The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition, which control solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in the concentrations of these components, which wil...

Members of the kinesin superfamily are force-generating ATPases that drive movement and influence cytoskeleton organization in cells. Often, more than one kinesin is implicated in a cellular process, and many kinesins are proposed to have overlapping functions. By using conventional kinesin as a model system, we have developed an approach to activate or inhibit a specific kinesin allele in the ...

BACKGROUND Patients who continue to experience asthma symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Leukotriene receptor antagonists (LTRA) and long-acting beta(2)-agonists (LABA) agents may both be considered as add-on therapy to inhaled corticosteroids (ICS). OBJECTIVES We compared the efficacy and safety profile of adding either daily LABA ...

The cysteinyl leukotrienes (CysLTs) are potent biological mediators in the pathophysiology of inflammatory diseases, in particular of airway obstruction in asthma. Pharmacological studies have suggested the existence of at least two types of CysLT receptors, designated CysLT1 and CysLT2. The CysLT1 receptor has been cloned recently. Here we report the molecular cloning, expression, localization...

Clinical trials with leukotriene synthesis inhibitors and cysteinyl leukotriene (cys-LT) receptor antagonists have shown that cys-LTs (LTC4, LTD4, and LTE4) are the predominant mediators of bronchoconstriction in response to diverse asthma triggers including allergen, PAF, sulphur dioxide, and non-steroidal antiinflammatory drugs (NSAIDs). In addition, inhalation of a single dose of a cys-LT ca...

OBJECTIVE To assess the utilization of leukotriene modifiers (LM) relative to national guidelines and to investigate possible emergency room utilization differences for LMs as monotherapy versus inhaled corticosteroid (ICS) monotherapy or combination ICS and LM therapy. METHODS The utilization of leukotriene modifiers (montelukast sodium, zafirlukast, and zileuton), concurrent inhaled steroid...

Human B lymphocytes have similar capacity to produce leukotriene (LT) B4 as myeloid cells but the biological function of the 5-lipoxygenase (5-LO) pathway in B cells is unclear. In order to better understand the role of 5-LO and LTB4 in B cells we investigated which subsets of normal B cells from tonsils that expressed 5-LO. Based on immunostaining with a polyclonal antibody raised against 5-LO...