bw-540c and Disease-Models--Animal

An equine model of acute non-immune inflammation has been developed to facilitate studies of the inflammatory process and the actions of novel anti-inflammatory drugs. Five polyester sponge strips soaked in sterile 2% carrageenin solution were placed in subcutaneous pouches prepared under local anaesthesia in the necks of conscious ponies. Serial removal of the strips and harvesting of the exudate enabled studies to be made of the cellular, biochemical and mediator aspects of the localised, acute inflammation, and the heat generated by the lesion was monitored by infra-red thermometry. Maximal concentrations of the eicosanoids 6-keto-prostaglandin F1 alpha, thromboxane B2 and leukotriene B4 occurred at 9 h, whereas leukocyte numbers, lactate dehydrogenase (LDH) and total protein concentrations were greatest at 24 h. Lesional skin temperature was increased by approximately 4 degrees C throughout the 24 h period. The novel anti-inflammatory agent BW540C, administered orally at a dose-rate of 20 mg/kg, did not affect leukocyte infiltration or the concentrations of protein, LDH and eicosanoids in exudate but serum thromboxane B2 levels were reduced. Skin temperature rises were greater in drug-treated animals. It is concluded that higher doses of BW540C will be required for a clinically useful anti-inflammatory action in horses.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Disease Models, Animal; Exudates and Transudates; Female; Horse Diseases; Horses; Inflammation; L-Lactate Dehydrogenase; Leukocyte Count; Leukotriene B4; Proteins; Pyrazoles; Skin Temperature; Thromboxane B2

We have examined the effects of various topical formulations of BW 540C, a novel dual inhibitor of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, utilizing the model of ultraviolet irradiation of guinea-pig ears. During a series of studies, BW 540C preparations were compared with a range of corticosteroids, a cyclo-oxygenase inhibitor and a placebo using both subjective and objective measurements. Results showed BW 540C base to be the best overall agent for treating the pathological changes seen in this model.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Dermatitis; Disease Models, Animal; Drug Administration Schedule; Guinea Pigs; Pyrazoles; Skin; Ultraviolet Rays