I: History, Ecological and Zoological Aspects.- 1 History of Snake Venom Research.- References.- 2 Classification and Distribution of Venomous Snakes in the World.- References.- 3 The Venom Glands of Snakes and Venom Secretion.- A. Introduction.- B. General Morphology and Histology.- I. Venom Glands of Elapidae.- II. Venom Glands of Viperidae.- C. The Fine Structure of the Secretory Cell During the Venom Regeneration Cycle.- D. Intracellular Transport of Venom Proteins.- E. Venom Synthesis and Secretion.- I. The Venom Regeneration Cycle.- II. Synthesis and Secretion of Different Venom Components.- III. Total Venom Yield and the Amount of Venom Expelled During the Bite.- F. Concluding Remarks.- References.- II: Chemistry and Biochemistry of Snake Venoms.- 4 Enzymes in Snake Venom.- A. Introduction.- B. Distribution of Enzymes in Snake Venoms.- C. Methods for Purification, Isolation, and Crystallization of Snake Venom Enzymes.- I. Polyacrylamide Gel Electrophoresis.- II. Isoelectric Focusing.- III. Molecular-Sieve Chromatography.- IV. Ion-Exchange Chromatography.- D. Biochemical Properties of Snake Venom Enzymes.- I. Oxidoreductases.- 1. L-Amino Acid Oxidase.- 2. Lactate Dehydrogenase.- II. Enzymes Acting on Phosphate Esters.- 1. Endonuclease.- 2. Phosphodiesterase.- 3. 5?-Nucleotidase.- 4. Nonspecific Phosphomonoesterase.- 5. "Paraoxonase" (O,O-Diethyl O-p-Nitrophenyl Phosphate, O-p-Nitrophenyl Hydrolase).- III. Enzymes Acting on Glycosyl Compounds.- 1. Hyaluronidase.- 2. Heparinase-like Enzyme.- 3. NAD Nucleosidase.- IV. Enzymes Acting on Peptide Bonds.- 1. Endopeptidases.- 2. Peptidases.- 3. Arginine Ester Hydrolases.- 4. Kininogenase.- V. Enzymes Acting on Carboxylic Ester Bonds.- 1. Phospholipase A2.- 2. Phospholipase B and Phospholipase C.- 3. Acetylcholinesterase.- VI. Enzyme Acting on Arylamides.- E. Summary.- References.- 5 Chemistry of Protein Toxins in Snake Venoms.- A. Introduction.- B. Toxins with Postsynaptic Neurotoxin-Membrane Toxin Structure.- I. Curaremimetic Toxins.- 1. Introduction.- 2. Isolation of Curaremimetic Toxins.- 3. Characteristics of Curaremimetic Toxins.- 4. Interaction with the Acetylcholine Receptor.- 5. Structural Information.- 6. Chemical Modifications.- a) Amino Groups.- b) Arginine Residues.- c) Carboxyl Groups.- d) Tryptophan.- e) Tyrosine.- f) Disulfide Bridges.- g) Histidine.- h) Modifications Involving a Large Increase in Size.- 7. Discussion.- II. Membrane Toxins.- 1. Introduction.- 2. Mode of Action.- 3. Structural Information.- 4. Chemical Modifications.- C. Toxins with Phospholipase Structure.- I. Notexin and its Homologues.- II. Taipoxin.- III. Crotoxin.- IV. ?-Bungarotoxin.- V. Enhydrina schistosa Myonecrotic Toxins.- VI. Some Other Toxic Phospholipases A.- VII. Pharmacologic and Biochemical Effects.- 1. Presynaptic Neurotoxicity.- 2. Inhibition of High Affinity Choline Uptake.- 3. Postsynaptic Effects and Myotoxicity.- 4. Antagonism by High Mg2+, Ca2+, and Low Ca2+.- VIII. Phospholipase A Activity and Presynaptic Neurotoxicity.- IX. Concluding Remarks.- D. Other Toxins.- I. Crotamine.- II. Convulxin and Gyroxin.- III. Mojave Toxin.- IV. Other Crotalid Toxins.- V. Viperotoxin.- VI. Toxins from Bungarus caeruleus Venom.- 1. Ceruleotoxin.- 2. Post- and Presynaptic Neurotoxins.- E. Conclusion.- References.- 6 The Three-Dimensional Structure of Postsynaptic Snake Neurotoxins: Consideration of Structure and Function.- A. Introduction.- B. The Postsynaptic Neurotoxins: Survey of Three-Dimensional Prototype Structure; Deviant Toxins, Chemical Modification Studies. Preliminary Review.- I. Primary Sequence of Erabutoxin b.- II. Three-Dimensional Structure of Erabutoxin b.- 1. Molecular Size and Shape.- 2. Backbone Chain Conformation in the Erabutoxin Molecule.- III. Residue Sequences: Invariant and Conservative Substitutions in the Long and Short Chain Series of Neurotoxins.- IV. Chemistry and Chemical Modification Studies.- 1. Residues not Subject to Study by Group-Specific Reagents.