Research Topics
| A I AlayashSummaryAffiliation: Food and Drug Administration Country: USA Publications
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Detail Information
Publications
Hemoglobin-based blood substitutes: oxygen carriers, pressor agents, or oxidants?A I Alayash
Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drug Administration, NIH Campus, Bethesda, MD 20892, USA
Nat Biotechnol 17:545-9. 1999....- Site-specific cross-linking of human and bovine hemoglobins differentially alters oxygen binding and redox side reactions producing rhombic heme and heme degradationEnika Nagababu
Molecular Dynamics Section, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224-6823, USA
Biochemistry 41:7407-15. 2002..These findings establish the importance of these secondary oxidative reactions over autoxidation in evaluating the toxicity of HBOCs... - Hemoglobin-based blood substitutes and the hazards of blood radicalsA I Alayash
Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health Campus, Bethesda, Maryland 20892, USA
Free Radic Res 33:341-8. 2000..This article reviews our current understanding of heme-mediated toxicities and some of the emerging protective strategies used to overcome hemoglobin side reactions... - Redox reactions of hemoglobin and myoglobin: biological and toxicological implicationsA I Alayash
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Antioxid Redox Signal 3:313-27. 2001..Also discussed in this article is the role of heme-protein chemistry in relation to the toxicity of hemoproteins... - Effects of glutaraldehyde polymerization on oxygen transport and redox properties of bovine hemoglobinA I Alayash
Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
Arch Biochem Biophys 391:225-34. 2001..Glutaraldehyde polymerization of HbBv alters its normal allosteric mechanisms, autoxidation kinetics and other related redox properties, which may compromise its function and cause greater toxicity when used as an oxygen transport fluid... - Oxygen therapeutics: can we tame haemoglobin?Abdu I Alayash
Laboratory of Biochemistry, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Rev Drug Discov 3:152-9. 2004..Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function... - Oxidative mechanisms of hemoglobin-based blood substitutesA I Alayash
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Artif Cells Blood Substit Immobil Biotechnol 29:415-25. 2001..Further complications are thought to arise through the disruption of key signaling pathways resulting from alteration of or destruction of important physiological mediators... - Hemoglobin and free radicals: implications for the development of a safe blood substituteA I Alayash
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Mol Med Today 1:122-7. 1995..This article reviews current research into heme-mediated toxicities that potentially constitute serious impediments to the development of a usable blood substitute... - Reactions of sperm whale myoglobin with hydrogen peroxide. Effects of distal pocket mutations on the formation and stability of the ferryl intermediateA I Alayash
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
J Biol Chem 274:2029-37. 1999.... 
Serial oxygen equilibrium and kinetic measurements during RBC storageM P Gelderman
Laboratory of Cellular Hematology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA
Transfus Med 20:341-5. 2010..To contribute to the understanding of the biochemical changes associated with the RBC storage lesion...- Peroxynitrite-mediated heme oxidation and protein modification of native and chemically modified hemoglobinsA I Alayash
Laboratory of Cellular Hematology, Food and Drug Administration, Bethesda, Maryland 20892, USA
Arch Biochem Biophys 349:65-73. 1998.... - Redox cycling of diaspirin cross-linked hemoglobin induces G2/M arrest and apoptosis in cultured endothelial cellsA I Alayash
Laboratory of Plasma Derivatives, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Blood 98:3315-23. 2001..Catalase inhibited DBBF-Hb oxidation, the loss of thiols, and the onset of G2/M arrest and apoptosis. These data support a causative role for the ferric-ferryl redox cycle in the development of endothelial cell injury... - Redox side reactions of haemoglobin and cell signalling mechanismsL-H Yeh
Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
J Intern Med 253:518-26. 2003.... - Oxygen sensing in the circulation: "cross talk" between red blood cells and the vasculaturePaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA
