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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Malignant glioma represents one of the most lethal and angiogenic cancers. Angiogenesis is a fundamental process of blood vessel growth that is a hallmark of cancer. Although several molecular mechanisms contribute to tumor angiogenesis in gliomas, the vascular endothelial growth factor (VEGF) pathway appears particularly important and has been a prominent therapeutic target in cancer treatment. ⋯ Identification of biomarkers to predict response or resistance and to monitor antiangiogenic effects is important to enrich for patients who are likely to respond to therapy and to define the optimal biological dose. At present, antiangiogenic therapies remain palliative suggesting that overcoming antiangiogenic resistance may require multi-targeted agents, combination of agents targeting different angiogenic pathways or multi-modality combination with radiation, chemotherapy, other targeted therapeutics or immunotherapy. In this review, we will discuss the current development, promise and challenge of antiangiogenic therapy in malignant glioma.