Medicine and Health Sciences Commons^™

Effect Of Iron Chelators On Methemoglobin And Thrombin Preconditioning., Jing Chen-Roetling, Jesse Sinanan, Raymond F. Regan

Department of Emergency Medicine Faculty Papers

Cell loss immediately adjacent to an intracerebral hemorrhage may be mediated in part by the toxicities of extracellular hemoglobin (Hb) and thrombin. However, at low concentrations, these proteins induce tolerance to hemin and iron that may limit further peri-hematomal injury as erythrocyte lysis progresses. The mechanisms mediating these preconditioning effects have not been completely defined, but increased expression of both heme oxygenase (HO)-1 and iron binding proteins likely contributes. In the present study, we hypothesized that iron chelator therapy would attenuate this protective response. Pretreatment of cortical glial cultures (> 90 % GFAP+) with 3 μM methemoglobin (metHb) or 5 …

Cerebral And Lower Limb Near-Infrared Spectroscopy In Adults On Extracorporeal Membrane Oxygenation, Joshua K Wong, Thomas N Smith, Harrison T Pitcher, Hitoshi Hirose, Nicholas C. Cavarocchi

Department of Surgery Faculty Papers

Percutaneous femoral venoarterial (VA) or jugular venovenous (VV) extracorporeal membrane oxygenation (ECMO) can result in delivery of hypoxic blood to the brain, coronaries, and upper extremities. Additionally, VA-ECMO by percutaneous femoral artery cannulation may compromise perfusion to the lower limbs. Use of near-infrared spectroscopy (NIRS) detects regional ischemia and warns of impending hypoxic damage. We report the first known series with standardized monitoring of this parameter in adults on ECMO. This is an institutional review board-approved single institution retrospective review of patients with NIRS monitoring on ECMO from July 2010 until June 2011. Patients were analyzed for drops in NIRS …

Hypoxia-Sensitive Gene Expression In The Gastrocnemius Muscle Following Chronic Hind Limb Ischemia, Andrew Tilton

Biological Sciences

Chronic ischemia, caused by the formation atherosclerotic plaque occlusions in major conduit arteries, is the leading cause of morbidity and mortality in western societies. Vascular remodeling can help compensate for the adverse effects of atherosclerotic plaque formation. Vascular remodeling relies heavily on vascular endothelial growth factor (VEGF), a critical protein that contributes to all forms of vascular formation and remodeling including angiogenesis, arteriogenesisand vasculogenesis. VEGF itself is up-regulated by the transcription factor, hypoxia inducible factor 1 alpha (HIF-1α), which becomes activated in low oxygen environments.

Through the use of animal chronic hindlimb ischemia models, these genes can be evaluated as …

Pharmacological And Therapeutic Effects Of A3 Adenosine Receptor (A3ar) Agonists, Bruce T. Liang

UCHC Articles - Research

The G_i-coupled A₃ adenosine receptor (A₃AR) mediates anti-inflammatory, anticancer and anti-ischemic protective effects. The receptor is overexpressed in inflammatory and cancer cells, while low expression is found in normal cells, rendering the A₃AR as a potential therapeutic target. Highly selective A₃AR agonists have been synthesized and molecular recognition in the binding site has been characterized. The present review summarizes preclinical and clinical human studies demonstrating that A₃AR agonists induce specific anti-inflammatory and anticancer effects via a molecular mechanism that entails modulation of the Wnt and the NF-κB signal transduction …

Newer Agents In Antiplatelet Therapy: A Review., Jennifer Yeung, Michael Holinstat

Cardeza Foundation for Hematologic Research

Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use …

Dietary Boron Intake Does Not Change The Ischemic Tolerance And Preconditioning Response In Isoproterenol-Induced Myocardial Injury In Healthy Rats, Mehmet Fati̇h Karakaş, Mustafa Kurt, Uğur Arslantaş, Göktürk İpek, Esra Karakaş, Emi̇ne Bi̇len, Hüsametti̇n Erdamar

Turkish Journal of Medical Sciences

Boron is important for many enzymes, most of which also have a role in the ischemic tolerance of the myocardium. We aimed to evaluate the influence of dietary boron intake on ischemic tolerance in a rat model. Materials and methods: Rats were divided into 3 groups according to the ischemia protocol: Sham (S) (n = 20 total), ischemia only (Isc-only) (n = 40 total), and remote ischemic preconditioning + ischemia (RIPC+Isc) (n = 40 total) groups. These 3 groups were further divided into 4 according to the amount of daily dietary boron (

Effects Of In Vivo Hepatic Ischemia-Reperfusion Injury On The Hepatobiliary Disposition Of Rhodamine 123 And Its Metabolites In Isolated Perfused Rat Livers, Ridhi Parasrampuria, Imam H. Shaik, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose. A few studies have shown that normothermic hepatic ischemia-reperfusion (IR) injury may affect the mRNA and/or protein levels of canalicular transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2). However, the effects of the injury on the functions of these canalicular transporters with respect to the biliary excretion of drugs remain largely unknown. Therefore, the purpose of this study was to investigate the effects of warm hepatic IR on the hepatobiliary disposition of rhodamine 123 (RH-123), a P-gp substrate, and its glucuronidated metabolite (RH-Glu), an Mrp2 substrate, in rats.

Methods. Twenty four or 72 h following a …