{"product_id":"chemistry-and-biochemistry-of-oxygen-therapeutics-isbn-9780470686683","title":"Chemistry and Biochemistry of Oxygen Therapeutics","description":"Human blood performs many important functions including defence against disease and transport of biomolecules, but perhaps the most important is to carry oxygen – the fundamental biochemical fuel - and other blood gases around the cardiovascular system. Traditional therapies for the impairment of this function, or the rapid replacement of lost blood, have centred around blood transfusions. However scientists are developing chemicals (oxygen therapeutics, or “blood substitutes”) which have the same oxygen-carrying capability as blood and can be used as replacements for blood transfusion or to treat diseases where oxygen transport is impaired.  \u003cp\u003e\u003ci\u003eChemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood\u003c\/i\u003e links the underlying biochemical principles of the field with chemical and biotechnological innovations and pre-clinical development.\u003c\/p\u003e \u003cp\u003eThe first part of the book deals with the chemistry, biochemistry, physiology and toxicity of oxygen, including chapters on hemoglobin reactivity and regulation; the major cellular and physiological control mechanisms of blood flow and oxygen delivery;  hemoglobin and myoglobin;  nitric oxide and oxygen; and the role of reactive oxygen and nitrogen species in ischemia\/reperfusion Injury.\u003c\/p\u003e \u003cp\u003eThe book then discusses medical needs for oxygen supply, including acute traumatic hemorrhage and anemia; diagnosis and treatment of haemorrhages in \"non-surgical\" patients; management of perioperative bleeding; oxygenation in the preterm neonate; ischemia\u003c\/p\u003e \u003cp\u003enormobaric and hyperbaric oxygen therapy for ischemic stroke and other neurological conditions; and transfusion therapy in β thalassemia and sickle cell disease\u003c\/p\u003e \u003cp\u003eFinally “old”and new strategies for oxygen supply are described. These include the political, administrative and logistic issues surrounding transfusion;  conscientious objection in patient blood management; causes and consequences of red cell incompatibility; biochemistry of red blood cell storage;  proteomic investigations on stored red blood cells; red blood cells from stem cells; the universal red blood cell;  allosteric effectors of hemoglobin; hemoglobin-based oxygen carriers;  oxygen delivery by natural and artificial oxygen carriers; cross-linked and polymerized hemoglobins as potential blood substitutes; design of novel pegylated hemoglobins as oxygen carrying plasma expanders; hb octamers by introduction of surface cysteines; hemoglobin-vesicles as a cellular type hemoglobin-based oxygen carrier; animal models and oxidative biomarkers to evaluate pre-clinical safety of extracellular hemoglobins; and academia – industry collaboration in blood substitute development.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eChemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood\u003c\/i\u003e is an essential reference for clinicians, haematologists, medicinal chemists, biochemists, molecular biologists, biotechnologists and blood substitute researchers.\u003c\/p\u003e  \u003cb\u003e\u003ci\u003eList of Contributors\u003c\/i\u003e xvii\u003c\/b\u003e  \u003cp\u003e\u003cb\u003e\u003ci\u003ePreface\u003c\/i\u003e xxiii\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1. Introduction 1\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRichard B. Weiskopf\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eReferences 5\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart I. Oxygen: Chemistry, Biochemistry, Physiology and Toxicity 9\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2. Hemoglobin Reactivity and Regulation 11\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eStefano Bettati and Andrea Mozzarelli\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 11\u003c\/p\u003e \u003cp\u003e2.2 Oxygen Loading and Transport 11\u003c\/p\u003e \u003cp\u003e2.3 NO Reactivity with Hb 15\u003c\/p\u003e \u003cp\u003e2.4 Hb Oxidation 16\u003c\/p\u003e \u003cp\u003e2.5 Nitrite Reactivity with Hb 16\u003c\/p\u003e \u003cp\u003e2.6 Amino-acid Determinants of Hb Reactivity:\u003c\/p\u003e \u003cp\u003eNatural and Engineered Hbs 17\u003c\/p\u003e \u003cp\u003e2.6.1 Modulation of Oxygen Affinity and Cooperativity 17\u003c\/p\u003e \u003cp\u003e2.6.2 NO Reactivity and Oxidation 18\u003c\/p\u003e \u003cp\u003e2.7 Conclusion 18\u003c\/p\u003e \u003cp\u003eAcknowledgments 19\u003c\/p\u003e \u003cp\u003eReferences 19\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3. The Major Physiological Control Mechanisms of Blood Flow and Oxygen Delivery 23\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRaymond C. Koehler\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 23\u003c\/p\u003e \u003cp\u003e3.2 Autoregulation of Blood Flow to Changes in Perfusion Pressure 23\u003c\/p\u003e \u003cp\u003e3.3 Metabolic Regulation of Blood Flow 26\u003c\/p\u003e \u003cp\u003e3.4 O2 Transport 27\u003c\/p\u003e \u003cp\u003e3.5 O2 Delivery 27\u003c\/p\u003e \u003cp\u003e3.6 Endothelial Control of Vasomotor Tone 29\u003c\/p\u003e \u003cp\u003e3.7 Effect of Cell-free Hb on Endothelial Function 31\u003c\/p\u003e \u003cp\u003e3.8 Hypoxic Hypoxia 33\u003c\/p\u003e \u003cp\u003e3.9 Carbon Monoxide Hypoxia 36\u003c\/p\u003e \u003cp\u003e3.10 Anemia 36\u003c\/p\u003e \u003cp\u003e3.11 Conclusion 39\u003c\/p\u003e \u003cp\u003eReferences 39\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4. The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen 47\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eTim J. McMahon and Joseph Bonaventura\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 47\u003c\/p\u003e \u003cp\u003e4.2 Role of Mammalian Mb in O2 Homeostasis 47\u003c\/p\u003e \u003cp\u003e4.3 What’s Missing in the Mb Knockout Mouse 48\u003c\/p\u003e \u003cp\u003e4.4 Evolutionary Origins of Mb and the Nitrogen Cycle 49\u003c\/p\u003e \u003cp\u003e4.5 Human Hb: Evolved Sensor of pO2 and Redox 49\u003c\/p\u003e \u003cp\u003e4.6 Broad Reactivity and Influence of NO: Lessons from the Microcosm Hb 49\u003c\/p\u003e \u003cp\u003e4.7 Some Fish Demonstrate a Fundamental “Need” for Hb-dependent NO Cycling, as in Humans 50\u003c\/p\u003e \u003cp\u003e4.8 Reactions of NO with Hb that Preserve NO Bioactivity 52\u003c\/p\u003e \u003cp\u003e4.9 Mammalian RBC\/Hb–NO Interactions 52\u003c\/p\u003e \u003cp\u003e4.10 A Mutant Mouse Challenges the SNO-Hb Hypothesis, but does not Overthrow it 54\u003c\/p\u003e \u003cp\u003e4.11 Signaling by Hb-derived SNO: A Metabolically Responsive, Regulated Pathway 54\u003c\/p\u003e \u003cp\u003e4.12 Signaling by Hb-derived SNO: Pathway Complexity Revealed by Multiple Defects in Disease States 55\u003c\/p\u003e \u003cp\u003e4.13 Therapeutic Implications of the Hb–NO Signaling System 56\u003c\/p\u003e \u003cp\u003e4.14 HBOCs, NO, and SNO 56\u003c\/p\u003e \u003cp\u003e4.15 Other Gaseous Hb Ligands of Potential Therapeutic Significance 57\u003c\/p\u003e \u003cp\u003e4.16 NO-related Enzymatic Activities of Hb: Reconciling Nitrite Reductase and SNO Synthase Functions 57\u003c\/p\u003e \u003cp\u003e4.17 Measuring Biologically Relevant Hb–NO Adducts 58\u003c\/p\u003e \u003cp\u003e4.18 Conclusion 58\u003c\/p\u003e \u003cp\u003eAcknowledgments 58\u003c\/p\u003e \u003cp\u003eReferences 59\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5. The Role of Reactive Oxygen and Nitrogen Species in Ischemia\/Reperfusion Injury 63\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eEster Spagnolli and Warren M. Zapol\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 63\u003c\/p\u003e \u003cp\u003e5.2 Redox System and Free Radicals in Biological Systems 64\u003c\/p\u003e \u003cp\u003e5.3 Pathophysiology of Ischemia\/Reperfusion Injury 65\u003c\/p\u003e \u003cp\u003e5.3.1 Cell Death 65\u003c\/p\u003e \u003cp\u003e5.3.2 The Inflammatory Response 67\u003c\/p\u003e \u003cp\u003e5.4 Protection Against I\/R Injury 67\u003c\/p\u003e \u003cp\u003e5.4.1 Ischemic Pre- and Post-conditioning 67\u003c\/p\u003e \u003cp\u003e5.4.2 Pharmacological Conditioning 68\u003c\/p\u003e \u003cp\u003e5.4.2.1 The Protective Role of ROS and Antioxidants 68\u003c\/p\u003e \u003cp\u003e5.4.2.2 The Protective Role of NO 69\u003c\/p\u003e \u003cp\u003e5.4.2.3 NO-based Therapies for I\/R Injury 70\u003c\/p\u003e \u003cp\u003e5.5 Conclusion 72\u003c\/p\u003e \u003cp\u003eAcknowledgments 72\u003c\/p\u003e \u003cp\u003eReferences 72\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart II. Medical Needs for Oxygen Supply 79\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6. Acute Traumatic Hemorrhage and Anemia 81\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLena M. Napolitano\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 81\u003c\/p\u003e \u003cp\u003e6.2 Blood Transfusion in Trauma 83\u003c\/p\u003e \u003cp\u003e6.2.1 Massive Transfusion 83\u003c\/p\u003e \u003cp\u003e6.2.2 Massive Transfusion and Coagulopathy 83\u003c\/p\u003e \u003cp\u003e6.2.3 Hypotensive or Delayed Resuscitation 84\u003c\/p\u003e \u003cp\u003e6.2.4 Hemostatic Resuscitation 84\u003c\/p\u003e \u003cp\u003e6.2.5 Massive Transfusion Protocols 86\u003c\/p\u003e \u003cp\u003e6.2.6 Transfusion after Hemorrhage Control 86\u003c\/p\u003e \u003cp\u003e6.2.7 Efficacy of RBC Transfusion in Trauma and Associated Risks 86\u003c\/p\u003e \u003cp\u003e6.3 Oxygen Therapeutics in Trauma 88\u003c\/p\u003e \u003cp\u003e6.3.1 Diaspirin Crosslinked Hb 90\u003c\/p\u003e \u003cp\u003e6.3.2 Hemopure 90\u003c\/p\u003e \u003cp\u003e6.3.3 PolyHeme 91\u003c\/p\u003e \u003cp\u003e6.3.4 MP4OX 93\u003c\/p\u003e \u003cp\u003e6.3.5 Recombinant Human Hb 95\u003c\/p\u003e \u003cp\u003e6.3.6 Adverse Effects of HBOCs 95\u003c\/p\u003e \u003cp\u003e6.3.7 HBOCs in Trauma: A Way Forward? 