Current medicinal chemistry
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Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. ⋯ In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.
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Oxytocin (OT) is a neurohypophysial hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OT-like substances have been identified in all vertebrates, OT has been found only in mammals where it plays a major role in the onset and maintaining of behaviors which are typical of these animals, such as labour and lactation. ⋯ MEDLINE and PubMed (1972-2007) databases were searched for English language articles by using the following keywords: oxytocin, physiology, cognitive functions, attachment, psychopathology, psychiatric disorders. Papers were examined that addressed the following aspects of the OT system: synthesis and localization, receptors, physiology: In addition, latest findings showing abnormalities of OT and OT system in several neuropsychiatric disorders, including autism, obsessive-compulsive disorder, eating disorders, addiction, schizophrenia, post-traumatic stress disorder and Prader-Willy syndrome, will be also discussed together with the possible clinical use of OT or its analogues and/or antagonists.
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It is estimated that a third of the world's population is currently infected with tuberculosis, leading to 1.6 million deaths annually. The current drug regimen is 40 years old and takes 6-9 months to administer. In addition, the emergence of drug resistant strains and HIV co-infection mean that there is an urgent need for new anti-tuberculosis drugs. ⋯ This review considers new potential first-line anti-tuberculosis drug candidates, in particular those with novel mechanisms of action, as these are most likely to prove effective against resistant strains. A brief overview of current first-line and recent drugs (such as fluoroquinolones, rifampicin and isoniazid analogues) is initially presented. This is followed by a description of structure-activity relationships, in vitro and in vivo activity, pharmacokinetics, mechanism of action, combination regimens and clinical trials of the new drug candidates SQ109, PA-824, OPC-67683, TMC207 and others.
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Multiple sclerosis (MS) is the most common disabling neurological disease in young adults and is thought to result from an autoimmune attack against autoantigens within the myelin sheath. A characteristic feature of MS is the broad heterogeneity of clinical, histopathological and immunological phenotypes, which urges a more differentiated defining of patients by biological markers that reflect the underlying disease process and allow the prediction of disease courses and treatment responses. Here we review the current research on the identification of biomarkers for MS in cerebrospinal fluid and/or blood. We will focus on antibodies to myelin and non-myelin antigens, cells and soluble molecules of the immune system and the brain as biomarkers for 1) the diagnosis and prediction of clinical courses, 2) disease activity and 3) treatment response in MS.
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Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. ⋯ GPX and TxnRed are selenocysteine dependent enzymes, and their activity is known to be dependent upon an adequate supply of dietary selenium. Moreover, various studies suggest that the supply of selenium as a cofactor also regulates gene expression of these selenoproteins. As such, dietary selenium supplementation may provide a safe and convenient method for increasing antioxidant protection in aged individuals, particularly those at risk of ischemic heart disease, or in those undergoing clinical procedures involving transient periods of myocardial hypoxia.