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Emerging Drugs (emerging + drug)
Selected AbstractsEmerging drugs: mechanism of action, mass spectrometry and doping control analysisJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2009Mario Thevis Abstract The number of compounds and doping methods in sports is in a state of constant flux. In addition to ,traditional' doping agents, such as anabolic androgenic steroids or erythropoietin, new therapeutics and emerging drugs have considerable potential for misuse in elite sport. Such compounds are commonly based on new chemical structures, and the mechanisms underlying their modes of action represent new therapeutic approaches arising from recent advances in medical research; therefore, sports drug testing procedures need to be continuously modified and complementary methods developed, preferably based on mass spectrometry, to enable comprehensive doping controls. This tutorial not only discusses emerging drugs that can be categorized as anabolic agents (selective androgen receptor modulators, SARMs), gene doping [hypoxia-inducible factor stabilizers, peroxisome-proliferator-activated receptor (PPAR),-agonists] and erythropoietin-mimetics (Hematide) but also compounds with potentially performance-enhancing properties that are not classified in the current list of the World Anti-Doping Agency. Compounds such as ryanodine-calstabin-complex modulators (benzothiazepines) are included, their mass spectrometric properties discussed, and current approaches in sports drug testing outlined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Old and emerging therapies in chronic hepatitis C: an updateJOURNAL OF VIRAL HEPATITIS, Issue 1 2008M. Deutsch Summary., The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response currently defined as undetectable HCV-RNA in peripheral blood determined with the most sensitive polymerase chain reaction technique 24 weeks after the end of treatment. This goal is practically equivalent with eradication of HCV infection and cure of the underlying HCV-induced liver disease. The current standard in hepatitis C treatment consists in combination regimens of pegylated interferon-, (Peg-INF-,) with Ribavirin (RBV). Such treatment schemes are quite successful in patients with HCV genotypes 2 and 3 infections achieving HCV eradication rates of 75,90%. However, they are much less effective in patients with genotypes 1 and 4 infections with eradication rates ranging between 45% and 52%. Moreover, they have several, and sometimes severe, adverse effects and contraindications, further limiting their efficacy and applicability in an appreciable number of patients with chronic HCV-induced liver disease. Therefore, the need for improvement of existing therapies and for development of new effective, safe and tolerable drugs is a matter of great clinical relevance and importance. In this article, recent improvements in the current standard of therapy with IFN-, and RBV in various subsets of patients with chronic hepatitis C and in the clinical development of new emerging drugs, particularly small molecules, will be reviewed and commented. The article is divided in two main parts: (i) improvements in the standard combination therapies and schemes of approved Peg-INF-, with RBV and expectations from new interferons, interferon inducers and alternatives to RBV; (ii) new drugs for HCV in clinical development focusing mostly on specific inhibitors of HCV and less so on other drugs including immune therapies. [source] Reassessing the Cardiovascular Risks and Benefits of ThiazolidinedionesCLINICAL CARDIOLOGY, Issue 9 2008Andrew Zinn MD Abstract This article is designed for the general cardiologist, endocrinologist, and internist caring for patients with diabetes and coronary artery disease. Despite the burden of coronary disease in diabetics, little is known about the impact of commonly used oral hypoglycemic agents on cardiovascular outcomes. As the untoward effects of insulin resistance (IR) are increasingly recognized, there is interest in targeting this defect. Insulin resistance contributes to dyslipidemia, hypertension, inflammation, hypercoagulability, and endothelial dysfunction. The aggregate impact of this process is progression of systemic atherosclerosis and an increased risk of adverse cardiovascular outcomes. As such, much attention has been paid to the peroxisome-proliferator-activated receptor gamma (PPARg) agonists rosiglitazone and pioglitazone (thiazolidinediones [TZDs]). Many studies have demonstrated a beneficial effect on the atherosclerotic process; specifically, these agents have been shown to reduce markers of inflammation, retard progression of carotid intimal thickness, prevent restenosis after coronary stenting, and prevent cardiovascular death and myocardial infarction in 1 large trial. Such benefits come at the risk of fluid retention and heart failure (HF) exacerbation, and the net effect on plasma lipids is still poorly understood. Thus, the aggregate risk-benefit ratio is poorly defined. A recent meta-analysis has raised significant concerns regarding the overall cardiovascular safety of 1 particular PPARg agonist (rosiglitazone), prompting international debate and regulatory changes. This review scrutinizes the clinical evidence regarding the cardiovascular risks and benefits of PPARg agonists. Future studies of PPARg agonists, and other emerging drugs that treat IR and diabetes, must be designed to look at cardiovascular outcomes. Copyright © 2008 Wiley Periodicals, Inc. [source] | ||||||||||