Current medicinal chemistry
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On undergoing an operation under general anesthesia, we tend to lose consciousness, and on recovering from the anesthetic effect, we realize a memory loss during the operation, but do remember the happenings before the operation. It implies that the anesthesia deprivers us of short-term memory without affecting long-term memory. Drosophila melanogaster is known to be an excellent model for genetic studies related to general anesthesia and memory. ⋯ Memory and adhesion pathways of the anesthetic action are developed in the Drosophila melanogaster model. Many mutants of general anesthesia and those of memory are overlapped suggesting that common molecules and signal pathways are involved in both phenomena. In this review, we will describe the relation between anesthesia and memory, especially highlighting the interaction between the general anesthetics and STM and MTM processes in Drosophila, especially concentrating on the cAMP/PKA signaling and molecular adhesion pathways.
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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.
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Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system. It is estimated that 75-150 million people in the United States have a chronic pain disorder. Neuropathic pain has a great impact on the quality of life. ⋯ Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. Nowadays, pain research is directing on new molecular methods, such as gene therapy, stem cell therapy and viral vectors for delivery of biologic antinociceptive molecules. These methods could provide a new therapeutic approach to neuropathic pain relief.
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The increase in diagnostic imaging procedures that require infusion of intravenous radiographic contrast has led to a parallel increase in the incidence of contrast-induced nephropathy (CIN). Since CIN accounts for a significant increase of hospital-acquired renal failure, length of stay and mortality, several additive strategies to prevent CIN are presently advocated, including N-acetylcysteine (NAC), sodium bicarbonate, theophylline or fenoldopam, and peri-procedural hemofiltration/hemodialysis. ⋯ Since NAC has only few side-effects, we presently advise NAC as an additive preventive measure in the intensive care setting. Theophylline or sodium bicarbonate hydration are viable options, either in conjunction NAC or as alternatives.
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Review
Recent advances in computational prediction of drug absorption and permeability in drug discovery.
Approximately 40%-60% of developing drugs failed during the clinical trials because of ADME/Tox deficiencies. Virtual screening should not be restricted to optimize binding affinity and improve selectivity; and the pharmacokinetic properties should also be included as important filters in virtual screening. ⋯ Recent developments in the prediction of drug absorption, especially with the application of new machine learning methods and newly developed software are also discussed. Future directions for research are outlined.