Intravascular challenge of isolated perfused and ventilated guinea pig lung (IPL) from actively sensitized guinea pigs, with cumulatively increasing (10-10,000 microg) doses of ovalbumin (OVA), resulted in dose-dependent and reproducible reductions in lung conductance. The antihistamines mepyramine (1 microM) and metiamide (1 microM), the leukotriene antagonist zafirlukast (0.1 microM), or the ...

BACKGROUND A dry powder inhaler of KP-496 is currently in clinical development in Japan as an anti-asthmatic agent. The aim of this study was to evaluate the in vitro pharmacological profile of KP-496. METHODS The antagonistic activities of KP-496 for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors were examined using the LTD(4)- and U46619-induced contractions of the isolated guine...

Sørensen BH, Thorsteinsdottir UA, Lambert IH. Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate. Am J Physiol Cell Physiol 307: C1071–C1080, 2014. First published September 24, 2014; doi:10.1152/ajpcell.00274.2014.—Cisplatin resistance is a major challenge in the treatment of cancer and develops through ...

Asthma is a chronic inflammatory disease that affects >300 million people worldwide. However, inhaled corticosteroids (ICS), the gold standard therapy for persistent asthma, cannot suppress every component of airway inflammation and often fail to adequately penetrate the small airways in order completely suppress eosinophilia. Cysteinyl leukotrienes are important inflammatory factors that are i...

Gastrointestinal fluid is a complex milieu and it is recognised that gut drug solubility is different to that observed in simple aqueous buffers. Simulated gastrointestinal media have been developed covering fasted and fed states to facilitate in vitro prediction of gut solubility and product dissolution. However, the combination of bile salts, phospholipids, fatty acids and proteins in an aque...

Leukotrienes are potent pro-inflammatory lipid mediators derived from arachidonic acid through several enzymatic pathways. They have an essential role in allergic inflammation, where they induce bronchoconstriction, airway edema, and chemotaxis of the inflammatory cells in the airways, nasal and conjunctival tissues. Leukotriene modifiers include leukotriene receptor antagonists (montelukast, z...

Response to Letter Regarding Article, “Ticagrelor in Patients With Acute Coronary Syndromes and Stroke: Interpretation of Subgroups in Clinical Trials” Drs Serebruany and DiNicolantonio are repeatedly accusing the platelet inhibition and patient outcomes (PLATO) investigators, executive committee, and sponsor for trial misconduct and deliberate misinterpretations. These are extremely serious ac...