Anti-Inflammatory Drugs

ISBN-13: 9783642668937 / Angielski / Miękka / 2012 / 952 str.

C.G. van Arman

Opis

With contributions by numerous experts

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Screening and Toxicity of Anti-Inflammatory Drugs.- 19 Screening and Assessment of the Potency of Anti-Inflammatory Drugs in vitro.- A. Introduction.- B. Interaction With Non-Enzymic Proteins.- I. Binding to Plasma Proteins.- 1. Displacement Reactions.- 2. Disulphide Interchange Reactions.- 3. Protection Against Protein Denaturation.- 4. Fibrinolytic Activity.- II. Interaction With Biological Membranes.- 1. Effects on Erythrocyte Membrane.- 2. Effects on Lysosomal Membrane.- 3. Cytotoxic Properties.- 4. Effects on Leucocyte Migration.- C. Interaction With Enzymic Proteins.- I. General Considerations.- II. Interaction With Enzymes Involved in Carbohydrate, Protein, and Nucleic Acid Metabolism.- 1. Carbohydrate, Protein, and Amino Acid Metabolism.- 2. Nucleic Acid and Nucleotide Metabolism.- III. Inhibition of Prostaglandin Synthetase.- 1. Prostaglandin Synthetase System.- 2. Assay of Prostaglandin Synthetase Activity.- 3. Prostaglandin Synthetase Inhibitors.- 4. Inhibition of Platelet Aggregation.- 5. Effects on Smooth Muscle.- D. Conclusions.- References.- 20 Inhibition of Erythema and Local Hyperthermia.- A. Introduction.- B. Ultraviolet (UV) Light and the Erythematous Response.- C. Instrumentation.- I. Light Sources for Induction of Erythema.- II. Measurement of Erythema and Local Hyperthermia.- 1. Erythema.- 2. Skin Temperature.- D. Procedures.- I. Erythema.- 1. UV-Induced.- 2. Thurfyl Nicotinate-Induced.- 3. Miscellaneous Procedures for Producing Erythema.- II. Local Hyperthermia.- 1. Local Hyperthermia in Paws of Rats Injected With Irritants.- 2. Local Hyperthermia in UV-Irradiated Skin.- E. Inhibition of Erythema and Local Hyperthermia.- I. UV-Induced Erythema.- 1. Systemic Administration of Drugs.- 2. Topically or Intradermally.- II. Tetrahydrofurfuryl Nicotinate (THFN) Erythema.- III. Other Erythemas.- IV. Local Hyperthermia.- F. Conclusion.- References.- 21 Oedema and Increased Vascular Permeability.- A. General Principles of Assays.- I. Statistical Considerations in Assay Work.- 1. Relationship of Dose to Effect.- 2. Definition of ED50.- 3. Confidence Limits.- 4. Coefficent of Variation.- 5. The g Value.- 6. The Lambda Value, ?.- 7. Errors of Types I and II.- B. Methods for Producing and Measuring Oedema and Increased Vascular Permeability.- I. Oedemas of the Rat’s Paw.- 1. Measurement.- 2. Agents Causing Paw Oedema; Characteristics of Oedemas Caused by Several Agents.- II. Increased Vascular Permeability.- III. Oedema in the Pleural Space.- C. Conclusion.- References.- 22 Short-Term Drug Control of Crystal-Induced Inflammation.- A. Historical Aspects.- B. Mechanism of Crystal-Induced Inflammation.- I. Phagocytosis.- II. Membranolysis.- III. Inflammatory Mediators.- IV. Chemotactic Factors.- C. Experimental Models.- I. Animal.- II. Man.- D. Therapy of Acute Attacks of Gout and Pseudogout.- I. Gout.- II. Pseudogout.- E. Summary.- References.- 23 Experimental Models of Arthritis in Animals as Screening Tests for Drugs to Treat Arthritis in Man.- A. Introduction.- B. Advantages and Disadvantages of Models of Arthritis—Comparison With Acute Models.- C. Adjuvant-Induced Arthritis.