The effect of reduced frequency of administration of misoprostol on its ability to prevent aspirin-induced gastric injury was evaluated. Twenty-four random-source dogs were divided into 4 groups which received aspirin and misoprostol as follows: Group I, 25 mg/kg aspirin PO TID and placebo PO TID; Group II, 25 mg/kg aspirin PO TID and misoprostol 3 ug/kg PO TID; Group III, 25 mg/kg aspirin PO TID, misoprostol 3 ug/kg PO BID and placebo PO QD; and Group IV, 25 mg/kg aspirin PO TID, misoprostol 3 ug/kg PO QD and placebo PO BID for 28 days. Groups were stratified to contain an equal number of dogs positive or negative for Helicobacter spp. based on results of ‘CLO test’. Gastroscopy was performed on days –9, 5, 14 and 28. Each region of the stomach was evaluated separately and visible lesions were scored on a scale of 1 (submucosal hemorrhage) to 11 (perforating ulcer). The scores for each region were summed and the median total score for each group at each day and median total score within each group between days was compared using a Kruskal-Wallis test. No difference in total score was identified between Group I and IV on any day. Median total scores for Groups II and III were significantly(p < 0.05) lower compared to Groups I and IV on day 5. Significant difference was observed on Day 14 between the total score of Group III and Group IV. Group III had a significantly lower score (p < 0.05) than Groups I, II and IV on day 28. Gastric erosions were present in all groups in the study. This study suggests that misoprostol 3 ug/kg PO BID dosing is as effective as misoprostol 3 ug/kg PO TID dosing at preventing aspirin-induced gastric injury in this model. However, misoprostol 3 ug/kg PO TID dosing was less effective in preventing aspirin-induced gastric injury on days 14 and 28 than in previous studies. The lack of efficacy of TID dosing on days 14 and 28 may be related to higher salicylate concentrations in Group II dogs or individual variation within the small study population. / Master of Science

This study tested the hypothesis that administration of immunosuppressive doses of prednisone in conjunction with ultralow-dose aspirin (0.5 mg/kg/day) would result in gastroduodenal lesion scores similar to those found in dogs administered only immunosuppressive doses of prednisone, but that the gastroduodenal scores from both of these treatment groups would be significantly higher than placebo when administered to healthy dogs for 27 days. Eighteen healthy adult purpose-bred dogs were divided randomly into three groups. Group I received placebo capsules and placebo suspension, Group II received prednisone capsules (mean 2.3 mg/kg, range 2.0-2.4) and placebo suspension, and Group III received prednisone capsules (mean 2.3 mg/kg, range 2.3-2.5) and aspirin suspension (0.5 mg/kg) by mouth once daily for 27 days. Gastroduodenoscopy was performed on days -7 (baseline), 5, 14, and 27 of treatment. Four regions of the stomach (angularis incisura, body, pylorus, and cardia) and the proximal descending duodenum were systematically scored on a scale of 1 (normal) to 11 (perforating ulcer) by an experienced observer who was blinded to the treatment groups and clinical signs of each subject. Dogs were observed every 8 hours for vomiting, diarrhea, and inappetence. Feces were scored on a scale of 1-5 with diarrhea defined as a fecal score <4. Lesion scores for each group, at each location, and total scores, at each time period were evaluated for the effects of time and treatment using a Kruskal-Wallis test. Total dog days of vomiting and dog days of diarrhea in each group were compared using a Wilcoxon rank sums test. Significance was determined at p<0.05. There were no significant differences in median total gastric lesion scores between any of the groups at any time during the study. There was no location effect on regional gastroduodenal lesion scores and there was no significant change in gastroduodenal lesion scores over time in any of the groups during treatment. Significantly more dog-days of diarrhea occurred within the prednisone and aspirin group during the experimental period (Period 2) in comparison to Period 1. However, no significant differences were found between any of the groups for dog-days of vomiting, diarrhea or inappetence at any time in the study. / Master of Science

This study tested the hypothesis that administration of deracoxib, a cyclooxygenase-2 specific (COX-2) inhibitor, would result in lower gastric lesion scores than administration of buffered aspirin and gastric lesion scores similar to placebo when administered to healthy dogs for 28 days. Twenty-four, healthy, random source dogs were divided into three groups. Group I received buffered aspirin, 23.6 mg/kg PO q 8h, group II received deracoxib, 1.6 mg/kg PO q 24h and placebo twice daily PO q 8h after deracoxib administration, and group III received placebo PO q 8h. Gastroscopy was performed on days -7, 6, 14, and 28 of treatment. Four regions of the stomach (pylorus, incisura, cardia, and body) were evaluated separately and lesions scored on a scale of 1 (mucosal hemorrhage) to 12 (perforating ulcer) by an observer unaware of which treatments the dogs received. Dogs were observed every 8 hours for vomiting, diarrhea and anorexia. Feces were scored from 1-5 (scores <4 were considered diarrhea). Lesion scores for each group, at each location, and total scores, at each time period, were evaluated for the effects of time and treatment using a Kruskal-Wallis test. Total dog days of vomiting and dog days of diarrhea in each group were compared using a Wilcoxon rank sums test. Significance was determined at p<0.05. Significantly higher median total gastric lesion scores were found in the aspirin group compared to the deracoxib or placebo groups on days 6, 14, and 28. There were no significant differences in median total gastric lesion scores between the deracoxib or placebo groups at any time during the study. There was no location effect on gastric lesion scores and there was no significant change in gastric lesion scores over time in any of the groups during treatment. Significantly more dog-days of vomiting occurred in the aspirin group as compared to the deracoxib group. No significant differences were found between groups for dog-days of diarrhea. In this study, the administration of deracoxib to healthy dogs resulted in significantly lower gastric lesion scores compared to dogs receiving aspirin and lesion scores similar to those receiving placebo. / Master of Science

