Chemistry and Biochemistry of Oxygen Therapeutics

Want create site? Find Free WordPress Themes and plugins.

Chemistry and Biochemistry of Oxygen Therapeutics eBook Free Download

Chemistry and Biochemistry of Oxygen Therapeutics eBook PDF Free Download

Edited by Stefano Bettati and Andrea Mozzarelli

From Transfusion to Artificial Blood

Published by Wiley

About the Book

This Chemistry and Biochemistry of Oxygen Therapeutics is edited by Stefano Bettati and Andrea Mozzarelli. This First Edition 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 β thalassemia and sickle cell disease.

Skip to Download Link

What You will Learn

The Topics Covered in this Textbook are

Part I. Oxygen: Chemistry, Biochemistry, Physiology and Toxicity

Hemoglobin Reactivity and Regulation
Oxygen Loading and Transport
NO Reactivity with Hb
Hb Oxidation
Nitrite Reactivity with Hb
Amino-acid Determinants of Hb Reactivity: Natural and Engineered Hbs
Modulation of Oxygen Affinity and Cooperativity
NO Reactivity and Oxidation
The Major Physiological Control Mechanisms of Blood Flow and Oxygen Delivery
Autoregulation of Blood Flow to Changes in Perfusion Pressure
Metabolic Regulation of Blood Flow
O2 Transport
O2 Delivery
Endothelial Control of Vasomotor Tone
Effect of Cell-free Hb on Endothelial Function
Hypoxic Hypoxia
Carbon Monoxide Hypoxia
The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen
Role of Mammalian Mb in O2 Homeostasis
What’s Missing in the Mb Knockout Mouse
Evolutionary Origins of Mb and the Nitrogen Cycle
Human Hb: Evolved Sensor of pO2 and Redox
Broad Reactivity and Influence of NO: Lessons from the Microcosm Hb
Some Fish Demonstrate a Fundamental “Need” for Hb-dependent NO Cycling, as in Humans
Reactions of NO with Hb that Preserve NO Bioactivity
Mammalian RBC/Hb–NO Interactions
A Mutant Mouse Challenges the SNO-Hb Hypothesis, but does not Overthrow it
Signaling by Hb-derived SNO: A Metabolically Responsive, Regulated Pathway
Signaling by Hb-derived SNO: Pathway Complexity Revealed by Multiple Defects in Disease States
Therapeutic Implications of the Hb–NO Signaling System
HBOCs, NO, and SNO
Other Gaseous Hb Ligands of Potential Therapeutic Significance
NO-related Enzymatic Activities of Hb: Reconciling Nitrite Reductase and SNO Synthase Functions
Measuring Biologically Relevant Hb–NO Adducts

The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury
Redox System and Free Radicals in Biological Systems
Pathophysiology of Ischemia/Reperfusion Injury
Cell Death
The Inflammatory Response
Protection Against I/R Injury
Ischemic Pre- and Post-conditioning
Pharmacological Conditioning
The Protective Role of ROS and Antioxidants
The Protective Role of NO
NO-based Therapies for I/R Injury

Part II. Medical Needs for Oxygen Supply
Acute Traumatic Hemorrhage and Anemia
Blood Transfusion in Trauma
Massive Transfusion
Massive Transfusion and Coagulopathy
Hypotensive or Delayed Resuscitation
Hemostatic Resuscitation
Massive Transfusion Protocols
Transfusion after Hemorrhage Control
Efficacy of RBC Transfusion in Trauma and Associated Risks
Oxygen Therapeutics in Trauma
Diaspirin Crosslinked Hb
Recombinant Human Hb
Adverse Effects of HBOCs
HBOCs in Trauma: A Way Forward?
Diagnosis and Treatment of Haemorrhages in ‘Nonsurgical’ Patients
Aetiopathogenetic Classification
Multifactorial Pathogenesis
Haemorrhagic Syndromes from Antithrombotic Treatment or Prophylaxis
Clinical Assessment
Medical History
Physical Examination
Laboratory Tests
Screening Tests
Second-level Laboratory Tests
Other Tests
Haemorrhagic Syndromes Clinically Indicative of Systemic Defects with Normal Screening Tests
Blood and Blood Components in the Treatment of Haemorrhagic Syndromes