- I. First Observation. First Use as a Screen for Anti-Inflammatory/ Antirheumatic Drugs.- II. Production.- 1. Adjuvant.- 2. Route of Injection.- 3. Species Variation and Strain Variation.- 4. Time Course of the Disease.- III. Aetiology.- 1. Role of Lymphatic System.- 2. Immunological Mechanisms.- 3. Histology.- 4. Lysosomal Enzymes.- IV. Assessment.- 1. Physical Assessment—Gross Measurements.- 2. Physiological/Functional Parameters.- 3. Biochemical Parameters.- 4. Period of Dosing of Compounds.- V. Effect of Drugs.- 1. Non-Steroid Anti-Inflammatory Drugs.- 2. Steroid Anti-Inflammatory Drugs.- 3. Gold, Chloroquine, and Penicillamine.- 4. Immunosuppressant Drugs.- 5. Antilymphocytic Serum, Antigens.- 6. Non-Specific Inhibition.- 7. The Effect of Adjuvant Arthritis on Drugs.- D. Arthritis Produced by Intra-Articular Injection of Antigens and Antibodies.- E. Arthritis Produced by Intra-Articular Injection of Lysosome Labilisers.- F. Arthritis Induced by Infectious Agents.- E. Conclusions.- References.- 24 Antagonism of Bradykinin Bronchoconstriction by Anti-Inflammatory Drugs.- A. Introduction.- B. Production of Kinins and Other Mediators of Anaphylaxis in the Lungs.- I. In vitro.- II. In vivo.- III. Release of Catecholamines in vivo.- C. Action of Bradykinin on Lung Function.- I. Bronchial Smooth Muscle in vitro and in vivo.- II. Pulmonary Circulation.- D. Release of Prostaglandins and Precursors From Lungs by Bradykinin.- E. Actions of Prostaglandins in the Lungs.- I. Bronchial Smooth Muscle.- F. Interaction of Bradykinin With Prostaglandins in the Lungs.- I. As a Mediator.- II. As a Potentiator.- III. As a Mediator of Vascular Leakage.- G. Metabolism of Kinins in the Pulmonary Circulation.- H. Inhibition of Bronchoconstriction by Anti-Inflammatory Acids.- I. In vivo and in vitro Studies.- II. Comparison With Other Bronchoconstrictor Agents.- I. Possible Actions and Interactions of Kinins and Prostaglandins in Asthma.- J. Summary and Conclusions.- References.- 25 Interference of Anti-Inflammatory Drugs With Hypotension.- A. Interference of Non-Steroidal Anti-Inflammatory Drugs With Hypotensive Effects of Potential Inflammatory Mediators.- I. Kinin Peptides.- II. Prostaglandins.- B. Interference by Non-Steroidal Anti-Inflammatory Drugs With the Hypotensive Effects of Agents That Release Potential Inflammatory Mediators.- I. Proteolytic Enzymes.- 1. Kininogenases.- 2. Thrombin.- 3. Other Proteolytic Enzymes.- II. Inhibition of Hypotension Due to Substances That Activate Plasma Kininogenase.- 1. Carrageenin.- 2. Other Activators of Plasma Kininogenase.- III. Phospholipase A2.- C. Interference of Anti-Inflammatory Drugs With Hypotensive Responses to Lipid Derivatives.- I. Effects of Arachidonic Acid on Arterial Blood Pressure.- 1. Mechanism of Action of Arachidonic Acid on Blood Pressure.- II. Effects of Fatty Acids Other Than Prostaglandin Precursors.- III. Slow Reacting Substance C.- 1. Mechanism of Action of Slow Reacting Substance C.- D. Interference of Non-Steroidal Anti-Inflammatory Agents With Effects of Miscellaneous Agents.- I. Adenosine Nucleotides.- II. Collagen.- III. Anaphylatoxin.- IV. Depressor Active Substance (DAS).- V. Platelet Clumping Substance.- VI. Barium Sulphate and Other Particulate Materials.- E. Interference of Non-Steroidal Anti-Inflammatory Agents With Hypotension in Endotoxin Shock.