Biochemical Pharmacology of Blood and Bloodforming Organs

ISBN-13: 9783642758676 / Angielski / Miękka / 2012 / 587 str.

K. Agrawal;B.S. Beckman;R.L. Capizzi

Opis

The subject of this volume is to review chemical agents which affect blood and blood-forming organs. Significant ad- vances made over the past several years in the purification of several hematopoietic growth factors, such as erythro- poietin and colony stimulating factor; the availability of several other growth factors, such as the interleukins which are important in regulating the production of red blood cells, leukocytes, megakaryocytes and platelets are discus- sed. Numerous toxic chemical substances are being produced in our environment which people are exposed todaily causing a suppression of erythropoiesis, myelopoiesis and megakaryo- cytopoiesis. Attempts to evaluate both the therapeutic role of some of the newer growth factors, such as erythropoietin in the anemia of end stage disease, as well as colony stimu- lating factors in somehematopoietic abnormalities are also covered in this volume. In addition, numerous chemical fac- tors in our environment which suppress major hematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 1-alpha, 1-beta, 2,3,4,5,6, and 7 are also in- cluded. In addition, chapters on the use of erythropoietin in the treatment of anemia of end stage renal disease can provide the practicing hematologist and nephrologist with updated information on the use of erythropoietin for this disease. The book includes chapters on the fundamental con- trol of hematopoiesis and other mechanisms of action of erythropoietin, and finally an up-to-date overview of the chemotherapy of leukemia. This book will prove useful to in- vestigators in the fields of pharmacology, physiology, nephrology, urology, hematology, pathology, endocrinology, biochemistry, and molecular and cell biology.

