The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketorolac

Combinations of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids are widespread in the management of pain, allowing better analgesia with reduced side effects. Cannabinoids are promising-analgesic drugs that have pharmacological properties similar to those of opioids. However, the beneficial effects of cannabinoids for pain treatment are counterbalanced by their psychotomimetic side effects. We designed the present study to evaluate the antinociceptive interaction between cannabinoids and NSAIDs in mice, using the acetic acid-induced writhing test and tail-flick test. Interactions were analyzed using isobolographic analysis. WIN 55,212-2, a cannabinoid agonist, and the NSAID ketorolac, either alone or in combination, produced dose-dependent antinociception in the writhing test. Isobolographic analysis showed additive interactions between WIN 55,212-2 and ketorolac when they were coadministered systemically. Ketorolac is inactive in the radiant heat tail-flick test in which WIN 55,212-2 was active. Ketorolac did not influence WIN 55,212-2-induced antinociception in the tail-flick test. This study demonstrated an additive antinociceptive interaction between WIN 55,212-2 and ketorolac in an inflammatory visceral pain model. The combination of cannabinoids and NSAIDs may have utility in the pharmacotherapy of pain

Immune response of cattle to botulinum type C and D toxoid administered on three occasions

The aims of the present study were to investigate the antibody response of cows from an outbreak region to vaccination with a bivalent botulinum toxoid (Type C and D) on three occasions and to investigate the antibody response to vaccination with the botulinum toxoid in the presence of anti-BoNT antibodies. Twenty-two cows from an outbreak region and 10 cows from a farm without a history of botulism were used in this study. Blood samples were collected before each vaccination and three weeks after the third vaccination (days 0, 21, 42 and 63). The level of anti-BoNT/C antibodies steadily increased after each vaccination (0.471 +/- 0.04, 0.566 +/- 0.03 and 0.663 +/- 0.04, respectively); however, the levels of anti-BoNT/ D antibodies were not significantly different after the second and third vaccinations (0.377 +/- 0.03, 0.493 +/- 0.03 and 0.465 +/- 0.03, respectively). Post vaccination antibody responses of animals found positive and negative for anti-BoNT antibodies at the beginning of the study were similar. The results of the present study indicated that vaccination of cattle with botulinum toxoid on three occasions is recommended, particularly in outbreaks that are suspected to be caused by BoNT/C and that presence of naturally acquired antibodies against BoNT did not interfere with post vaccination immune response.Türkiye Cumhuriyeti Kalkınma Bakanlığ