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shapes of the elimination phases in time versus plasma concentration curves were similar after each treatment, suggesting that clearance of carprofen remained unchanged. Activated charcoal has not been reported to affect clearance of other NSAIDs. 23

Full access
in American Journal of Veterinary Research

, platelet activation has preceded the onset of lameness. 5 One measure of platelet activation in experimentally induced acute laminitis is an increase in circulating concentrations of serotonin, which is detectable in the interval between oligofructose

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in American Journal of Veterinary Research

SUMMARY

The effects of exogenous platelet-activating factor (paf) were determined in anesthetized ponies. Administration of paf induced a decrease in cardiac index that resulted in systemic hypotension. This was followed by tachycardia, hypertension, and a return of cardiac index to baseline. Pulmonary aterial pressure increased markedly because of pulmonary vasoconstriction. Exogenous paf also caused leukopenia and thrombocytopenia. The specific PAP receptor antagonist (WEB 2086) blocked all paf-induced changes. Flunixin meglumine, a cyclooxygenase inhibitor, abolished the pulmonary hypertension and tachycardia, and attenuated the systemic hypotension but did not change the paf-induced peripheral cellular changes. The paf antagonist also inhibited platelet aggregation induced by paf in vitro. The paf-induced changes are similar to those reported after endotoxin exposure in horses.

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.

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in American Journal of Veterinary Research

Abstract

Objective

To evaluate coagulation variables in 2 groups of dogs after tromethamine administration.

Animals

13 Beagles.

Procedures

Both groups of dogs received a 30-minute IV infusion of 10 ml of 0.3M tromethamine/kg of body weight. In unsedated dogs (group 1, n = 8), prothrombin time, activated partial thromboplastin time, normalized ionized calcium concentration, platelet numbers, and platelet function were measured prior to treatment, at the end of the infusion, and 1 hour after the infusion. In xylazine-sedated dogs (group 2, n = 5), buccal mucosal bleeding time and plasma percentage of von Willebrand factor antigen were measured before and 1 hour after infusion, and fibrin degradation products concentration was measured 1 hour after infusion. Platelet function was assessed by determining platelet aggregation and by measuring ATP release from the aggregating platelets over 6 minutes, using a whole blood aggregometer, with 20, 10, and 5 μM ADP and 5 and 10 μg of collagen/ml as platelet activation agonists.

Results

There was no significant change in any of the variables measured in either group of dogs, compared with baseline values.

Conclusions and Clinical Relevance

When administered to healthy dogs, tromethamine does not change the coagulation indices measured. (Am J Vet Res 1997;58:777–780)

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in American Journal of Veterinary Research

Abstract

Objectives

To examine effects of histamine on equine eosinophil adherence in vitro and to determine the histamine receptor subtype(s) and cell surface adhesion molecules that mediate this response. In addition, to determine the receptor subtypes involved in histamine-induced eosinophil migration.

Animals

8 healthy ponies.

Procedure

Effects of histamine on equine eosinophil adherence to serum- or fibronectin-coated plastic, and migration in a microchemotaxis assay were examined. In some experiments, eosinophils were pretreated with histamine receptor antagonists or monoclonal antibodies raised against cell adhesion molecules. For comparison, the effect of histamine on equine neutrophil adherence and migration was studied.

Results

Histamine induced adherence of equine eosinophils, but not neutrophils, to serum- and fibronectin-coated plastic (P < 0.01). Histamine also caused migration of equine eosinophils, but not neutrophils (P < 0.01). Histamine-induced adherence and migration of equine eosinophils were inhibited by histamine, (H1)-receptor antagonists chlorpheniramine and mepyramine (P < 0.01 ), but not H2- or H3-receptor antagonists cimetidine and thioperamide. Monoclonal antibodies raised against CD18, but not very late antigen 4, reduced histamine-induced equine eosinophil adherence to serum- and fibronectin-coated plastic (P < 0.01).

Conclusions

When released from mast cells or basophils, histamine could stimulate adherence and migration of equine eosinophils via H1 receptor activation and induce adherence of equine eosinophils to opsonized surfaces or dermal connective tissue matrix proteins via CD18 activation.

Clinical Relevance

Histamine may have a part in regulating equine eosinophil function during parasitic killing or antigen-induced responses in horses with insect hypersensitivity. (Am J Vet Res 1998;59:1153— 1159)

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in American Journal of Veterinary Research

Abstract

Objective

Because of the implication of histamine in canine atopic dermatitis, H1-antihistamines may provide a valid alternative to glucocorticoid therapy. In vitro study of these drugs prior to clinical testing can allow the most promising compounds to be selected for trials and render trials with drugs of doubtful efficacy unnecessary.

Sample Population

Isolated canine cutaneous mast cells.

Procedure

Cells were preincubated with antihistamines at increasing concentrations and incubated with concanavalin A (1,000 µg/ml), calcium ionophore A23187 (1 µM), and substance P (100 µM). Compound 48/80 was not used because it proved to be cytotoxic.