Management of Perioperative Bleeding
Pathomechanisms of Coagulopathy in Massive Bleeding
Perioperative Coagulation Monitoring
Limitations of Routine Coagulation Tests in the Perioperative Setting
Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM)
Procoagulant Interventions
Algorithm for Coagulation Management
Oxygenation in the Preterm Neonate
Physiology of Oxygen Transport in Fetal and Postnatal Life
Oxygenation of the Fetus
Measuring Oxygenation in the Neonate
Oxygen Therapy in the Postnatal Period
Oxidative Stresses in the Newborn Period
Clinical Sequelae of Hyperoxia
Retinopathy of Prematurity
Oxygen and Chronic Lung Disease
Oxygen and Periventricular Leukomalacia
Oxygen and Resuscitation of the Newborn Infant
Transfusion in the Newborn
ROP and Transfusions
Energy Failure
Cell Membrane Damage
Increased Cytosolic Calcium
The No-reflow Phenomenon
Free Radicals and Reactive Oxygen Species
Therapeutic Potentials
Anti-inflammation Therapy
Therapeutic Hypothermia
Hydrogen Sulfide
Hyperoxia and Hyperbaric Oxygen
Hemoglobin-based Oxygen Carriers
Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions
Rationale of Oxygen Therapy in AIS
Normobaric Oxygen Therapy
The Status of Supplemental Oxygen Delivery
Safety Concerns
HBO and NBO in Other Conditions
Transfusion Therapy in β Thalassemia and Sickle Cell Disease
β Thalassemia and Transfusion
Sickle Cell Disease and Transfusion
Iron Chelation Tools