- I. Dogs.- II. Cats.- III. Other Animal Species.- F. Mechanism of Action of Hypotensive Agents Liable to Inhibition by Non-Steroid Anti-Inflammatory Drugs.- I. Structure-Activity Correlations.- 1. Thiol and Anti-Oxidant Compounds.- II. Stereospecificity.- III. Mechanism of Action of Hypotensive Agents Subject to Inhibition by Non-Steroidal Anti-Inflammatory Drugs.- 1. Bradykinin.- 2. Collagen.- 3. Carrageenin.- 4. Adenosine Nucleotides.- IV. Conclusions.- 1. Relevance of Hypotensive Responses to Inflammation and to Study of Inflammatory Events.- 2. Multisequential Activation and Acute Hypotensive Responses: Prospects of Research.- References.- 26 Antagonism of Pain and Hyperalgesia.- A. Introduction.- I. Terminology.- II. Historical Introduction to Analgesic Testing in Hyperalgesic Animals.- B. Non-Hyperalgesic Mild Analgesic Assays.- I. Stretching Tests.- C. Assessment of Mild Analgesia in Humans.- I. Clinical Avaluation of Mild Analgesic Agents.- D. Conclusion.- References.- 27 Inhibition of Cell Migration in vivo and Granuloma Formation.- A. General Introduction.- I. Mechanisms of Cell Migration.- II. The Sequence of Cell Migration.- III. Fate of Emigrated Cells.- 1. Polymorphs.- 2. Mononuclear Cells.- IV. Granuloma Formation and Evolution.- B. Models for Leucocyte Emigration in vivo.- I. Generalities.- II. Histological Method.- III. Cell Collection From Cavities.- 1. Natural Cavities.- 2. Artificial Cavities.- IV. Cell Collection From Early Granulomata.- V. Cell Labelling.- C. Models for Granuloma Formation in vivo.- I. Cotton-Pellet Granuloma.- II. Granuloma Pouch.- III. Carrageenin Granuloma.- IV. Plastic Ring Granuloma.- V. Filter Paper Granuloma.- D. Inhibition of Cell Migration in vivo.- I. Steroids.- 1. Neutrophils.- 2. Mononuclear Cells.- II. Non-Steroid Anti-Inflammatory Drugs.- III. Immunosuppressive Agents.- IV. Endogenous Substances.- E. Inhibition of Granuloma Formation.- I. Steroid Anti-Inflammatory Drugs.- II. Non-Steroid Anti-Inflammatory Drugs.- III. Immunosuppressive Agents.- IV. Endogenous Substances.- F. Conclusions.- References.- 28 Inhibition of Fever.- A. Introduction.- B. Pathogenesis of Fever.- I. Exogenous and Endogenous Pyrogen.- II. Site of Action of Pyrogens.- III. Mechanism of Action of Pyrogens.- 1. Change in Set-Point or Gain?.- 2. Role of Prostaglandins.- 3. Role of Monoamines and Cyclic-AMP.- 4. Ionic Mechanisms in Fever.- C. Antipyretics.- I. Possible Sites of Action of Antipyretics.- 1. Inactivation of Bacterial Pyrogen (Site I).- 2. Inhibition of Endogenous Pyrogen Production or Release (Site II).- 3. Inhibition of Endogenous Pyrogen Activity (Site III).- 4. Access of Endogenous Pyrogen to the Central Nervous System (Site IV).- 5. Hypothalamic Thermoregulatory Centres (Site V).- 6. Suppression of Heat Production (Site VI).- II. Possible Mechanisms of Antipyretic Action.- 1. Inhibition of Prostaglandin Synthesis/Release.- 2. Competitive Antagonism Between Pyrogens and Antipyretics for a Receptor Site.- 3. Alteration in the Activity of Neurones in the Hypothalamus.- III. Antipyresis.- D. Inhibition of Fever by Other Means.- I. Increased Heat Loss.- II. Monoamine Blockade and Depletion.- III. Cholinergic Blockade.- E. Conclusion.- References.- 29 Evaluation of the Toxicity of Anti-Inflammatory Drugs.- A. Introduction.- I. Historical Overview.