OBJECTIVE To investigate the safety of daily oral administration of grapiprant to dogs. ANIMALS Thirty-six 9-month-old Beagles of both sexes. PROCEDURES Dogs were randomly assigned to groups that received grapiprant via oral gavage at 0, 1, 6, or 50 mg/kg (total volume, 5 mL/kg), q 24 h for 9 months. Each group contained 4 dogs of each sex (ie, 8 dogs/group), except for the 50 mg/kg group, which included 4 additional dogs that were monitored for an additional 30 days after treatment concluded (recovery period). All dogs received ophthalmologic, ECG, and laboratory evaluations before treatment began (baseline) and periodically afterward. All dogs were observed daily. Dogs were euthanized at the end of the study for necropsy and histologic evaluation. RESULTS All dogs remained clinically normal during treatment, with no apparent changes in appetite or demeanor. Emesis and soft or mucoid feces that occasionally contained blood were observed in all groups, although these findings were more common in dogs that received grapiprant. In general, clinicopathologic findings remained within baseline ranges. Drug-related changes in serum total protein and albumin concentrations were detected, but differences were small and resolved during recovery. No drug-related gross or microscopic pathological changes were detected in tissue samples except mild mucosal regeneration in the ileum of 1 dog in the 50 mg/kg group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested the safety of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in the treatment of dogs with osteoarthritis needs to be evaluated in other studies.

OBJECTIVE To analyze the transit time from various locations in the intestines of cows with cecal dilatation-dislocation (CDD), healthy control cows, and cows with left displacement of the abomasum (LDA). ANIMALS 15 cows with naturally occurring CDD (group 1), 14 healthy control cows (group 2), and 18 cows with LDA (group 3). PROCEDURES 5 electronic transmitters were encased in capsules and placed in the lumen of the ileum, cecum, proximal portion of the colon, and 2 locations in the spiral colon (colon 1 and colon 2) and used to measure the transit time (ie, time between placement in the lumen and excretion of the capsules from the rectum). Excretion time of the capsules from each intestinal segment was compared among groups. RESULTS Cows recovered well from surgery, except for 1 cow with relapse of CDD 4 days after surgery and 2 cows with incisional infection. High variability in capsule excretion times was observed for all examined intestinal segments in all groups. Significant differences were detected for the excretion time from the colon (greater in cows with CDD than in healthy control cows) and cecum (less in cows with LDA than in cows of the other 2 groups). CONCLUSIONS AND CLINICAL RELEVANCE The technique developed to measure excretion time of capsules from bovine intestines was safe and reliable; however, the large variability observed for all intestinal segments and all groups would appear to be a limitation for its use in assessment of intestinal transit time of cattle in future studies.

OBJECTIVE To characterize the expression of monocarboxylate transporters (MCTs) 1 and 4 and the ancillary protein CD147 in the intestinal tract of healthy equids and determine the cellular location of CD147 in the intestinal epithelium. ANIMALS 12 healthy horses and ponies slaughtered for meat production or euthanized for reasons unrelated to gastrointestinal tract disease. PROCEDURES The entire gastrointestinal tract was removed from each equid within 45 minutes after slaughter or euthanasia. Tissue samples were obtained from the antimesenteric side of the duodenum, jejunum, ileum, middle part of the cecum, sternal flexure of the ventral colon, pelvic flexure, sternal flexure of the dorsal colon, and descending colon (small colon). Expressions of MCT1, MCT4, and the ancillary protein CD147 were examined in tissue samples from each of the 8 intestinal locations by means of quantitative PCR assay, immunoblotting, and immunohistochemical analyses. RESULTS Expression of MCT1 was most abundant in the cecum and colonic sites, whereas expression of MCT4 was predominantly in the proximal section of the intestine (small intestinal sites and cecum). Immunohistochemical analysis revealed that MCT1 and CD147 were present in the membranes of enterocytes (in crypts and villi). CONCLUSIONS AND CLINICAL RELEVANCE The anatomic distribution of MCT1 and MCT4 in the equine intestinal tract determined in this study together with the previous knowledge of the sites of substrate absorption indicated that MCT1 might predominantly contribute to the uptake of short-chain fatty acids in the large intestine and MCT4 might predominantly contribute to the uptake of lactate in the small intestine.

OBJECTIVE To evaluate the effects of dietary nonphytate phosphorus (NPP) content on ileal lymphocyte subpopulations and cytokine expression in the cecal tonsils and spleen of hens that were or were not inoculated with Salmonella Typhimurium. ANIMALS 64 Salmonella-free hens. PROCEDURES Hens were fed a diet with 0.22% (control; n = 32) or 0.42% (high-P; 32) NPP for 6 weeks and then orally inoculated with S Typhimurium (5 × 107 CFUs) or PBSS. Tissues were obtained from 8 S Typhimurium–inoculated and 8 PBSS-inoculated hens from each group at 2 and 7 days postinoculation (DPI). Percentages of ileal CD4+ and CD8+ lymphocytes were determined by flow cytometry. Cytokine mRNA expression was determined by quantitative real-time PCR assays. RESULTS For S Typhimurium–inoculated hens, plasma parathyroid hormone concentration was significantly increased and 1,25-dihydroxyvitamin D3 concentration was decreased in hens fed the high-P diet, compared with values in hens fed the control diet. Salmonella Typhimurium inoculation caused an increase in the percentage of ileal CD8+ lymphocytes and the expression of interleukin (IL)-1β, IL-6, IL-8, interferon-γ, IL-12, and IL-18 in the cecal tonsils and spleen and a decrease in the expression of IL-4 and IL-10 in the cecal tonsils. Hens fed the high-P diet had significantly increased splenic expression of interferon-γ at 2 DPI and IL-1β, IL-6, IL-12, and IL-18 at 7 DPI, compared with hens fed the control diet. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested there was a T-helper 1 cytokine reaction in the cecal tonsils and spleen of S Typhimurium–inoculated hens, and dietary NPP content altered calcium regulation hormone concentrations and affected splenic cytokine expression.