Current medicinal chemistry
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Sepsis remains a common cause of death in the intensive care units worldwide. However, in the last decade a significant development could be noticed in sepsis research regarding diagnostic markers that can help the physicians to recognize the disease in the early phase, which is the clue of the successful treatment of sepsis. This development provided the identification of new molecules and structures (i.e. cytokines, cell surface markers, receptors) that are potential biomarkers of sepsis in the clinical settings. ⋯ We will describe the presumed pathophysiological role and diagnostic value of sepsis markers that are used even more widely in the clinical practice (i.e. procalcitonin, IL-6), summarize the data regarding the sepsis marker candidates that are investigated in some initial study (i.e. matrix metalloproteinases, microRNA fingerprints), and we will discuss substances that may be specific markers for certain organ failures related to sepsis (i.e. neutrophil gelatinase-derived lipocalin in acute renal failure). Furthermore, we will review the mediators of the immuno-inflammatory cascade in sepsis concerning their potential applicability as therapeutic targets in the treatment of this often lethal disease. In addition, we present some insights into the identification of genetic markers of sepsis.
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Cardiac troponins (cTn) are considered to be the 'gold standard' biomarker for the diagnosis of acute coronary syndrome (ACS); a pathological spectrum which includes cardiac ischemia, angina, myocardial infarction and ultimately cardiac failure. The growing evidence base for the diagnostic and prognostic use of cTn in ACS has resulted in a universal redefinition of acute myocardial infarction (AMI). Recently a number of immunoassays with claims of superior sensitivity have been produced. ⋯ It is unknown if such mild elevations in cTn detected by sensitive assays are of clinical concern. What is certain is that AMI remains a clinical not a biochemical diagnosis and interpretation of cTn concentrations should be made according to the clinical context. This review highlights the development of the sensitive assays, documents their analytical and clinical performance and reviews the usefulness of cTn elevation in non-ACS conditions.
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Angiogenesis is known to be essential for the development and progression of cancer. Vascular endothelial growth factor (VEGF) is a critical mediator in tumor angiogenesis for many solid malignancies, including breast cancer. Increased levels of VEGF have been associated with poor clinical outcomes, including reduced survival. ⋯ Several trials to define the role of bevacizumab in different setting of disease and in combination with different chemotherapy regimens and targeted therapy in breast cancer patients are ongoing. Other small molecule inhibitors of VEGF tyrosine kinase activity (TKIs) such as sunitinib, vandetanib and sorafenib are being tested in MBC. This review will focus on bevacizumab and on the developements of the main antiangiogenic agents in the treatment of breast cancer.
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Voltage-gated sodium channels produce fast depolarization, which is responsible for the rising phase of the action potential in neurons, muscles and heart. These channels are very large membrane proteins and are encoded by ten genes in mammals. Sodium channels are a crucial component of excitable tissues; hence, they are a target for various neurotoxins that are produced by plants and animals for defence and protection, such as tetrodotoxin, scorpion toxins and batrachotoxin. ⋯ In this review, we discuss aspects of voltage-gated sodium channel genes with an emphasis on cardiac muscle sodium channels. In addition, we report novel mutations that underlie a spectrum of diseases, such as Brugada, long QT syndrome and inherited conduction disorders. Furthermore, this review explains commonalities and differences among the channel subtypes, the channelopathies caused by the sodium channel gene mutation and the specificity of toxins and blockers of the channel subtypes.