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SUMMARY

Objectives

To study effects of hypochlorous acid (HOCI) on equine colonic mucosa in vitro, and determine whether addition of ascorbic acid protects against the effects.

Animals

6 healthy horses and ponies.

Procedure

Short-circuit current was measured in mucosa mounted in Ussing chambers. Incubation conditions were: control (no additions); 5 mM HOCI; 1 mM HOCI; same and 5 mM ascorbic acid; 3 mM HOCI; 3 mM HOCI and 5 mM ascorbic acid; 7 mM HOCI; and 7 mM HOCI plus 5 mM ascorbic acid. Permeability was measured with [3H]mannitol and, at the conclusion of each experiment, tissues were examined microscopically to assess the effects of HOCI and ascorbic acid, alone or in combination.

Results

Short circuit current and conductance increased transiently in response to 1 mM HOCI. Tissues had mild surface epithelial damage, as evident by swelling and separation of isolated cells. These changes were abolished when tissues were coincubated with 5 mM ascorbic acid and 1 mM HOCI. At 3 and 7 mM concentrations, HOCI caused marked increase in tissue conductance, short circuit current, and permeability to mannitol; these changes were associated with histologic damage. Again, coincubation with 5 mM ascorbic acid protected against these changes. Additional studies indicated that the effects of HOCI and the protective effects of ascorbic acid were not mediated through changes in pH.

Conclusions

HOCI in low concentrations is capable of increasing the short-circuit current in equine colon, possibly by increasing secretions; however, higher concentrations can cause tissue damage. The addition of 5 mM ascorbic acid blocks these changes.

Clinical Relevance

The concentration of HOCI produced by activated neutrophils could damage equine colonic mucosa and potentially contribute to or cause reperfusion injury. The ability of ascorbic acid to ameliorate this injury in an in vitro setting offers a potential method for pharmacologic evaluation of this injury and for treatment. (Am J Vet Res 1998;59:82–87)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of reactive oxygen metabolites (ROMs), with and without flunixin meglumine, on equine right ventral colon (RVC) in vitro.

Animals—18 healthy horses and ponies.

Procedures—In 3 groups of 6 animals each, short-circuit current and conductance were measured in RVC mucosa in Ussing chambers. The 3 groups received physiologic saline (0.9% NaCl) solution, IV, 10 minutes before euthanasia and tissue incubation in Krebs-Ringer-bicarbonate (KRB) solution; flunixin meglumine (1.1 mg/kg, IV) 10 minutes before euthanasia and tissue incubation in KRB solution; or physiologic saline solution, IV, 10 minutes before euthanasia and incubation in KRB solution with 2.7 × 10−5M flunixin meglumine. Incubation conditions included control (no addition) and ROM systems, including addition of 1mM xanthine and 80 mU of xanthine oxidase (to produce the superoxide radical), 1mM H2O2, and 1mM H2O2 and 0.5mM ferrous sulfate (to produce the hydroxyl radical).

Results—All ROMs that were added or generated significantly increased the short-circuit current except in tissues coincubated with flunixin meglumine, and they induced mild epithelial vacuolation and apoptosis, but did not disrupt the epithelium nor change conductance, lactate dehydrogenase release, or [3H]mannitol flux.

Conclusions and Clinical Relevance—Responses to ROMs could be attributed to increased chloride secretion and inhibited neutral NaCl absorption in equine RVC, possibly by stimulating prostaglandin production. The ROMs examined under conditions of this study could play a role in prostaglandin-mediated colonic secretion in horses with enterocolitis without causing direct mucosal injury.

Full access
in American Journal of Veterinary Research

Abstract

Objectives—To study the functional and structural responses of the right dorsal colon (RDC) of ponies to phenylbutazone (PBZ) in vitro at a concentration that could be achieved in vivo.

Animals—8 adult ponies.