Antioxid Redox Signal 6:1000-10. 2004..We believe that there are important and yet unexplored mechanisms by which RBCs can directly or indirectly communicate via redox intermediates with extravascular sites as part of the global O(2) sensing mechanism... - Acellular haemoglobin attenuates hypoxia-inducible factor-1alpha (HIF-1alpha) and its target genes in haemodiluted ratsDominador J Manalo
LBVB Laboratory of Biochemistry and Vascular Biology, Division of Hematology, CBER Center for Biologics Evaluation and Research, FDA Food and Drug Administration, NIH National Institutes of Health, Bethesda, MD 20892, USA
Biochem J 414:461-9. 2008.... - Structural and functional characterization of glutaraldehyde-polymerized bovine hemoglobin and its isolated fractionsPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research (CBER, Food and Drug Administration (FDA, Bethesda, Maryland 20892, USA
Anal Chem 77:3466-78. 2005..Structural modification imparted by glutaraldehyde resulted in nearly identical functional characteristics of PolyHbBv and its fractions with regard to oxygen equilibrium, ligand binding, and autoxidative kinetics... - The heme pocket geometry of Lucina pectinata hemoglobin II restricts nitric oxide and peroxide entry: model of ligand control for the design of a stable oxygen carrierWalleska De Jesus Bonilla
Department of Chemistry, University of Puerto Rico, Mayaguez Campus, P O Box 9019, Mayagüez 00681 9019, Puerto Rico
Biochemistry 46:10451-60. 2007..Engineering of second-generation Hb-based oxygen therapeutics that are resistant to NO/H2O2-driven oxidation may ultimately require further optimization of the heme pocket architecture to limit heme exposure to solvent... 
Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivoJacqueline Dunne
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK
Biochem J 399:513-24. 2006..g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis...- Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathwayYiping Jia
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
J Biol Chem 282:4894-907. 2007.... - First-generation blood substitutes: what have we learned? Biochemical and physiological perspectivesAbdu I Alayash
Center for Biologics Evaluation and Research, Food and Drug Administration, Laboratory of Biochemistry and Vascular Biology, Division of Hematology, National Institutes of Health Campus, Bethesda, MD 20892, USA
Expert Opin Biol Ther 7:665-75. 2007..Here the authors provide an overview of their research experiences, novel insights into the molecular basis of toxicities of these products and some lessons learned... - Effects of cell-free hemoglobin on hypoxia-inducible factor (HIF-1alpha) and heme oxygenase (HO-1) expressions in endothelial cells subjected to hypoxiaLi Hong Yeh
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Antioxid Redox Signal 6:944-53. 2004..DBBF-Hb modulates key cell-signaling pathways by competing with peroxides required for the deactivation of HIF-1alpha, which may modulate important physiological mediators... - Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pigPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
J Pharmacol Exp Ther 323:49-60. 2007..The present findings suggest the importance of plasma AA in maintaining the stability of acellular Hb susceptible to oxidation, and they may be relevant to humans, which display a similar plasma/tissue antioxidant status to guinea pig... - Stopped-flow fluorescence method for the detection of heme degradation products in solutions of chemically modified hemoglobins and peroxideYiping Jia
Center for Biologics Evaluation and Research (CBER, Food and Drug Administration (FDA, Bethesda, Maryland 20892, USA
Anal Biochem 308:186-8. 2002 - Comparison of effects of two hemoglobin-based O(2) carriers on intestinal integrity and microvascular leakageAnn L Baldwin
Department of Physiology, College of Medicine, University of Arizona, Tucson 85724 5051, USA
Am J Physiol Heart Circ Physiol 283:H1292-301. 2002..These results indicate that intravascular PolyHbBv produces significantly less disruption of the intestinal exchange barrier than does DBBF-Hb, probably because the heme is not so easily oxidized... - A role for the myoglobin redox cycle in the induction of endothelial cell apoptosisFELICE D'AGNILLO
Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Free Radic Biol Med 33:1153-64. 2002..These results suggest a role for the Mb redox cycle in the induction of endothelial cell apoptosis, which may be relevant in the pathophysiology of diseases characterized by the release of Mb from damaged muscle... - Sodium selenite reduces hemoglobin-induced venular leakage in the rat mesenteryAnn L Baldwin
Department of Physiology, College of Medicine, University of Arizona, Tucson 85724 5051, USA
