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The Search for the Mechanism of Nitric Oxide Release in Hydroxyurea Therapy

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The Search for the Mechanism of Nitric Oxide Release in Hydroxyurea Therapy
Lockamy, Virginia L
Hydroxyurea (HU) is an FDA approved drug that has shown promise in the treatment of sickle cell anemia. Increases in the production of nitric oxide metabolites (iron nitrosyl hemoglobin (HbNO), nitrite, and nitrate) have been reported in sickle cell disease patients receiving HU therapy. The exact mechanism by which HU produces HbNO in vivo is still not completely understood. The purpose of this research was to further investigate the reactions of NO and NO-producing compounds on blood and other blood constituents. The kinetics of polymerization and solubility effects of HU and NO were studied for the reaction of sickle cell hemoglobin (HbS) with HU. While HU and NO prolonged the delay time of polymerization for HbS in buffers of high phosphate concentration, NO had no solubilizing effect on HbS under physiological conditions. Experiments involving HU, NO, and hydroxylamine (HA) were conducted to determine the kinetics and products of their respective reactions with blood and blood constituents, as well as to determine how these NO-producing compounds alleviate some of the symptoms of sickle cell disease.
absorption spectroscopy
electron paramagnetic resonance spectroscopy
iron nitrosyl hemoglobin
nitric oxide
sickle cell disease
lockvl0@wfu.edu (authorEmail)
S. Bruce King (committee chair)
G. Eric Matthews (committee member)
Natalie A.W. Holzwarth (committee member)
Martin Guthold (committee member)
Daniel B. Kim-Shapiro (committee member)
Lockamy, Virginia L
2008-09-28T10:53:36Z (accessioned)
2010-06-18T19:00:02Z (accessioned)
2005-07-02 (available)
2008-09-28T10:53:36Z (available)
2010-06-18T19:00:02Z (available)
2004-04-29 (issued)
null (defenseDate)
Physics (discipline)
Wake Forest University (grantor)
PHD (level)
http://hdl.handle.net/10339/14915 (uri)
etd-05182004-115414 (oldETDId)
Release the entire work immediately for access worldwide. (accessRights)
I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Wake Forest University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. (license)

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