Normale Und Pathologische Physiologie Der Haut III / Normal and Pathologic Physiology of the Skin III

ISBN-13: 9783642674365 / Angielski / Miękka / 2011 / 950 str.

W. G. Forssmann; A. J. Jong; J. W. H. Mali

Opis

In this handbook the opportunity has been taken firstly to present the waterbalance in the horny layer and the sweat secretion process with particular emphasis on their relationship to the pharmacodynamical aspects of the micro circulation and permeability of the skin. F. A. 1. THIELE was unable to witness the printing of his life-work concerning the water balance of skin, which he had compiled at the university in Nijmegen with J. W. H. MALI and G. 1. DE JONGH and D. A. REAY from Great Britain. Their contribution concentrates on evaluating the cooling function of the sweat glands with their heat-pipe system and on the physico-chemical effects of dermatological therapy and topically applied cosmetics. A certain amount of overlapping with Volume I/4A (E. SCHWARZ) could not be avoided, and yet the presentation by THIELE and co-workers considers different aspects. The pharmacodynamics of externally applied substances involved in microcirculation are related thematically also to percutaneous resorption. Function and morphology of pharmacodynamics in microcirculation are inseparable. Therefore the structural alterations of the blood vessels in reaction to foreign agents or as an adaptation to endogenous tissue hormone release have been examined electronmicroscopically by W. G. FORSSMANN and his team, and relay a distinct picture of the microcirculation in the area of skin reactiveness. The direct pharmacological aspects of the skin and the systemic effects on blood vessels and their permeability have been listed according to the latest research material."

