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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…mehr
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. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood links the underlying biochemical principles of the field with chemical and biotechnological innovations and pre-clinical development. The 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. The 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 normobaric and hyperbaric oxygen therapy for ischemic stroke and other neurological conditions; and transfusion therapy in beta thalassemia and sickle cell disease Finally "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. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood is an essential reference for clinicians, haematologists, medicinal chemists, biochemists, molecular biologists, biotechnologists and blood substitute researchers.
Professor Andrea Mozzarelli, Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Parma, Italy Andrea 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/). Professor Stefano Bettati, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Parma, Italy.
Inhaltsangabe
1. Introduction (Richard B. Weiskopf). Part 1. Oxygen: chemistry, biochemistry, physiology and toxicity. 2. Hemoglobin Reactivity and Regulation (Stefano Bettati and Andrea Mozzarelli). 3. The Major Cellular and Physiological Control Mechanisms of Blood Flow and Oxygen Delivery (Raymond C. Koehler). 4. The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen (Tim J. McMahon and Joseph Bonaventura). 5. The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury (Ester Spagnolli and Warren Zapol). Part 2. Medical needs for oxygen supply. 6. Acute Traumatic Hemorrhage and Anemia (Lena M. Napolitano). 7. Diagnosis and Treatment of Haemorrhages in "Non-surgical" Patients (Umberto Rossi and Rosa Chianese). 8. Management of Perioperative Bleeding (Sibylle A. Kozek-Langenecker). 9. Oxygenation in the Preterm Neonate (Vidheya Venkatesh, Priya Muthukuma, Anna Curley and Simon Stanworth). 10. Ischemia (Hooman Mirzakhani and Ala Nozari). 11. Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions (Ari Moskowitz, Yu-Feng Yvonne Chan and Aneesh B. Singhal). 12. Transfusion Therapy in Thalassemia and Sickle Cell Disease (Carlo Brugnara and Lucia De Franceschi). Part 3. "Old"and new strategies for oxygen supply. 13. Transfusion: Political, Administrative and Logistic Issues (John R. Hess and Giuliano Grazzini). 14. Conscientious Objection in Patient Blood Management (Kenneth E. Nollet and Hitoshi Ohto). 15. Red Cell Transfusion in Clinical Practice (Harvey G. Klein). 16. Causes and Consequences of Red Cell Incompatibility (Chisa Yamada and Robertson Davenport). 17. Biochemistry of Red Blood Cell Storage (Ryan Stapley, Dario A. Vitturi and Rakesh P. Patel). 18. Proteomic Investigations on Stored Red Blood Cells (Lello Zolla and Angelo D'Alessandro). 19.Red Blood Cells from Stem Cells (Anna Rita Migliaccio, Carolyn Whitsett and Giovanni Migliaccio). 20. The Universal Red Blood Cell (Luca Ronda and Serena Faggiano). 21. Allosteric Effectors of Hemoglobin: Past, Present and Future (Martin K. Safo and Stefano Bruno). 22. Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials (Jonathan S. Jahr, Arezou Sadighi, Linzy Doherty, Alvin Li and Hae Won Kim). 23. Oxygen Delivery by Natural and Artificial Oxygen Carriers (Enrico Bucci). 24. Cross-Linked and Polymerized Hemoglobins as Potential Blood Substitutes (Kenneth W. Olsen and Eugene Tarasov). 25. Design of Novel PEGylated Hemoglobins as Oxygen Carrying Plasma Expanders: Engineering the Structure of PEG-Hb Adducts for Supra Perfusion (Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Kulal Ananda and Fantao Meng). 26. Hb Octamers by Introduction of Surface Cysteines Véronique (Baudin-Creuza, Chien Ho and Michael C. Marden). 27. Hemoglobin-vesicles as a Cellular Type Hemoglobin-based Oxygen Carrier (Hiromi Sakai, Hirohisa Horinouchi, Eishun Tsuchida and Koichi Kobayashi). 28. Animal Models and Oxidative Biomarkers to Evaluate Pre-clinical Safety of Extracellular Hemoglobins (Paul W. Buehler and Felice D'Agnillo). 29. Academia - Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal (Hae Won Kim, Andrea Mozzarelli, Hiromi Sakai and Jonathan S. Jahr).
