Pharmacology of the Skin I: Pharmacology of Skin Systems Autocoids in Normal and Inflamed Skin (Handbook of Experimental Pharmacology, 87 / 1)

ISBN 10: 3642737994 / ISBN 13: 9783642737992

Editore: Springer, 2012

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• Titolo: Pharmacology of the Skin I: Pharmacology of Skin Systems Autocoids in Normal and Inflamed Skin (Handbook of Experimental Pharmacology, 87 / 1)
• Editore: Springer
• Data di pubblicazione: 2012
• Lingua: Inglese
• ISBN 10: 3642737994
• ISBN 13: 9783642737992
• Rilegatura: Paperback
• Condizione: Like New
• Tipo di libro: book

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Riassunto

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin, where they may be more relevant to human physiology and diseases, as in animal models. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of etiology and mechanism. For example, whilst the argument continued unresolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis-retinoic acid was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on etiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as an important step in the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Contenuti

Section A: Pharmacology of Skin Systems.- 1 The Epidermis.- A. The Structure of Epidermis.- I. The External Surface of Skin.- II. Histology of Epidermis.- 1. Introduction.- 2. The Basement Membrane.- 3. Fine Structure of Epidermal Cells.- 4. Lamellar Granules.- 5. Intercellular Junctions.- 6. Regional Differences in Epidermal Structure.- B. Epidermal Replacement.- I. Epidermal Renewal Rates.- II. Effects of External Influences.- III. Migration Out of the Basal Layer.- IV. The Formation of Epidermal Cell Columns.- V. The “Zipper Mechanism” Leading to Column Formation.- C. The Langerhans Cell.- I. Morphological Features.- II. Origin.- III. Functional Properties.- IV. Role in Disease.- D. Conclusion.- References.- 2 Keratin.- A. Introduction.- B. Fibrous Proteins.- C. Keratohyalin.- D. Cornifled Envelope.- E. Desmosomes.- F. Membrane Coating Granules.- References.- 3 Regulation of Epidermal Growth.- A. Cyclic Nucleotides.- I. Effects of Cyclic AMP on Different Epidermal Cells.- II. Cyclic GMP.- III. Receptors.- B. Prostaglandins.- C. Epidermal Growth Factor.- I. Chemical Composition and Properties.- II. Human EGF.- III. Level of EGF.- IV. EGF Receptor.- V. EGF in Cell Proliferation and Differentiation.- D. Chalones of the Skin.- E. Calcium and Calmodulin.- F. Histamine.- G. Conclusion.- References.- 4 Epidermal Lipogenesis (Essential Fatty Acids and Lipid Inhibitors).- A. Introduction and Historical Considerations.- B. Essential Fatty Acids.- I. Biosynthesis and Metabolism.- II. Physiological Functions in the Skin.- III. Role as Precursors of Prostaglandins and Related Lipids.- C. Essential Fatty Acid Deficiency.- I. Macroscopic and Microscopic Appearance of the Skin During Deficiency.- II. Altered Patterns of Polyunsaturated Fatty Acids.- III. Increased Metabolic Activity During Deficiency.- IV. Deficiency in Human Skin.- D. Epidermal Lipogenesis and Its Regulation.- I. Interrelationships of Metabolic Pathways.- II. Regulation of Epidermal Lipogenesis.- References.- 5 Fibroblasts, Collagen, Elastin, Proteoglycans and Glycoproteins.- A. Introduction.- B. Fibroblasts Are Differentiated Cells.- C. Collagen.- I. Molecular Structure and Distribution.- II. Biosynthesis.- III. Polymerisation.