Spis treści

The Water Balance of the Horny Layer and the Functional Characteristics of the Atrichial Sweat Glands of Human Skin.- I. The Functions of the Atrichial (Human) Sweat Gland.- Measurements on the Surface of the Skin and its Sweat Glands.- A. General Introduction.- I. The Water Loss by Skin.- 1. The Significance of Evaluating Water Flow Through Skin.- a) Water Meters.- b) Symbols for Water Flux Related to Quantity and Pathway.- 2. The Possible Role of the Eccrine (Epitrichial and Atrichial) Sweat Glands in Gaseous and/or Liquid Exudation of Water and Carbon Dioxide by Skin.- a) Reasons for the Development of Adequate Measuring Techniques.- 3. The Actual Surface Area, the Porosity of Skin, and the Microcirculatory System Surrounding the Sweat Glands.- a) The Actual Surface of 1 cm2 Skin Site.- b) The Porosity of Skin.- c) The Capillary System of the Sweat Glands (Sweat Gland Size Shape, Location and Function).- 4. Reasons for Comparative Measurements With Different Water Meters.- a) The Electrolytic Water Analyzer and the Dew Point Meter.- b) The Gaschromatographic Meter (Gas Master).- c) The Resistance Hygrometer.- d) Additional Remarks.- 5. The Water Meters.- a) The Electrolytic Water Analyzer (Meeco).- b) The Salt Crystal Meter.- c) The Resistance Hygrometer (Relative Humidity Recording).- d) The Gas Master.- 6. The Thermistor Measuring Bridge.- 7. Sample Collection of Skin Specimens (Biological Membranes).- a) Isolation.- b) Control of Damage.- c) Bacterial Contamination and Decomposition.- d) Structural Changes.- 8. Synthetic Membranes.- 9. Measurements on Synthetic Membranes, Excised or Isolated Skin Specimens “in vitro” and Skin Surfaces of Man and Animals “in vivo”.- a) Polycarbonate Membranes.- b) Cellophane Membranes with Large Pores.- c) Polyethylene, Saran, and Polycarbonate Membranes vs. Skin Membranes (Excised Abdominal Skin).- 10. Measurements on Skin (in vivo) With Meeco, Salt Crystal and Gas Master.- a) Results.- b) Evidence of Drainage.- 11. The Water Loss by Normal, Diseased and Damaged Human and Animal Skin (The Results of in vivo and in vitro Measurements).- a) Human Skin.- b) Animal Skin Devoid of Sweat Glands (Rat/Mouse).- 12. The Water Loss by Human Skin.- a) The Establishment of an Equilibrium (Thermal) Between the Test Subject and its Environment.- b) The Water Loss by Skin of New-Born Babies and Adults.- c) The Relationship Between Skin Temperature and Water Loss by Skin.- d) The Relationship Between Water Loss and Skin Temperature Under Comfortable Environmental Conditions.- e) The Water Loss by the Palms of the Hand.- f) The Relationship Between Water Loss and Skin Temperature under Comfortable and Less Comfortable Environmental Conditions.- g) The Relationship Between Water Loss and Amino Acid Excretion by the Sweat Glands.- h) Variations in Water Loss and Thickness of Stratum Corneum.- i) Measurements of Stratum Corneum Thickness.- k) The Water Content of the Horny Layer in situ.- l) The Overall Composition of Isolated Epidermis.- m) The Compactness and/or Porosity of the Horny Layer.- n) The Characterization of the Stratum Corneum Membrane.- o) The Water Loss of Alkali-Damaged Skin Sites: Sweat Gland Damage.- p) The Relationship Between Water Loss and Skin Temperature: the Significance of the 17 °C Intercept With the Temperature Axis.- q) The Arrhenius Plot of Water Flux and Skin Temperatur.- r) The Relationship Between Skin Temperature, Ambient Temperature, Sweat Gland Activity and Sweat Gland Density.- s) The Relationship Between Ambient Temperature, Skin Temperature, and Sweating Rate.- t) Introduction to Heat Pipe Performance by the Sweat Gland.- u) Some Aspects of Heat Transfer Across the Skin.- II. The Measurement of Carbon Dioxide Release by Skin and Sweat Glands.- 1. Introduction.- 2. The Carbon Dioxide Meter.- 3. Short Summary of Results.- III. The Measurement of the Impedance of Human Skin and its Adnexa.- 1. Introduction.- 2. Impedance Meters.- a) Radiometer Impedance Meter (a Compensation Device).- b) The Phase-Voltmeter.- IV. The Evaluation of Skin Reactions.- 1. The Composition of a Test Panel.- 2. The Alternative Pathway for Penetration of Ions and Molecules : the Sweat Gland.- a) Sodium Azide (NaN3).- b) Hydrogen Peroxide (H2O2).- c) Sodium Chloride (NaCl).- d) Pre-treatment of a Test Area by Corticosteroids.- e) Crescent Effects.- f) The Effect of Local Cooling and Stimulated Circulation (Blood Flow).- g) Alkaline Earth Hydroxides (Li—Na—Rb—Cs).- h) Alkaline Earth Laurates (Li—Cs).- i) Sodium Hydroxide Solution pH 12.0, 10.0, Na3PO4 and TPP.- k) Nickel Eczema.- l) Astra Blue (10–50 ?A Intophoresis).- m) Micellar Catalysis.- V. The Horny Layer and Sweat Glands as Ion-Exchangers.- 1. The Interaction with the Horny Layer Proteins and/or Sweat Gland Cells/Mucopolysaccharides.- 2. General Observation.- 3. The Interaction With the Skin Surface.- a) Chelation and Ion Exchange.- b) The Sorption on the Skin Surface and the Skin Reaction.- c) The Ion Exchangers.- d) The Order of Selective Binding.- 4. The Working Hypothesis.- 5. The Severity of the Skin Reactions.- 6. The Role of the Sweat Glands in Skin Reactions.