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The primary hypothesis of this study is that glutamine supplementation will improve the erythrocyte glutamine/glutamate ratio, a biomarker of oxidative stress, hemolysis and pulmonary hypertension (PH) in sickle cell disease (SCD) and thalassemia (Thal) patients with PH. PH is defined as a tricuspid regurgitant jet velocity (TRV) on Doppler echocardiography > 2.5 m/s. We also predict that glutamine therapy will increase arginine bioavailability and subsequently alter sickle red cell endothelial interaction that can be identified using endo-PAT technology through nitric oxide (NO) generation, leading to changes in biological markers, and clinical outcome. Specifically our second hypothesis is that oral glutamine will decrease biomarkers of hemolysis and adhesion molecules, and improve the imbalanced arginine-to-ornithine ratio that occurs in hemolytic anemias, leading to improved arginine bioavailability and clinical endpoints of endothelial dysfunction and PH in patients with SCD and Thal.
Allocation: Non-Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Children's Hospital & Research Center Oakland
Children's Hospital & Research Center Oakland
Published on BioPortfolio: 2014-08-27T03:16:40-0400
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Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.
An enzyme that catalyzes the synthesis of fructose-6-phosphate plus GLUTAMINE from GLUTAMATE plus glucosamine-6-phosphate.
An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and glutamine. This enzyme is important in the de novo biosynthesis of pyrimidines. EC 188.8.131.52.
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
Familial or idiopathic hypertension in the PULMONARY CIRCULATION which is not secondary to other disease.
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