- IV. Degradation.- D. Elastin.- I. The Elastic Fibre.- II. Biosynthesis, Polymerisation and Degradation.- E. Proteoglycans and Glycosaminoglycans.- I. Molecular Structure.- II. Biosynthesis, Organisation and Degradation.- F. Structural Glycoproteins.- I. Fibronectin, Laminin, Entactin and Others.- II. Biosynthesis.- G. Regulation and Diseases.- I. Fibroblasts.- II. Collagen.- III. Elastin.- IV. Proteoglycans.- V. Structural Glycoproteins.- H. Interaction Between the Macromolecules of the Connective Tissue.- J. Conclusions.- References.- 6 Dermal Blood Vessels and Lymphatics.- A. Dermal Blood Circulation.- I. Functions of Dermal Vascular Bed.- II. Anatomy of Dermal Blood Vessels.- 1. Distributing Arteries.- 2. Arterioles and Metarterioles.- 3. Capillary Bed.- 4. Arteriovenous Anastomoses (Shunts).- 5. Venules.- III. Physiology of Dermal Blood Flow.- 1. Role of Cutaneous Circulation in Body Temperature Regulation.- IV. Neural Regulation of Dermal Blood Flow.- 1. Sympathetic Trunks and Postganglionic Pathways.- 2. Adrenergic Sympathetic Control of Dermal Vessels.- 3. Adrenergic Neuroeffector End Organs.- 4. Cutaneous Vasodilator Sympathetic Nerves.- V. Other Mechanisms for Regulation of Dermal Blood Flow.- 1. Hormonal Control.- 2. Local Control.- VI. Therapeutic Modulation of Dermal Blood Flow by Drugs.- 1. Vasodilator Agents.- 2. Vasoconstrictor Agents.- B. Dermal Lymphatic Circulation.- I. Anatomical Considerations.- 1. Dermal Lymph Capillaries (Initial Lymphatics).- 2. Dermal Collecting Lymph Channels and Trunks.- 3. Dermal Lymphatic System in the Limbs.- II. Physiological Considerations.- 1. Methods for Study of Lymph Flow.- 2. Mechanisms Involved in Passage of Fluids and Particulate Matter into Lymphatic Capillaries.- 3. Factors Involved in Transport of Lymph.- 4. Alterations in Concentration of Lymph in Its Passage Through the Lymphatics.- 5. Response of Lymphatics to Inflammation.- III. Pharmacological Considerations.- References.- 7 Blood Flow ― Including Microcirculation.- A. Visual Assessment.- B. Thermal Measurements.- I. Thermometry and Thermography.- II. Thermal Clearance (Conductance).- C. Radioisotopic Techniques.- I. Isotope Extraction.- II. Clearance of Locally Injected Radiolabels.- D. Red Blood Cell Velocity Measurements.- E. Doppler Shift Techniques.- I. Ultrasound Doppler.- II. Laser Doppler.- F. Plethysmography.- G. Electromagnetic Flowmeters.- H. Conclusion.- References.- 8 Immunopharmacology of Mast Cells.- A. Mast Cell Content of Human Skin.- B. Mast Cell Structure.- C. The Ontogeny of Mast Cells.- D. Preformed Granule-Associated Mediators.- I. Biogenic Amines.- 1. Histamine.- 2. 5-Hydroxytryptamine.- II. Neutral Proteases.- III. Acid Hydrolases.- IV. Other Mast Cell Enzymes.- V. Chemotactic Factors.- VI. Proteoglycans.- E. Newly Generated Inflammatory Mediators.- I. Cyclo-oxygenase Products of Arachidonic Acid.- II. The Lipoxygenase Pathway.- III. Platelet Activating Factor.- F. Mechanisms of Mast Cell Activation.- I. Mechanisms of IgE-Dependent Mediator Secretion from Mast Cells.- II. Human Mast Cell Activation by IgE-Dependent and IgE-Independent Stimuli.- G. Pharmacological Modulation of Mediator Secretion from Skin Mast Cells.- H. Conclusions.- References.- 9 Lymphocytes.- A. Introduction.- B. Lymphokines.- C. Lymphokines as Mediators of Cellular Immunity.- D. Regulation of Lymphocyte Activation.- I. Role of Arachidonic Acid.- II. Role of Interleukins.