Current pharmaceutical design
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Antithrombotic and powerful antiplatelet therapies, in addition to early percutaneous coronary intervention (PCI) are considered the treatment of choice for moderate- to high-risk patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction). However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors (GPI), and thienopyridines, the rate of adverse ischemic events still remains unacceptably high. Intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty as well as surgical revascularization procedures, elicit a high rate of bleeding complications. ⋯ It remains to be a matter of discussion whether there are still patient subgroups being in need of more aggressive treatment strategies including GPI. In practice, it might be reasonable to perform a baseline assessment of hemorrhagic risk facilitating the choice of an antithrombotic regimen with a favourable safety and efficacy profile. With this tailored therapy it might be possible to further improve outcomes for individual patients with ACS.
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The often fatal sepsis syndrome is characterized by the systemic release of inflammatory mediators, which is regulated and counterbalanced by the coordinated expression of anti-inflammatory molecules. The magnitude of sepsis-induced tissue injury and subsequent risk of infectious complications is dictated by the balance between the expression of pro- and anti-inflammatory mediators. ⋯ Functional defects in leukocytes isolated from patients with sepsis include diminished expression of important cell surface molecules, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis. In this article, we review the current literature supporting the notion that dysregulation of host immunity occurs during sepsis syndrome, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.
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New compounds having affinity to various melanocortin receptors have recently been identified as possible neuroprotective agents. This review is focused on the role of neuroprotective effects of melanocortins in CNS injury and repair mechanisms. ⋯ This effect of the compounds is related with their ability to attenuate blood-spinal cord barrier permeability. The functional significance and possible therapeutic strategies of these compounds in CNS injury are discussed.
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Functional recovery following acute CNS injury in humans, such as spinal cord injury and stroke, is exceptionally limited, leaving the affected individual with life-long neurological deficits such as loss of limb movement and sensation leading to a compromised quality of life. As yet, there is no effective treatment on the market for such injuries. This lack of functional recovery can at least in part be attributed to the restriction of axonal regeneration and neuroplasticity by several CNS myelin proteins that have been shown to be potent inhibitors of neurite outgrowth in vitro, namely myelin-associated glycoprotein (MAG), Nogo-A and oligodendrocyte myelin glycoprotein (OMgp). ⋯ Although the receptor(s) for amino-Nogo-A are unknown, amino-Nogo-A and NgR ligands mutually activate the small GTPase RhoA. Consistent with their neurite outgrowth inhibitory function, approaches counter-acting Nogo-A using function-blocking antibodies, NgR using peptide antagonists and receptor bodies or RhoA using deactivating enzymes have been shown to significantly enhance axonal regeneration and neuroplasticity leading to improved functional recovery in animal models of acute CNS injury. These in vivo findings thus provide a sound basis for the development of an effective treatment for acute CNS injuries in humans.