Spis treści

1 Introduction.- 2 Fundamental Control of Hematopoiesis.- A. Introduction.- B. Hierarchical Organization of Hematopoietic Cells.- C. Assay and Characterization of In Vitro Clonogenic Cells.- D. Use of In Vitro Clonogenic Cell Assays.- E. Newer Assays for More Primitive Cells.- F. Regulatory Mechanisms.- G. Future Outlook.- References.- 3 Kidney Regulation of Erythropoietin Production.- A. Introduction.- B. Model for the Control of Erythropoietin Production.- C. Hypoxia and Erythropoietin Production.- D. Adenosine and Erythropoietin Production.- References.- 4 The Mechanism of Action of Erythropoietin: Erythroid Cell Response.- A. Introduction.- I. The Erythropoietin Gene.- II. The Erythropoietin Molecule.- III. Erythropoietin-Responsive Cells.- IV. The Erythroid Burst-Forming Unit.- V. The Colony-Forming Unit Erythroid.- B. Model Systems for Studying the Interaction of Erythropoietin with Erythroid Progenitor Cells.- I. The Erythropoietin Receptor.- C. Interaction of Other Growth and Development Factors with Erythroid Progenitor Cells.- D. The Erythroid Differentiation Program.- I. Gene Expression During Erythroid Cell Differentiation.- E. Signal Transduction in Erythroid Progenitor Cells.- F. Erythropoietin as a Competence or Progression Factor.- G. Conclusion.- References.- 5 The Arachidonic Acid Cascade and Erythropoiesis.- A. Introduction.- I. Background.- II. Classification of Eicosanoids and Their Chemistry.- 1. Prostaglandins.- 2. Thromboxanes.- 3. Hydroperoxy/Hydroxy Fatty Acids.- 4. Leukotrienes.- 5. Diglyceride, Phosphatidic Acid, and Lysophosphatidic Acid.- III. Erythropoiesis and Eicosanoids.- B. Evidence for the Roles of Arachidonic Acid Metabolism in Erythropoiesis.- I. Criteria for Implicating Eicosanoids.- II. Target Cell Responses.- III. Cell-Cell Interactions.- IV. Specific Involvement of the Lipoxygenase Pathway.- C. Future Directions for Research.- References.- 6 Iron Deficiency and Megaloblastic Anemias.- A. Iron-Deficiency Anemia.- I. Introduction.- II. Iron Metabolism.- 1. Iron Absorption.- a) Nonheme Iron Absorption.- b) Heme Iron Absorption.- c) Regulation of Iron Absorption.- 2. Iron Transport.- 3. Intracellular Iron Metabolism.- 4. Iron Storage.- III. Biochemical and Physiologic Roles of Iron in Mammalian Tissues.- IV. Iron-Deficiency Anemia.- 1. Clinical Aspects.- 2. Diagnosis of Iron Deficiency.- 3. Management of Iron Deficiency.- a) Oral Iron Therapy.- b) Parenteral Iron Therapy.- B. Megaloblastic Anemias.- I. Definition and Differential Diagnosis.- II. Clinical Manifestations.- III. Biochemistry of Folic Acid and Vitamin B12.- IV. Vitamin B12 Deficiency.- 1. General Considerations.- 2. Vitamin B12 Metabolism.- a) Vitamin B12 Binding Proteins.- b) Vitamin B12 Absorption.- c) Transport and Intracellular Metabolism of Vitamin B12.- 3. Causes of Vitamin B12 Deficiency.- 4. Diagnosis of Vitamin B12 Deficiency.- 5. Management of Vitamin B12 Deficiency.- V. Folate Deficiency.- 1. General Considerations.- 2. Folate Metabolism.- a) Folate Absorption.- b) Transport and Intracellular Metabolism of Folate.- 3. Causes of Folate Deficiency.- 4. Diagnosis of Folate Deficiency.- 5. Management of Folate Deficiency.- References.- 7 Erythropoietin in the Anemia of End-Stage Renal Disease.- A. Assay of Erythropoietin.- B. Pathogenesis of the Anemia of Chronic Renal Failure.- I. Inhibition of Erythropoietin Action.- II. Inhibition of Heme Synthesis.- III. Inhibition of Colony Formation.- C. Kidney Production of Erythropoietin.- D. Erythropoietin in Therapy of Renal Anemia.- E. Conclusions.- References.- 8 Humoral Control of Thrombocytopoiesis.- A. Introduction.- B. Model for Megakaryocytopoiesis.- C. Controlling Factors.- I. Megakaryocyte-Colony Stimulating Factor.- II. Autoregulation of Megakaryocytopoiesis.- III. Thrombopoietin.- 1. Background and Historical Aspects.- 2. Assays.- 3. Site of Production.- 4. Antibodies to Thrombopoietin.- 5. Purification.- a) Methods for Purification.- b) Characterization of the Molecule.- 6. Effects on Megakaryocytopoiesis.- a) In Vitro Effects.- b) In Vivo Effects.- 7. Effects on Thrombocytopoiesis.- a) Platelet Counts.- b) Platelet Sizes.- c) Isotope Incorporation.- D. Other Factors Affecting Thrombocytopoiesis.- I. Effects of Hypoxia.- II. Effects of Erythropoietin and Other Growth Factors.- E. Clinical Aspects of Thrombopoietin.- F. Future of Thrombopoietin.- References.