Right dorsal colitis in horses: A multicenter retrospective study of 35 cases.

BACKGROUND: Right dorsal colitis (RDC) is a nonsteroidal anti-inflammatory drug (NSAID) induced, protein losing enteropathy in horses associated with a high case fatality rate. OBJECTIVES: To describe signalment, NSAID usage, clinical presentations, clinical pathology, ultrasonographic findings, treatments, outcomes, and factors associated with survival in horses diagnosed with RDC. ANIMALS: Thirty-five horses from 7 Australian equine hospitals diagnosed with RDC. METHODS: Retrospective case series. Clinical records of cases were accepted if definitively or presumptively diagnosed by an internist with RDC and had ≥3 of: hypoproteinemia or hypoalbuminemia; diarrhea with negative test results for infectious diseases; colic for which other diseases were excluded or right dorsal colon thickening on ultrasound. Descriptive data analysis was performed for categorical and continuous variables. Univariate binominal logistic regressions were used to assess factors associated with survival. RESULTS: An overdose of NSAIDs occurred in 84% (21/25) cases where dose was known. Common clinical presentations included diarrhea (69%; 22/32), colic (61%; 20/33), and tachycardia (53%, 17/32). Common clinicopathological findings included hypoalbuminemia (83%; 26/31), hypocalcaemia (79%, 23/29), and hyperlactatemia (77%, 14/18). The right dorsal colon wall appeared subjectively thickened in 77% (24/31) cases using ultrasonography. Case fatality rate was 43% (15/35). Odds of survival significantly decreased with increasing heart rate (odds 0.84, 95% CI = 0.71-0.92, P = .01), packed cell volume (odds 0.91, 95% CI 0.82-0.98, P = .05) and abnormal appearance of mucous membranes (odds 0.05, 95% CI 0.005-0.28, P = .001) on hospital presentation. CONCLUSIONS AND CLINICAL IMPORTANCE: An overdose of NSAIDs is common in horses diagnosed with RDC. Serum albumin concentrations should be monitored in horses receiving a prolonged course of NSAIDs. Overall prognosis for RDC remains fair.

Causes of equine perinatal mortality.

The peripartum period is critical in equine medicine for maintaining healthy mares, and ensuring the delivery of healthy neonatal foals. The field of perinatal mortality in horses is continuously evolving, with several advances being recently made in causes of perinatal fetal and foal loss. This review details the main causes of perinatal loss in horses, through late pregnancy, parturition and the neonatal period. Recent advances in identification of infectious organisms and indicators of survival in neonatal foals will be discussed. Continued advances in reproductive and neonatal medicine will aid improved survival of foals through fewer pregnancy losses, and improved management of high-risk pregnancies and critically ill neonatal foals.

Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses.

BACKGROUND: Doramapimod, a p38 MAPK inhibitor, is a potent anti-inflammatory drug that decreases inflammatory cytokine production in equine whole blood in vitro. It may have benefits for treating systemic inflammation in horses. OBJECTIVE: To determine whether doramapimod is well tolerated when administered IV to horses, and whether it has anti-inflammatory effects in horses in a low-dose endotoxemia model. ANIMALS: Six Standardbred horses. METHODS: Tolerability study, followed by a blinded, randomized, placebo-controlled cross-over study. Horses were given doramapimod, and clinical and clinicopathological variables were monitored for 24 hours. Horses then were treated with doramapimod or placebo, followed by a low dose infusion of lipopolysaccharide (LPS). Clinical variables (heart rate, rectal temperature, noninvasive blood pressure), leukocyte count and tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) concentrations were measured at multiple time points until 6 hours post-LPS infusion. RESULTS: No adverse effects or clinicopathological changes were seen in the safety study. When treated with doramapimod as compared to placebo, horses had significantly lower heart rates (P = .03), rectal temperatures (P = .03), and cytokine concentrations (P = .03 for TNF-α and IL-1ß), and a significantly higher white blood cell count (P = .03) after LPS infusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Doramapimod has clinically relevant anti-inflammatory effects in horses, likely mediated by a decrease in leukocyte activation and decrease in the release of pro-inflammatory cytokines. To evaluate its potential as a novel treatment for systemic inflammatory response syndrome in horses, clinical trials will be necessary to determine its efficacy in naturally occurring disease.

Anti-inflammatory effects of a p38 MAP kinase inhibitor, doramapimod, against bacterial cell wall toxins in equine whole blood.

Doramapimod (BIRB-796-BS), is an anti-inflammatory compound, acting through p38 MAPK inhibition, but its anti-inflammatory effects have not previously been studied in the horse. Whole blood aliquots from healthy horses diluted 1:1 with cell culture medium were incubated for 21 h with 1 µg/ml of lipopolysaccharide (LPS), lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of doramapimod (3 × 10-8 M to 10-5 M). Cell bioassays were used to measure TNF-α and IL-1ß activity. Doramapimod significantly and potently inhibited TNF-α and IL-1ß activity induced by all three bacterial toxins. There was no significant difference in IC50 or maximum inhibition of TNF-α or IL-1ß production between any of the toxins. Maximum inhibition of IL-1ß was higher than that of TNF-α for all toxins, and this difference was significant for LPS (P = 0.04). Doramapimod was a potent inhibitor of TNF-α and IL-1ß for inflammation induced by LPS, LTA and PGN, with potency much greater than that of other drugs previously tested using similar methods.