Modulation of In Vitro Macrophage Responses via Primary and Secondary Bile Acids in Dogs.

Bile acids (BA) are important metabolites secreted into the intestinal lumen and impacted by luminal microbes and dietary intake. Prior studies in humans and rodents have shown that BAs are immunologically active and that primary and secondary BAs have distinct immune properties. Therefore, the composition of the gut BA pool may influence GI inflammatory responses. The current study investigated the relative immune modulatory properties of primary (cholic acid, CA) and secondary BAs (lithocholic acid, LCA) by assessing their effects on canine macrophage cytokine secretion and BA receptor (TGR5) expression. In addition, RNA sequencing was used to further interrogate how CA and LCA differentially modulated macrophage responses to LPS (lipopolysaccharide). We found that exposure to either CA or LCA influenced LPS-induced cytokine production via macrophages similarly, with suppression of TNF-α secretion and enhancement of IL-10 secretion. Neither BA altered the expression of the BA receptor TGR5. Transcriptomic analysis revealed that CA activated inflammatory signaling pathways in macrophages involving type II interferon signaling and the aryl hydrocarbon receptor, whereas LCA activated pathways related to nitric oxide signaling and cell cycle regulation. Thus, we concluded that both primary and secondary BAs are active modulators of macrophage responses in dogs, with differential and shared effects evident with sequencing analysis.

Primary extraskeletal osteosarcoma of the post-hepatic caudal vena cava in a dog-Case report.

Extraskeletal osteosarcoma (EOSA) in dogs is a rare malignant mesenchymal tumor of somatic soft tissues or more commonly visceral organs with a poor prognosis. In dogs, EOSAs have been described as arising from multiple locations, but differently from humans, never from a main vessel. In this report, we describe the first case of an EOSA arising from the post-hepatic caudal vena cava in a 7-year-old male neutered mix breed dog. This report focuses on the description of the diagnostic challenges to obtain a preoperative diagnosis, highlights the importance of histopathology for a correct diagnosis, and introduces a new differential diagnosis for an animal presenting with a suspected thrombus of the vena cava.

Efficacy of an elemental diet in achieving clinical remission in dogs with chronic enteropathy.

BACKGROUND: Diet may induce clinical remission in dogs with chronic enteropathy (CE). Elemental diets (EDs), providing protein as amino acids, modulate intestinal immunity and microbiome in rodents and humans. HYPOTHESIS: Evaluate the impact of an amino acid-based kibble (EL) on CE clinical activity and gastrointestinal (GI)-relevant variables. ANIMALS: Client-owned dogs (n = 23) with inadequately controlled CE. METHODS: Prospective, uncontrolled clinical trial. Diagnostic evaluation including upper and lower GI endoscopy was performed before study entry. Canine chronic enteropathy clinical activity index (CCECAI), serum biomarkers, and fecal microbiome were evaluated before and after 2 weeks of EL. Dogs with stable or improved CE remained in the study for another 6 weeks. Pre- and post-EL clinical and microbiological variables were compared statistically using a mixed model. RESULTS: After 2 weeks of EL, 15 of 22 dogs (68%; 95% confidence interval [CI], 47%-84%) consuming the diet were classified as responders with a median (range) decrease in CCECAI from 6 (3-12) to 2 (0-9; P < .001). Fourteen of 15 responders and 2/7 nonresponders at 2 weeks completed the trial; all 16 were experiencing adequate control at week 8 with a median CCECAI of 2 (0-3). In total, 16/23 dogs (70%; 95% CI, 49%-84%) were responders. Feeding EL caused shifts in fecal bacterial communities, which differed between responders and nonresponders. Serum biomarker concentrations were unchanged throughout the study apart from serum alkaline phosphatase activity. CONCLUSIONS: Exclusive feeding of EL improved clinical signs in 16 of 23 dogs with uncontrolled CE. Fecal microbiome shifts were associated with response to diet and may represent a mechanism for clinical improvement.

Escherichia coli-associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling.

BACKGROUND: Eradication of intramucosal Escherichia coli correlates with remission of periodic acid-Schiff-positive E coli-associated granulomatous colitis (GC). Treatment failures attributed to multidrug resistant (MDR) bacteria necessitate alternative approaches. HYPOTHESIS/OBJECTIVES: Determine clinical outcome of E coli-associated GC in dogs treated based on antimicrobial susceptibility profiling and characterize E coli phylogeny and resistance mechanisms. ANIMALS: Twenty Boxers and 4 French Bulldogs with E coli-associated GC. METHODS: Culture, antimicrobial susceptibility profiling, and molecular characterization of E coli were performed and response to treatment was evaluated. RESULTS: Initial biopsy sample culture yielded fluoroquinolone-sensitive (FQ-S) E coli from 9/24 dogs and fluoroquinolone-resistant (FQ-R) E coli from 15/24. All but 1 FQ-R E coli were MDR with susceptibility to macrophage-penetrating antimicrobials restricted to carbapenems in 13/15 dogs. Of 22/24 treated based on susceptibility profiling, 8/9 FQ-S dogs had complete initial clinical response (CR) during fluoroquinolone (FQ) treatment, whereas 9/13 FQ-R dogs had complete or partial response (PR) during meropenem or doxycycline treatment. In 5/9 FQ-S and 12/13 FQ-R dogs with follow-up ≥3 months, CR was sustained in 5/5 FQ-S (median, 25 months; range, 4-46) whereas 6/12 FQ-R had long-term CR (median, 59 months; range 15-102), 4/12 PR (median, 19 months; range, 5-65), and 2/12 had no response (NR). Four dogs with long-term follow-up died within 4 years of diagnosis, including 2 euthanized for refractory colitis. Escherichia coli were genetically diverse. Fluoroquinolone resistance was associated with mutations in gyrA and parC, with plasmid-mediated resistance less common. CONCLUSIONS AND CLINICAL IMPORTANCE: Antimicrobial treatment guided by susceptibility profiling was associated with positive long-term outcomes in >80% of cases. Fluoroquinolone-resistance was widespread and not clonal. Further study is required to optimize treatment for dogs with MDR E coli-associated GC.