- B. Evaluation of Toxicity in Man.- I. Gastrointestinal Tract.- II. Central Nervous System.- III. Dermatological Disorders.- IV. Haematopoietic System.- V. Ocular Disturbances.- VI. Renal Side Effects.- VII. Miscellaneous Side Effects.- C. Methods Used to Evaluate Toxicity in Animals.- I. Gastrointestinal.- II. Kidney.- III. Haematopoietic System.- IV. Liver.- V. Skin.- VI. Eye.- VII. Central Nervous System.- D. Correlation of Experimental Models With Clinical Toxicity.- I. Non-Steroid Anti-Inflammatory Drugs.- 1. Salicylates.- 2. Indomethacin.- 3. Phenylbutazone.- 4. Arylalkanoic Acids.- 5. Gold.- II. Steroids.- E. Summary.- References.- Pharmacology of the Anti-Inflammatory Agents.- 30 Prostaglandin Synthetase Inhibitors I.- A. Introduction.- B. Inhibiton of Synthetase by Substrate Analogues and Fatty Acid Derivatives.- I. Unsaturated Fatty Acids.- II. Bicyclic Analogues.- C. Regulation of Enzymic Factors: Co-Factors, Stimulation, and Catabolism.- I. Regulation of Biosynthesis.- II. Catabolic Enzymes.- D. Inhibition by Non-Steroid Anti-Inflammatory Agents.- I. An Overview of Structure-Activity Relationship.- 1. Correlation of PG Syntheatase Inhibition With Anti-Inflammatory Action.- 2. General Structure-Activity Relationship.- II. Salicylates.- III. Indomethacin, Sulindac, and Congeners.- IV. Substituted Aryl Aliphatic Acids.- V. Fenamates.- VI. Other Acidic Anti-Inflammatory Agents.- VII. Non-Acidic Anti-Inflammatory Agents.- E. Effects of Corticosteroids.- F. Inhibition and Stimulation by Other Pharmacological Agents.- I. Anti-Arthritic and Related Compounds.- II. Psychotropic Drugs.- III. Sulphydryl Reagents and Derivatives.- IV. Hormones and Mediators.- V. Inactive Pharmacological Agents.- G. The Search for New Inhibitors.- I. Current Research Trend.- II. Biochemical and Physiological Specificity.- III. Pharmacodynamic and Metabolic Control.- IV. Multiple-Action Inhibitors.- V. Synthetic and Physicochemical Approaches.- H. Pharmacokinetics of Prostaglandin Synthetase Inhibitors.- I. Conclusion.- References.- 31 Mode of Action of Anti-Inflammatory Agents Which are Prostaglandin Synthetase Inhibitors.- A. Mediators and Inflammatory Responses.- B. Mechanism of Anti-Inflammatory Action.- I. Action on Step 1: Diminution of the Capability of Tissue Cells to Respond to Inflammatory Mediators.- 1. Increased Dilatation and Vascular Permeability.- 2. Pain and Hyperalgesia.- 3. Increased Fibroblast Proliferation and Secretion.- II. Action on Step 2: Pharmacological Receptor Antagonism.- III. Action on Step 3: Inhibition of Extracellular Enzymic Activities Which Generate Inflammatory Mediators or Cause Injury to Cell Membranes and/or Tissue Components.- IV. Action on Step 4: Inhibition of the Release of Intracellular Lytic Enzymes or Mediator-Genases or Stored Receptor-Mediators.- V. Action on Step 5: Inhibition of the Synthesis of Inflammatory Mediators.- 1. Prostaglandin Synthesis and Release.- 2. Prostaglandins and Inflammatory Signs and Symptoms.- 3. Correlation Between in vitro Inhibition of Prostaglandin Synthesis and Anti-Inflammatory Activity.- 4. Inhibition of Prostaglandin Synthesis in vivo and Inflammatory Signs and Symptoms.- VI. Action on Step 6: Inhibition of Cell Migration.- VII. Action on Step 7: Inhibition of the Generation of the Effective Inflammatory Trauma.