RESUMO
BACKGROUND: There exists an increasing array of treatments proposed to prevent, alleviate, and abort symptoms of a migraine; however, for patients who undergo reconstructive microsurgery, caution must be taken to preserve vascular integrity. This study is the first-to-date scoping review of vascular and bleeding risk of current migraine therapies, with the purpose of identifying potential therapeutic agents for postoperative migraine management appropriate for microsurgical patients. METHODS: Currently available migraine therapeutics were compiled from UpToDate and the American Academy of Family Physicians. A PubMed literature review was performed for each therapeutic's effect on bleeding or vascular involvement. Data were compiled into tables of abortive, symptom-controlling and prophylactic, and non-pharmacologic treatments. Expert microsurgeons reviewed the data to provide recommendations for optimized patient care. RESULTS: Triptans and other ergot derivatives demonstrated strong evidence of vasoconstriction and were greatly advised against for immediate post-microsurgical use. Novel pharmaceutical therapies like Lasmiditan and CGRP antagonists have no literature indicating potential for vasoconstriction or hematoma and remain an investigational option for abortive medical treatment. For symptom control, acetaminophen appears the safest option, with clinical judgment and further research needed for use of NSAIDs. Alternative treatment techniques may include migraine prophylaxis with botulinum toxin injection or nutraceutical treatment via magnesium supplementation or Coenzyme Q10 administration, minimizing the need for additional medication in the postoperative setting. CONCLUSIONS: Patients undergoing reconstructive microsurgery have a unique medical profile limiting the therapeutic options available to treat migraines. This review provides preliminary evidence to be considered as a guide for prescribing therapeutics for migraine in the postoperative setting.
RESUMO
Ascorbic acid (AA) exhibits significant anticancer activity at pharmacologic doses achievable by parenteral administration that have minimal effects on normal cells. Thus, AA has potential uses as a chemotherapeutic agent alone or in combination with other therapeutics that specifically target cancer-cell metabolism. We compared the effects of AA and combinations of AA with the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO) on the viability of three non-small cell lung cancer (NSCLC) cell lines to the effects on an immortalized lung epithelial cell line. AA concentrations of 0.5 to 5 mM caused a complete loss of viability in all NSCLC lines compared to a <10% loss of viability in the lung epithelial cell line. Combinations of AA and 3-PO synergistically enhanced cell death in all NSCLC cell lines at concentrations well below the IC50 concentrations for each compound alone. A synergistic interaction was not observed in combination treatments of lung epithelial cells and combination treatments that caused a complete loss of viability in NSCLC cells had modest effects on normal lung cell viability and reactive oxygen species (ROS) levels. Combination treatments induced dramatically higher ROS levels compared to treatment with AA and 3-PO alone in NSCLC cells and combination-induced cell death was inhibited by addition of catalase to the medium. Analyses of DNA fragmentation, poly (ADP-ribose) polymerase cleavage, annexin V-binding, and caspase activity demonstrated that AA-induced cell death is caused via the activation of apoptosis and that the combination treatments caused a synergistic induction of apoptosis. These results demonstrate the effectiveness of AA against NSCLC cells and that combinations of AA with 3-PO synergistically induce apoptosis via a ROS-dependent mechanism. These results support further evaluation of pharmacologic concentrations of AA as an adjuvant treatment for NSCLC and that combination of AA with glycolysis inhibitors may be a promising therapy for the treatment of NSCLC.