- E. Conclusion.- References.- 10 Structure, Function and Control: Afferent Nerve Endings in the Skin.- A. Introduction.- B. Fibre Composition of Cutaneous Nerves.- C. Mechanoreceptors.- I. Introduction.- II. Rapidly Adapting Mechanoreceptors.- 1. Pacinian Corpuscles.- 2. RA and Field Receptors.- 3. Hair Follicle Receptors.- III. Slowly Adapting Mechanoreceptors.- 1. Type SA I.- 2. Type SA II.- 3. Slowly Adapting Hair Follicle Units.- 4. C-Mechanoreceptors.- IV. Summary.- D. Thermoreceptors.- I. Cold Units.- II. Warm Units.- E. Nociceptors.- I. High Threshold Mechanoreceptor Units.- II. Polymodal Nociceptor Units.- F. Overview: Types of Cutaneous Mechanoreceptor, Thermoreceptor and Nociceptor.- G. Modulation of Sensitivity of Cutaneous Receptors by Drugs.- I. Introduction.- II. Catecholamines.- 1. Mechanoreceptors.- 2. Thermoreceptors.- 3. Nociceptors.- 4. Nerve Endings in Neuromas.- III. Inflammatory Mediators.- 1. Histamine.- 2. Serotonin.- 3. Bradykinin.- 4. Prostaglandins.- 5. Mediators and Sensitisation.- IV. Other Agents that Excite Cutaneous Receptors.- 1. Capsaicin.- 2. Substance P.- 3. Acetylcholine.- 4. Other Irritants.- V. Other Agents that Modulate the Responses of Cutaneous Nerve Endings.- VI. Overview: Drugs and Cutaneous Receptors.- References.- 11 Sweat Glands: Eccrine and Apocrine.- A. Anatomical Features.- B. Fine Structure.- I. Eccrine Glands.- II. Apocrine Glands.- C. Innervation.- I. Eccrine Glands.- II. Apocrine Glands.- D. Secretory Function of Eccrine Glands.- I. The Secretory Process and Sweat Formation.- E. Apocrine Gland Function.- F. Pharmacology of Sweating.- I. Eccrine Glands.- II. Neurohumoral Aspects.- 1. Denervation.- 2. Axon Reflex Sweating.- 3. Hyperhidrosis.- III. Apocrine Glands.- References.- 12 Thermoregulation and the Skin.- A. Skin Blood Flow.- I. Vascular Effects on Heat Exchange.- II. Nervous Control of Cutaneous Blood Flow.- III. Reflex Control of Skin Blood Flow.- IV. Central Control of Skin Blood Flow.- V. Interactions Between Thermal Receptors.- VI. Effects of Local Temperature.- B. Sweating.- I. Neural, Humoral and Local Control.- II. Acclimation and Fatigue of Sweat Glands.- References.- 13 Hair and Nail.- A. Hair Follicle and Hair Shaft.- I. Follicle Structure.- II. Hair Shaft Structure.- III. Hair Cycle.- IV. Endocrine Control Factors.- B. Nail Apparatus.- References.- 14 The Sebaceous Glands.- A. Introduction.- B. Development.- C. Sebum.- I. Formation.- II. Composition.- III. Function.- IV. Factors Affecting the Rate of Sebum Production.- D. Control.- I. Non-endocrine Control.- II. Endocrine Control.- 1. Androgens.- 2. Oestrogens.- 3. Progesterone.- 4. Glucocorticoids.- 5. Thyroid Hormones.- 6. Insulin.- 7. The Pituitary.- 8. The Early Endocrine Environment.- References.- 15 Metabolism of Sex Steroids.- A. Introduction.- B. Hydroxysteroid Dehydrogenase Activities.- I. Androgens.- 1. Dehydroepiandrosterone.- 2. ?4-Androstene-3,17-dione.- II. Oestrogens.- III. Progesterone.- C. 5?-Reduction of Testosterone and Progesterone.- I. Testosterone.- II. Progesterone.- D. 3?- and 3?-Hydroxysteroid Dehydrogenases.- I. Androgens.- II. Progesterone.- E. Normal Control of Androgen Metabolism in Human Skin.- F. Abnormal Control of Androgen Metabolism in Human Skin.- G. Conclusion.- References.- 16 Melanophores, Melanocytes and Melanin: Endocrinology and Pharmacology.- A. Pigment Cells.- B. Dermal Melanophores.- C. Epidermal Melanophores.