1 The novel thromboxane (TX) antagonist, BAY u3405, has been evaluated against bronchoconstriction induced by the TXA2 mimetic U-46619, prostaglandin D2 (PGD2), 5-hydroxytryptamine (5-HT), leukotriene D4 (LTD4) and histamine in the guinea-pig in vivo by use 6 The action of BAY u3405 (l0mgkg-,p.o.) was long lasting, causing significant inhibition of U-46619-induced bronchoconstriction 7 h after dosing. 7 At 1 mg kg-1, i.v., a dose that abolished the response to U-46619 and PGD2, BAY u3405 had no effect on histamine-, 5-HT-or LTD4-induced bronchoconstriction. 8 BAY u3405 potently and selectively antagonized U-46619-or PGD2-induced bronchoconstriction in the Konzett-Rbssler model of guinea-pig lung function. It should therefore prove to be a useful tool for defining the role of TXA2-and PGD2 in airway diseases such as asthma.
The existing drugs for treatment of osteoporosis are limited in scope, tolerability, and efficacy. Newer osteoclast-targeted agents like inhibitors of receptor activator nuclear factor kappaB pathway, Cathepsin K, and integrins are under clinical development. Osteoblast-targeted therapies include the agents acting through the Wnt signaling pathway like sclerostin antagonists. The potential molecular targets and the emerging drugs for treatment of osteoporosis are discussed in this review.
1 The novel leukotriene antagonist Bay x7195, has been evaluated against bronchoconstriction induced by leukotriene D 4 (LTD 4 ), the thromboxane A 2 (TXA 2 ) mimetic U46619, histamine and antigen, in the guinea-pig in vivo by use of a modi®ed Konzett-RoÈ ssler preparation. 2 LTD 4 , given intravenously (i.v.) at 1 or 3 mg kg 71 in the presence of indomethacin and sotalol, caused a 50 ± 70% maximal bronchoconstriction in most animals. 5 When given intravenously, in the presence of selected antagonists, BAY x7195 caused a dose-related reduction in the antigen-induced response, with an approximate ID 50 of 2 mg kg 71 . 6 At 3 mg kg 71 , i.v., a dose which abolished the response to LTD 4 , BAY x7195 had no eect on U46619-or histamine-induced bronchoconstriction. 7 BAY x7195 is a potent, selective and long acting antagonist of LTD 4 -induced bronchoconstriction, in an anaesthetized, ventilated guinea-pig model. It is therefore worthy of clinical evaluation in diseases believed to involve the sulphidopeptide leukotrienes, such as asthma.
The histamine H1 receptor antagonist (antihistamines) are an important class of commonly used medications for the relief of symptoms associated with common cough and cold occurring in children. We report two cases of antihistaminic induced febrile seizure in children below five year. We consider importance of reporting such cases in view of their common usage and propensity to provoke seizure in susceptible children.
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