96\u003c\/p\u003e \u003cp\u003e6.4 Conclusion 97\u003c\/p\u003e \u003cp\u003eReferences 97\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7. Diagnosis and Treatment of Haemorrhages in ‘Nonsurgical’ Patients 107\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eUmberto Rossi and Rosa Chianese\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 107\u003c\/p\u003e \u003cp\u003e7.1.1 Aetiopathogenetic Classification 107\u003c\/p\u003e \u003cp\u003e7.1.2 Multifactorial Pathogenesis 108\u003c\/p\u003e \u003cp\u003e7.1.3 Haemorrhagic Syndromes from Antithrombotic Treatment or Prophylaxis 108\u003c\/p\u003e \u003cp\u003e7.2 Clinical Assessment 111\u003c\/p\u003e \u003cp\u003e7.2.1 Medical History 111\u003c\/p\u003e \u003cp\u003e7.2.2 Physical Examination 112\u003c\/p\u003e \u003cp\u003e7.3 Laboratory Tests 113\u003c\/p\u003e \u003cp\u003e7.3.1 Screening Tests 113\u003c\/p\u003e \u003cp\u003e7.3.2 Second-level Laboratory Tests 113\u003c\/p\u003e \u003cp\u003e7.3.3 Other Tests 114\u003c\/p\u003e \u003cp\u003e7.4 Haemorrhagic Syndromes Clinically Indicative of Systemic Defects with Normal Screening Tests 117\u003c\/p\u003e \u003cp\u003e7.5 Blood and Blood Components in the Treatment of Haemorrhagic Syndromes 118\u003c\/p\u003e \u003cp\u003eFurther Reading 118\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8. Management of Perioperative Bleeding 121\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eSibylle A. Kozek-Langenecker\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 121\u003c\/p\u003e \u003cp\u003e8.2 Pathomechanisms of Coagulopathy in Massive Bleeding 121\u003c\/p\u003e \u003cp\u003e8.3 Perioperative Coagulation Monitoring 122\u003c\/p\u003e \u003cp\u003e8.4 Limitations of Routine Coagulation Tests in the Perioperative Setting 123\u003c\/p\u003e \u003cp\u003e8.5 Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) 124\u003c\/p\u003e \u003cp\u003e8.6 Procoagulant Interventions 124\u003c\/p\u003e \u003cp\u003e8.7 Algorithm for Coagulation Management 126\u003c\/p\u003e \u003cp\u003eReferences 127\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9. Oxygenation in the Preterm Neonate 131\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eVidheya Venkatesh, Priya Muthukumar, Anna Curley and Simon Stanworth\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 131\u003c\/p\u003e \u003cp\u003e9.2 Physiology of Oxygen Transport in Fetal and Postnatal Life 132\u003c\/p\u003e \u003cp\u003e9.2.1 Oxygenation of the Fetus 132\u003c\/p\u003e \u003cp\u003e9.2.2 Measuring Oxygenation in the Neonate 133\u003c\/p\u003e \u003cp\u003e9.3 Oxygen Therapy in the Postnatal Period 133\u003c\/p\u003e \u003cp\u003e9.3.1 Oxidative Stresses in the Newborn Period 134\u003c\/p\u003e \u003cp\u003e9.3.2 Clinical Sequelae of Hyperoxia 134\u003c\/p\u003e \u003cp\u003e9.3.2.1 Retinopathy of Prematurity 134\u003c\/p\u003e \u003cp\u003e9.3.2.2 Oxygen and Chronic Lung Disease 135\u003c\/p\u003e \u003cp\u003e9.3.2.3 Oxygen and Periventricular Leukomalacia 136\u003c\/p\u003e \u003cp\u003e9.4 Oxygen and Resuscitation of the Newborn Infant 136\u003c\/p\u003e \u003cp\u003e9.5 Transfusion in the Newborn 137\u003c\/p\u003e \u003cp\u003e9.6 ROP and Transfusions 137\u003c\/p\u003e \u003cp\u003e9.7 Conclusion 137\u003c\/p\u003e \u003cp\u003eReferences 138\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10. Ischemia 145\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHooman Mirzakhani and Ala Nozari\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 145\u003c\/p\u003e \u003cp\u003e10.2 Pathophysiology 145\u003c\/p\u003e \u003cp\u003e10.2.1 Energy Failure 145\u003c\/p\u003e \u003cp\u003e10.2.2 Cell Membrane Damage 146\u003c\/p\u003e \u003cp\u003e10.2.3 Increased Cytosolic Calcium 146\u003c\/p\u003e \u003cp\u003e10.2.4 Inflammation 148\u003c\/p\u003e \u003cp\u003e10.2.5 The No-reflow Phenomenon 149\u003c\/p\u003e \u003cp\u003e10.2.6 Free Radicals and Reactive Oxygen Species 149\u003c\/p\u003e \u003cp\u003e10.2.7 Excitotoxicity 150\u003c\/p\u003e \u003cp\u003e10.3 Therapeutic Potentials 150\u003c\/p\u003e \u003cp\u003e10.3.1 Preconditioning 150\u003c\/p\u003e \u003cp\u003e10.3.2 Antioxidants 151\u003c\/p\u003e \u003cp\u003e10.3.3 Anti-inflammation Therapy 151\u003c\/p\u003e \u003cp\u003e10.3.4 Therapeutic Hypothermia 151\u003c\/p\u003e \u003cp\u003e10.3.5 Hydrogen Sulfide 152\u003c\/p\u003e \u003cp\u003e10.3.6 Hyperoxia and Hyperbaric Oxygen 152\u003c\/p\u003e \u003cp\u003e10.3.7 Hemoglobin-based Oxygen Carriers 152\u003c\/p\u003e \u003cp\u003e10.4 Conclusion 153\u003c\/p\u003e \u003cp\u003eReferences 153\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11. Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions 159\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAri Moskowitz, Yu-Feng Yvonne Chan and Aneesh B. Singhal\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 159\u003c\/p\u003e \u003cp\u003e11.2 Rationale of Oxygen Therapy in AIS 160\u003c\/p\u003e \u003cp\u003e11.3 Hyperbaric Oxygen Therapy 162\u003c\/p\u003e \u003cp\u003e11.4 Normobaric Oxygen Therapy 164\u003c\/p\u003e \u003cp\u003e11.5 The Status of Supplemental Oxygen Delivery 165\u003c\/p\u003e \u003cp\u003e11.6 Comparison of HBO and NBO in AIS 165\u003c\/p\u003e \u003cp\u003e11.7 Safety Concerns 168\u003c\/p\u003e \u003cp\u003e11.8 HBO and NBO in Other Conditions 169\u003c\/p\u003e \u003cp\u003e11.9 Conclusion 169\u003c\/p\u003e \u003cp\u003eReferences 170\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12. Transfusion Therapy in β Thalassemia and Sickle Cell Disease 179\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eCarlo Brugnara and Lucia De Franceschi\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 179\u003c\/p\u003e \u003cp\u003e12.2 β Thalassemia and Transfusion 179\u003c\/p\u003e \u003cp\u003e12.3 Sickle Cell Disease and Transfusion 182\u003c\/p\u003e \u003cp\u003e12.4 Iron Chelation Tools 185\u003c\/p\u003e \u003cp\u003e12.5 Conclusion 186\u003c\/p\u003e \u003cp\u003eReferences 186\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart III. “Old” and New Strategies for Oxygen Supply 193\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13. Transfusion: Political, Administrative and Logistic Issues 195\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJohn R. Hess and Giuliano Grazzini\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eDisclaimer 195\u003c\/p\u003e \u003cp\u003e13.1 Introduction 195\u003c\/p\u003e \u003cp\u003e13.2 Blood Safety 196\u003c\/p\u003e \u003cp\u003e13.3 Blood Availability 198\u003c\/p\u003e \u003cp\u003e13.4 Cost and Fairness 200\u003c\/p\u003e \u003cp\u003e13.5 Transfusion Medicine 201\u003c\/p\u003e \u003cp\u003eReferences 202\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14. Conscientious Objection in Patient Blood Management 205\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eKenneth E. Nollet and Hitoshi Ohto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 205\u003c\/p\u003e \u003cp\u003e14.2 Conscientious Objection 205\u003c\/p\u003e \u003cp\u003e14.3 Patient Blood Management 206\u003c\/p\u003e \u003cp\u003e14.4 Jehovah’s Witnesses 207\u003c\/p\u003e \u003cp\u003e14.5 Will the Real Objection Please Stand Up? 208\u003c\/p\u003e \u003cp\u003e14.6 Conscientious Objection in Relation to Oxygen Therapeutics and Other Innovations 208\u003c\/p\u003e \u003cp\u003eAcknowledgements 209\u003c\/p\u003e \u003cp\u003eReferences 210\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15. Red-cell Transfusion in Clinical Practice 213\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHarvey G. Klein\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 213\u003c\/p\u003e \u003cp\u003e15.2 Red-cell Use 214\u003c\/p\u003e \u003cp\u003e15.3 The Red-cell-transfusion Trigger 215\u003c\/p\u003e \u003cp\u003e15.4 Risks of Red-cell Transfusion 216\u003c\/p\u003e \u003cp\u003e15.5 Conclusion 218\u003c\/p\u003e \u003cp\u003eDisclaimer 218\u003c\/p\u003e \u003cp\u003eReferences 218\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16. Causes and Consequences of Red Cell Incompatibility 221\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eChisa Yamada and Robertson Davenport\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 221\u003c\/p\u003e \u003cp\u003e16.2 Red Cell Antigens 221\u003c\/p\u003e \u003cp\u003e16.2.1 ABO and the H System 221\u003c\/p\u003e \u003cp\u003e16.2.2 The Lewis System and Structurally Related Antigens 222\u003c\/p\u003e \u003cp\u003e16.2.3 The Rh System 222\u003c\/p\u003e \u003cp\u003e16.2.4 Other Blood Group Systems 222\u003c\/p\u003e \u003cp\u003e16.3 Red Cell Antibodies 223\u003c\/p\u003e \u003cp\u003e16.3.1 Naturally Occurring Antibodies and Immune Antibodies 223\u003c\/p\u003e \u003cp\u003e16.3.2 Autoantibodies 224\u003c\/p\u003e \u003cp\u003e16.3.3 Drug Induced Antibodies 224\u003c\/p\u003e \u003cp\u003e16.4 Compatibility Testing 224\u003c\/p\u003e \u003cp\u003e16.4.1 ABO and Rh D Typing 224\u003c\/p\u003e \u003cp\u003e16.4.2 Antibody Screening and Identification 224\u003c\/p\u003e \u003cp\u003e16.4.3 Selection of Appropriate Blood 225\u003c\/p\u003e \u003cp\u003e16.4.4 Crossmatch Testing 225\u003c\/p\u003e \u003cp\u003e16.5 Hemolytic Transfusion Reactions 225\u003c\/p\u003e \u003cp\u003e16.5.1 Pathophysiology 226\u003c\/p\u003e \u003cp\u003e16.5.2 Prevention 228\u003c\/p\u003e \u003cp\u003eReferences 228\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17. Biochemistry of Storage of Red Blood Cells 231\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRyan Stapley, Dario A. Vitturi and Rakesh P. Patel\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 231\u003c\/p\u003e \u003cp\u003e17.2 Pathologic Consequences of Transfusion with Aged RBCs 232\u003c\/p\u003e \u003cp\u003e17.3 Changes in Oxygen Affinity During RBC Storage 232\u003c\/p\u003e \u003cp\u003e17.4 Role of Oxidative Damage During RBC Storage 233\u003c\/p\u003e \u003cp\u003e17.5 Changes in the Physical Properties of RBCs During Storage 234\u003c\/p\u003e \u003cp\u003e17.6 RBCs as Modulators of Vascular Flow 234\u003c\/p\u003e \u003cp\u003e17.6.1 ATP Release Hypothesis 234\u003c\/p\u003e \u003cp\u003e17.6.2 SNO-hemoglobin