- D. Melanosome Dispersion.- E. Melanogenesis.- F. Melanocyte Stimulating Hormone.- I. Physiological Significance of MSH Peptides as a Pigmentary Hormone in Man.- G. Catecholamines.- H. Melatonin.- J. Steroids.- K. Prostaglandins.- References.- 17 Cytokines in Relation to Inflammatory Skin Disease.- A. Introduction.- B. Interleukins: Structure and Physicochemical Properties.- C. Biological Activities of Interleukins.- D. Interleukins and Normal Skin.- E. Dermatological Disorders and IL-1.- F. Dermatological Disorders and IL-2.- G. Dermatological Disorders, Interleukins, and Leukocyte-Endothelial Interactions.- H. Comment.- References.- Section B: Autocoids in Normal and Inflamed Skin.- 18 Histamine, Histamine Antagonists and Cromones.- A. Introduction.- B. Histamine Content of Skin.- C. Histamine-Forming Capacity in Skin.- D. Histamine Catabolism in Skin.- E. The Release of Histamine from Skin.- F. Application of Histamine to the Skin and the Pharmacological Modification of Its Effects.- I. Vascular Effects.- II. Sensory Effects.- III. Other Effects.- IV. Anti-allergic Drugs.- G. Clinical Conditions Associated with Histamine in Skin.- H. Concluding Remarks.- References.- 19 Kallikreins and Kinins.- A. Introduction.- B. Chemistry and Biological Activities of Kinins.- I. Principal Types of Kinins.- II. Mechanisms of Biological Actions.- III. Actions on Blood Vessels.- IV. Pain-Producing Effects.- V. Other Actions of Kinins.- C. Kinin Formation in Mammals.- I. Specific and Non-specific Kinin-Forming Enzymes.- II. Kinin Formation by Plasma Kallikreins and Other Plasma Enzymes.- III. Kinin Formation by Blood Cells.- IV. Glandular Kallikreins.- V. Kinin Formation in Human Skin.- D. Inhibitors of Kinin Formation.- E. Fate in the Body of Formed Plasma Kinins.- F. Kinins in Experimental and Clinical Damage of Human Skin.- I. Assessment of the Role of Kinins.- II. Inflammation and Related Conditions.- G. Concluding Remarks.- References.- 20 Acetylcholine, Atropine and Related Cholinergics and Anticholinergics.- A. Cholinergic Agents.- I. Acetylcholine.- 1. Distribution.- 2. Biosynthesis and Storage.- 3. Physiological Inactivation.- 4. Acetylcholine in Skin.- 5. Pharmacological Actions.- 6. Functional Significance in Skin.- II. Anticholinesterase Agents.- 1. Pharmacological Actions.- III. Other Cholinomimetic Agents.- 1. Stable Esters of Choline.- 2. Pilocarpine.- B. Anticholinergic Drugs.- I. Chemistry.- 1. Belladonna Alkaloids and Their Derivatives.- 2. Synthetic Anticholinergic Agents.- II. Mechanism of Action.- III. Pharmacological Actions.- 1. Cardiovascular System.- 2. Gastrointestinal Tract.- 3. Respiratory Tract.- 4. Eye.- 5. Urinary Tract.- 6. Secretory Glands.- 7. Central Nervous System.- 8. Skin.- IV. Adverse Effects.- V. Other Classes of Drug Possessing Pronounced Anticholinergic Activity.- 1. Histamine H1-Receptor Antagonists.- 2. Tricyclic Antidepressants.- 3. Haloalkylamine ?-Adrenoceptor Blocking Agents.- References.- 21 Prostaglandins, Leukotrienes, Related Compounds and Their Inhibitors.- A. Discovery of the Prostaglandins.- B. Biosynthesis of Prostaglandins.- C. Action of Prostaglandins in Skin.- I. Vasodilatation.- II. Oedema Formation.- III. Leukocyte Accumulation.- IV. Pain.- D. Generation of Prostaglandins in Skin.- E. Discovery of the Lipoxygenase Pathway.- F. The Leukotrienes.- G. Action of Lipoxygenase Products in Skin.- I. Vasoactive Effects.- II. Leukocyte Accumulation.