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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Human ether-a-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current, IKr, which is crucial for repolarization of cardiac action potentials. Moderate hERG blockade may produce a beneficial class III antiarrhythmic effect. In contrast, a reduction in hERG currents due to either genetic defects or adverse drug effects can lead to hereditary or acquired long QT syndromes characterized by action potential prolongation, lengthening of the QT interval on the surface ECG, and an increased risk for "torsade de pointes" arrhythmias and sudden death. ⋯ Recently, mutations in hERG have been shown to cause current increase and hereditary short QT syndrome with a high risk for life-threatening arrhythmias. Finally, the discovery of adrenergic mechanisms of hERG channel regulation as well as the development of strategies to enhance hERG currents and to modify intracellular hERG protein processing may provide novel antiarrhythmic options in repolarization disorders. In conclusion, the increasing understanding of hERG channel function and molecular mechanisms of hERG current regulation could improve prevention and treatment of hERG-associated cardiac repolarization disorders.
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Asthma is a complex disease caused by a poorly characterized set of genetic and environmental factors whose pathology is a result of immune dysregulation. Toll-like receptors are pathogen associated molecular pattern receptors expressed by many airway and pulmonary tissues as well as cells of the innate and adaptive immune system. ⋯ These ligands and their receptors are therefore prime candidates in the search for immunotherapeutic treatments of asthma. The use of murine models of allergic asthma as tools for the genetic dissection of this disease should allow the molecular mechanisms underlying asthma to be identified and possibly used as further immunotherapeutic targets.
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Tobacco use is the leading risk factor for lung cancer, yet in addition to smoking habit, diet may also play a role in the disease's appearance. While there are reports to indicate that antioxidant vitamins and carotenoids may decrease the risk of lung cancer, results to date have been somewhat ambiguous. This review aimed to describe the results yielded by different studies, which have addressed antioxidant vitamin intake and lung cancer, and to indicate the mechanisms whereby these nutrients might be exercising their activity. ⋯ Insofar as provitamin A carotenoids were concerned, lutein/zeaxanthin, lycopene and alpha-carotene displayed a certain protective trend, yet beta-carotene exhibited no protective effect whatsoever; and indeed, there was speculation as to whether it might even be pernicious in smokers. Beta-criptoxanthin, on the other hand, showed a more consistent protective effect. The study highlighted the need to conduct further research on smokers and non-smokers alike, and in particular, to investigate the effect, if any, on lung cancer of carotenoids or vitamins when ingested in differing dosages.