- 9 Arachidonic Acid Metabolism Platelets and Thromboembolic Disease.- A. Arachidonic Acid Metabolism.- I. Introduction.- II. The Cyclooxygenase Pathway.- III. Shunting of Endoperoxides.- IV. The Lipoxygenase Pathway.- V. The Epoxygenase Pathway.- VI. Pharmacology of Antiplatelet Agents.- B. Thromboembolic Disease.- I. Introduction.- II. Unstable Angina.- III. Acute Myocardial Infarction.- 1. Secondary Prevention.- 2. Coronary Thrombolysis.- 3. Primary Prevention.- IV. Coronary Bypass Grafts.- V. Peripheral Arterial Grafts.- VI. Cerebrovascular Disease.- VII. Prosthetic Valves.- VIII. Coronary Angioplasty.- C. Concluding Comments.- References.- 10 Chemical Agents That Inhibit Platelet Aggregation.- A. Introduction.- B. Platelet Physiology.- C. Platelet Structure.- D. Platelet Involvement in Thrombosis.- E. Platelet Responses.- I. Shape Change.- II. Adhesion.- III. Aggregation.- F. Inhibition of Platelet Aggregation.- I. Cyclic AMP.- II. Cyclic GMP.- III. Receptor Antagonism.- 1. Catecholamines.- 2. Serotonin.- 3. ADP.- 4. Prostaglandin Endoperoxides and Thromboxane A2.- 5. Vasopressin.- 6. Platelet Activating Factor.- 7. Thrombin.- 8. Collagen.- IV. Arachidonate Metabolism.- 1. Source of Arachidonate.- 2. Inhibitors of Phospholipase A2.- 3. Inhibitors of Cyclooxygenase.- 4. Thromboxane Synthase Inhibitors.- 5. Inhibitory Prostaglandins.- V. Experimental Drugs with Unknown Actions.- G. Conclusions.- References.- 11 Anticoagulants, Antithrombotic and Thrombolytic Agents.- A. Anticoagulants.- I. Heparin.- 1. Clinical Applications.- 2. Prophylactic (Low-Dose) Heparin.- 3. Complications.- II New Therapies.- 1. Heparin plus Dihydroergotamine.- 2. Low Molecular Weight Heparins.- III. Oral Anticoagulants.- 1. Complications.- B. Thrombolytic Therapy.- I. Streptokinase.- II Urokinase (and Single Chain Urokinase).- III. Tissue Plasminogen Activator.- IV. Acyl Plasminogen Streptokinase Activation Complex.- V. Novel Approaches.- 1. Defibrotide and Brinase.- VI. Side Effects and Complications.- VII. Clinical Considerations.- 1. Acute Myocardial Infarction (Coronary Thrombosis).- 2. Arterial Occlusion.- 3. Pulmonary Embolism.- 4. Deep Venous Thrombosis.- C. Antithrombotic Therapy.- I. Dextrans.- II. Physical Methods.- III. Refibrinogenating Agents.- References.- 12 Granulocyte-Macrophage Growth Factors.- A. Introduction.- B. Historical Background.- C. Growth Factors.- I. Colony Stimulating Factor-1.- II. Granulocyte-Macrophage-Colony Stimulating Factor.- III. Granulocyte-Colony Stimulating Factor.- IV. Interleukin-3.- D. Other Interleukins.- I. Interleukin-1.- II. Interleukin-2.- III. Interleukin-4.- IV. Interleukin-5.- V. Interleukin-6.- VI. Interleukin-7.- E. Inhibitors.- F. Cellular Production and Networking.- G. Microenvironment.- H. Conclusions.- References.- 13 Chemical Agents Which Suppress Myelopoiesis: Agranulocytosis and Leukemia.- A. Introduction.- B. Normal Marrow Cell Kinetics.- C. Pathophysiologic Mechanisms for Drug-Induced Neutropenia.- D. Neutropenia Associated with Cytotoxic Chemotherapeutic Agents.- E. Drug-Induced Myeloid Suppression.- I. Ethanol.- II. Phenothiazines.- III. Anticonvulsants.- IV. Antiinflammatory Agents.- V. Antiviral Agents.- VI. H2 Receptor Antagonists.- VII. Miscellaneous Agents.- F. Idiosyncratic Neutropenias.- I. Analgesics.- II. Antibiotics.- III. Cardiovascular Drugs and Diuretics.- IV. Thyrostatic Agents.- V. Sulfonamides.- G. Pseudoneutropenia.- I. Complement Activation.- II. Expression of Membrane Adhesion Molecules.- H. Secondary Leukemia.- J. Conclusions.- References.- 14 Drugs Useful in the Chemotherapy of the Acute Leukemias.- A. Introduction.- B. Antimetabolites.- I. Cytosioc Arabinoside (1-?-D-arabinofuranosylcytosine).- II. 6-Mercaptopurine and 6-Thioguanine.- III. Methotrexate.- C. Drugs that Intercalate in DNA.- I. Daunorubicin and Doxorubicin.- II Amsacrine.- D. Podophyllotoxin Derivatives.- I. Etoposide and Teniposide.- E. Vinca Alkaloids.- I. Vincristine.- F. Alkylating/DNA Binding Agents.- I. Cyclophosphamide.- II Carboplatin.- G. Adrenal Glucocorticoids.- I. Prednisone.- H. Enzymes.- I. Asparaginase.- J. Multidrug Resistance.- References.

O autorze

How do certain substances, known as growth factors, cause blood to be built in the human body? In what way do the chemicals we are exposed to every day affect the blood-building system? Cell biologists and hematologists will find the latest answers in this volume.