- a) Serine-Threonine.- b) Glycine.- c) Proline.- d) Asparagine.- e) Alanine, Leucine, Isoleucine, and Valine.- 2. Invariant and Conservatively Substituted Residues as Studied by Chemical Modification.- a) Disulfide Linkages.- b) Tyrosine.- c) Tryptophan.- d) Aspartic Acid, Glutamic Acid.- e) Arginine.- f) Amino Groups.- 3. Toxin Modification by Deletion or by Size Increase.- a) Carboxyl-Terminal Deletion of a Long Chain Toxin.- b) Polymerization.- 4. Summary.- V. Physicochemical Studies of Neurotoxins and Their Derivatives.- 1. Spectroscopic Studies of Native Toxin Conformation in Aqueous and Aqueous-Organic olvent.- a) Optical Rotatory Dispersion (ORD) and Circular Dichroism (CD) Spectra.- b) Laser-Raman Spectra.- 2. Spectroscopic Studies of Chemically Modified and/or Denatured Neurotoxins.- a) Disulfide Linkages.- b) Tyrosine.- c) Tryptophan.- VI. Theoretical and Model Studies of Neurotoxin Conformation and Three-Dimensional Structure.- 1. Prediction of Conformation in the Neurotoxins.- a) ? Helix.- b) ? Pleated Sheet.- c) ? Turns.- 2. Predictions of Three-Dimensional Structure in the Neurotoxin Series.- a) Model Structure Studies.- b) Energy Minimization Studies.- c) Theoretical Chemical Models.- VII. X-ray Crystal Structure Studies of Other Neurotoxins.- 1. Erabutoxin a (Asn 26 Erabutoxin b).- 2. Neurotoxin b from Laticauda semifasciata (Philippines).- 3. Erabutoxin c.- 4. Laticotoxin a and Cobrotoxin.- C. Structure-Function Relationship in the Postsynaptic Neurotoxins. The Three-Dimensional Structure of Erabutoxin b as Prototype in both Long and Short Toxins.- I. Erabutoxin b and the Short Toxins: The Reactive Site.- II. Erabutoxin b and the Short Toxins: Nonreactive Site Regions.- III. Erabutoxin and the Long Toxins: Reactive Site.- IV. Erabutoxin and the Long Toxins: Nonreactive Site Regions.- V. Long and Short Toxins: Biochemical and Biological Differences.- VI. Erabutoxin b and the Short Toxin Series: Detailed Intramolecular Packing.- 1. ? Pleated Sheet and ? Turns.- 2. Intramolecular Interactions: Particularly Those Involving Invariant and Type-Conserved Residues.- a) Main Chain-Main Chain and Main Chain-Side Chain Hydrogen Bonds.- b) Side Chain-Side Chain Interactions.- D. Conclusions.- I. The Present View.- 1. Structure: General.- 2. Comparison of Short and Long Toxins.- 3. Structural and Functional Residues.- a) Structural Residues.- b) Functional Groupings.- c) Residues of Uncertain Role.- II. Future Studies-New Questions and Their Resolution.- References.- 7 The Evolution of Toxins Found in Snake Venoms.- A. Introduction.- I. The Toxin-Types of Snake Venoms.- II. Methods Used in Studying Protein Phylogenetics.- 1. Matrix Methods.- 2. Ancestor Sequence Method.- 3. Maximum Parsimony Method.- 4. Subjective Methods.- B. Historic Development of Snake Toxin Phylogenetics.- C. Current Views on the Evolution of Snake Toxins.- D. Future Possibilities.- References.- 8 Nerve Growth Factors in Snake Venoms.- A. Introduction.- B. Distribution.- C. Properties.- I. Elapidae.- 1. Naja naja.- 2. Other Elapids.- II. Crotalidae.- 1. Agkistrodon piscivorus.- 2. Crotalus adamanteus.- 3. Bothrops jararaca.- 4. Other Crotalids.- III. Viperidae.- 1. Vipera russellii.- 2. Other Viperids.- D. Comparison of Nerve Growth Factors.- I. Relationship of Venom NGFs.- 1. Intrafamily.- a) Elapidae.- b) Crotalidae.- c) Viperidae.- 2. Interfamily.- II. Relationship of Venom and Mouse NGFs.- E. Role of NGF in Snake Venom.- F. Concluding Remarks.- References.- 9 Metal and Nonprotein Constituents in Snake Venoms.- A. Introduction.- B. Inorganic Constituents.- I. Metal Content.- II. Nonmetal Inorganic Content.- C. Organic Constituents.- I. Lipids.- II. Carbohydrates.- III. Riboflavin.- IV. Nucleosides and Nucleotides.- V. Amino Acids and Peptides.- 1. Amino Acids.- 2. Peptides.- a) Structural Studies.- b) Physiologic Studies.- VI. Amines.- D.