Hypothesis 235\u003c\/p\u003e \u003cp\u003e17.6.3 Nitrite Reductase\/Anhydrase Hypothesis 236\u003c\/p\u003e \u003cp\u003e17.7 RBC-dependent Modulation of Inflammation 237\u003c\/p\u003e \u003cp\u003e17.8 Conclusion 237\u003c\/p\u003e \u003cp\u003eAcknowledgements 238\u003c\/p\u003e \u003cp\u003eReferences 238\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18. Proteomic Investigations of Stored Red Blood Cells 243\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLello Zolla and Angelo D’Alessandro\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 243\u003c\/p\u003e \u003cp\u003e18.2 RBC Ageing and Metabolism \u003ci\u003ein vivo\u003c\/i\u003e 244\u003c\/p\u003e \u003cp\u003e18.3 RBC Storage Lesions Through Proteomics 248\u003c\/p\u003e \u003cp\u003e18.4 Conclusion 252\u003c\/p\u003e \u003cp\u003eReferences 252\u003c\/p\u003e \u003cp\u003e\u003cb\u003e19. Red Blood Cells from Stem Cells 257\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAnna Rita Migliaccio, Carolyn Whitsett and Giovanni Migliaccio\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 257\u003c\/p\u003e \u003cp\u003e19.2 Stem-cell Sources for \u003ci\u003eex vivo\u003c\/i\u003e Generation of Erythroid Cells as a Transfusion Product 258\u003c\/p\u003e \u003cp\u003e19.3 Conditions that Favor \u003ci\u003eex vivo\u003c\/i\u003e Erythroid Cell Expansion 260\u003c\/p\u003e \u003cp\u003e19.4 A Clinical-grade Production Process for \u003ci\u003eex vivo\u003c\/i\u003e Generation of Red-cell Transfusion Products 261\u003c\/p\u003e \u003cp\u003e19.4.1 The Nature of the Production Process 261\u003c\/p\u003e \u003cp\u003e19.4.2 Cellular Composition of the Product 263\u003c\/p\u003e \u003cp\u003e19.4.3 Functional Status of Product 264\u003c\/p\u003e \u003cp\u003e19.4.4 Safety Considerations 265\u003c\/p\u003e \u003cp\u003e19.5 Time Line of the Clinical Application of \u003ci\u003eex vivo\u003c\/i\u003e-generated Erythroid Cells 266\u003c\/p\u003e \u003cp\u003e19.5.1 Drug Discovery 266\u003c\/p\u003e \u003cp\u003e19.5.2 Drug Delivery 267\u003c\/p\u003e \u003cp\u003e19.5.3 \u003ci\u003eEx vivo\u003c\/i\u003e-expanded EBs for Alloimmunized Patients 268\u003c\/p\u003e \u003cp\u003eReferences 268\u003c\/p\u003e \u003cp\u003e\u003cb\u003e20. The Universal Red Blood Cell 273\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLuca Ronda and Serena Faggiano\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 Introduction 273\u003c\/p\u003e \u003cp\u003e20.1.1 ABO Antigens 274\u003c\/p\u003e \u003cp\u003e20.1.2 The Rh System 274\u003c\/p\u003e \u003cp\u003e20.2 Enzymatic Removal of A and B Antigens 275\u003c\/p\u003e \u003cp\u003e20.2.1 Conversion of B RBCs to Group O 275\u003c\/p\u003e \u003cp\u003e20.2.2 Conversion of A RBCs to Group O 277\u003c\/p\u003e \u003cp\u003e20.3 RBC Camouflage Through PEGylation 277\u003c\/p\u003e \u003cp\u003e20.3.1 Functionalized Methoxy PEG 278\u003c\/p\u003e \u003cp\u003e20.3.2 Cyanuric Chloride PEG 279\u003c\/p\u003e \u003cp\u003e20.3.3 Extension Arm-facilitated RBC PEGylation 279\u003c\/p\u003e \u003cp\u003e20.3.4 Increasing the Degree of RBC PEGylation 280\u003c\/p\u003e \u003cp\u003e20.4 Conclusion 280\u003c\/p\u003e \u003cp\u003eReferences 280\u003c\/p\u003e \u003cp\u003e\u003cb\u003e21. Allosteric Effectors of Hemoglobin: Past, Present and Future 285\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMartin K. Safo and Stefano Bruno\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e21.1 Introduction 285\u003c\/p\u003e \u003cp\u003e21.2 Natural and Synthetic Allosteric Effectors 288\u003c\/p\u003e \u003cp\u003e21.2.1 Organic Phosphates 288\u003c\/p\u003e \u003cp\u003e21.2.2 Synthetic Aromatic Propionate Right-shifters 289\u003c\/p\u003e \u003cp\u003e21.2.3 Aromatic Aldehyde Left-shifters 290\u003c\/p\u003e \u003cp\u003e21.3 Molecular Mechanism of Action of Allosteric Effectors 293\u003c\/p\u003e \u003cp\u003e21.3.1 Oxygen Binding Curve and Hb Structural Changes 293\u003c\/p\u003e \u003cp\u003e21.3.2 How Allosteric Effectors can Bind to the Same Site and Have Opposite Allosteric Properties 294\u003c\/p\u003e \u003cp\u003e21.3.3 Decreasing Subunit Mobility and Changes in Allosteric Properties: Molecular Ratchets 294\u003c\/p\u003e \u003cp\u003e21.4 The First Visualization of an Important Pharmacological Theory via Hb Allosteric Effector Binding 295\u003c\/p\u003e \u003cp\u003e21.5 The Clinical Importance of Hemoglobin Allosteric Effectors 295\u003c\/p\u003e \u003cp\u003eReferences 296\u003c\/p\u003e \u003cp\u003e\u003cb\u003e22. Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials 301\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJonathan S. Jahr, Arezou Sadighi, Linzy Doherty, Alvin Li and Hae Won Kim\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e22.1 Introduction 301\u003c\/p\u003e \u003cp\u003e22.2 American Society of Anesthesiologists Guidelines and Risks of Blood Transfusion 302\u003c\/p\u003e \u003cp\u003e22.3 Limitations of Blood Transfusion 302\u003c\/p\u003e \u003cp\u003e22.4 History 302\u003c\/p\u003e \u003cp\u003e22.5 Development 303\u003c\/p\u003e \u003cp\u003e22.6 Definitive Clinical Trials 304\u003c\/p\u003e \u003cp\u003e22.6.1 Diaspirin Crosslinked Hemoglobin (DCLHb, HemeAssist, Baxter Laboratories, Deerfield, IL) 304\u003c\/p\u003e \u003cp\u003e22.6.2 Hemoglobin Raffimer (HR, Hemolink, Hemosol Inc., Ontario, Canada) 306\u003c\/p\u003e \u003cp\u003e22.6.3 Human Polymerized Hemoglobin (PolyHeme, Northfield Laboratories, Evanston, IL) 307 22.6.4 Hemoglobin Glutamer-250 (Bovine) (HBOC-201, Hemopure, Biopure Corp., Cambridge, MA) 308\u003c\/p\u003e \u003cp\u003e22.6.5 Maleimide-polyethylene Glycol-modified Hemoglobin (MP4, Hemospan, Sangart Inc., San Diego, CA) 309\u003c\/p\u003e \u003cp\u003e22.7 Current Status and Future Directions of HBOCs 311\u003c\/p\u003e \u003cp\u003eReferences 314\u003c\/p\u003e \u003cp\u003e\u003cb\u003e23. Oxygen Delivery by Natural and Artificial Oxygen Carriers 317\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eEnrico Bucci\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e23.1 Introduction 317\u003c\/p\u003e \u003cp\u003e23.2 The Role of Oxygen Carriers 317\u003c\/p\u003e \u003cp\u003e23.3 The Role of Natural Cell-bound Oxygen Carriers 318\u003c\/p\u003e \u003cp\u003e23.4 Matching the Rate of Oxygen Delivery with the Rate of Oxygen Consumption 320\u003c\/p\u003e \u003cp\u003e23.4.1 The Imbalance 320\u003c\/p\u003e \u003cp\u003e23.4.2 The Rate of Oxygen Release from the Red Cells 320\u003c\/p\u003e \u003cp\u003e23.4.3 Matching the Delivery\/Consumption Rates 321\u003c\/p\u003e \u003cp\u003e23.4.4 The Hematocrit is a Critical Parameter 321\u003c\/p\u003e \u003cp\u003e23.5 The Role of Artificial Cell-free Oxygen Carriers 321\u003c\/p\u003e \u003cp\u003e23.5.1 Facilitated Diffusion 321\u003c\/p\u003e \u003cp\u003e23.5.2 Toxicity 322\u003c\/p\u003e \u003cp\u003e23.6 Other Parameters 322\u003c\/p\u003e \u003cp\u003e23.7 Clinical Use? 323\u003c\/p\u003e \u003cp\u003eAcknowledgments 324\u003c\/p\u003e \u003cp\u003eReferences 324\u003c\/p\u003e \u003cp\u003e\u003cb\u003e24. Crosslinked and Polymerized Hemoglobins as Potential Blood Substitutes 327\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eKenneth W. Olsen and Eugene Tarasov\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e24.1 Introduction 327\u003c\/p\u003e \u003cp\u003e24.2 Crosslinking the Hb Tetramer 328\u003c\/p\u003e \u003cp\u003e24.3 Hb Polymers 332\u003c\/p\u003e \u003cp\u003e24.4 Conclusion 337\u003c\/p\u003e \u003cp\u003eReferences 338\u003c\/p\u003e \u003cp\u003e\u003cb\u003e25. Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion 345\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eSeetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Kulal Ananda and Fantao Meng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e25.1 Introduction 345\u003c\/p\u003e \u003cp\u003e25.2 Enzon DecaPEGylated Bovine Hb is Nonhypertensive 346\u003c\/p\u003e \u003cp\u003e25.3 EAF HexaPEGylated Hb (EAF P5K6-Hb) is Nonhypertensive 347\u003c\/p\u003e \u003cp\u003e25.4 Molecular and Solution Properties of EAF HexaPEGylated Human Hb (EAF-P5K6-Hb) 347\u003c\/p\u003e \u003cp\u003e25.5 High O2 Affinity of EAF HexaPEGylated Hb and Tissue Oxygenation in Extreme Hemodilution 349\u003c\/p\u003e \u003cp\u003e25.6 Influence of Total PEG Mass Conjugated to Hb on O2 Affinity and Tissue Oxygenation by PEG-Hbs 350\u003c\/p\u003e \u003cp\u003e25.7 Influence of PEGylation Chemistry on Structural, Functional, and Solution Properties of HexaPEGylated Hb 351\u003c\/p\u003e \u003cp\u003e25.8 Reductive PEGylation-induced Weakening of Interdimeric Interactions of Tetrameric Hbs 352\u003c\/p\u003e \u003cp\u003e25.9 PEGylation-promoted Dissociation of Hb Tetramer is Attenuated by the Extension Arms of EAF PEGylated Hbs 353\u003c\/p\u003e \u003cp\u003e25.10 Does Urethane-linkage-mediated PEGylation of Hb Promote its Dissociation? 354\u003c\/p\u003e \u003cp\u003e25.11 Hemospan: Prototype of EAF HexaPEGylated Hb Designed at Einstein 354\u003c\/p\u003e \u003cp\u003e25.12 EAF HexaPEGylated Hb Compared to other Blood Substitutes of Earlier Designs 355\u003c\/p\u003e \u003cp\u003e25.13 Reversible Protection of Cys-93(β) during EAF PEGylation of Hb and Crosslinked Hbs: A Structural Requirement to Generate Medium- and Low-O2-affinity PEG-Hbs 355\u003c\/p\u003e \u003cp\u003e25.14 Engineering Extension Arms between the Protein Core and PEG Shell Attenuates PEGylation-promoted Tetramer Dissociation 356\u003c\/p\u003e \u003cp\u003e25.15 Attenuation of Direct HexaPEGylation-promoted Dissociation of Hb Tetramers by Increasing the Tetramer Stability Through Chemical Modification 359\u003c\/p\u003e \u003cp\u003e25.16 Influence of the Extension Arm on the HexaPEGylation-enhanced Thermal Stability of Hb 359\u003c\/p\u003e \u003cp\u003e25.17 PEGylation of Hb Induces a Hydrostatic Molecular Drag to the PEG-Hb Conjugate 360\u003c\/p\u003e \u003cp\u003e25.18 EAF HexaPEGylated Hb is a Superperfusion Agent 360\u003c\/p\u003e \u003cp\u003e25.19 EAF PEG-Hb-induced Vasodilation 