Evaluation of polymyxin B in an ex vivo model of endotoxemia in horses
| Autor: | Natalie N. Norton, Michelle H. Barton, Anna K. Parviainen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Salmonella typhimurium
Cross-Over Studies Time Factors General Veterinary Tumor Necrosis Factor-alpha Chemistry Tumor Necrosis Factor alpha biosynthesis General Medicine Polymyxin B Sulfate medicine.disease_cause Crossover study Endotoxemia Anti-Bacterial Agents Microbiology Endotoxins Escherichia coli medicine Animals Horse Diseases Horses Ex vivo Polymyxin B medicine.drug |
| Zdroj: | American Journal of Veterinary Research. 62:72-76 |
| ISSN: | 0002-9645 |
| DOI: | 10.2460/ajvr.2001.62.72 |
| Popis: | Objective— To evaluate effects of polymyxin B sulfate (PMB) on response of horses to endotoxin, using an ex vivo model. Animals—8 healthy horses. Procedure—In a crossover design, 3 doses of PMB (100, 1,000, and 10,000 U/kg of body weight) and physiologic saline solution (control) were evaluated. Prior to and for 24 hours after administration of PMB, blood samples were collected into heparinized tubes for use in 2 assays. For the endotoxin-induced tumor necrosis factor (TNF) assay, blood samples were incubated (37 C for 4 h) with 1 ng of Escherichia coli or Salmonella Typhimurium endotoxin/ml of blood. Plasma was harvested and assayed. For the residual endotoxin activity assay, plasma was collected into sterile endotoxin-free borosilicate tubes, diluted 1:10 with pyrogen-free water, and incubated for 10 minutes at 70 C. Escherichia coli endotoxin (0.1 or 1 ng/ml of plasma) was added to the thawed samples prior to performing the limulus ameobocyte lysate assay. Serum creatinine concentrations were monitored for 1 week. Results—Compared with baseline values, PMB caused a significant dose- and time- dependent decrease in endotoxin-induced TNF activity. Compared with baseline values, residual endotoxin activity was significantly reduced after administration of 10,000 U of PMB/kg. Compared with baseline values, 1,000 and 5,000 U of PMB/kg should inhibit 75% of endotoxin-induced TNF activity for 3 and 12 hours, respectively. Serum creatinine concentrations remained within the reference range. Conclusion and Clinical Relevance—Results of the study suggest that PMB is a safe, effective inhibitor of endotoxin-induced inflammation in healthy horses. ( Am J Vet Res 2001; 62:72–76) |
| Databáze: | OpenAIRE |
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