Prophylaxis of Envenomation with Toxoids (Vaccines) Prepared from Purified Hemorrhagic Principles.- F. Concluding Remarks.- References.- 15 Cardiovascular Effects of Snake Venoms.- Cardiovascular Effects of Crotalid and Viperid Venoms.- A. Hemodynamic Effects of Crotalid Venoms.- I. Rattlesnake (Crotalus) Venoms.- 1. C. horridus (Timber Rattlesnake) and C. atrox (Western Diamond-back Rattlesnake) Venoms.- 2. C. adamanteus (Eastern Diamond Rattlesnake) Venom.- 3. C. viridis helleri (Southern Pacific Rattlesnake) Venom.- 4. C. durissus terrificus (Tropical Rattlesnake) Venom.- 5. C. scutulatus (Mojave Rattlesnake) Venom and Mojave Toxin.- 6. Basic Protein Toxins from Rattlesnake Venoms.- II. Other Crotalid Venoms.- 1. Agkistrodon Venoms.- 2. Trimeresurus Venoms.- 3. Bothrops Venoms.- III. Thrombinlike Enzymes from Crotalid Venoms.- B. Mechanism of the Depressor Action of Crotalid Venoms.- I. Site of Action.- II. Venom Components Responsible for the Depressor Action.- C. Hemodynamic Effects of Viperid Venoms.- I. Russell's Viper (Vipera russellii) Venom.- II. Other Viper Venoms.- 1. Vipera ammodytes Venom.- 2. Vipera palestinae Venom.- 3. Echis carinatus and Echis coloratus Venoms.- 4. Bitis arietans Venom.- D. Mechanism of the Depressor Action of Viperid Venoms.- I. Mode of Hypotensive Action.- II. Venom Components Responsible for the Hypotensive Action.- Cardiovascular Effects of Elapid and Sea Snake Venoms.- A. Cobra (Naja) Venoms.- I. Action on the Heart.- II. Cardiotoxin and its Action on the Heart.- III. Hemodynamic Effects.- 1. Pressor Effect.- 2. Depressor Effect.- a) Analysis of the Initial Depressor Effect.- b) Venom Components Responsible for the Initial Depressor Effect.- B. Other Elapid Venoms.- I. Krait (Bungarus) Venoms.- II. Mamba (Dendroaspis) Venoms.- III. Coral Snake (Micrurus) Venoms.- IV. Australian Elapid Venoms.- C. Sea Snake Venoms.- Summary and Conclusions.- A. Crotalid and Viperid Venoms.- B. Elapid and Sea Snake Venoms.- References.- 16 Liberation of Pharmacologically Active Substances by Snake Venoms.- General Introduction.- A. Histamine.- I. Introduction.- II. Survey of the Histamine-Releasing Activity of Snake Venoms.- III. Mechanistic Aspects.- 1. Phospholipase A Activity and Histamine Release.- 2. Histamine Release by Snake Venom Components Other Than Phospholipase A.- IV. Contribution of Histamine Toward Toxic Effects of Snake Venoms.- B. 5-Hydroxytryptamine.- I. Survey of 5-Hydroxytryptamine-Releasing Activity of Snake Venoms.- II. Systemic Effects.- III. Local Effects.- C. Bradykinin.- I. Introduction.- II. Survey of the Kinin-Forming Capacity of Snake Venoms.- III. Mechanistic Aspects.- 1. Arginine Ester Hydrolase Activity and Kinin Release.- 2. Substrate Requirements.- 3. Kinin Peptides Released by Snake Venoms.- 4. Inhibition of Kinin-Releasing Activity.- IV. Contribution of Bradykinin Toward Systemic and Local Effects of Snake Venoms.- 1. Hypotension.- 2. Lethality.- 3. Increased Vascular Permeability and Pain.- 4. Potentiation of Bradykinin Effects.- D. Slow-Reacting Substances, Prostaglandins, and Lysophosphatides.- I. Background.- II. Mechanistic Aspect.- III. Sites of Formation.- 1. Tissues.- 2. Cells.- IV. Contribution Toward Toxic Effects of Venoms.- 1. Lysophosphatides.- 2. Prostaglandins.- E. Catecholamines.- Adrenaline.- F. Anaphylatoxin.- I. Background.- II. Contribution Toward Toxic Effects of Elapid Snake Venoms.- References.- 17 Snake Venoms as an Experimental Tool to Induce and Study Models of Microvessel Damage.- A. Introduction.- I. By Way of Speculating About Disease Models.- II. Venoms as Stores of Vasculotoxic Materials.- B. Morphology, Methodology, and Phenomenology of Venom-Induced Vessel Lesion.- I. Comparative Morphology of Lung and Cremaster Vessels.- 1. Capillaries.- 2. Arterioles and Venules.- II. Methology and Phenomenology of Vessel Lesions in Different Tissues.- 1. Pulmonary Vessels.- a) Canine Lung Surface Test.- b) Rodent Intrathoracic Test.- 2. Cremaster Vessels.- 3. Rat Paw Edema.