Current pharmaceutical design
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Colchicine is an old drug originally employed for the treatment of inflammatory disorders such as acute gout and familiar Mediterranean fever. ⋯ Colchicine has been established as a first line medication in the treatment of acute (first episode) and recurrent pericarditis on top of the conventional treatment as well as for the prevention of postpericardiotomy syndrome. It depicts a good safety profile with gastrointestinal intolerance being the most common side effect.
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Traumatic brain injury (TBI) is an important public health concern plagued by high rates of mortality and significant long-term disability in many survivors. Post-traumatic seizures (PTS) are not uncommon following TBI, both in the early (within 7 days post-injury) and late (after 7 days post-injury) period. ⋯ Prophylactic antiepileptic drug (AED) administration has been proposed as a measure to reduce the incidence of PTS and the ultimate development of PTE in TBI patients. In this topical review, we discuss the pathophysiologic mechanisms of early and late PTS and the development of PTE following TBI, the pharmacodynamic and pharmacokinetic properties of AEDs commonly used to prevent post-traumatic seizures, and summarize the available clinical evidence for employing AEDs for seizure prophylaxis after TBI.
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Review
Anti-EGFRvIII Chimeric Antigen Receptor-Modified T Cells for Adoptive Cell Therapy of Glioblastoma.
Glioblastoma (GBM) is one of the most devastating brain tumors with poor prognosis and high mortality. Although radical surgical treatment with subsequent radiation and chemotherapy can improve the survival, the efficacy of such regimens is insufficient because the GBM cells can spread and destroy normal brain structures. Moreover, these non-specific treatments may damage adjacent healthy brain tissue. ⋯ Immunotherapy is a promising approach due to its capability to suppress the growth of various tumors in preclinical model and clinical trials. Adoptive cell therapy (ACT) using T cells engineered with chimeric antigen receptor (CAR) targeting an ideal molecular marker in GBM, e.g. epidermal growth factor receptor type III (EGFRvIII) has demonstrated a satisfactory efficacy in treating malignant brain tumors. Here we summarize the recent progresses in immunotherapeutic strategy using CAR-modified T cells oriented to EGFRvIII against GBM.
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Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. ⋯ Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGERAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart.
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There is an increasing prevalence of cardiovascular diseases that warrant antithrombotic therapy. Antithrombotic therapy includes antiplatelet agents and anticoagulation therapy with vitamin K antagonists (VKAs) or non-Vitamin K oral anticoagulants (NOACs). Antithrombotic therapy is associated with increased rates of bleeding. ⋯ Andexanet alpha is a factor Xa-specific inhibitor that is currently undergoing FDA review. Until andexanet alpha becomes available we recommend discontinuation of the factor Xa inhibitor and administration of 50 units/kg 4- factor PCC. The decision to discontinue and/or reverse antithrombotic therapy should be made on a case-by-case basis and the competing risk from discontinuation and/or reversal of antithrombotic therapy should be taken into consideration.