Current pharmaceutical design
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Tuberculosis (TB) is the second cause of death from a single infectious agent, the M. tuberculosis bacillus. Nearly two billion people are infected and about 8.7 million new cases and 1.4 million deaths were reported by the World Health Organization (WHO) in 2013. ⋯ The aim of this review is to summarize the current status of different QSAR based strategies for the design of novel anti-TB drugs based upon the most active anti-TB agent known, INH. A case study puts in evidence that the judicious application of quantitative structure- activity relationships can be successfully used to rationally design new INH-based derivatives, active against INH-resistant strains harboring mutations in the most frequent resistance related target (katG), and therefore develop candidate-compounds against MDR-TB, thus revisiting the unique effectiveness of INH against TB.
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Caveolae are flask-like invaginations of the cell surface that have been identified as signaling epicenters. Within these microdomains, caveolins are structural proteins of caveolae, which are able to interact with numerous signaling molecules affecting temporal and spatial dimensions required in cardiac protection. ⋯ In this review we will outline a general overview of caveolae and caveolins and their role in protective signaling with a focus on the effects of volatile anesthetics. These recent developments have allowed us to better understand the mechanistic effect of volatile anesthetics and their potential in cardiac protection.
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Review
Anesthetic cardioprotection in clinical practice from proof-of-concept to clinical applications.
In 2007, the American Heart Association (AHA) recommended (class IIa, level of evidence B) in their guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery volatile anesthetics as first choice for general anesthesia in hemodynamically stable patients at risk for myocardial ischemia. This recommendation was based on results from patients undergoing coronary artery bypass grafting (CABG) surgery and thus subject to criticism. However, since a "good anesthetic" often resembles a piece of art in the complex perioperative environment, and is difficult to highly standardize, it seems unlikely that large-scale randomized control trials in noncardiac surgical patients will be performed in the near future to tackle this question. ⋯ In patients at risk for perioperative cardiovascular complications, it is essential to abandon the use of "anti-conditioning" drugs (sulfonylureas and COX-2 inhibitors) and probably glitazones. There is significant interference in cardioprotection between sevoflurane and propofol, which should not be used concomitantly during anesthesia if possible. Any type of ischemic "conditioning" appears to exhibit markedly reduced protection or completely loses protection in the presence of volatile anesthetics and/or opioids.
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Review
Statin treatment non-adherence and discontinuation: clinical implications and potential solutions.
Statins are the most powerful lipid lowering drugs in clinical practice. However, the efficacy of statin therapy, as seen in randomized control trials, is undermined by the documented non-adherence observed in clinical practice. Understanding the clinical consequences of statin non-adherence is an important step in implementing successful interventions aimed at improving adherence. ⋯ Statin adherence, therefore, represents an important modifiable risk factor. Numerous interventions to improve adherence have shown promise, including copayment reduction, automatic reminders, mail-order pharmacies, counseling with a health professional, and fixed-dose combination therapy. Given the complexity of causes underlying statin non-adherence, successful strategies will likely need to be tailored to each patient.
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Tuberculosis caused by Mycobacterium tuberculosis is an infectious bacterial disease which is a leading cause of mortality affecting more than 9 million people worldwide. The current standard regimens that are available for the treatment of TB are severely hampered due to the occurrence of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of Mycobacterium tuberculosis. In the past few years, a huge and constantly expanding effort has been developed to understand the chemical-biological interaction of many new anti-tubercular drugs and their targets in mathematical terms. Here, we have elected to review only those studies concerning 2D and 3D QSAR models that contain different DFT based descriptors as their parameters.