- 4. Skin Vascular Lesions.- 5. Miscellaneous Vascular Beds.- C. Elapid Snake and Bee Venoms.- I. Morphologic Aspects of Elapid Venom Effects on Lung and Cremaster.- 1. Lung Effects.- 2. Cremaster Effects.- II. Pharmacologic Aspects.- 1. Individual Venom Components: Role of Various Polypeptides and Phospholipase A2.- 2. Pharmacologic Influences on Venom-Induced Vessel Injury.- a) Antihistamines.- b) Nonsteroid (Acidic) Anti-Inflammatory Drugs (NSAID).- c) Corticosteroids.- d) Protease Inhibitors.- e) Estrogens.- f) Flavonoids.- g) Polyphloretin Phosphate.- h) Heparin.- i) Cyclic Adenosine Monophosphate (cAMP).- 3. Rat Paw Edema and Permeability Increase Due to Elapid and Bee Venoms.- a) Rat Paw Edema.- b) Skin Vascular Permeability.- D. Crotalid Venoms and Enzymes Simulating Their Effects.- I. Morphologic Aspects of Crotalid Venom: Effects on Lung and Cremaster.- 1. Lung Effects.- 2. Cremaster Effects.- II. Pharmacologic Aspects.- 1. Similarities and Differences Between Effects of Some Crotalid Snake Venoms.- 2. Lung Effects of Collagenase and Other Proteolytic Enzymes.- III. Pharmacologic Influences on Crotalid Snake Venoms and Collagenase-Induced Hemorrhagic Effects.- 1. In Vitro Inactivation of Vasculotoxic Materials.- 2. Local Application of Putative Inhibitors to the Tissue.- 3. Intravenous Administration of Putative Inhibitors.- 4. Effects of Collagenase in the Rodent Intrathoracic Test.- IV. Effects of Different Enzymes on the Lung Surface Vessels.- V. Rat Paw Edema Due to Crotalid Snake Venoms.- VI. Rat Paw Edema and Skin Vascular Permeability Effects of Bacterial Collagenase.- VIL Increase in Skin Vascular Permeability Due to Crotalid Snake Venoms.- E. General Conclusions: Interrelationships Between Morphology and Function.- F. Speculations on the Significance of Venom-Induced Inflammation of Microvessels.- References.- 18 Snake Venoms and Blood Coagulation.- A. Blood Coagulation Mechanisms.- I. Blood Coagulation Nomenclature.- II. Three Basic Reactions of Blood Coagulation.- III. Formation of Fibrin.- IV. Cross Linking of Fibrin.- V. Formation of Thrombin.- VI. Formation of Autoprothrombin C (Factor Xa).- VII. General Procoagulant Effects.- VIII. Inhibition of Procoagulants.- 1. Nature of Anticoagulant Systems.- 2. Fibrinogen and Fibrin Degradation Products (FDP).- 3. Prothrombin Derivatives.- 4. Antithrombin III.- 5. Other Plasma Inhibitors.- 6. Thrombin.- IX. Clot Retraction.- X. Fibrinolytic System.- B. Physiology of Hemostasis.- C. Snake Venoms and Blood Coagulation.- I. Introductory Remarks.- II. Snake Venoms and Fibrinogen.- III. Formation of Fibrin.- IV. Thrombin-Like Enzymes and Cross-Linking of Fibrin.- V. Platelets and Thrombin-Like Enzymes.- VI. Animal and Clinical Work.- VII. Autoprothrombin II-A and Fibrinolysis.- VIII. Defibrination and Fibrinolysis with Acetylated Thrombin.- IX. Miscellaneous Aspects.- 1. Units of Activity.- 2. Elimination of Thrombin-Like Enzyme.- 3. Inhibitors.- 4. Hemostasis.- 5. Rheology.- 6. Metastasis Formation.- 7. Phospholipase A2.- X. Venoms and Direct Fibrinolysis.- XI. Snake Venoms and Thrombin Formation.- XII. Snake Venoms and Autoprothrombin C (Factor Xa) Formation.- XIII. Snake Venoms and Platelets.- 1. Platelet Membrane Structural Changes Induced by Phospholipase A and Direct Lytic Factor (DLF) of Snake Venoms.- 2. Platelet Aggregation Induced by Coagulant and Noncoagulant Venoms.- 3. Venom Inhibitors of Platelet Aggregation.- D. Overview.- References.- IV: Immunological and Clinical Aspects.- 19 Immunological Properties of Snake Venoms.- A. Introduction.- I. Definitions.- II. Historical Data.- B. Snake Venoms are a Mosaic of Antigens.- C. Stimulation of the Immune System by Venom Antigens.- I. General Remarks on Antivenom Sera.- II. Immunogenic Properties of Some Proteins Extracted from Snake Venoms.- III. Role of Adjuvant Substances.- IV. Other Examples of Immunogenicity of Proteins Extracted in a Pure Form from Snake Venoms.- V.