Equine gastric glandular mucosal ulceration can have a prevalence of 58%, yet its etiology is poorly understood. In man Helicobacter pylori is the most common cause of gastritis and peptic ulcer disease. Helicobacter is uniquely able to colonize the stomach, via the action of cytoplasmic urease. Different Helicobacter species have been isolated from many mammals but none has yet been cultured from the horse. Three tests used to identify human Helicobacter infection were applied to the horse. Test 1: PCR amplification of Helicobacter specific DNA, n=12. Test 2: the Pyloritek™ rapid urease test (RUT), n=15. Test 3: the 13C-urea blood test, n=8. Gastroscopy and antral biopsy was performed in all horses. All horses demonstrated the presence of Helicobacter specific gene material by PCR. Biopsy specimens from 7/15 horses were urease positive by RUT. Significant 13C enrichment of the body CO2 pool was found in all horses after intragastric administration 13C-urea (p<0.05). As Helicobacter is currently the only known gastric urease positive microorganism, the demonstration of this activity in horses positive by PCR strongly supports the presence of an equine gastric Helicobacter species. Variations of 13C-urea blood test were further examined and a single protocol was found to be most applicable. As the horse is a hind gut fermenter, the effect of cecal urease on the test was examined by laparoscopic intracecal administration of 13C-urea. Significant cecal urease activity was demonstrated however the timing of peak 13C enrichment may limit any effect on the gastric test to 90 minutes onwards. / Master of Science

Twenty-four healthy, mixed breed dogs were divided into four groups. Group I received a placebo PO BID, group II received an average 16.5 (range, 15.1-17.8) mg/kg buffered aspirin PO BID, group III received an average 2.2 (range, 2.0-2.4) mg/kg carprofen PO BID, and group IV received an average 12.8 (range, 11.7-13.8) mg/kg etodolac PO QD (with a placebo in the P.M.). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days – 9, 0, 5, 14 and 28. Multiple gastric biopsies were obtained endoscopically on day – 9 to determine each dog's Helicobacter spp. status. Five areas, consisting of four regions in the stomach and one in the proximal duodenum, were evaluated endoscopically, and each was assigned a score from 1 to 11 based on qualitative assessment of submucosal hemorrhage, erosion, or ulceration. These scores for each region were then summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment during the course of the study. There was no predilection site for lesion development in any group. Median total score on days 0, 5, 14, and 28 were as follows: group I, 5.0, 5.0, 5.0, 5.0; group II, 5.0, 27.0, 26.0, 27.5; group III, 5.0, 5.0, 6.0, 5.0; group IV, 5.0, 7.0, 5.0, 5.0, respectively. There was no significant difference between dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin. Thirty healthy, random source, dogs were evaluated to determine the prevalence of Helicobacter spp., and to compare the ‘Campylobacter-like organism’ test (CLOtest®) to histopathologic identification of Helicobacter spp. organisms. Gastric mucosal biopsies from each of four gastric regions (cardia, pyloric antrum, greater curvature, and angularis incisura) were obtained endoscopically for use in the CLOtest® and for histopathologic evaluation. Twenty-seven of 30 dogs (90%) were positive for spiral bacteria suspected to be Helicobacter spp. by histopathologic evaluation in at least one of the four gastric regions. Three dogs (10%) were negative for Helicobacter spp. in all gastric regions by histopathologic evaluation. The CLOtest® was found to have a sensitivity, specificity, and positive predictive value of 84%, 81%, and 92%, respectively, when compared to histopathologic evaluation. When only the angularis incisura was evaluated, the sensitivity, specificity, and positive predictive value increased to 92%, 94%, and 96%, respectively. The angularis incisura had the highest, whereas the pyloric antrum had the lowest, prevalence of positive test results when compared to dogs determined to be overall Helicobacter spp. positive (histopathologic positive in at least one gastric region). The results of this study suggest the prevalence of Helicobacter spp. in apparently healthy dogs is high. For accurate and economical detection of Helicobacter spp. in a dog undergoing upper gastrointestinal endoscopy, a tissue sample should be taken from the angularis incisura for CLOtest® sampling. / Master of Science