Current medicinal chemistry
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The latest advancement in neurobiological research provided an increasing evidence that inflammatory and neurodegenerative pathways play a relevant role in depression. Preclinical and clinical studies on depression highlighted an increased production of inflammatory markers, such as interleukin (IL)-1, IL-6, tumor necrosis factor-α and interferon- α and γ. On the other hand, acute and chronic administration of cytokines or cytokine inducers were found to trigger depressive symptoms. ⋯ Besides the 5-HT system, other targets, possibly within the I&ND pathways, should be considered for the future treatment of depression: cytokines and their receptors, intracellular inflammatory mediators, IDO, TRYCATs, glucocorticoid receptors, neurotrophic factors may all represent possible therapeutic targets for novel antidepressants. In addition, it should be also clarified the role of the existing anti-inflammatory drugs in the treatment of depression, and those compounds with the anti-inflammatory and anti-oxidative properties should be examined either as monotherapy or adjunctive therapy. In conclusion, the molecular inflammatory and neurodegenerative pathways might provide new targets for antidepressant development and might be crucial to establish a rational treatment of depression aimed, hopefully, to its causal factors.
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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.
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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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Renin-angiotensin II-aldosterone axis has long been known as a regulator of blood pressure and fluid homeostasis. Yet, local renin-angiotensin II systems have been discovered and novel actions of angiotensin II (AngII) have emerged among which its ability to act as a immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, Angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. ⋯ The balance between ACE and ACE2 is crucial for controlling AngII levels. ACE and ACE2 also appear to modify the severity of Acute Respiratory Distress Syndrome (ARDS), with ACE2 playing a protective role. Finally, mention is made to the recent discovery of ACE2 as a receptor for the SARS Corona Virus.