Evaluation of two scopolamine and physostigmine pretreatment regimens against nerve agent poisoning in the dog.

Currently, there is no viable protection against chemical warfare agents for the working dog. Physostigmine (PHY) and scopolamine (SCO) have been shown to protect dogs against nerve agents with minimal side effects. The goal of this study was to investigate whether reported protective SCO/PHY plasma concentrations of 0.2 and 0.7 ng/mL, respectively, could be reached and maintained with minimal side-effects thereby identifying possible pretreatment regimens. Two continuous regimens of SCO/PHY were administered to beagle dogs. The first regimen consisted of administering transdermal SCO and intraocular PHY, the second consisted of transdermal SCO and rectal PHY. SCO/PHY plasma concentrations for each regimen were determined, individual protective times were calculated and a computerized pharmacokinetic analysis was performed. The results showed transdermal SCO and intraocular PHY routes of delivery achieved sustained protective drug concentrations with minimal side-effects and the rectal route of delivery did not. Group median protective times for the first regimen were 54.45 h for SCO and 64.35 h for PHY, and for the second regimen 63.75 h for SCO and 0 h for PHY. The combined transdermal patch and intraocular regimen may provide a safe and effective regimen against nerve agent poisoning in dogs.

Signaling mechanism for equine neutrophil activation by immune complexes.

Neutrophils (PMN) are critical host defense cells that have a role in the pathophysiology of a variety of inflammatory diseases, particularly those diseases associated with antigen-antibody immune complexes (IC) deposited in tissues. Activation of PMN by IC is most efficient if the IC are presented immobilized on a surface. Adhesion to the immobilized IC is important for subsequent activation of PMN effector functions, such as generation of reactive oxygen metabolites. Adhesion of human PMN to immobilized IC requires the expression and activation of adhesion receptors called integrins. Of the integrins expressed on PMN, the beta 2 family has been found to be of particular importance for PMN function. The mechanism of beta 2 integrin activation during adhesion to IC has been studied in human PMN, but not in equine PMN. We show here that adhesion of equine PMN to immobilized IC requires beta 2 integrins. Like adhesion, IC-induced respiratory burst activity is dependent on beta 2 integrins. Furthermore, the signaling pathway triggering beta 2 integrin-dependent adhesion of equine PMN to IC and subsequent generation of respiratory burst activity is inhibited by the specific phosphatidylinositol 3-kinase (PI3K) antagonists wortmannin and LY294002 with IC(50) (concentration at which 50% inhibition is achieved) similar to the published values for inhibition of PI3K enzymatic activity. In contrast, PMA-induced activation of beta 2 integrin-dependent adhesion and respiratory burst activity are wortmannin and LY294002 insensitive. These data demonstrate that like in human PMN, IC-induced activation of beta 2 integrins and beta 2 integrin-dependent functions in equine PMN is dependent on PI3K activity.

Clinical signs, evaluation of bronchoalveolar lavage fluid, and assessment of pulmonary function in horses with inflammatory respiratory disease.

OBJECTIVE: To evaluate the association among clinical signs, results of cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and measures of pulmonary function in horses with inflammatory respiratory disease. ANIMALS: 9 healthy horses, 5 horses with inflammatory airway disease (IAD), and 9 horses with chronic obstructive pulmonary disease (COPD). PROCEDURES: Clinical examination, lung function tests, and BAL were performed on each horse. RESULTS: Standard lung mechanics of horses with exacerbated COPD differed significantly from those of healthy horses; however, there were few differences among horses with IAD, horses with COPD during remission, and healthy horses. Most variables for forced expiration (FE) in horses with COPD or IAD differed significantly from those for healthy horses. Results of clinical examination had low to moderate sensitivity and predictive values for a diagnosis of COPD (range, 67 to 80%). Results of FE tests had high sensitivity, specificity, and predictive values for a diagnosis of COPD (79 to 100%), and results of standard lung mechanics tests had low sensitivity and predictive values (22 to 69%). Percentage of neutrophils in BAL fluid was highly sensitive (100%) but moderately specific (64%) for a diagnosis of COPD. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical examination is moderately accurate for establishing a diagnosis of COPD. Forced expiration tests can specifically detect early signs of airway obstruction in horses with COPD and IAD that may otherwise be inapparent. Cytologic evaluation of BAL fluid allows early detection of inflammatory respiratory disease, but it is not specific for COPD.

Treatment of granular cell tumor via complete right lung resection in a horse.

A 7-year-old warmblood mare was referred because of a respiratory tract disorder; pulmonary granular cell tumor was diagnosed. Pulmonary granular cell tumor is a locally invasive but rare type of tumor with low metastatic potential. The entire right lung was resected to ensure removal of all neoplastic tissue. The horse recovered well and has minimal difficulties functioning with one lung. Most of these tumors are diagnosed during postmortem examination. To our knowledge, this is the first report of pulmonary granular cell tumor treated by complete lung resection in a horse.