Part III. “Old” and New Strategies for Oxygen Supply
Transfusion: Political, Administrative and Logistic Issues
Blood Safety
Blood Availability
Cost and Fairness
Transfusion Medicine
Conscientious Objection in Patient Blood Management
Conscientious Objection
Patient Blood Management
Jehovah’s Witnesses
Will the Real Objection Please Stand Up?
Conscientious Objection in Relation to Oxygen Therapeutics and Other Innovations
Red-cell Transfusion in Clinical Practice
Red-cell Use
The Red-cell-transfusion Trigger
Risks of Red-cell Transfusion
Causes and Consequences of Red Cell Incompatibility
Red Cell Antigens
ABO and the H System
The Lewis System and Structurally Related Antigens
The Rh System
Other Blood Group Systems
Red Cell Antibodies
Naturally Occurring Antibodies and Immune Antibodies
Drug Induced Antibodies
Compatibility Testing
ABO and Rh D Typing
Antibody Screening and Identification
Selection of Appropriate Blood
Crossmatch Testing
Hemolytic Transfusion Reactions
Biochemistry of Storage of Red Blood Cells
Pathologic Consequences of Transfusion with Aged RBCs
Changes in Oxygen Affinity During RBC Storage
Role of Oxidative Damage During RBC Storage
Changes in the Physical Properties of RBCs During Storage
RBCs as Modulators of Vascular Flow
ATP Release Hypothesis
SNO-hemoglobin Hypothesis
Nitrite Reductase/Anhydrase Hypothesis
RBC-dependent Modulation of Inflammation
Proteomic Investigations of Stored Red Blood Cells
RBC Ageing and Metabolism in vivo
RBC Storage Lesions Through Proteomics
Red Blood Cells from Stem Cells
Stem-cell Sources for ex vivo Generation of Erythroid Cells as a Transfusion Product
Conditions that Favor ex vivo Erythroid Cell Expansion
A Clinical-grade Production Process for ex vivo Generation of Red-cell Transfusion Products
Cellular Composition of the Product
Functional Status of Product
Safety Considerations
Time Line of the Clinical Application of ex vivo-generated Erythroid Cells
Drug Discovery
Drug Delivery
Ex vivo-expanded EBs for Alloimmunized Patients
The Universal Red Blood Cell
ABO Antigens
The Rh System
Enzymatic Removal of A and B Antigens
Conversion of B RBCs to Group O
Conversion of A RBCs to Group O
RBC Camouflage Through PEGylation
Functionalized Methoxy PEG
Cyanuric Chloride PEG
Extension Arm-facilitated RBC PEGylation
Increasing the Degree of RBC PEGylation
Allosteric Effectors of Hemoglobin: Past, Present and Future
Natural and Synthetic Allosteric Effectors
Organic Phosphates
Synthetic Aromatic Propionate Right-shifters
Aromatic Aldehyde Left-shifters
Molecular Mechanism of Action of Allosteric Effectors
Oxygen Binding Curve and Hb Structural Changes
How Allosteric Effectors can Bind to the Same Site and Have Opposite Allosteric Properties
Decreasing Subunit Mobility and Changes in Allosteric Properties: Molecular Ratchets
The First Visualization of an Important Pharmacological Theory via Hb Allosteric Effector Binding
The Clinical Importance of Hemoglobin Allosteric Effectors 295
Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials
American Society of Anesthesiologists Guidelines and Risks of Blood Transfusion
Limitations of Blood Transfusion
Definitive Clinical Trials
Diaspirin Crosslinked Hemoglobin (DCLHb, HemeAssist, Baxter Laboratories, Deerfield, IL)
Hemoglobin Raffimer (HR, Hemolink, Hemosol Inc., Ontario, Canada)
Human Polymerized Hemoglobin (PolyHeme, Northfield Laboratories, Evanston, IL) 307 22.6.4 Hemoglobin Glutamer-250 (Bovine) (HBOC-201, Hemopure, Biopure Corp., Cambridge, MA)
Maleimide-polyethylene Glycol-modified Hemoglobin (MP4, Hemospan, Sangart Inc., San Diego, CA)
Current Status and Future Directions of HBOCs
Oxygen Delivery by Natural and Artificial Oxygen Carriers
The Role of Oxygen Carriers
The Role of Natural Cell-bound Oxygen Carriers
Matching the Rate of Oxygen Delivery with the Rate of Oxygen Consumption
The Imbalance
The Rate of Oxygen Release from the Red Cells
Matching the Delivery/Consumption Rates
The Hematocrit is a Critical Parameter
The Role of Artificial Cell-free Oxygen Carriers
Facilitated Diffusion
Other Parameters
Clinical Use?
Crosslinked and Polymerized Hemoglobins as Potential Blood Substitutes
Crosslinking the Hb Tetramer
Hb Polymers
Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion
Enzon DecaPEGylated Bovine Hb is Nonhypertensive
EAF HexaPEGylated Hb (EAF P5K6-Hb) is Nonhypertensive
Molecular and Solution Properties of EAF HexaPEGylated Human Hb (EAF-P5K6-Hb)
High O2 Affinity of EAF HexaPEGylated Hb and Tissue Oxygenation in Extreme Hemodilution
Influence of Total PEG Mass Conjugated to Hb on O2 Affinity and Tissue Oxygenation by PEG-Hbs
Influence of PEGylation Chemistry on Structural, Functional, and Solution Properties of HexaPEGylated Hb
Reductive PEGylation-induced Weakening of Interdimeric Interactions of Tetrameric Hbs 352
PEGylation-promoted Dissociation of Hb Tetramer is Attenuated by the Extension Arms of EAF PEGylated Hbs
Does Urethane-linkage-mediated PEGylation of Hb Promote its Dissociation?
EAF HexaPEGylated Hb Compared to other Blood Substitutes of Earlier Designs
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
Engineering Extension Arms between the Protein Core and PEG Shell Attenuates PEGylation-promoted Tetramer Dissociation
Attenuation of Direct HexaPEGylation-promoted Dissociation of Hb Tetramers by Increasing the Tetramer Stability Through Chemical Modification
Influence of the Extension Arm on the HexaPEGylation-enhanced Thermal Stability of Hb
Hb Octamers by Introduction of Surface Cysteines
Genetic Engineering of Proteins with Cysteines
Protein Expression
Oligomer Size
Disulfide Bond Formation
Functional Properties of the Octamers
Octamer Properties
Octamer Constraint
Hemoglobin Vesicles as a Cellular-type Hemoglobin-based Oxygen Carrier
The Concept of Hb Encapsulation in Liposomes
Hb Encapsulation Retards Gas Reactions
HBOCs as a Carrier of not only O2 but also CO
Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins
HBOC Safety and Efficacy
Proposed Mechanisms of Toxicity
Oxidative Stress
Safety Pharmacology and Toxicology Studies
In vivo Models of Efficacy “Proof of Concept”
Tissue Blood Flow and Oxygenation
Traumatic Hemorrhage
Local Ischemia
Sickle Cell Disease
Experimental Approaches to Assessing Preclinical Safety of HBOCs
Species Antioxidant Status (Natural Evolution)
Chemically Induced Antioxidant Depletion
Endothelial Dysfunction
Sepsis and Endotoxemia
Experimental Oxidative Biomarkers and Extracellular Hb Exposure
Heme Iron Oxidation
Amino-acid Oxidation
Heme Catabolism and Iron Sequestration
Markers of in vivo Oxidative Stress and Tissue Damage
hydroxy-2-nonenal (4-HNE) Protein Adducts
hydroxy-2-deoxyguanosine (8-OHdG)
Academia–Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal
Generic Issues in Academia–Industry Collaboration
Academia–Industry Collaboration in HBOC Development
Proposal for a New Academia–Industry Collaboration Model in HBOC Development: an HBOC Research Consortium (a Conceptual Model)
Guiding Principles
Key Objectives

For Whom is this Book For



Format of the eBook: PDF      Size: 3.9 MB


Important Note
Below Premium Download Link Works Only for “Premium” or “Gold” Members.
If you are a Premium or Gold Member then Use “Login Form” in Sidebar for Login
Else Sign-up for Premium Membership

Premium Download LinkDoesn't Work for Free Members and Non-Members

If the Download Links of eBook / PDF are Not Working or Broken, then Contact Us Immediately via Broken Links Form.

Most Searched Terms

Chemistry and Biochemistry of Oxygen Therapeutics eBook Free Download

Chemistry and Biochemistry of Oxygen Therapeutics PDF Free Download

Did you find apk for android? You can find new Free Android Games and apps.