Toxins and Hemostasis (eBook)

From Bench to Bedside

R. Manjunatha Kini, Kenneth J Clemetson, Francis S. Markland, Mary Ann McLane, Takashi Morita (Herausgeber)

eBook Download: PDF

2010 | 2011
XXIII, 797 Seiten
Springer Netherland (Verlag)
978-90-481-9295-3 (ISBN)

Infos

Circulation of blood is vital for the survival of vertebrates, including man. Mainly, it plays an important role in carrying food nutrients and oxygen to every tissue and organ and in removing all waste products and carbon dioxide. Any imbalance in the hemostatic and cardiovascular systems can lead to death and severe debility. A number of animals have developed mechanisms to target these systems and exploit the vulnerability. In some species (for example, snakes), such mechanisms are used to immobilize and kill the victim/prey, whereas in others (for example, insects, such as leaches, mosquitoes and ticks), they are used to provide a continuous supply of blood. These mechanisms include, but are not limited to, procoagulant and anticoagulant actions that affect the coagulation cascade and platelet aggregation, as well as altering vasodilatory responses. In all these various animals, these mechanisms have evolved to perfection over millions of years to support their survival. In last 3-4 decades, due to the efforts of scientists from various backgrounds including biology, protein chemistry, molecular biology, pharmacology, hematology, and structural biology, significant progress in understanding the structure-function relationships, as well as the mechanism of action have been made in a number of exogenous factors that affect blood coagulation, platelet aggregation and vasodilation from various animals. These exogenous factors have contributed significantly to the development of research tools as well as providing new therapeutic agents. With the increase average age of the population coupled with changes in life style in recent years, there has been a significant increase in cardiovascular and hematological disorders. Thus scientists in both academic institutions as well as the pharmaceutical industry are developing better therapeutic agents to improve the quality of life. This impetus has lead to the search for novel agents from various sources that interfere with cardiovascular and hematalogical processes. Although at first glance exogenous factors appear to function as 'villains', several life-saving drugs have been developed based upon these factors. Such drugs or drug leads include those that inhibit the angiotensin converting enzymes (Captopril and Enalapril), that block platelet receptors (Eptifibatide and Tirofiban), or that digest thrombotic plugs (Alfimeprase and bat plasminogen activator) to name a few. Several new and exciting success stories are currently unfolding. In this book, recent studies on some of the exogenous factors that play crucial roles in cardiovascular and hematological disorders are reviewed in order to consolidate the efforts in this area of research and to recruit new, talented researchers. The 25-30 review chapters, each written by experts in their field, compiled herein are devoted to exogenous factors affecting platelet aggregation, anticoagulant and procoagulant proteins, fibrinolytic proteins and hypotensive agents (For details see, Contents of the Book). This book is intended to help to create elevated awareness and enthusiasm in the field of exogenous factors. I believe that this book will provide greater impetus to the search for novel proteins based on naturally occurring exogenous factors. This will be the first book dealing extensively with exogenous factors in the last 25 years. The book will provide a ready reference to the different approaches used to solve complex problems in protein chemistry and pharmacology of exogenous factors. The book will update our understanding of the structure-function relationships and mechanisms of action of exogenous factors and provide great insights into future directions for solving the remaining challenges.

Inhalt

Preface 5
Acknowledgments 8
Contents 10
Contributors 14
About the Editors 19
Introduction 22
From Bench to Bedside 31
From the Bothrops Jararaca Bradykinin Potentiating Peptides to Angiotensin Converting Enzyme Inhibitors 32
The Omics – The Search Is On 37
Sialomic Perspectives on the Evolution of Blood- Feeding Behavior in Arthropods: Future Therapeutics by Natural Design 38
Snake Venomics, Antivenomics, and Venom Phenotyping: The Ménage à Trois of Proteomic Tools Aimed at Understanding the Biodiversity of Venoms 62
Insights in to Venom and Toxin Activities and Pharmacological/ Therapeutic Potential Using Gene Expression Profiling 90
Bioactive Peptides and Proteins from Wasp Venoms 99
The Theory of Intraspecies Variation is Not the Exception, But Simply the Rule: The Diverse Hemostatic Activities of Snake Venoms 112
Tiny Ticks are Vast Sources of Antihaemostatic Factors 128
Sialogenins and Immunomodulators Derived from Blood Feeding Parasites 146
Salivary Protease Inhibitors with Non Anti- Hemostatic Functions 168
Anticoagulant Proteins 180
Blood Coagulation Factor IX/Factor X- Binding Protein 181
Bothrojaracin – A Potent Thrombin Inhibitor 192
Anticoagulant Phospholipases A2 Which Bind to the Specific Soluble Receptor Coagulation Factor Xa 214
Hematophagy and Inhibition of the Extrinsic and Intrinsic Tenase Complexes 231
Thrombin Inhibitors from Haematophagous Animals 250
Anticoagulants from Scorpion Venoms 266
Antiplatelet Proteins 278
The Discovery of Disintegrins 279
Brief History and Molecular Determinants of Snake Venom Disintegrin Evolution 295
Anti-Angiogenesis and Disintegrins 311
Hematophagy and Inhibition of Platelet Aggregation 340
Snaclecs (Snake C-Type Lectins) that Inhibit Platelet Receptors 367
Fibrinolytic Proteins 377
Plasminogen Activators from Snake Venoms 378
Bat Plasminogen Activator: Desmoteplase – From Bat to Bench to Bedside of Stroke Victims 400
Fibrolase and Its Evolution to Clinical Trials: A Long andWinding Road 415
Streptokinase 434
Procoagulant Proteins 450
Activation of Factor X by Snake Venom Proteases 451
Structural Aspects of the Factor X Activator RVV- X from Russell’s Viper Venom 469
Snake Venom Prothrombin Activators – The History 489
Origin and Evolution of Snake Venom Prothrombin Activators 504
Thrombin-Like Enzymes in Snake Venoms 521
Procoagulant Factors from Lonomia Caterpillars 560
Staphylocoagulase 576
Procoagulant Properties of Plant Latex Proteases 592
Platelet Aggregation Inducers 605
The Biologic Activity of Aggretin/Rhodocytin, a Snake Venom C- Type Lectin Protein ( Snaclec) 606
Snaclecs (Snake C-Type Lectins) that Activate Platelets 620
The Effect of Bacterial Toxins on Platelet Function 636
Hypotensive Factors 651
Hypertensive and Hypotensive Snake Venom Components 652
Hypotensive Proteins from Hematophagous Animals 670
Hemorrhage and Coagulopathies 694
Snakebite-Induced Coagulopathy and Bleeding Disorders 695
Antivenoms and Coagulation 707
Biological Activities of Snake Venom Metalloproteinases on Platelets, Neutrophils, Endothelial Cells, and Extracellular Matrices 718
Applications 728
Leeches in Microsurgery – An Evidence-Based Approach 729
Diagnostic Use of Snake Venom Components in the Coagulation Laboratory 740
Index 760

Produkt-Details

• Erscheint lt. Verlag: 19.10.2010
• Zusatzinfo: XXIII, 797 p.
• Verlagsort: Dordrecht
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Hämatologie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie
• Schlagworte: Anticoagulant proteins • Blood coagulation inhibitors • Hypertension • Platelet aggregation • Procoagulant proteins
• ISBN-10: 90-481-9295-1 / 9048192951
• ISBN-13: 978-90-481-9295-3 / 9789048192953