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.

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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. Thermorecepto…