Current pharmaceutical design
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Fibromyalgia (FM) is continuing to be a challenging and confusing disorder for researchers and clinicians with its diverse symptoms, poorly understood etiology and pathophysiology. The use of multiple outcome variables reflecting the complexity of FM and co-morbid syndromes, makes it difficult to evaluate the efficacy or effectiveness of the treatment in clinical trials. Additionally researchers inevitably rely on patients' self-reported outcome data, which is prone to error and bias. ⋯ Consequently, clinicians and researchers have various highly validated and adequate outcome domains to assess FM symptoms and new researches continue to add new valuable domains. Nevertheless the current problem is to conclude, which treatment works best for whom and which are the outcome domains suitable for FM patients or patients' subgroups with different prominent features. Standardised and appropriate core outcome domains for FM clinical trails will encourage more complete investigations, relevant outcome reporting and well-designed multicenter trials.
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Tuberculosis (TB) is a growing international health concern, since it is the leading infectious cause of death in the world today. In particular, the increasing prevalence of multidrug-resistant (MDR)-TB has greatly contributed to the increased difficulties in the control of TB. Because of the global health problems of TB, the increasing rate of MDR-TB and the high rate of a co-infection with HIV, the development of potent new anti-TB drugs without cross-resistance with known antimycobacterial agents is urgently needed. ⋯ In addition, the future development of new antitubercular drugs is briefly discussed according to the potential pharmacological targets. New critical information on the whole genome of Mycobacterium tuberculosis (MTB) was recently elucidated and increasing knowledge on various mycobacterial virulence genes will promote the progression in the identification of genes that code for new drug targets. Using such findings on MTB genome, drug development using quantitative structure-activity relationship may be possible in the near future.
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Asthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone, thereby addressing two processes fundamental to asthma: bronchoconstriction and inflammation. Superior control--including a reduction in severe exacerbations--of asthma and COPD by ICS/LABA combination therapy has been demonstrated. Results from clinical studies suggest additive and potentially synergistic effects when the two agents are used in combination. ⋯ An ICS/LABA combination in a single inhaler represent safe, effective and convenient treatment options for the management of patients with asthma and COPD. Clinical results also suggest that adjustable dosing with budesonide/formoterol provides better asthma control than fixed dosing. Further elucidation of the underlying mechanisms responsible for this superior disease control is needed.
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The mechanisms of action of anesthetics are unclear. Much attention has been focused on ion channels in the central nervous system as targets for anesthetics. During the last decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein-coupled receptor (GPCR) signaling. ⋯ However, an estimated 500-800 additional GPCRs have been classified as "orphan" receptors (oGPCRs) because their endogenous ligands have not yet been identified. Given that known GPCRs are targets for anesthetics, these oGPCRs represent a rich group of receptor targets for anesthetics. This article highlights the effects of anesthetics on Gq-coupled receptors, and discusses whether GPCRs other than Gq-coupled receptors are targets for anesthetics.