List of Contributors xvii Preface xxiii 1. Introduction 1 Richard B. Weiskopf References 5 Part I. Oxygen: Chemistry, Biochemistry, Physiology and Toxicity 9 2. Hemoglobin Reactivity and Regulation 11 Stefano Bettati and Andrea Mozzarelli Natural and Engineered Hbs 17 Acknowledgments 19 References 19 3. The Major Physiological Control Mechanisms of Blood Flow and Oxygen Delivery 23 Raymond C. Koehler References 39 4. The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen 47 Tim J. McMahon and Joseph Bonaventura Acknowledgments 58 References 59 5. The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury 63 Ester Spagnolli and Warren M. Zapol Acknowledgments 72 References 72 Part II. Medical Needs for Oxygen Supply 79 6. Acute Traumatic Hemorrhage and Anemia 81 Lena M. Napolitano References 97 7. Diagnosis and Treatment of Haemorrhages in 'Nonsurgical' Patients 107 Umberto Rossi and Rosa Chianese Further Reading 118 8. Management of Perioperative Bleeding 121 Sibylle A. Kozek-Langenecker References 127 9. Oxygenation in the Preterm Neonate 131 Vidheya Venkatesh, Priya Muthukumar, Anna Curley and Simon Stanworth References 138 10. Ischemia 145 Hooman Mirzakhani and Ala Nozari References 153 11. Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions 159 Ari Moskowitz, Yu-Feng Yvonne Chan and Aneesh B. Singhal References 170 12. Transfusion Therapy in ² Thalassemia and Sickle Cell Disease 179 Carlo Brugnara and Lucia De Franceschi References 186 Part III. "Old" and New Strategies for Oxygen Supply 193 13. Transfusion: Political, Administrative and Logistic Issues 195 John R. Hess and Giuliano Grazzini Disclaimer 195 References 202 14. Conscientious Objection in Patient Blood Management 205 Kenneth E. Nollet and Hitoshi Ohto Acknowledgements 209 References 210 15. Red-cell Transfusion in Clinical Practice 213 Harvey G. Klein Disclaimer 218 References 218 16. Causes and Consequences of Red Cell Incompatibility 221 Chisa Yamada and Robertson Davenport References 228 17. Biochemistry of Storage of Red Blood Cells 231 Ryan Stapley, Dario A. Vitturi and Rakesh P. Patel Acknowledgements 238 References 238 18. Proteomic Investigations of Stored Red Blood Cells 243 Lello Zolla and Angelo D'Alessandro References 252 19. Red Blood Cells from Stem Cells 257 Anna Rita Migliaccio, Carolyn Whitsett and Giovanni Migliaccio References 268 20. The Universal Red Blood Cell 273 Luca Ronda and Serena Faggiano References 280 21. Allosteric Effectors of Hemoglobin: Past, Present and Future 285 Martin K. Safo and Stefano Bruno References 296 22. Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials 301 Jonathan S. Jahr, Arezou Sadighi, Linzy Doherty, Alvin Li and Hae Won Kim References 314 23. Oxygen Delivery by Natural and Artificial Oxygen Carriers 317 Enrico Bucci Acknowledgments 324 References 324 24. Crosslinked and Polymerized Hemoglobins as Potential Blood Substitutes 327 Kenneth W. Olsen and Eugene Tarasov References 338 25. Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion 345 Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Kulal Ananda and Fantao Meng Acknowledgments 366 References 367 26. Hb Octamers by Introduction of Surface Cysteines 371 V¿eronique Baudin-Creuza, Chien Ho and Michael C. Marden References 378 27. Hemoglobin Vesicles as a Cellular-type Hemoglobin-based Oxygen Carrier 381 Hiromi Sakai, Hirohisa Horinouchi, Eishun Tsuchida and Koichi Kobayashi Acknowledgments 387 References 387 28. Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins 391 Paul W. Buehler and Felice D'Agnillo Disclaimer 391 References 405 29. Academia-Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal 413 Hae Won Kim, Andrea Mozzarelli, Hiromi Sakai and Jonathan S. Jahr Appendix: Successful Academia-Industry Collaboration Cases in HBOC Development 422 Case A: Waseda-Keio-Industry Research Collaboration 422 Case B: EuroBloodSubstitutes Consortium 424 References 426 Index 429