Am J Physiol Heart Circ Physiol 284:H81-91. 2003..In vitro, Na(2)SeO(3) reduced the oxidation rate of DBBF-Hb while in the presence of oxidants. These results suggest that Na(2)SeO(3) reduces DBBF-Hb-induced microvascular leakage partly by retarding the oxidation of its heme iron... - Differential effects of sodium selenite in reducing tissue damage caused by three hemoglobin-based oxygen carriersAnn L Baldwin
Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724 5051, USA
J Appl Physiol 96:893-903. 2004.... - Oxygen binding and oxidation reactions of human hemoglobin conjugated to carboxylate dextranYiping Jia
Laboratory of Biochemistry and Vascular Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Biochim Biophys Acta 1672:164-73. 2004..However, the reduction in the allosteric function of this protein and the lack of apparent quaternary T-->R transition may hinder its physiological role as an oxygen transporter... - Toxicities of hemoglobin solutions: in search of in-vitro and in-vivo model systemsPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Bethesda, Maryland, USA
Transfusion 44:1516-30. 2004.... - Allosteric effects on oxidative and nitrosative reactions of cell-free hemoglobinsCelia Bonaventura
Nicholas School of the Environment and Earth Sciences, Duke University Marine Laboratory, Beaufort, North Carolina 28516, USA
IUBMB Life 59:498-505. 2007..These redox reactions can drive formation of SNO-Hb and other reactive species and are of significance for the use of cell-free Hbs in vivo... - Effects of (-)-epigallocatechin gallate on the redox reactions of human hemoglobinYiping Jia
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health Campus, Bethesda, MD 20892, USA
Free Radic Biol Med 45:659-66. 2008..A balance between pro and antioxidant properties of EGCG should be taken into account if EGCG is used in combination therapy with redox active acellular Hbs... - Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathwaysPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research CBER, U S Food and Drug Administration FDA, Rockville, Maryland, USA
Antioxid Redox Signal 10:1449-62. 2008..Based on these results, a rational and systematic approach to HBOC design may be used to optimize interaction with endogenous Hb clearance and detoxification pathways... - Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD163, a scavenger receptorDominik J Schaer
Medical Clinic B Research Unit, University of Zurich, Switzerland
Antioxid Redox Signal 9:991-9. 2007..Here, an overview and novel insights into the role of CD163 in Hb redox inactivation and clearance are provided... - Redox biology of blood revisited: the role of red blood cells in maintaining circulatory reductive capacityPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Antioxid Redox Signal 7:1755-60. 2005..In the current short review, we have revisited the topic of redox biology of blood and focused on yet another emerging area of research, which deals with the reductive power of blood and the physiological Redox Signal... - CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobinDominik J Schaer
Medical Clinic B Research Unit, University Hospital, CH 8091 Zurich, Switzerland
Blood 107:373-80. 2006..These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion... - O-raffinose crosslinked hemoglobin lacks site-specific chemistry in the central cavity: structural and functional consequences of beta93Cys modificationRobert A Boykins
Laboratory of Biophysics, Division of Bacterial, Parasitic and Allergenic Products, Bethesda, Maryland 20892, USA
Proteins 59:840-55. 2005..Structural data presented here when taken together with the oxidative instability of O-R-PolyHbA0 may provide some basis for the reported toxicity of this oxygen carrier... - Redox biology of bloodAbdu I Alayash
Antioxid Redox Signal 6:941-3. 2004 - Hemodilution with stroma-free [correction of stoma-free] hemoglobin at physiologically maintained viscosity delays the onset of vasoconstrictionGéraldine Rochon
Department of Hematology and Physiology, School of Pharmacy, University Henri Poincaré Nancy, France
Hypertension 43:1110-5. 2004.... - Cross-linking with O-raffinose lowers oxygen affinity and stabilizes haemoglobin in a non-cooperative T-state conformationYiping Jia
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research (CBER, Food and Drug Administration (FDA, Bethesda, Maryland 20892, USA
Biochem J 384:367-75. 2004..Although the physiological ramifications of locking HbA(0) in the T conformation with the O-raffinose are still unknown, valuable insights into haemoglobin function are provided by these studies of O-R-polyHbA(0)...