Long-term impact of tylosin on fecal microbiota and fecal bile acids of healthy dogs.

BACKGROUND: Tylosin is commonly prescribed to dogs with diarrhea. Orally administered antibiotics may alter the intestinal microbiota, which is responsible for crucial key bile acid (BA) biotransformation reactions. OBJECTIVES: To prospectively evaluate the impact of tylosin administration on fecal microbiota and unconjugated bile acids (UBAs) over time. ANIMALS: Sixteen healthy adult dogs. METHODS: Prospective, randomized controlled clinical trial. Dogs were randomized to receive 20 mg/kg of tylosin or a placebo capsule PO q12h for 7 days while undergoing daily fecal scoring. Fecal samples were collected on days 0, 7, 21, and 63. The microbiota was assessed using quantitative PCR and 16S rRNA gene sequencing. Unconjugated BAs were assessed using gas chromatography-mass spectrometry (GC-MS). RESULTS: Fecal scores were unchanged during placebo and tylosin administration. In the placebo group, no significant changes were observed in fecal microbiota or UBA concentrations. Day 7 samples from tylosin-exposed dogs exhibited decreased bacterial diversity (observed species, Chao1, Shannon, P < .001) characterized by decreases in anaerobes Fusobacteriaceae (linear discriminant analysis [LDA] score, 5.03) and Veillonellaceae (LDA score, 4.85). Primary UBA concentrations were increased at day 21 (median, [range]; 7.42, [0.67-18.77] µg/kg; P = .04) and day 63 (3.49 [0-28.43] µg/kg; P = .02) compared to day 0 (.14 [.03-1.19] µg/kg) in dogs receiving tylosin. At day 63, bacterial taxa were not significantly different compared to day 0, but the extent of microbial recovery was individualized. CONCLUSIONS AND CLINICAL IMPORTANCE: Tylosin causes fecal dysbiosis in healthy dogs with corresponding shifts in fecal UBAs. Changes did not uniformly resolve after discontinuation of tylosin.

Acute respiratory distress syndrome and septic shock in a cat with disseminated toxoplasmosis.

OBJECTIVE: To describe acute respiratory distress syndrome (ARDS) and septic shock in a cat with disseminated toxoplasmosis. CASE SUMMARY: A 2-year-old neutered male domestic shorthair cat was presented for acute respiratory distress. At the time of presentation it had been receiving cyclosporine for treatment of eosinophilic dermatitis. Thoracic radiographs revealed severe mixed nodular interstitial and alveolar patterns. An endotracheal wash was performed, which confirmed a diagnosis of pulmonary toxoplasmosis. Despite initial treatment with oxygen supplementation and intravenous clindamycin, the cat developed refractory hypoxemia and hypotension requiring mechanical ventilation and vasopressor support within 24 hours of hospital admission. Cardiac arrest occurred 56 hours after admission. Necropsy was performed and histopathology revealed protozoal organisms disseminated throughout the heart, lungs, liver, and brain. NEW OR UNIQUE INFORMATION PROVIDED: The clinical and necropsy findings presented here are consistent with ARDS secondary to disseminated toxoplasmosis in a cat. This is the first detailed report of ARDS in a cat. Toxoplasma titer testing and antimicrobial prophylaxis should be considered in cats prior to immunosuppressive treatment with cyclosporine.

Laparoscopic-guided compared to skilled instructor support for student rectal examination training using live horses in the veterinary curriculum.

OBJECTIVES: To evaluate the veterinary student learning outcome of 2 methods of equine rectal examination training. STUDY DESIGN: Randomized prospective study. SAMPLE POPULATION: Veterinary students (3rd and 4th year; n = 40) and practicing equine veterinarians (n = 10). METHODS: Year 1: Group 1 (n = 11) and Group 2 students (n = 10) received skilled instructor (SI) and laparoscopic-guidance (LG), respectively, during rectal exam instruction. All students were tested on rectal identification of 4 abdominal organs. Year 2: One group of students (n = 19) was trained and subsequently tested using each technique, first SI, followed by LG. Subjective evaluation of laparoscopy as a teaching tool was achieved with veterinary students and equine practitioners. RESULTS: A significantly greater percentage of students having LG compared to SI were able to correctly identify the left kidney (Year 1) and the spleen, cecum, and right ovary (Year 2). A significantly greater proportion of LG trained students in years 1 and 2 (100% and 95%, respectively) were also able to identify 75% of organs compared with SI (27% and 21%, respectively). Both students and veterinarians uniformly provided favorable feedback for LG in teaching rectal palpation skills. CONCLUSION: The LG method of equine rectal examination instruction resulted in improved learning for identification of several key abdominal organs compared with SI.