Current pharmaceutical design
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3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are primarily used to treat dyslipidemia. Yet, these medications have a number of additional important pleiotropic properties that confer patient benefit in terms of reduced cardiovascular morbidity. Investigators have reported that statins may be underutilized in patients undergoing cardiac surgical procedures. ⋯ Mechanisms for statin's demonstrated benefit include improved endothelial function, antiinflammatory properties and stabilization of atherosclerotic plaque. While there are well-recognized side effects to statin therapy, its beneficial impact on patient cardiovascular outcomes is clear. Further research is necessary to determine specific patients who would best benefit from preoperative statin therapy, the dose and duration of therapy prior to surgical interventions and the influence of administration following surgery.
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This update aims to provide an evidence based review of natural and synthetic colloids with a special emphasis on the various generations of the synthetic colloid hydroxyethyl starch. The effect of 1(st), 2(nd) and 3(rd) generation hetastarches on bleeding, coagulopathy, acute kidney injury and mortality will be discussed. The results of randomised controlled trials addressing morbidity and mortality outcomes of colloid versus crystalloid resuscitation in critically ill patients will be described. In addition, the rationale and evidence behind early goal directed fluid therapy (EGDFT) including a practical approach to assessment of dynamic measures of fluid responsiveness will be presented.
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Identifying biological and clinical markers of treatment response in depression is an area of intense research that holds promise for increasing the efficiency and efficacy of resolving a major depressive episode and preventing future episodes. Collateral benefits include decreased healthcare costs and increased workplace productivity. Despite research advances in many areas, efforts to identify biomarkers have not revealed any consistently validated candidates. ⋯ We propose that an integrated study of a range of biomarker candidates from across different modalities is required. Furthermore, advanced mathematical modeling and pattern recognition methods are required to detect important biological signatures associated with treatment outcome. Through an informatics-based integration of the various clinical, molecular and imaging parameters that are known to be important in the pathophysiology of depression, it becomes possible to encompass the complexity of contributing factors and phenotypic presentations of depression, and identify the key signatures of treatment response.
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New knowledge of the pathophysiology and evolution of hypoxic-ischemic brain injuries has made feasible interventions to improve clinical outcomes for newborns surviving birth asphyxia. Brain injury following hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. The specific pathologic processes preceding the onset of irreversible cerebral injury appear to be a combination of several mechanisms that are variable according to the severity and duration of the insult and to biochemical modifications in the brain. ⋯ It is becoming evident that the association of moderate hypothermia with neuroprotective drugs may enhance the outcome. By virtue of their pleiotropic effects without toxic effects, melatonin and statins may act at different levels of the multiple mechanisms responsible for the progression of the neurodegenerative process and represent promising neuroprotectants, alone or as additional adjunctive therapy, for reducing brain injury and its long-term sequelae in infants. More clinical studies are needed to clarify the role of these potential neuroprotective drugs.
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In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. ⋯ Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions.