With contributions by numerous experts

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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. Cel…