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  • Author or Editor: Robert J. MacKay x
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Summary

A total of 378 serum samples from 240 hospitalized horses and 47 sera from healthy control horses were assayed for growth effects on actinomycin d-treated L929 cells. On average, patient and control sera stimulated cell growth; however, mean percentage of the relative growth index (rgi) of sera from clinical cases was significantly (P < 0.001) lower than that of control sera. Approximately 35% of patient sera and 6% of control sera had tumor necrosis factor-like cytotoxic activity for L929 cells (ie, rgi < 100%). Sera from horses with either peritoneal leakage of gastrointestinal tract contents or any bacterial infection were significantly (P < 0.05) more cytotoxic than sera from horses that did not have these clinical factors. A clear tendency was evident for horses that had the highest serum cytotoxicity (rgi < 75%) to also have clinical profiles suggestive of endotoxemia. Fever, leukopenia, diarrhea, and gastrointestinal tract leakage were significantly (P < 0.05) overrepresented among these horses, compared with horses without serum cytotoxicity. Bacterial infections and abdominal surgeries were also increased in this group, but not significantly. Of the 14 horses with serum rgi < 75%, 13 had some form of gastrointestinal tract disease and the other had gram-negative septicemia. Survival to discharge was significantly (P < 0.05) lower among horses in the high-cytotoxicity group than among horses without serum cytotoxicity. Diarrhea and bacterial infections were the only clinical factors found more frequently in horses with low serum cytotoxicity than in horses without serum cytotoxicity. The finding of circulating cytotoxic activity in horses at risk for endotoxemia was consistent with the proposed role for tumor necrosis factor as an important mediator of inflammation.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To investigate the use of a specific antibody index (AI) that relates Sarcocystis neurona–specific IgG quotient (QSN) to total IgG quotient (QIgG) for the detection of the anti–S neurona antibody fraction of CNS origin in CSF samples obtained from horses after intragastric administration of S neurona sporocysts.

Animals—18 adult horses.

Procedures—14 horses underwent intragastric inoculation (day 0) with S neurona sporocysts, and 4 horses remained unchallenged; blood and CSF samples were collected on days – 1 and 84. For purposes of another study, some challenged horses received intermittent administration of ponazuril (20 mg/kg, PO). Sarcocystis neurona–specific IgG concentrations in CSF (SNCSF) and plasma (SNplasma) were measured via a direct ELISA involving merozoite lysate antigen and reported as ELISA units (EUs; arbitrary units based on a nominal titer for undiluted immune plasma of 100,000 EUs/mL). Total IgG concentrations in CSF (IgGCSF) and plasma (IgGplasma) were quantified via a sandwich ELISA and a radial immunodiffusion assay, respectively; QSN, QIgG, and AI were calculated.

Results—Following sporocyst challenge, mean ± SEM SNCSF and SNplasma increased significantly (from 8.8 ± 1.0 EUs/mL to 270.0 ± 112.7 EUs/mL and from 1,737 ± 245 EUs/mL to 43,169 ± 13,770 EUs/mL, respectively). Challenge did not affect total IgG concentration, QSN, QIgG, or AI.

Conclusions and Clinical RelevanceS neurona–specific IgG detected in CSF samples from sporocyst-challenged horses appeared to be extraneural in origin; thus, this experimental challenge may not reliably result in CNS infection. Calculation of a specific AI may have application to the diagnosis of S neurona–associated myeloencephalitis in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objectives—To measure serum polymyxin B concentration after single and repeated IV infusions in horses.

Animals—5 healthy horses.

Procedures—In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-α. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary γ-glutamyl transferase (GGT)to-creatinine ratios.

Results—In study 1, mean ± SEM maximal serum polymyxin B concentration was 2.93 ± 0.38 μg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 ± 0.81 μg/mL and 1.91 ± 0.50 μg/mL, respectively. Mean trough concentration for all doses was 0.22 ± 0.01 μg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration.

Conclusions and Clinical Relevance—Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.

Full access
in American Journal of Veterinary Research

Summary

Antisera raised in rabbits against either purified recombinant-derived human tumor necrosis factor (tnf)- α (hutnf) or hutnf peptide-bovine thyroglobulin conjugates were evaluated for anti-equine tnf (eqtnf) activity. Binding and neutralizing anti-eqtnf activities were found in antisera raised against whole hutnf or against either of the peptides containing the N-terminal 15 amino acids of hutnf (hutnf[1-15] and hutnf[1-31]). Anti-eqtnf activity was not detected in antisera raised against hutnf[65-79], hutnf[98-111] or hutnf[124-141] peptides. The addition of excess hutnf[1-15] completely inhibited the ability of anti-hutnf[1-15] to bind eqtnf and reduced by approximately 25% the anti-eqtnf activity of an antiserum raised against whole hutnf. Nonconjugated hutnf[1-15] did not have eqtnf agonist or antagonist activity. Results were consistent with previous structural and functional data implicating the N-terminus of hutnf in receptor binding and indicate that the homologue of hutnf[1-15] on eqtnf may be a potentially important target for neutralizing anti-eqtnf antibodies.

Free access
in American Journal of Veterinary Research

Summary

Because hepatocyte-stimulating factor/interleukin 6 (il-6) is the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating il-6 activity was monitored in 4 adult horses for 72 hours after iv administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin—1,000, 30, 1, and 0 ng/kg of body weight. Plasma il-6 activity was quantified as the ability to promote growth of the il-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 ± 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P < 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kg dosage of endotoxin, peak plasma il-6 activity (10,128 ± 4,096 and 1,555 ± 1,326 U/ml, respectively) was observed for 3 hours. The il-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma il-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

Abstract

Case Description—A 6-year-old Appaloosa mare was examined because of inappetance, difficulty eating, and swelling and mucopurulent discharge in the right eye.

Clinical Findings—Results of a CBC and serum bio-chemical analysis revealed no important findings. Ophthalmologic examination revealed scarring and ulcer-ation of the superficial layers of the cornea. Endoscopic examination of the upper portion of the respiratory tract and auditory tube diverticula (guttural pouches) revealed abnormal thickness of the right stylohyoid bone and a plaque suggestive of mycotic growth on the left internal carotid artery. Radiographic examination revealed right-sided otitis media. Temporohyoid osteoarthropathy in the right guttural pouch and mycosis in the left guttural pouch were diagnosed.

Treatment and Outcome—Ceratohyoidectomy of the right stylohyoid bone was performed, and the left internal carotid artery was occluded via placement of stainless steel spring embolization coils. The mare regained the ability to eat without difficulty and improved clinically for approximately 4 weeks. However, the mare returned to the medical center 53 days after surgery with left-sided Horner syndrome, atrophy of the right side of the tongue, and a 3-week history of dysphagia and weight loss. Endoscopic evaluation revealed progression of mycotic growth in the left guttural pouch. The mare was euthanatized.

Clinical Relevance—Although the mycotic lesion in the left guttural pouch was an incidental finding at the time of initial examination, the lesion progressed to cause dysphagia and Horner syndrome after occlusion of the left internal carotid artery, a treatment that is typically associated with resolution of guttural pouch mycosis. Arterial occlusion is not necessarily a reliable method of resolving guttural pouch mycosis.

Full access
in Journal of the American Veterinary Medical Association