Relationships Between Chemical Composition, Structure and Immunological Properties of Some Antigens of Snake Venoms.- 1. Chemical Modifications.- a) Influence of S-S Bridges.- b) Modification of Amino-Groups.- c) Modification of Histidyl Residues.- d) Modification of Tryptophanyl Residues.- e) Modification of Tyrosyl Residues.- f) The Problem of Aminoacid Residue Modifications.- 2. Immunological Analysis.- D. Nature of Antivenom Antibodies and Measurement of the Activity of Immune Sera.- E. Hypersensitivity to Snake Venoms.- F. Action of Snake Venoms on Cellular and Humoral Factors of Immunity.- References.- 20 Production and Standardization of Antivenin.- A. Introduction.- B. Antivenin Production.- I. The Animal.- II. The Antigens.- III. Immunization.- 1. New Horses.- 2. Immune Horses.- IV. Collection and Processing of Plasma.- C. Antivenin Standardization.- D. Conclusions.- E. List of Antivenin Producers.- References.- 21 Common Antigens in Snake Venoms.- A. Introduction.- B. Paraspecific Neutralization in Animals.- C. Demonstration of Common Antigens by Immunodiffusion.- D. Common Antigens in Venom and Snake Serum.- E. Discussion and Summary.- References.- 22 Snakes and the Complement System.- A. Introduction.- B. Early Complement Research.- C. Early Work on Snake Body Fluids and Complement.- D. Present State of Knowledge of the Complement System.- E. Modern Studies of the Interaction Between Snake Venom and Complement.- F. Epilog.- References.- 23 Vaccination Against Snake Bite Poisoning.- A. Historic Outlook.- B. Snake Venom Toxoids.- I. Habu Toxoids.- 1. DHTA Toxoid.- a) Preparation of the Toxoid.- b) Detoxification Tests.- c) Toxicity of the Toxoid.- d) Sterility Test.- e) Safety Test.- f) Immunogenicity Test.- 2. Crude Formalin Toxoid (CRF).- 3. Heat and Alcohol-Treated Formalin Toxoid (HAF).- a) Preparation of the Toxoid.- b) Immunogenicity of the Toxoid.- 4. Alcohol-Precipitated Formalin Toxoid (APF).- a) Purification and Detoxification of the Venom.- b) Immunogenicity of the Toxoid.- 5. Mixed Toxoid (MiF).- a) Preparation of MiF Toxoid.- b) Safety Test of MiF Toxoid.- c) Immunogenicity of the MiF and CRF Toxoids.- 6. Comparison of Antihemorrhagic, Antinectrotic and Antilethal Effect of APF, CRF, MiF, and DHTA Toxoids.- II. Toxoids from Venoms of Other Trimeresurus Species.- III. Toxoids from Venoms of Agkistrodon Species.- IV. Toxoids from Venoms of Other Viperidae Snakes.- V. Toxoid from Venoms of Elapidae Snakes.- 1. Toxoid from the Venom of Naja naja atra (Taiwan Cobra).- a) Preparation of the Toxoid.- b) Immunogenicity of the Toxoid.- c) Relationship Between Antilethal Antibody in the Blood of Immunized Rabbits and Resistance to Challenge with the Venom.- d) Reversion of Toxicity of the Toxoid.- 2. Toxoid from the Venom of Bungarus multicinctus.- 3. Toxoid from the Venom of Notechis scutatus.- C. Active Immunization.- I. Habu Toxoids.- 1. DHTA Toxoid.- a) Dosage and Interval of Injection of the Toxoid.- b) Reactions.- c) The Antivenin Level of Circulating Blood.- d) Clinical Analysis of the Habu Bites After the Immunization.- e) Hypersensitivity Acquired After Injection of the Toxoid.- 2. APF and MiF Toxoids.- a) Dosage and Intervals.- b) Reactions.- II. Tiger Snake Venom and Toxoid.- 1. Dosage and Intervals.- 2. Level of Circulating Antivenin.- 3. Reactions.- III. Indian Cobra (Naja naja) Venom.- 1. Dosage and Intervals.- 2. Antivenin Titer of Serum.- 3. Reactions.- 4. Effectiveness of the Vaccination.- D. Antigenic Quality of the Prophylactic Toxoid.- 1. Immunogenicity of the Toxoid.- 2. Detoxification and Immunogenicity of Toxoid.- 3. Differences in Antigenicity of Toxoid for Various Animal Species.- 4. Chemical Modification of Antigen.- E. Concluding Remarks.- References.- 24 Symptomatology, Pathology, and Treatment of the Bites of Elapid Snakes.- A. The Incidence of Envenomation.- B. Snakebite Wound.- I. The Wound.- II. Local Evidence of Envenomation.- 1. Most Elapids.