- C. Side-Effects of Anti-Inflammatory Drugs Which are Prostaglandin Synthetase Inhibitors.- D. Theories and Theories.- References.- 32 Penicillamine and Drugs With a Specific Action in Rheumatoid Arthritis.- A. Classification of Antirheumatic Drugs.- B. Penicillamine.- I. Actions in Man.- II. Possible Mode of Action and Effects in Animal Models.- C. Gold Salts.- D. Chloroquine and Other Antimalarials.- E. Levamisole.- F. Other Imidazole Derivatives.- G. Immunosuppressives.- H. Alclofenac.- I. Steroids.- J. Summary.- References.- 33 Antagonists of Histamine, 5-Hydroxytryptamine and SRS—A.- A. Classification of Antihistamines.- B. Histamine H1 Antagonists: Structure-Activity Relationships.- C. Histamine H1 Antagonists: Inhibition of Responses to Histamine Involved in Inflammatory and Anaphylactic Reactions.- I. Guinea Pig.- II. Rat.- III. Rabbit.- IV. Mouse.- V. Man.- D. Histamine H2 Antagonists: Chemical Considerations.- E. Inhibition of Cardiovascular Responses to Histamine by H1 and H2 Antagonists.- F. Chemical and Pharmacological Classes of 5-Hydroxytryptamine Antagonists.- I. Chemical Classes.- II. “M” and “D” Receptors.- III. 201C;Musculotropic” and “Neurotropic” Receptors.- G. Antagonists of 5-Hydroxytryptamine: Inhibition of Responses to 5-HT Involved in Inflammatory and Anaphylactic Reactions.- I. Guinea Pig.- II. Rat.- III. Rabbit.- IV. Mouse.- V. Man.- H. Effects of Antagonists of Histamine (H1 Receptors) and 5-HT in Various Types of Inflammation.- I. Guinea Pig.- 1. Thermal and Ultraviolet Injury.- 2. Local Anaphylaxis.- 3. Systemic Anaphylaxis.- 4. Compound 48/80 and Polymyxin B.- 5. Bradykinin.- II Rat.- 1. Thermal and Ultraviolet Injury.- 2. Local Anaphylaxis.- 3. Systemic Anaphylaxis.- 4. Compound 48/80, Polymyxin, Dextran, and Egg White.- 5. Turpentine Pleurisy.- 6. Carrageenin Oedema.- 7. Croton Oil.- 8. Bradykinin.- III. Rabbit.- 1. Thermal Injury.- 2. Anaphylactic Reactions.- 3. Inflammation Associated With Bacterial Infections.- IV. Mouse.- 1. General Anaphylaxis.- 2. Cutaneous Anaphylaxis.- 3. Other Local Inflammatory Reactions.- 4. Systemic Reactions Involving Inflammation.- V. Man.- 1. Burns.- 2. Compound 48/80 and Polymyxin.- 3. Hypersensitivity States.- 4. Rheumatoid Arthritis and 5-HT Antagonists.- VI. Bovine Anaphylaxis.- I. Antagonists of SRS-A.- I. Non-Steroid Anti-Inflammatory Drugs.- II. Polyphloretin Phosphate (PPP).- III. FPL 55712.- IV. Hydratropic Acids.- J. Prospects for New Drugs.- References.- 34 Inhibitors of the Release of Anaphylatic Mediators.- A. Characteristics of Anti-Allergic Agents Discussed.- B. Cromoglycate and Similar Compounds.- I. Identification and Screening.- 1. The Passive Cutaneous Anaphylaxis Reaction (PCA) in Rats.- 2. Lung Anaphylaxis in vivo.- 3. Passive Peritoneal Anaphylaxis.- 4. Human Tissues in vitro.- 5. Rat Tissues in vitro.- II. Structure-Activity Relationships.- III. Anti-Allergic Properties.- 1. Tissue and Species Selectivity.- 2. Inhibition of Mast Cell Reactions Provoked by Stimuli Other Than Antigen-Antibody Interactions.- 3. Time Course Studies.- 4. Tachyphylaxis.- IV. Studies of the Mechanism of Anti-Allergic Action.- V. Other Pharmacological Effects.- VI. Pharmacokinetics.- C. Other Inhibitors of Mediator Release.- I. Isosteres of Theophylline.- 1. Structure-Activity Relationships.- 2. Anti-Allergic Properties.- II. Antihistamines and Histamine.