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- Author or Editor: M. Katherine Tolbert x
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Abstract
OBJECTIVE To investigate the effects of specific cysteine protease (CP) inhibitors on cytopathic changes to porcine intestinal epithelial cells induced by Tritrichomonas foetus isolated from naturally infected cats.
SAMPLE T foetus isolates from 4 naturally infected cats and nontransformed porcine intestinal epithelial cells.
PROCEDURES T foetus isolates were treated with or without 0.1 to 1.0mM of the CP inhibitors antipain, cystatin, leupeptin, and chymostatin and the vinyl sulfone inhibitors WRR-483 and K11777. In-gel gelatin zymography was performed to evaluate the effects of these inhibitors on CP activity of T foetus isolates. Each treated or untreated isolate was also cocultured with monolayers of porcine intestinal epithelial cells for 24 hours, and cytopathic effects of T foetus were evaluated by light microscopy and crystal violet spectrophotometry.
RESULTS Results of in-gel gelatin zymography suggested an ability of WRR-483, K11777, and cystatin to target specific zones of CP activity of the T foetus isolates. These inhibitors had no effect on T foetus growth, and the cytopathic changes to the intestinal epithelium induced by all 4 T foetus isolates were significantly inhibited.
CONCLUSIONS AND CLINICAL RELEVANCE This study revealed that certain protease inhibitors were capable of inhibiting regions of CP activity (which has been suggested to cause intestinal cell damage in cats) in T foetus organisms and of ameliorating T foetus–induced cytopathic changes to porcine intestinal epithelium in vitro. Although additional research is needed, these inhibitors might be useful in the treatment of cats with trichomonosis.
Abstract
CASE DESCRIPTION A 6-year-old castrated male Boxer was evaluated for a 5-week history of frequent vomiting, melena, and signs of abdominal pain following accidental ingestion of 5 to ten 15-mg meloxicam tablets (approx ingested dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]).
CLINICAL FINDINGS Clinical signs persisted despite 3 weeks of treatment with sucralfate (41.8 mg/kg [19 mg/lb], PO, q 8 h) and omeprazole (0.8 mg/kg [0.36 mg/lb], PO, q 24 h). Results of a CBC and serum biochemical analysis were unremarkable. Abdominal ultrasonography revealed peptic ulceration, and esophagogastroduodenoscopy confirmed the presence of severe proximal duodenal ulceration.
TREATMENT AND OUTCOME A radiotelemetric pH-monitoring capsule was placed in the gastric fundus under endoscopic guidance for continuous at-home monitoring of intragastric pH and response to treatment. Treatment was continued with sucralfate (as previously prescribed) and omeprazole at an increased administration frequency (0.8 mg/kg, PO, q 12 h). Intragastric pH was consistently ≥ 3.0 for > 75% of the day during treatment, with the exception of 1 day when a single dose of omeprazole was inadvertently missed. Ulceration and clinical signs completely resolved.
CLINICAL RELEVANCE Continuous radiotelemetric monitoring of intragastric pH in the dog of this report was useful for confirming that treatment achieved a predetermined target pH and for demonstrating the impact of missed doses. Duodenal ulceration resolved with twice-daily but not once-daily omeprazole administration. Findings suggested that twice-daily administration of omeprazole may be necessary to achieve this target pH and that a pH ≥ 3.0 for 75% of the day may promote healing of peptic ulcers in dogs.
Abstract
OBJECTIVE
To characterize gastrointestinal transit times (GITTs) and pH in dogs, and to compare to data recently described for cats.
ANIMALS
7 healthy, colony-housed Beagles.
PROCEDURES
The GITTs and pH were measured using a continuous pH monitoring system. For the first period (prefeeding), food was withheld for 20 hours followed by pH capsule administration. Five hours after capsule administration, dogs were offered 75% of their historical daily caloric intake for 1 hour. For the second period (postfeeding), food was withheld for 24 hours. Dogs were allowed 1 hour to eat, followed by capsule administration. Both periods were repeated 3 times. The GITTs and pH were compared to published feline data.
RESULTS
The mean ± SD transit times in dogs for the pre- and postfeeding periods, respectively, were esophageal, 3 ± 5 minutes and 13 ± 37 minutes; gastric, 31 ± 60 minutes and 829 ± 249 minutes; and intestinal, 795 ± 444 minutes and 830 ± 368 minutes. The mean ± SD gastrointestinal pH in dogs for the pre- and postfeeding periods, respectively, were esophageal, 6.6 ± 0.6 and 5.7 ± 1.0; gastric, 3.0 ± 1.4 and 1.8 ± 0.3; intestinal, 7.9 ± 0.3 and 7.7 ± 0.6; first-hour small intestinal, 7.6 ± 0.5 and 7.1 ± 0.4; and last-hour large intestinal, 7.9 ± 0.6 and 7.7 ± 1.0. The first-hour small intestinal pH and total transit times varied between dogs and cats depending on feed period (P = .002 and P = .04, respectively). Post hoc analysis revealed significantly shorter total transit times in dogs prefeeding (P = .005; mean ± SD for cats, 2,441 ± 1,359 minutes; for dogs, 828 ± 439 minutes) and postfeeding (P = .03; mean ± SD for cats, 3,009 ± 1,220 minutes; for dogs, 1,671 ± 513 minutes). Total transit time for dogs was also shorter pre- versus postfeeding (P = .003).
CLINICAL RELEVANCE
GITT is faster in Beagles compared to cats, but gastrointestinal pH are similar when fed the same diet.