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Abstract

Objective

To determine whether administration of amphotericin B in a fat emulsion solution would reduce the nephrotoxicity of amphotericin B, compared with that associated with administration of amphotericin B in 5% dextrose solution.

Design

Prospective controlled study.

Animals

2 groups of 5 adult male Beagles.

Procedure

Dogs received amphotericin B (1 mg/kg of body weight/d) prepared in 5% dextrose solution or in 20% fat emulsion daily for 6 doses. Serum biochemical analysis, CBC, urinalysis, and endogenous creatinine clearance were performed on days 0 and 8, 2 days after the last dose of amphotericin B. On day 8, dogs were euthanatized and gross necropsies were performed. Unbiased semiquantitative scoring of the kidneys for the degree of injury was performed by use of light microscopy.

Results

There were no significant differences in serum creatinine, urea nitrogen, or potassium concentrations, urine specific gravity, endogenous creatinine clearance, or degree of tubulo-interstitial injury between the 2 groups.

Conclusion

In this model, the degree of nephrotoxicity of amphotericin B was not significantly different for dogs receiving the drug in a fat emulsion versus its administration in 5% dextrose. (Am J Vet Res 1996;57:1054–1058)

Free access
in American Journal of Veterinary Research

Abstract

Objectives

To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-α) in lungs of calves experimentally infected with Pasteurella haemolytica.

Animals

12 weight-ranked Holstein calves.

Procedure

Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 × 108 P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3- hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. Soluble TNF-α and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA.

Results

Treatment with tilmicosin resulted in significant (P< 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-α concentrations were not significantly affected by tilmicosin.

Conclusion

Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function.

Clinical Relevance

By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs. (Am J Vet Res 1998;59:765-771)

Free access
in American Journal of Veterinary Research

Summary

The role of platelet-activating factor (paf) in mediating the colonic damage that develops after large-colon torsion was studied in 14 ponies. Morphologic changes in areas of the ascending colon and selected abdominal and thoracic viscera after 1 hour of large-colon torsion and 3 to 5 hours of reperfusion were determined, as well as the protective effects of systemic administration of a specific paf antagonist (WEB 2086). Ponies were selected then allocated at random and in equal numbers to 2 groups that received 1 of 2 treatments prior to induction of large-colon torsion: group 1 —control (saline solution), and group 2 — WEB 2086 (3 mg/kg of body weight loading dose and 3 mg/kg/h for the remainder of the study). In each pony, full-thickness tissue specimens from the gastrointestinal tract —cecum, pelvic flexure, left and right ventral colon, and right dorsal colon —heart, left lung, liver, left adrenal gland, spleen, and right kidney were collected and histologically evaluated. Edema, mucosal necrosis, and neutrophil infiltration in colonic sections were graded from 0 (normal) to 3 (most severe changes). Sections of liver and lung from 3 ponies in each group, and colon from 1 pony in each group, also were examined by transmission electron microscopy to determine the presence of ultrastructural alterations.

Ischemia and reperfusion induced marked changes in all sections of colon in all ponies: moderate to severe submucosal edema, moderate necrosis of the superficial epithelium and lamina propria, and necrosis of the mucosal crypt epithelium. Extra-vascular neutrophil accumulation was evident in all sections of colon and cecum, but not in other tissues. Ultrastructural lesions were not present in hepato-cytes or pneumocytes, or in the endothelial cells of liver, lung, and colon. Bacteria were observed by electron microscopy in 5% of hepatic sinusoids. Administration of a specific paf antagonist, WEB 2086, failed to reduce severity of the observed lesions, indicating that it was not cytoprotective at the dosage used in this model of ischemia-reperfusion injury.

Free access
in American Journal of Veterinary Research

SUMMARY

Anesthesia was induced in 8 healthy llamas by administration of guaifenesin and ketamine, and was maintained with halothane in oxygen. On 2 separate experimental days, atracurium was given to induce 95 to 99% reduction of evoked hind limb digital extensor tension (twitch). For the first part of the study, atracurium was given IV as repeat boluses, with muscle twitch strength being allowed to return without intervention to 75% of baseline after each bolus before the subsequent bolus was given. A total of 5 bolus doses of atracurium was given. For the first bolus, 0.15 mg/kg of body weight IV, and for subsequent boluses, 0.08 mg/kg, induced desired relaxation. Onset of relaxation was slightly more rapid for repeat, compared with initial, bolus. Duration of relaxation and recovery time were similar to initial and repeat doses. Maximal twitch reduction was observed in 4 ± 0.2 minutes (mean ± SEM). Duration from maximal twitch reduction to 10% recovery was 6.3 ± 0.4 minutes. Twitch recovery from 10 to 50% of baseline took 11.6 ± 0.6 minutes. Twitch recovery from 10 to 75% recovery took 19.5 ± 1.1 minutes. Recovery from 10% twitch to 50% fade took 12.8 ± 0.5 minutes. Fade at 50% recovery of twitch was 39 ± 0.02%. Significant (P < 0.05) animal-to-animal variation was observed in twitch recovery times.

For the second part of the study, atracurium was initially given IV as a 0.15-mg/kg bolus, followed by infusion for 1 to 2 hours. Infusion rate required some early adjustment to maintain desired relaxation, but the rate that prevailed was 1.07 ± 0.07 ml/kg/h (0.4 mg of atracurium/ml of saline solution). Recovery of muscle twitch was similar to that previously mentioned for repeat bolus administration. At the end of the study, edrophonium (0.5 mg/kg) with atropine (0.01 mg/kg, IV) was effective in antagonizing residual neuromuscular blockade by atracurium. All llamas recovered without injury from anesthesia, although 1 llama had a rough recovery. It was concluded that atracurium can provide neuromuscular blockade by either repeat bolus administration or continuous infusion in llamas.

Free access
in American Journal of Veterinary Research

Hepatitis results in high morbidity and mortality rates in horses, 1,2 and investigation of new therapeutic agents is needed. Oxidative injury is a prominent mechanism of hepatic injury, and the positive effects of the milk thistle derivative

Full access
in American Journal of Veterinary Research

prior to clinical use of a drug. Meloxicam is an enolic acid NSAID of the oxicam group 3 and is approved for use in dogs in Europe, Canada, and the United States. In small animals, meloxicam is used for the treatment of musculoskeletal injuries, 5

Full access
in American Journal of Veterinary Research

and an agonist of prostanoid receptor subtypes E2, E3, and E4, is FDA approved for use in humans for the prevention of NSAID-related gastric and duodenal injury 4 and therefore represents one such medication. In adult horses, misoprostol has been

Full access
in American Journal of Veterinary Research

-tailed hawks are also maintained as nonreleasable animals in educational facilities, as display birds in zoos, and as companions in the falconry community. They are often evaluated for traumatic injuries, some of which include underlying infectious disease

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in American Journal of Veterinary Research

disease or to improve or restore bone quality after injury. Tiludronate disodium, a non—nitrogen-containing biphosphonate drug, affects osteoclastic activity 5–7 and has been used to prevent the resorption of bone in humans. 8 Tiludronate is currently

Full access
in American Journal of Veterinary Research

. Several studies have used ischemia-reperfusion injury to create gastric ulcers in animals. 31 Although such methods require occlusion of blood flow to the stomach or severe decreases in systemic arterial blood pressure from simulated hemorrhage that were

Full access
in American Journal of Veterinary Research