Procedure—Short circuit current and conductance were measured in mucosa from the RDC. Tissues incubated with and without HCO3 were exposed to PBZ, bumetanide, or indomethacin. Bidirectional Cl fluxes were determined. After a baseline flux period, prostaglandin E2 (PGE2) was added to the serosal surfaces and a second flux period followed. Light and transmission electron microscopy were performed.

Results—Baseline short circuit current was diminished significantly by PBZ and indomethacin, and increased significantly after addictions of PGE2. After PGE2 was added, Cl secretion increased significantly in tissues in HCO3--free solutions and solutions with anti-inflammatory drugs, compared with corresponding baseline measurements and with control tissues exposed to PGE2. Bumetanide did not affect baseline short circuit current and Cl fluxes. The predominant histologic change was apoptosis of surface epithelial cells treated with PBZ and to a lesser extent in those treated with indomethacin.

Conclusions and Clinical Relevance—Prostaglandin- induced Cl secretion appeared to involve a transporter that might also secrete HCO3 . Both PBZ and indomethacin altered ion transport in RDC and caused apoptosis; PBZ can damage mucosa through a mechanism that could be important in vivo. The clinically harmful effect of PBZ on equine RDC in vivo could be mediated through its effects on Cl and HCO3 secretion. (Am J Vet Res 2002;220:934–941)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To study the effects of phenylbutazone, indomethacin, prostaglandin E2 (PGE2), glutamine, and butyrate on restitution of oxidant-injured right dorsal colon of horses in vitro.

Sample Population—Right dorsal colon from 9 adult horses euthanatized for reasons other than gastrointestinal tract disease.

Procedure—Mucosal segments from the right dorsal colon were injured via exposure to HOCl and incubated in Ussing chambers in solutions containing phenylbutazone, indomethacin, indomethacin and PGE2, glutamine, and butyrate. Transepithelial resistance and mucosal permeability to mannitol were measured, and all mucosal segments were examined histologically.

Results—The HOCl-injured mucosa had lower resistance and higher permeability to mannitol, compared with control tissue. Histologic changes were also evident. Resistance of HOCl-injured mucosa recovered partially during the incubation period, and glutamine improved recovery. Phenylbutazone and indomethacin increased resistance, but these increases were not significant. Butyrate and PGE2 had no effects, compared with nontreated HOCl-injured tissues. Mucosal permeability to mannitol was lower in glutamine-treated tissue, compared with nontreated tissue. Histologic changes reflected the resistance and permeability changes.

Conclusions and Clinical Relevance—According to our findings, phenylbutazone and indomethacin do not seem to interfere with restitution of oxidant-injured mucosa of equine colon in vitro, and glutamine could facilitate mucosal restitution. (Am J Vet Res 2004;65:1589–1595)

Full access
in American Journal of Veterinary Research

Abstract

Objectives—To evaluate the in vitro protective effects of acetylcysteine and response of resident mucosal eosinophils in oxidant-induced injury to tissues of right dorsal colon of horses.

Animals—9 adult horses.

Procedure—Gastrointestinal mucosa was damaged in vitro with 3mM hypochlorous acid (HOCl), with and without prior exposure to 6mM acetylcysteine. Control tissues were not exposed to HOCl or acetylcysteine. Control and damaged tissues were incubated in Krebs-Ringer-bicarbonate solution and tissue resistance measured during 240 minutes. Tissue permeability to radiolabeled mannitol was also used to assess mucosal barrier integrity. Tissues were examined by light microscopy before and after HOCl exposure and during and after incubation.

Results—Exposure to HOCl caused tissue damage and decreased tissue resistance. Restitution did occur during the incubation period. Eosinophils were located near the muscularis mucosae in freshly harvested tissues and migrated towards the luminal surface in response to HOCl-induced injury. Compared with tissues treated with HOCl without acetylcysteine, pretreatment with acetylcysteine prevented HOCl-induced tissue damage, changes in resistance, and histologically detectable eosinophil migration. The permeability to mannitol increased to the same extent in tissues treated with HOCl alone or with acetylcysteine and HOCl.

