridium chauvoei causes blackleg in cattle. The disease has been reported worldwide, and although it can be prevented by vaccination, sporadic cases and occasional outbreaks still occur. We describe a case of blackleg in a 2-y-old, pregnant Gyr cow with in utero transmission to the fetus. The cow had characteristic gross and microscopic lesions of blackleg including widespread necrohemorrhagic and emphysematous skeletal and myocardial myositis, and fibrinous pericarditis. Her uterus contained a near-term, markedly emphysematous fetus with skeletal muscle and myocardial lesions similar to those seen in the dam. Histopathology of dam and fetal tissues revealed numerous gram-positive bacilli, many of them with sub-terminal spores, in multiple tissues. These bacilli were identified as C. chauvoei by immunohistochemistry. Anaerobic culture and fluorescent antibody tests performed on skeletal muscle from both the dam and fetus were positive for C. chauvoei, confirming a diagnosis of blackleg. Blackleg is a so-called endogenous infection, and the currently accepted pathogenesis involves ingestion of spores that are transported to muscle tissues where they lie dormant until anaerobiosis prompts germination. Germinating bacteria are histotoxic, producing severe, local necrosis and ultimately lethal toxemia. This model, however, has not been confirmed experimentally and also fails to explain some cases of the disease. A presumptive diagnosis of blackleg is based on clinical, gross, and histologic findings. Diagnostic confirmation necessitates the detection of C. chauvoei by culture, PCR, or immunodetection methods.

Infection by Theiler’s murine encephalomyelitis virus (TMEV) is a model for neurological outcomes caused by virus infection because it leads to diverse neurological conditions in mice, depending on the strain infected. To extend knowledge on the heterogeneous neurological outcomes caused by TMEV and identify new models of human neurological diseases associated with antecedent infections, we analyzed the phenotypic consequences of TMEV infection in the Collaborative Cross (CC) mouse population. We evaluated 5 different CC strains for outcomes of long-term infection (3 months) and acute vs. early chronic infection (7 vs. 28 days post-infection), using neurological and behavioral phenotyping tests and histology. We correlated phenotypic observations with haplotypes of genomic regions previously linked to TMEV susceptibility to test the hypothesis that genomic diversity within CC mice results in variable disease phenotypes in response to TMEV. None of the 5 strains analyzed had a response identical to that of any other CC strain or inbred strain for which prior data are available, indicating that strains of the CC can produce novel models of neurological disease. Thus, CC strains can be a powerful resource for studying how viral infection can cause different neurological outcomes depending on host genetic background.