- 2. Cobra.- C. Preparalytic Symptoms and Signs of Envenomation.- I. Those Common to Most Elapid Bites.- 1. Vomiting.- 2. Headache.- 3. Loss of Consciousness.- 4. Vasomotor Signs (Pallor, Sweating, Weak to Absent Pulse, Hypotension).- 5. Abdominal Pain.- II. Other Preparalytic Symptoms and Signs.- 1. Pain in Regional Lymph Nodes - Tenderness and Enlargement.- 2. Spitting, Vomiting, Coughing of Blood.- 3. The Passing of Blood-stained Urine.- 4. Other Nervous System Symptoms.- 5. Drowsiness.- 6. Allergic Reaction Following Snakebite.- 7. Cobra Venom Conjunctivitis.- D. Clinical Signs of Elapid Envenomation.- I. Muscle Paralysis.- 1. Clinical Picture.- 2. Duration of Muscle Paralysis.- II. Other Effects of Elapid Envenomation.- 1. Blood.- 2. Kidney.- 3. Heart and Blood Pressure.- III. Features of Envenomation from Different Elapid Snakes.- 1. Cobra.- 2. Krait.- 3. Mamba.- 4. Coral Snake.- E. Pathology.- I. Local Reaction.- II. Viscera.- III. Lymph Nodes.- IV. Muscles.- V. Post-Mortem Diagnosis.- F. The Treatment of Snakebite.- I. First-Aid Treatment.- II. Management of a Suspected Venomous Snakebite.- III. Definite Elapid Bite-No Evidence of Envenomation.- IV. Antivenene (AV).- 1. Dosage and Route of Administration.- 2. Method of Administration.- 3. Complications of Antivenene Therapy.- V. Other Modes of Treatment.- 1. Neostigmine.- 2. Corticosteroids.- 3. Intubation, Tracheostomy, IPPR, Intensive Care Nursing.- VI. Treatment of Local Wound (Cobra Bites).- References.- 25 Symptomatology, Pathology, and Treatment of the Bites of Sea Snakes.- A. Epidemiology.- I. Incidence of Sea Snakebite.- II. Incidence of Poisoning in Sea Snakebites.- III. Sex, Age, and Race of Victims.- IV. Occupation of Victims and Circumstances of Bites.- V. Site of the Bite, Repeated Bites, Other Factors.- VI. Village Treatment; Bite-Hospital Admission Interval.- VII. Conclusions on Epidemiology.- B. Medically Important Sea Snakes.- I. World Distribution.- II. Venom Yields and Lethal Toxicity.- C. Symptomatology of Sea Snakebite Poisoning.- I. Medical Literature.- II. Bite Marks: Early Symptoms.- III. Trivial Poisoning.- IV. Serious Poisoning.- V. Fatal Poisoning.- D. Diagnosis.- E. Prognosis.- F. Pathology.- I. Clinical Pathology.- II. Pathophysiology in Experimental Animals.- III. Pathophysiology in Man.- G. Treatment.- I. First-Aid Measures.- II. Medical Treatment.- 1. Supportive Treatment.- 2. Antivenom.- H. Summary.- References.- 26 Symptomatology, Pathology, and Treatment of the Bites of Viperid Snakes.- A. Introduction.- B. Incidence.- C. Symptomatology.- I. Natural History.- Case Report 1.- Case Report 2.- II. Review of Recent Literature.- III. Envenomation Caused by Other Genera of Viperid Snakes.- 1. Echis colorata.- 2. Atractaspis.- D. Prognosis and Sequela.- E. Pathology.- I. Gross Anatomy.- II. Histology.- III. Laboratory Examinations.- F. Pathogenesis of the Envenomation.- G. Treatment of Viper Bite.- H. Summary of Management of Snakebites.- References.- 27 The Clinical Problem of Crotalid Snake Venom Poisoning.- A. Introduction.- B. Identification.- C. Epidemiology.- D. Clinical Manifestations.- E. Laboratory Tests.- F. Treatment.- I. First Aid.- II. Medical Treatment.- References.- 28 Snake Venoms and Nephrotoxicity.- A. Introduction.- B. Renal Pathologic Changes.- I. Glomerular Lesions.- II. Vascular Lesions.- III. Tubulointerstitial Lesions.- IV. Cortical Necrosis.- C. Pathogenesis.- I. Glomerular Lesions.- 1. Direct Irritation by Snake Venom.- 2. Fibrin Deposition.- 3. Immunologic Reaction.- II. Vascular Lesions.- III. Renal Failure.- 1. Role of Hypotension.- 2. Role of Intravascular Coagulation.- 3. Role of Intravascular Hemolysis.- 4. Role of Myoglobinuria.- 5. Role of Arteritis.- 6. Role of Glomerular Lesions.- 7. Nephrotoxic Effect of the Venom.- D. Clinical Manifestations.- I. General Manifestations.- II. Renal Manifestations.- E. Treatment.- References.- Author Index.