- III. Diethylcarbamazine.- 1. Rat Peritoneal Cells in vivo.- 2. Lung Tissue.- 3. Human Leucocytes.- 4. Passive Cutaneous Anaphylaxis Reactions.- IV. Chlorphenesin.- D. Prospects for New Drugs.- References.- 35 Cytostats With Effects in Chronic Inflammation.- A. Introduction.- B. General Pharmacology of Cytostats Effective in Chronic Inflammation.- I. “Immunosuppressants”.- 1. Alkylating Agents.- 2. Anti-Metabolites.- II. Microtubular Inhibitors.- 1. Colchicine.- C. Some Properties of Selected Compounds.- I. Microtubular Inhibitors.- 1. Cytostatic Effects of Colchicine.- II. Cyclophosphamide.- 1. Metabolism.- 2. Properties of Some Metabolites.- 3. Site of Action.- 4. Some Side-Effects.- III. Chlorambucil.- 1. Metabolism.- 2. Anti-Inflammatory Effects.- 3. Mode of Action.- IV. Methotrexate.- V. Azathioprine.- D. Current Problems.- Appendix. Synovectomy and Destruction of Pannus.- References.- Addendum.- 36 Control of Hyperuricemia.- A. Introduction.- B. Uric Acid Metabolism.- C. Biochemical Pharmacology of Hypouricemic Drugs.- I. Drugs Reducing Uric Acid Synthesis.- 1. Allopurinol and Oxipurinol.- 2. Thiopurinol.- 3. Other Inhibitors of Uric Acid Synthesis.- II. Uricosuric Agents.- III. Uricolytic Agents.- D. Clinical Use of Hypouricemic Drugs.- I. Criteria for Selecting a Hypouricemic Drug.- II. Use of Individual Hypouricemic Drugs.- III. Toxicity of Hypouricemic Agents.- References.- 37 Anti-Inflammatory Steroids: Mode of Action in Rheumatoid Arthritis and Homograft Reaction.- A. General Considerations.- B. Scope of the Review.- C. Naturally Occurring Anti-Inflammatory Steroids.- D. Synthetic Anti-Inflammatory Steroids.- E. Biological Activities Observed With Physiological Amounts of Cortisol-Like Steroids.- I. Metabolic Effects.- 1. Gluconeogenesis.- 2. Protein Metabolism.- 3. DNA Synthesis.- 4. Molecular Basis for Metabolic Effects.- 5. Onset and Duration of Cortisol Action.- 6. Mechanism of Action of Cortisol.- 7. Glycogenosis.- 8. Lipolysis.- 9. Relationship to Anti-Inflammatory, Anti-Allergic and Anti-Rheumatic Action.- 10. Relationship to Clinically Undesirable Effects.- 11. Implications for the Future.- II. Sodium Retaining Activity.- III. Control of Adrenocorticotrophic Hormone (ACTH) Synthesis and Secretion.- 1. Neuroendocrine Control.- 2. Negative Feedback Control.- 3. Basis for Negative Feedback Control.- 4. Role of Cytoplasmic Steroid Receptors.- 5. Relationship to Clinically Desirable Effects.- 6. Relationship to Clinically Undesirable Effects.- IV. Cardiovascular Effects.- 1. Heart and Peripheral Blood Vessels in Adrenalectomised State.- 2. Microcirculation.- 3. Relationship to Anti-Inflammatory, Anti-Allergic, and Anti-Rheumatic Action.- 4. Relationship to Clinically Undesirable Effects.- 5. Pharmacological Implications.- F. Mode of Action in Homograft Reaction.- I. Interference With the Development of Circulating Sensitized Lymphocytes.- II. Effectiveness Against Inflammation Due to Locally Sensitized Lymphocytes.- III. Effectiveness Against Inflammation Due to Circulating Sensitized Lymphocytes.- IV. Clinical Relevance of Experimental Observations.- V. Relevance to Evaluation of More Effective Anti-Rejection and Anti-Rheumatic Drugs.- G. Concluding Remarks.- References.- 38 Anti-Inflammatory Agents of Animal Origin.- A. Introduction.- B. Definition and Evaluation of Anti-Inflammatory Activity.