Current pharmaceutical design
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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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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.
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The tumor suppressor PTEN serves as a negative regulator of PI3K/PTEN/Akt signaling pathway that regulates cellular functions such as cell growth, differentiation, proliferation and migration. The PI3K/PTEN/Akt signaling cascades might also have effect on glucose uptake via translocation of GLUT-4. Insulin controls energy storage and the whole body glucose homeostasis. Its binding to insulin receptor on the surface of diverse cells allows glucose entry into cells, and activates a variety of cellular actions. Insulin resistance is a common metabolic feature and established risk factor of many diseases. Its fundamental principle is inability of insulin to exert its normal metabolic effects, and nutrient imbalance and abnormal lipid accumulation in skeletal muscle, liver and adipose tissues. ⋯ Considering PTEN's important role in insulin resistance and tumor regulation, targeting the PTEN gene and/or protein will likely provide an efficient strategy for therapeutic intervention in cancer and metabolic diseases like type 2 diabetes mellitus, obesity, and cardiovascular dysfunction.
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Intracerebral hemorrhage (ICH) is one of the most common forms of cerebral hemorrhage, the morbidity and death of ICH is high worldwide. ICH can be spontaneous or caused by hypertension, coagulopathy, angiopathy, head trauma, bleeding disorders, tumors, or drug usage. ICH is the most serious and least treatable form of hemorrhagic stroke, with rapidly increasing hematoma size and often resulting in significant brain injury and long term neurological deficits. Surgical hematoma evacuation remains controversial. The currently therapy is mainly supportive with limited benefit. New therapeutic approaches are desperately needed. ⋯ Although ICH remains without an approved treatment proven to decrease morbidity and mortality, notable advances in the understanding of ICH pathophysiology and new drug development have been made in the last decade.