Summary.- References.- III: Pharmacology of Snake Venoms.- 10 The Action of Snake Venoms on Nerve and Muscle.- A. Introduction.- B. Pharmacokinetics of Snake Venoms.- I. Absorption.- II. Distribution.- 1. Elapid Venoms and Postsynaptic Toxins.- 2. Viperid and Crotalid Venoms.- 3. Distribution in the Central Nervous System.- III. Fate and Excretion.- C. Toxicity and Cause of Death.- I. Cobra Venoms.- 1. Toxicity.- 2. Symptoms.- 3. Cause of Respiratory Paralysis.- II. Krait Venoms.- III. Australian Snake Venoms.- IV. Other Elapid Venoms.- 1. Desert Cobra (Walterinnesia aegyptia) Venoms.- 2. Coral Snake (Micrurus) Venoms.- 3. Mamba (Dendroaspis) Venoms.- V. Sea Snake (Hydrophiidae) Venoms.- VI. Viperid and Crotalid Venoms.- D. Effects on Neuromuscular Transmission.- I. Introduction to Pharmacology of Neuromuscular Transmission.- II. Cobra Venoms and Cobra Neurotoxins.- 1. Whole Venom.- 2. Postsynaptic Toxins.- III. Krait (Bungarus) Venoms and Their Toxins.- 1. Formosan Krait (Bungarus multicinctus) Venom.- 2. Indian Krait (Bungarus caeruleus) Venom.- 3. Banded Krait (Bungarus fasciatus) Venom.- 4. ?-Bungarotoxin.- 5. ?-Bungarotoxin.- a) Electrophysiologic Study.- b) Ultrastructural Effects.- c) Kinetic Study and Mode of Action.- d) Specificity of Action.- e) Biochemical Study.- IV. Australian Snake Venoms and Their Toxins.- 1. Tiger Snake (Notechis scutatus) Venom ans Notexin.- 2. Taipan (Oxyuranus scutellatus) Venom and Taipoxin.- 3. Death Adder (Acanthophis antarcticus) and Copperhead (Denisonia superba) Venoms.- V. Other Elapid Venoms.- 1. Mamba (Dendroaspis) Venoms.- 2. Desert Cobra (Walterinnesia aegyptia) Venom.- 3. Coral Snake (Micrurus) Venoms.- VI. Sea Snake Venoms.- VII. Viperid and Crotalid Venoms.- 1. Rattlesnake Venoms.- 2. Crotoxin.- 3. Mojave Toxin.- VIII. Postsynaptic Toxins, Specificity and Reversibility of Action.- 1. Specificity and Reversibility.- 2. Comparison with D-Tubocurarine.- IX. Comparison of Presynaptic Toxins.- 1. Pharmacologic Considerations.- 2. The Relation with Phospholipase A.- 3. Presynaptic Toxins of Other Origins.- 4. Mutual Antagonism Between Presynaptic Toxins.- E. Effects on Skeletal Muscle.- I. Cobra, Mamba, and Coral Snake Venoms.- 1. Cardiotoxins - Membrane-Active Polypeptides.- a) Pharmacologic Effects.- b) Antagonism by Ca2+ and Other Cations.- c) Histologic Effects.- d) Concluding Remarks.- 2. Phospholipase A and Its Interaction with Cardiotoxin.- II. Krait Venoms.- III. Australian Elapid Venoms.- IV. Sea Snake Venoms.- V. Viperid and Crotalid Venoms.- 1. Whole Venoms and Phospholipase A.- 2. Crotamine and Related Basic Polypeptides.- F. Effects on Peripheral Nerve.- I. Effects on Ganglionic Transmission.- II. Effects on Axonal Conduction.- G. Effects on the Central Nervous System.- I. Central Effects After Systemic Application.- 1. Neuropathologic Effects.- 2. Pharmacologic Effects.- II. Effects when Applied Directly to the Central Nervous System.- References.- 11 The Use of Snake Toxins for the Study of the Acetylcholine Receptor and its Ion-Conductance Modulator.- A. Introduction.- B. Isolation and Radiolabeling of Neurotoxins.- C. Neurotoxins as Specific Labels for Nicotinic ACh Receptors.- I. Techniques Used for Detection of Binding.- II. Use in Identification and Localization of ACh Receptors.- III. Use in Purification and Characterization of Nicotinic ACh Receptors.- D. Utilization of Neurotoxins to Compare Junctional and Extrajunctional ACh Receptors.- E. Neurotoxins as a Tool for Studies of Drug-Receptor Interactions.- F. Use in Studies of the Ion Conductance Modulator of the ACh-Receptor.- G. Use of Neurotoxins in Myasthenia Gravis Research.- H. Conclusion.- References.- 12 Pharmacology of Phospholipase A2 from Snake Venoms.- A. Introduction.- I. Scope of Chapter and Prior Reviews.- II. Purification, Properties, Assays, and Inhibitors of PhA2.- III. Sources of Error in Interpreting PhA2 Data.- 1. Use of Impure Preparations of PhA2.- 2. Neglecting Effects of Hydrolytic Products.