- III. Oedema Formation.- H. Generation of Lipoxygenase Products in Skin.- J. Inhibitors of Arachidonate Metabolism.- K. Conclusion.- References.- 22 Slow Reacting Substance of Anaphylaxis.- A. Introduction.- B. Physico-chemical Characterisation.- C. Functional Characterisation.- D. Inactivation of SRS-A.- E. Summary.- References.- 23 Complement.- A. Introduction.- B. The Classical Pathway.- C. The Alternative Pathway.- D. Terminal Events in the Complement Cascade.- E. Biological Activities Resulting from Complement Activation.- I. Diffusible Products.- II. Retained Complement Products.- III. Membrane Lysis.- IV. Solubilisation of Immune Complexes.- F. Regulation of Complement Activation.- I. CT Inhibitor.- II. C4 Binding Protein.- III. Factors H and I.- G. Inherited Deficiencies of Complement Components.- I. Bacterial Infections.- II. Auto-immune or Immune Complex Diseases.- H. Complement in Skin Disease.- I. Immune Complex Disease.- II. Bullous Skin Diseases.- References.- 24 Neutrophil and Eosinophil Chemotaxis and Cutaneous Inflammatory Reactions.- A. Introduction.- B. Methods of Measuring Chemotaxis and Cell Accumulation.- C. Chemotactic Factors for Neutrophils and Eosinophils.- I. Complement-Derived Factors.- II. Cell-Derived Factors.- III. Lymphokines.- IV. Coagulation Products.- V. Micro-organisms.- D. Other Properties of Chemotactic Factors.- E. Control of Neutrophil and Eosinophil Locomotion.- F. Defects in Chemotaxis.- I. Impaired Generation of Chemoattractants.- II. Inhibition of Chemotaxis.- III. Intrinsic Disorders of Granulocyte Locomotion.- G. Skin Diseases Associated with Neutrophil Infiltration.- H. Skin Disease Associated with Eosinophil Infiltration.- J. Conclusions.- References.- 25 Neuropeptides and the Skin.- A. Introduction.- B. Biochemistry of Peptide-Mediated Signalling.- C. Distribution and Functions of Peptides in Mammalian Skin.- I. Tachykinins and CGRP.- II. Vasoactive Intestinal Peptide.- III. Other Neuropeptides.- IV. Neuropeptides as Growth Factors?.- D. Conclusions and Clinical Implications.- References.- 26 Polyamines.- A. Occurrence and Metabolism of Polyamines.- I. Introduction.- II. Structure and Occurrence.- III. Polyamine Metabolism.- IV. Regulation of Polyamine Biosynthesis.- V. Inhibitors of Polyamine Biosynthesis.- B. Polyamines and Growth.- I. Polyamines and Cell Growth.- II. Polyamines and Tissue Growth.- III. The Biochemical Role of Polyamines.- C. Polyamines and Hyperproliferative Diseases.- D. Polyamines in Skin.- I. Induction of Polyamine Biosynthesis in Skin.- 1. Wound Healing.- 2. Epidermal Growth Factor.- 3. Ultraviolet Irradiation.- 4. Tumour Promoters.- II. Polyamines and Hyperproliferative Diseases of the Skin.- 1. Psoriasis.- 2. Skin Cancers.- References.- 27 Proteolytic Enzymes in Relation to Skin Inflammation.- A. Introduction.- B. Proteases of the Skin.- I. Classification.- 1. Proteinases.- 2. Exopeptidases.- II. Cellular Localisation and Functions.- 1. Localisation.- 2. Functions.- C. Proteases in Inflammatory Cells.- I. Granulocytes.- II. Macrophages.- III. Other Inflammatory Cells.- D. Plasma-Derived Proteases.- E. Protease Inhibitors and Enhancers.- I. Plasma-Derived Inhibitors.- II. Inhibitors in Skin.- III. Protease Enhancers.- F. Proteases in Different Phases of Inflammation.- I. Vasodilatation and Exudation.- II. Chemotaxis.- III. Fibrin Deposition and Fibrinolysis.- IV. Repair and Chronic Inflammation.- 1. Repair.- 2. ...