1. Introduction (Richard B. Weiskopf). Part 1. Oxygen: chemistry, biochemistry, physiology and toxicity. 2. Hemoglobin Reactivity and Regulation (Stefano Bettati and Andrea Mozzarelli). 3. The Major Cellular and Physiological Control Mechanisms of Blood Flow and Oxygen Delivery (Raymond C. Koehler). 4. The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen (Tim J. McMahon and Joseph Bonaventura). 5. The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury (Ester Spagnolli and Warren Zapol). Part 2. Medical needs for oxygen supply. 6. Acute Traumatic Hemorrhage and Anemia (Lena M. Napolitano). 7. Diagnosis and Treatment of Haemorrhages in "Non-surgical" Patients (Umberto Rossi and Rosa Chianese). 8. Management of Perioperative Bleeding (Sibylle A. Kozek-Langenecker). 9. Oxygenation in the Preterm Neonate (Vidheya Venkatesh, Priya Muthukuma, Anna Curley and Simon Stanworth). 10. Ischemia (Hooman Mirzakhani and Ala Nozari). 11. Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions (Ari Moskowitz, Yu-Feng Yvonne Chan and Aneesh B. Singhal). 12. Transfusion Therapy in Thalassemia and Sickle Cell Disease (Carlo Brugnara and Lucia De Franceschi). Part 3. "Old"and new strategies for oxygen supply. 13. Transfusion: Political, Administrative and Logistic Issues (John R. Hess and Giuliano Grazzini). 14. Conscientious Objection in Patient Blood Management (Kenneth E. Nollet and Hitoshi Ohto). 15. Red Cell Transfusion in Clinical Practice (Harvey G. Klein). 16. Causes and Consequences of Red Cell Incompatibility (Chisa Yamada and Robertson Davenport). 17. Biochemistry of Red Blood Cell Storage (Ryan Stapley, Dario A. Vitturi and Rakesh P. Patel). 18. Proteomic Investigations on Stored Red Blood Cells (Lello Zolla and Angelo D'Alessandro). 19.Red Blood Cells from Stem Cells (Anna Rita Migliaccio, Carolyn Whitsett and Giovanni Migliaccio). 20. The Universal Red Blood Cell (Luca Ronda and Serena Faggiano). 21. Allosteric Effectors of Hemoglobin: Past, Present and Future (Martin K. Safo and Stefano Bruno). 22. Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials (Jonathan S. Jahr, Arezou Sadighi, Linzy Doherty, Alvin Li and Hae Won Kim). 23. Oxygen Delivery by Natural and Artificial Oxygen Carriers (Enrico Bucci). 24. Cross-Linked and Polymerized Hemoglobins as Potential Blood Substitutes (Kenneth W. Olsen and Eugene Tarasov). 25. Design of Novel PEGylated Hemoglobins as Oxygen Carrying Plasma Expanders: Engineering the Structure of PEG-Hb Adducts for Supra Perfusion (Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Kulal Ananda and Fantao Meng). 26. Hb Octamers by Introduction of Surface Cysteines Véronique (Baudin-Creuza, Chien Ho and Michael C. Marden). 27. Hemoglobin-vesicles as a Cellular Type Hemoglobin-based Oxygen Carrier (Hiromi Sakai, Hirohisa Horinouchi, Eishun Tsuchida and Koichi Kobayashi). 28. Animal Models and Oxidative Biomarkers to Evaluate Pre-clinical Safety of Extracellular Hemoglobins (Paul W. Buehler and Felice D'Agnillo). 29. Academia - Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal (Hae Won Kim, Andrea Mozzarelli, Hiromi Sakai and Jonathan S. Jahr).
List of Contributors xvii Preface xxiii 1. Introduction 1 Richard B. Weiskopf References 5 Part I. Oxygen: Chemistry, Biochemistry, Physiology and Toxicity 9 2. Hemoglobin Reactivity and Regulation 11 Stefano Bettati and Andrea Mozzarelli Natural and Engineered Hbs 17 Acknowledgments 19 References 19 3. The Major Physiological Control Mechanisms of Blood Flow and Oxygen Delivery 23 Raymond C. Koehler References 39 4. The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen 47 Tim J. McMahon and Joseph Bonaventura Acknowledgments 58 References 59 5. The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury 63 Ester Spagnolli and Warren M. Zapol Acknowledgments 72 References 72 Part II. Medical Needs for Oxygen Supply 79 6. Acute Traumatic Hemorrhage and Anemia 81 Lena M. Napolitano References 97 7. Diagnosis and Treatment of Haemorrhages in 'Nonsurgical' Patients 107 Umberto Rossi and Rosa Chianese Further Reading 118 8. Management of Perioperative Bleeding 121 Sibylle A. Kozek-Langenecker References 127 9. Oxygenation in the Preterm Neonate 131 Vidheya Venkatesh, Priya Muthukumar, Anna Curley and Simon Stanworth References 138 10. Ischemia 145 Hooman Mirzakhani and Ala Nozari References 153 11. Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions 159 Ari Moskowitz, Yu-Feng Yvonne Chan and Aneesh B. Singhal References 170 12. Transfusion Therapy in ² Thalassemia and Sickle Cell Disease 179 Carlo Brugnara and Lucia De Franceschi References 186 Part III. "Old" and New Strategies for Oxygen Supply 193 13. Transfusion: Political, Administrative and Logistic Issues 195 John R. Hess and Giuliano Grazzini Disclaimer 195 References 202 14. Conscientious Objection in Patient Blood Management 205 Kenneth E. Nollet and Hitoshi Ohto Acknowledgements 209 References 210 15. Red-cell Transfusion in Clinical Practice 213 Harvey G. Klein Disclaimer 218 References 218 16. Causes and Consequences of Red Cell Incompatibility 221 Chisa Yamada and Robertson Davenport References 228 17. Biochemistry of Storage of Red Blood Cells 231 Ryan Stapley, Dario A. Vitturi and Rakesh P. Patel Acknowledgements 238 References 238 18. Proteomic Investigations of Stored Red Blood Cells 243 Lello Zolla and Angelo D'Alessandro References 252 19. Red Blood Cells from Stem Cells 257 Anna Rita Migliaccio, Carolyn Whitsett and Giovanni Migliaccio References 268 20. The Universal Red Blood Cell 273 Luca Ronda and Serena Faggiano References 280 21. Allosteric Effectors of Hemoglobin: Past, Present and Future 285 Martin K. Safo and Stefano Bruno References 296 22. Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials 301 Jonathan S. Jahr, Arezou Sadighi, Linzy Doherty, Alvin Li and Hae Won Kim References 314 23. Oxygen Delivery by Natural and Artificial Oxygen Carriers 317 Enrico Bucci Acknowledgments 324 References 324 24. Crosslinked and Polymerized Hemoglobins as Potential Blood Substitutes 327 Kenneth W. Olsen and Eugene Tarasov References 338 25. Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion 345 Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Kulal Ananda and Fantao Meng Acknowledgments 366 References 367 26. Hb Octamers by Introduction of Surface Cysteines 371 V¿eronique Baudin-Creuza, Chien Ho and Michael C. Marden References 378 27. Hemoglobin Vesicles as a Cellular-type Hemoglobin-based Oxygen Carrier 381 Hiromi Sakai, Hirohisa Horinouchi, Eishun Tsuchida and Koichi Kobayashi Acknowledgments 387 References 387 28. Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins 391 Paul W. Buehler and Felice D'Agnillo Disclaimer 391 References 405 29. Academia-Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal 413 Hae Won Kim, Andrea Mozzarelli, Hiromi Sakai and Jonathan S. Jahr Appendix: Successful Academia-Industry Collaboration Cases in HBOC Development 422 Case A: Waseda-Keio-Industry Research Collaboration 422 Case B: EuroBloodSubstitutes Consortium 424 References 426 Index 429
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