- 3. Failure to Quantitate Extent of Phospholipid Hydrolysis.- 4. Assumption that all Snake Venom Preparations of PhA2 are Similar.- 5. Conclusions.- B. Lethality of PhA2.- C. Actions of PhA2 on Bioelectrically Excitable Tissues.- I. Axons.- II. Synapses.- III. Muscles.- IV. Central Nervous System.- D. Release of Physiologically Active Compounds by PhA2.- E. Antimicrobial Properties of PhA2.- F. Effects of PhA2 on Metabolism.- G. Summary and Conclusions.- References.- 13 Hemolytic Effects of Snake Venoms.- A. Introduction.- B. Hemolysis in Envenomation.- I. Elapid Venoms.- II. Viperid and Crotalid Venoms.- C. Venom Factors Involved in the Hemolytic Process.- I. Phospholipase A.- II. The Direct Lytic Factor.- D. Nonmediated Effects of Phospholipase A and Direct Lytic Factor on the Red Cell Membrane.- I. Red Cell Membrane Structure and Function.- II. Action of Phospholipases on Red Cell Membrane Phospholipids.- 1. Nonlytic Phospholipid Degradation.- 2. Lytic Phospholipid Degradation.- III. Action of the Direct Lytic Factor on the Red Cell Membrane.- 1. Direct Hemolysis.- 2. Attachment to Membranes.- 3. Effects on Membrane Permeability and Transport.- IV. Synergistic Action of Phospholipase A and the Direct Lytic Factor.- V. Mode of Action of the Direct Lytic Factor.- VI. Sensitivity of Erythrocytes from Various Animal Species to Venom-Induced Hemolysis.- E. Mediated Effects of Venom Phospholipase A.- I. The Disk-Sphere Transformation.- 1. In Vitro Red Cell Shape Changes.- 2. In Vivo Red Cell Shape Changes.- II. The Indirect Hemolysis; Lytic Effects of Lysolecithin and Fatty Acids.- III. Effects of Serum Proteins on Phospholipase-Induced Hemolysis.- F. Hemolysis by a Cobra Venom Factor Acting Through the Complement System.- G. Concluding Remarks.- References.- 14 Hemorrhagic, Necrotizing and Edema-Forming Effects of Snake Venoms.- A. Introduction.- B. The Use of Weil-Defined Lesions in Experimental Animals to Specify and Determine Local Effects of Snake Venom.- C. Necrotizing Effect.- D. Edema-Forming Effect.- E. Hemorrhagic Effect.- I. Methods for Determining Hemorrhagic Activity.- 1. Skin Reaction.- 2. Lung Surface Reaction.- II. Distribution of Hemorrhagic Activity in Venoms of Crotalidae, Viperidae, and Elapidae.- III. Purification and Characterization of Hemorrhagic Principles.- 1. Purification and Characterization of HR 1.- a) Purification.- b) Properties.- 2. Purification and Characterization of HR 2.- a) Purification.- b) Properties.- IV. Dynamic Aspects of the Action of Hemorrhagic Principles on Microcirculation as Revealed by Cinematography.- V. Action of Hemorrhagic Principles on Smooth Muscles.- 1. Actions of Hemorrhagic Principles (HR 1 and HR 2) on Isolated Smooth Muscle Preparations.- 2. Mediators Released from Guinea-Pig Lungs and from Rat Peritoneal Cells by the Action of Hemorrhagic Principles (HRlandHR2).- VI. Mechanisms of Action of Hemorrhagic Principles.- 1. Effect on Vascular Permeability.- 2. Effect on Vessel Wall.- a) Effect on Vascular Endothelium.- b) Effect on Basement Membrane.- 3. Effect on the Hemostatic Mechanism.- VII. Involvement of an Endogenous or Exogenous Hemorrhagic Principle in General Physiological Mechanism of Hemorrhage A Suggestion from Venom Studies.- VIII. Antihemorrhagic Factor Present in the Sera of Snakes.- 1. Purification and Characterization of an Antihemorrhagic Factor from the Serum of Trimeresurus flavoviridis.- a) Purification.- b) Characterization.- c) Effects on the Hemorrhagic Activity of HR 1 and HR 2 and on the Lethal Toxicity of HR 1.- d) Inhibition of Hemorrhagic Activity of Venoms from Different Species of Snakes.- 2. Mechanism Involved in the Neutralization by the Serum of Vipera palestinae of a Toxic Fraction of Its Venom.- IX. Treatment with Specific Antivenin (Antiserum) and Prophylaxis with Toxoid (Vaccine) of Hemorrhagic Snake Venom Poisoning.- 1. Neutralization of Hemorrhagic Principles by Specific Antivenin (Antiserum).- 2.