Conclusions and Clinical Relevance—Eosinophils migrated toward the mucosal surface in equine colon in response to oxidant-induced damage in vitro. This novel finding could be relevant to inflammation in equine colon and a pathophysiologic feature of many colonic diseases. Acetylcysteine protected the mucosa against oxidant-induced injury and may be useful as a treatment option for various gastrointestinal tract disorders in horses. (Am J Vet Res 2003;64:1205–1212)

Full access
in American Journal of Veterinary Research

Abstract

Objectives—To establish reference values for the range of the number of eosinophils found in equine gastrointestinal mucosa and to describe the distribution of this cell within the equine gastrointestinal mucosa.

Sample Population—Gastrointestinal mucosal specimens from 14 adult horses euthanatized for reasons other than gastrointestinal disease.

Procedures—Gastrointestinal mucosal specimens were collected and grouped according to their anatomic regions. For histologic examination slides were stained with Luna's eosinophil stain to determine eosinophil accumulation and distribution. The mucosa was divided into 5 sections for each anatomic location, and the percentage of eosinophils in each of the 5 sections relative to the total eosinophil count in all sections was determined. Additionally, the number of eosinophils per square millimeter of mucosa was calculated as a measure of the degree of eosinophil accumulation.

Results—Lowest numbers of eosinophils were found in the stomach, and numbers increased from there to the cecum, then decreased from the ascending colon (right ventral colon, left ventral colon, pelvic flexure, left dorsal colon, and right dorsal colon) to small colon. In all gastrointestinal sections, most eosinophils were located near the muscularis mucosae and were rarely found near or on the luminal surface of the mucosa.

Conclusions and Clinical Relevance—The distribution of eosinophils in the gastrointestinal tract of horses followed a pattern within the mucosa and between different sections of the gastrointestinal tract. The derived reference values and distribution data could be used to detect changes in eosinophil response in the equine gastrointestinal mucosa caused by diseases states.

Full access
in American Journal of Veterinary Research

SUMMARY

One hundred four heartworm-free Beagles < 1 year old were studied to determine the efficacy of ivermectin chewable tablets and of 2 other ivermectin tablet formulations against heartworm larvae. At 30 days after sc inoculation of dogs with infective Dirofilaria immitis larvae, all ivermectin formulations were given orally at dosage of 6 μg/kg of body weight. The ivermectin chewable tablets also were given orally at dosage of 2 and 6 μg/kg at 30 and 45 days, respectively, after injection of larvae. Replicates of 6 or 8 dogs in each study were formed on the basis of gender and body weight and, within replicates, were randomly allocated to treatment groups. At 30 days after injection of larvae, the additional dogs (in replicates of 8) were assigned to the control group and to the group given ivermectin chewable tablets at dosage of 6 μg/kg. All dogs were housed individually. Necropsy was performed approximately 5 or 6 months after larvae were administered.

In both trials, all control dogs had heartworms at necropsy (Univerity of Illinois—geometric mean, 35.0; Florida—geometric mean, 26.1). In both trials, the ivermectin chewable tablet (6 μg/kg) and both tablet formulations (6 μg/kg) given at 30 days after larval injection, and the chewable formulation (6 μg/kg) given at 45 days after larval injection were 100% effective (P < 0.01) in preventing development of induced infection with D immitis. Of 8 dogs at the University of Illinois that were given ivermectin chewable tablets (2 μg/kg) at 30 days after larval injection, 6 had heartworms (geometric mean, 2.25; efficacy, 93.6%; P < 0.01) and 5 of 7 dogs treated similarly in Florida had heartworms (geometric mean, 4.4; efficacy, 83.3%; P < 0.05).

Drug-related adverse reactions were not observed in either trial.

Free access
in American Journal of Veterinary Research