361\u003c\/p\u003e \u003cp\u003e25.20 \u003ci\u003eIn vivo\u003c\/i\u003e Vasodilation by EAF PEG-Hb through its Enhanced Nitrite Reductase Activity 361\u003c\/p\u003e \u003cp\u003e25.21 EAF PEG-Hbs as Mechanotransducers of e-NOS Activity 363\u003c\/p\u003e \u003cp\u003e25.22 The Pattern of PEGylation of Intramolecularly Crosslinked Hbs Influences the Viscosity of the PEG-Hb Solution 364\u003c\/p\u003e \u003cp\u003e25.23 Conclusion 364\u003c\/p\u003e \u003cp\u003eAcknowledgments 366\u003c\/p\u003e \u003cp\u003eReferences 367\u003c\/p\u003e \u003cp\u003e\u003cb\u003e26. Hb Octamers by Introduction of Surface Cysteines 371\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eV´eronique Baudin-Creuza, Chien Ho and Michael C. Marden\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e26.1 Introduction 371\u003c\/p\u003e \u003cp\u003e26.2 Genetic Engineering of Proteins with Cysteines 373\u003c\/p\u003e \u003cp\u003e26.2.1 Protein Expression 373\u003c\/p\u003e \u003cp\u003e26.2.2 Oligomer Size 374\u003c\/p\u003e \u003cp\u003e26.2.3 Disulfide Bond Formation 375\u003c\/p\u003e \u003cp\u003e26.2.4 Functional Properties of the Octamers 376\u003c\/p\u003e \u003cp\u003e26.2.5 Octamer Properties 378\u003c\/p\u003e \u003cp\u003e26.2.6 Octamer Constraint 378\u003c\/p\u003e \u003cp\u003e26.3 Conclusion 378\u003c\/p\u003e \u003cp\u003eReferences 378\u003c\/p\u003e \u003cp\u003e\u003cb\u003e27. Hemoglobin Vesicles as a Cellular-type Hemoglobin-based Oxygen Carrier 381\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHiromi Sakai, Hirohisa Horinouchi, Eishun Tsuchida and Koichi Kobayashi\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e27.1 Introduction 381\u003c\/p\u003e \u003cp\u003e27.2 The Concept of Hb Encapsulation in Liposomes 382\u003c\/p\u003e \u003cp\u003e27.3 Hb Encapsulation Retards Gas Reactions 383\u003c\/p\u003e \u003cp\u003e27.4 HBOCs as a Carrier of not only O2 but also CO 385\u003c\/p\u003e \u003cp\u003e27.5 Conclusion 387\u003c\/p\u003e \u003cp\u003eAcknowledgments 387\u003c\/p\u003e \u003cp\u003eReferences 387\u003c\/p\u003e \u003cp\u003e\u003cb\u003e28. Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins 391\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePaul W. Buehler and Felice D’Agnillo\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eDisclaimer 391\u003c\/p\u003e \u003cp\u003e28.1 Introduction 391\u003c\/p\u003e \u003cp\u003e28.2 HBOC Safety and Efficacy 392\u003c\/p\u003e \u003cp\u003e28.2.1 Proposed Mechanisms of Toxicity 392\u003c\/p\u003e \u003cp\u003e28.2.1.1 Hypertension 392\u003c\/p\u003e \u003cp\u003e28.2.1.2 Oxidative Stress 392\u003c\/p\u003e \u003cp\u003e28.2.2 Safety Pharmacology and Toxicology Studies 393\u003c\/p\u003e \u003cp\u003e28.2.3 \u003ci\u003eIn vivo\u003c\/i\u003e Models of Efficacy “Proof of Concept” 395\u003c\/p\u003e \u003cp\u003e28.2.3.1 Tissue Blood Flow and Oxygenation 395\u003c\/p\u003e \u003cp\u003e28.2.3.2 Traumatic Hemorrhage 396\u003c\/p\u003e \u003cp\u003e28.2.3.3 Local Ischemia 397\u003c\/p\u003e \u003cp\u003e28.2.3.4 Sickle Cell Disease 397\u003c\/p\u003e \u003cp\u003e28.2.4 Experimental Approaches to Assessing Preclinical Safety of HBOCs 398\u003c\/p\u003e \u003cp\u003e28.2.4.1 Species Antioxidant Status (Natural Evolution) 398\u003c\/p\u003e \u003cp\u003e28.2.4.2 Chemically Induced Antioxidant Depletion 398\u003c\/p\u003e \u003cp\u003e28.2.4.3 Endothelial Dysfunction 399\u003c\/p\u003e \u003cp\u003e28.2.4.4 Sepsis and Endotoxemia 400\u003c\/p\u003e \u003cp\u003e28.3 Experimental Oxidative Biomarkers and Extracellular Hb Exposure 400\u003c\/p\u003e \u003cp\u003e28.3.1 Heme Iron Oxidation 400\u003c\/p\u003e \u003cp\u003e28.3.2 Amino-acid Oxidation 401\u003c\/p\u003e \u003cp\u003e28.3.3 Heme Catabolism and Iron Sequestration 401\u003c\/p\u003e \u003cp\u003e28.4 Markers of \u003ci\u003ein vivo\u003c\/i\u003e Oxidative Stress and Tissue Damage 403\u003c\/p\u003e \u003cp\u003e28.4.1 4-hydroxy-2-nonenal (4-HNE) Protein Adducts 403\u003c\/p\u003e \u003cp\u003e28.4.2 8-hydroxy-2-deoxyguanosine (8-OHdG) 403\u003c\/p\u003e \u003cp\u003e28.5 Conclusion 404\u003c\/p\u003e \u003cp\u003eReferences 405\u003c\/p\u003e \u003cp\u003e\u003cb\u003e29. Academia–Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal 413\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHae Won Kim, Andrea Mozzarelli, Hiromi Sakai and Jonathan S. Jahr\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e29.1 Introduction 413\u003c\/p\u003e \u003cp\u003e29.2 Generic Issues in Academia–Industry Collaboration 414\u003c\/p\u003e \u003cp\u003e29.3 Academia–Industry Collaboration in HBOC Development 415\u003c\/p\u003e \u003cp\u003e29.4 Proposal for a New Academia–Industry Collaboration Model in HBOC Development: an HBOC Research Consortium (a Conceptual Model) 417\u003c\/p\u003e \u003cp\u003e29.4.1 Mission 417\u003c\/p\u003e \u003cp\u003e29.4.2 Guiding Principles 417\u003c\/p\u003e \u003cp\u003e29.4.3 Key Objectives 417\u003c\/p\u003e \u003cp\u003e29.4.4 Structure 418\u003c\/p\u003e \u003cp\u003e29.4.5 Operation 419\u003c\/p\u003e \u003cp\u003e29.5 Discussion 420\u003c\/p\u003e \u003cp\u003e29.6 Conclusions 421\u003c\/p\u003e \u003cp\u003eAppendix: Successful Academia–Industry Collaboration Cases in HBOC Development 422\u003c\/p\u003e \u003cp\u003eCase A: Waseda–Keio–Industry Research Collaboration 422\u003c\/p\u003e \u003cp\u003eCase B: EuroBloodSubstitutes Consortium 424\u003c\/p\u003e \u003cp\u003eReferences 426\u003c\/p\u003e \u003cp\u003e\u003cb\u003e\u003ci\u003eIndex\u003c\/i\u003e 429\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eProfessor Andrea Mozzarelli, Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Parma, Italy\u003c\/b\u003e\u003cbr\u003eAndrea Mozzarelli is Full Professor of Biochemistry in the Pharmacy Faculty at the University of Parma, teaching general and applied Biochemistry. He is Member of the International Advisory Board for Vitamin B6, PQQ, Carbonyl Catalysis and Quinoproteins Meetings, and was scientific organizer of the international courses on \"From Structural Genomics to Drug Discovery\" held at the University of Parma in 2000, 2002 and 2004. Between 2004 and 2006 Professor Mozzarrelli was head of a research unit of a EU funded project on \"EuroBlood substitutes\". He is President of the XII International Symposium on Blood Substitutes, to be held in Parma, Italy, on August 25-28, 2009 (http:\/\/alice.bio.unipr.it\/blood2009\/).\u003c\/p\u003e \u003cp\u003e\u003cb\u003eProfessor Stefano Bettati\u003c\/b\u003e, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Parma, Italy.\u003c\/p\u003e  Human blood performs many important functions including defence against disease and transport of biomolecules, but perhaps the most important is to carry oxygen – the fundamental biochemical fuel - and other blood gases around the cardiovascular system. Traditional therapies for the impairment of this function, or the rapid replacement of lost blood, have centred around blood transfusions. However scientists are developing chemicals (oxygen therapeutics, or “blood substitutes”) which have the same oxygen-carrying capability as blood and can be used as replacements for blood transfusion or to treat diseases where oxygen transport is impaired.  \u003cp\u003e\u003ci\u003eChemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood\u003c\/i\u003e links the underlying biochemical principles of the field with chemical and biotechnological innovations and pre-clinical development.\u003c\/p\u003e \u003cp\u003eThe first part of the book deals with the chemistry, biochemistry, physiology and toxicity of oxygen, including chapters on hemoglobin reactivity and regulation; the major cellular and physiological control mechanisms of blood flow and oxygen delivery;  hemoglobin and myoglobin;  nitric oxide and oxygen; and the role of reactive oxygen and nitrogen species in ischemia\/reperfusion Injury.\u003c\/p\u003e \u003cp\u003eThe book then discusses medical needs for oxygen supply, including acute traumatic hemorrhage and anemia; diagnosis and treatment of haemorrhages in \"non-surgical\" patients; management of perioperative bleeding; oxygenation in the preterm neonate; ischemia\u003c\/p\u003e \u003cp\u003enormobaric and hyperbaric oxygen therapy for ischemic stroke and other neurological conditions; and transfusion therapy in β thalassemia and sickle cell disease\u003c\/p\u003e \u003cp\u003eFinally “old”and new strategies for oxygen supply are described. These include the political, administrative and logistic issues surrounding transfusion;  conscientious objection in patient blood management; causes and consequences of red cell incompatibility; biochemistry of red blood cell storage;  proteomic investigations on stored red blood cells; red blood cells from stem cells; the universal red blood cell;  allosteric effectors of hemoglobin; hemoglobin-based oxygen carriers;  oxygen delivery by natural and artificial oxygen carriers; cross-linked and polymerized hemoglobins as potential blood substitutes; design of novel pegylated hemoglobins as oxygen carrying plasma expanders; hb octamers by introduction of surface cysteines; hemoglobin-vesicles as a cellular type hemoglobin-based oxygen carrier; animal models and oxidative biomarkers to evaluate pre-clinical safety of extracellular hemoglobins; and academia – industry collaboration in blood substitute development.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eChemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood\u003c\/i\u003e is an essential reference for clinicians, haematologists, medicinal chemists, biochemists, molecular biologists, biotechnologists and blood substitute researchers.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47988908523749,"sku":"NP9780470686683","price":184.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9780470686683.jpg?v=1761782009","url":"https:\/\/k12savings.com\/es\/products\/chemistry-and-biochemistry-of-oxygen-therapeutics-isbn-9780470686683","provider":"K12savings","version":"1.0","type":"link"}