- C. Mechanisms of Action.- D. Individual Agents.- I. Alkoxyglycerols.- II. N(2-hydroxyethyl)Palmitamide.- III. Vitamins.- IV. Amino Acids.- V. Peptides.- 1. Peptide 401.- 2. Rabbit Skin Protease Inhibitor.- 3. Aprotinin (Trasylol).- VI. Proteins.- 1. Exogenous Enzymes.- 2. Orgotein.- 3. Inflamed Tissue Factors.- 4. Antileucotactic Agents.- 5. Antiproliferative Agents.- 6. Antilymphocytic Serum.- VII. Tissue Hydrolysates.- 1. Catrix.- 2. Livingston Lysate.- 3. Lysoartrosi.- VIII. Human Plasma Factor.- IX. Prostaglandins.- E. Summary and Conclusions.- References.- 39 Anti-Inflammatory Substances of Plant Origin.- A. Introduction.- B. Anti-Inflammatory Action of Phenylbenzo-?-Pyrone (Flavone) Derivatives.- I. The Occurrence of Flavonoid Compounds in Nature.- II. The Chemistry of Flavonoid Compounds.- III. The Anti-Inflammatory Action of Flavonoids.- 1. Influence on Mouse and Rat Paw Oedema.- 2. Generalized Dextran Oedema in Rats.- 3. Generalized Phospholipase Oedema in Rats.- 4. Effect on the Development of the Granuloma Pouch.- 5. Inflammation Caused by Cotton Pellet.- 6. Erythema Produced by UV Radiation.- 7. Inflammation Produced by Mustard Oil.- 8. Influence on the Permeability-Increasing Action of Inflammatory Exudate.- 9. Influence on the Inflammation Produced by Red Paprika (Capsicum annuum L. Solanaceae).- 10. Effect of Citrus Flavonoid Complex on Experimentally Induced Mucous Membrane Inflammation.- 11. Influence on Experimentally Induced Thrombophlebitis.- 12. Allergic and Hyperimmune Inflammation ofthe Skin and Joints.- 13. Data on the Mechanism of the Anti-Inflammatory Effect of Flavonoids.- 14. Discussion.- C. Anti-Inflammatory Activity of Natural Plant Coumarins (Benzo-?-Pyrones).- D. Anti-Inflammatory Activity of Natural Plant Triterpenoids.- I. Escin.- II. Gycyrrhetinic Acid.- III. Other Triterpenoids.- E. Colchicine.- F. Essential Components of Camomile.- I. The Azulenes.- II. (-)-?-Bisabolol.- III. EN—IN—Dicycloether.- IV. Flavonoids.- G. Miscellaneous.- References.- 40 A Critical Comparison of the Evaluation of Anti-Inflammatory Therapy in Animal Models and Man.- A. Introduction.- B. Comparison of Models of Inflammation With the Human Situation.- C. Analysis of Parameters of Inflammation in Man.- I. Stiffness.- II. Pain.- III. Joint Tenderness.- IV. Grip Strength.- V. Joint Size.- VI. Blood Flow and Vascular Permeability.- VII. Radiographic Changes.- VIII. Tests of Functional Ability.- IX. Laboratory Assessment of Disease Activity.- D. Clinical Trials.- I. Objectives.- 1. Improvement of Therapeutic Methods at Present Available.- 2. Optimum Benefit in a Patient.- 3. Improvement of Methods of Monitoring Inflammation in Patients.- 4. Development of New Human Models for the Evaluation of Drugs.- 5. Discovery of New Therapeutic Agents.- 6. Promotion of Scientific Management of Disease.- II. Assessment.- III. Patient Selection.- IV. Placebo Response.- V. Conclusions.- E. Treatment.- I. Rest.- II. Heat.- III. Exercise.- IV. Anti-Inflammatory Therapy.- 1. Non-Steroid Anti-Inflammatory Drugs.- 2. Gold, Penicillamine, and Chloroquine.- 3. Corticosteroids.- 4. Cytotoxic (Immunosuppressant) Therapy.- 5. Local Anti-Inflammatory Therapy.- 6. Lymphocyte Depletion.- 7. Immune Potentiation.- 8. Removal of Antibody.- 9. X-Ray Irradiation.- F. Summary.- References.- Author Index.