Setbacks in Blood Substitutes Research and Development: A Biochemical Perspective

被引：39
作者：
Alayash, Abdu I. [1 ]
机构：
[1] NIH, CBER, US FDA, Bethesda, MD 20892 USA
来源：
CLINICS IN LABORATORY MEDICINE | 2010年 / 30卷 / 02期
关键词：
Blood substitutes; Hemoglobin toxicity; Oxygen transport; NITRIC-OXIDE; HEMOGLOBIN; SCAVENGER; HIF-1-ALPHA; OXIDATION;
D O I：
10.1016/j.cll.2010.02.009
中图分类号：
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号：
1001 ;
摘要：
Recent setbacks in using Hb-based technology to develop oxygen carriers or blood substitutes may spur new and fundamentally different approaches for the development of a new generation of hemoglobin-based oxygen carriers (HBOCs). This article briefly details some underlying mechanisms that may have been responsible for the adverse-event profile associated with HBOCs, with a focus on the contribution of the author's laboratory toward identifying some of these biochemical pathways and some ways and means to control them. It is hoped that this will aid in the development of a safe and effective second generation of HBOCs.
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收藏
页码：381 / +
页数：10
相关论文
共 23 条
[1]  
Adamson JG, 1998, TISS ENG, P62
[2]   Oxygen therapeutics: Can we tame haemoglobin? [J].
Alayash, AI .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (02) :152-159
[3]   Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs [J].
Boretti, Felicitas S. ;
Buehler, Paul W. ;
D'Agnillo, Felice ;
Kluge, Katharina ;
Glaus, Tony ;
Butt, Omer I. ;
Jia, Yiping ;
Goede, Jeroen ;
Pereira, Claudia P. ;
Maggiorini, Marco ;
Schoedon, Gabrielle ;
Alayash, Abdu I. ;
Schaer, Dominik J. .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (08) :2271-2280
[4]   O-raffinose crosslinked hemoglobin lacks site-specific chemistry in the central cavity:: Structural and functional consequences of β93Cys modification [J].
Boykins, RA ;
Buehler, PW ;
Jia, YP ;
Venable, R ;
Alayash, AI .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2005, 59 (04) :840-855
[5]   Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathways [J].
Buehler, Paul W. ;
Vallelian, Florence ;
Mikolajczyk, Malgorzata G. ;
Schoedon, Gabriele ;
Schweizer, Thomas ;
Alayash, Abdu I. ;
Schaer, Dominik J. .
ANTIOXIDANTS & REDOX SIGNALING, 2008, 10 (08) :1449-1462
[6]   Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig [J].
Buehler, Paul W. ;
D'Agnillo, Felice ;
Hoffman, Victoria ;
Alayash, Abdu I. .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 323 (01) :49-60
[7]   Chemical characterization of diaspirin cross-linked hemoglobin polymerized with poly(ethylene glycol) [J].
Buehler, Paul W. ;
Boykins, Robert A. ;
Norris, Scott ;
Alayash, Abdu I. .
ANALYTICAL CHEMISTRY, 2006, 78 (13) :4634-4641
[8]   Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification [J].
Buehler, Paul W. ;
Abraham, Bindu ;
Vallelian, Florence ;
Linnemayr, Charlotte ;
Pereira, Claudia P. ;
Cipollo, John F. ;
Jia, Yiping ;
Mikolajczyk, Malgorzata ;
Boretti, Felicitas S. ;
Schoedon, Gabriele ;
Alayash, Abdu I. ;
Schaer, Dominik J. .
BLOOD, 2009, 113 (11) :2578-2586
[9]   Structural and functional characterization of glutaraldehyde-polymerized bovine hemoglobin and its isolated fractions [J].
Buehler, PW ;
Boykins, RA ;
Jia, YP ;
Norris, S ;
Freedberg, DI ;
Alayash, AI .
ANALYTICAL CHEMISTRY, 2005, 77 (11) :3466-3478
[10]   Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation [J].
Cosby, K ;
Partovi, KS ;
Crawford, JH ;
Patel, RP ;
Reiter, CD ;
Martyr, S ;
Yang, BK ;
Waclawiw, MA ;
Zalos, G ;
Xu, XL ;
Huang, KT ;
Shields, H ;
Kim-Shapiro, DB ;
Schechter, AN ;
Cannon, RO ;
Gladwin, MT .
NATURE MEDICINE, 2003, 9 (12) :1498-1505
123