Results

Generally, significant prodegranulating effect was not observed for most of the studied agents. Only terfenadine increased spontaneous histamine release at concentrations > 30 µM. Cetirizine did not block histamine release at any of the studied concentrations. Ketotifen had a low inhibitory effect only at the highest concentration (100 µM) after concanavalin A- (23.6 ± 2.8%) and calcium ionophore A23187- (29.8 ± 3.0%) induced release. Terfenadine caused a concentration-dependent inhibitory effect after ionophore A23187- (48.1 ± 2.2%) and concanavalin A- (28.9 ± 2.3%) activation, but was inactive against substance P-induced release. In contrast, loratadine had potent dose-dependent inhibition of concanavalin A- and ionophore A23187-induced histamine release, with maximal effect of 85.6 ± 3.1 % and 62.6 ± 4.7%, respectively, at 100 µM concentration. After substance P activation, histamine release was only slightly inhibited by loratadine (14.8 ± 1.1%).

Conclusions

This study documents the behavior of isolated canine cutaneous mast cells in the presence of nonimmunologic stimulation. Using this in vitro method, we were able to determine that loratadine is the only antihistamine that has potent inhibition of histamine release from dog cutaneous mast cells without a substantial prodegranulating effect. Loratadine is, therefore, a good candidate for clinical testing. (Am J Vet Res 1997;58:293–297)

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in American Journal of Veterinary Research

SUMMARY

Effects of a single iv administered therapeutic dose of vincristine sulfate on platelet numbers and function were evaluated in 16 clinically normal dogs over the 2 weeks after drug administration. Results were statistically compared with those of a previous control study in which the same 16 dogs were administered saline solution (iv), instead of vincristine. Of the 16 dogs, 8 were orally administered daily immunosuppressive doses of prednisone concurrently throughout the saline-control and vincristine study periods. Platelet numbers and mean platelet volume were measured, using an automated hematology analyzer. Platelet function was evaluated by turbidimetric measurement of platelet aggregation in response to collagen, platelet-activating factor, and adenosine diphosphate (adp), and by clot retraction (diluted whole-blood method) and buccal mucosa bleeding time.

Vincristine had a significant (P < 0.05) effect on circulating platelet numbers. Vincristine induced a transient mild decrease in platelet numbers, followed by a moderate increase in numbers, with peak platelet count observed 8 days after drug administration. Mean platelet volume was not significantly affected by administration of vincristine.

Vincristine had no significant effects on platelet aggregation in response to collagen, low or high doses of platelet-activating factor, and a high dose of adp. The maximal degree of platelet aggregation attained in response to a low dose of adp was not significantly affected by prior administration of vincristine. The maximal rate of platelet aggregation induced by a low dose of adp after vincristine administration, however, was significantly (P < 0.05) lower than the rate of aggregation induced by a similar dose of adp in the previous control study. Vincristine had no significant effects on clot retraction and bleeding time. Prednisone did not significantly affect platelet numbers and function, and did not modify vincristine's effects on the same variables.

Free access
in American Journal of Veterinary Research

SUMMARY

Effects of topical administration of a single dose of timolol maleate on intraocular pressure (iop) and pupil diameter were evaluated in normotensive eyes of 11 clinically normal dogs over 12 hours (7:00 am to 7:00 pm). Mean (± sem) normal iop was 15.5 (± 1.1) mm of Hg and diurnal fluctuation was observed, with the highest iop seen in the morning. Mean normal pupil diameter was 8.5 (± 0.3) mm. Topical treatment with 0.5% timolol resulted in reduction of iop in the treated and nontreated eyes. Mean reduction of iop in the treated eye was 2.5 mm of Hg, a reduction of 16.1%, with maximal reduction of 3.7 mm of Hg. Mean reduction of iop in the nontreated eye was 1.4 mm of Hg, a reduction of 9.0%. The treated eye had reduced pupil diameter at 30 minutes after treatment, which persisted throughout the 12 hours of the study. Mean reduction of pupil diameter in the treated eye was 2.9 mm, a reduction of 34.1%. In addition, a contralateral effect on pupil diameter was seen in the nontreated eye, with mean reduction of 1.2 mm, a reduction of 14.1%.

Topical administration of timolol maleate resulted in reduction of iop and pupil diameter in treated and contralateral eyes, thus supporting the use of timolol for treatment of glaucoma in dogs. Miosis indicates possible β-adrenergic inhibition or β-adrenergic activation of the sphincter muscle. β-Adrenergic blockade would then result in miosis.

Free access
in American Journal of Veterinary Research

SUMMARY

We evaluated the pharmacokinetics of iv administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (lpl) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, lpl activity, and activated partial thromboplastin time (aptt). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (auc) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for lpl activity increased less than proportionally with dose. Maximal lpl activity observed was independent of dose, averaging 4.8 μmol of free fatty acids/ml/h. The aptt was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for lpl activity vs either plasma heparin concentration or aptt were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma lpl activity.

Free access
in American Journal of Veterinary Research