- II. A Possible Contribution to Heat Transfer Through the Human Skin by the Eccrine (Atrichial) Sweat Gland.- Nomenclature Related to Heat Transport Capability of Sweat Glands and Calculation of Heat Pipe Performance.- 1. Introduction.- 2. Experimental Evidence of the Behaviour and Functioning of Human Eccrine Sweat Glands.- a) Galvanic Skin Response.- b) Surface Measurements of Sweat Gland Activity.- c) Methods for Evaluating Water Vapour Exudation.- d) Water Vapour Flow Inside the Eccrine Sweat Glands.- ?) The Relationship Between Water Loss and Skin Temperature.- ?) The Influence of Ambient Temperature (Ta) on Water Loss (WLEv) and Sweating Rate(Esw).- ?) Internal Sweating Rate.- ?) Subsurface Evaporation.- e) Sweat Gland Exhaustion.- f) Sweat Gland Blockage.- ?) Atropin.- ?) Blockage of the Effect of Acetylcholine.- ?) Sodium Chloride on the Skin Surface.- ?) NaCl Depletion.- ?) Sweat Gland Obstruction by Closure of the Orifice of the Duct.- ?) Infra-red Microscopic Experiments.- g) Sweat Gland Absence.- ?) Water Loss Measurements.- ?) Ninhydrin Paper Imprints and Permlastic Castings. Ectodermal Dysplasia.- h) Isolation of Eccrine Sweat Glands From Skin Biopsies and Electron Microscopic Documentation Related to Measurements of Sweat Duct Diameters.- 3. Eccrine Sweat Gland “Modus Operandi”.- 4. Heat Transport Capability of the Eccrine Sweat Gland. A Theoretical Analysis.- a) Nucleate Boiling.- b) Sonic Choking of the Vapour Space.- c) Entrainment.- d) Capillary Limitation.- 5. “Equivalent Heat Pipe”.- a) Total Heat Transport.- 6. Effect of Duct Diameter on Performance.- 7. The Thermal Conductivity of Skin, Calculated Using the Above Data.- 8. A Comparison of Sweat Gland Heat Transport and Water Loss (Evaporative).- 9. Conclusions.- 10. Résumé en Français.- III. Multivariate Data and Discriminant Analysis in Dermatology and Skin Physiology. (The Evaluation of Spontaneous Pathological Skin Conditions).- 1. Introduction.- 2. Remarks Concerning the Problem of Interdisciplinary Cooperation.- 3. The Approach to the Problem.- 4. Multivariate Data Analysis.- 5. Methodology of Statistical Analysis in Dermatology.- a) Principal Components Analysis.- ?) Factor 1. Hypothetically Denominated Skin Porosity.- ?) Factor 2. Hypothetically Denominated Sweat Gland Function.- ?) Factor 1 and 2. The Plot of Skin Porosity vs. Sweat Gland Function.- ?) Skin Porosity (Factor 1).- ?) Concluding Remarks.- b) Discriminant Analysis; Canonical Correlation.- c) Summary.- d) Concluding Remarks.- IV. The Sweat Gland and the Stratum Corneum.- I. General Introduction.- a) The Conformation of the Skin Proteins.- b) The Integrity of the Cell Membrane Envelope.- c) The Role of Water in the Outer Appearance of Human Skin (Stratum Corneum).- d) The Role of Lipids in the Outer Appearance of Human Skin (Stratum Corneum).- e) The Effects of Externally Supplemented Hygroscopic Compounds on Skin.- f) Summary.- II. The Amino Acids, Lactic Acid, Urea, and Other Essential Components of Aqueous Skin Surface Extracts (Experimental Test Solutions), Human Sweat (Capillary-Collected) and Horny Layer Eluates (Aqueous Filtrate of Pulverized Defatted Callus).- 1. The Aqueous Skin Eluates and the Bacterial Flora of Human Skin.- a) Methodology.- b) Results.- 2. The Urea Cycle Components (Diamino Carboxylic Acids) and the Hydroxy Amino Acids of Aqueous Skin Eluates (Citrulline, Ornithine, Arginine, and Serine/Threonine).- a) The Alkaline Skin Eluates.- ?) Analytical Results.- ?) Results of Potentiometrie Titrations.- ?) Carbon Dioxide Release.- ?) The Ratios of the umole Amounts of Amino Acids of the Different Skin Eluates.- ?) Conclusions.- b) The Detergent and Phosphate Skin Eluates.- ?) Horny Layer Effects and Skin Damage (Fragmentation of Horny Layer Proteins).- ?) Sweat Gland Effects.- ?) A Comparison and Interpretation of the Results of Skin Eluate Analyses.- ?) The Interpretation of the Analytical Results: Urea Cycle Interference and the Blockage of Cycle Conversions.- 3. The Amino Acid Analyses of Sweat, Polled Sweat, Horny Layer/Callus Filtrate, Horny Layer Protein, Protein Granules, and the Lactic Acid Content of Sweat, Skin Eluates and Horny Layer Filtrate.- a) The Amino Acid Composition of Horny Layer Filtrate, Protein Granules, and Horny Layer Sediment.- ?) The Alkali Soluble Fraction of Horny Layer Proteins.- ?) The Horny Layer Filtrate.- ?) The Amino Acid Composition of Collected Sweat.- ?) A Comparison of Analytical Results.- b) The Amino Acid and the Skin Temperature.- c) The Lactic Acid Content of Skin Eluates and Sweat.- ?) The Lactic Acid Content of Skin Eluates.- ?) The Lactic Acid Content of Horny Layer Filtrate and Sweat.- ?) The Concentration of Lactic Acid in Sweat and Horny Layer (Filtrate).- ?) Additional Remarks.- 4. The Effects of Particular Sweat Components and Hydrogen Ion Concentration on Skin Protein Conformation.- a) The pH Dependent Conformation of Skin Protein and Some Copolymers (Ion Exchange: Radio Cesium Chloride, Charged Dyes, Detergents).- b) The Apparent pH of Skin and the Potentiometrie Titrations of Sweat Components (Citrulline, Lactic Acid, Pyrroglutamic Acid/Pyrrolidone Carboxylic Acid) and other Components (Mandelic Acid, and its Derivatives Br, OH, OCH3), Di- and Tripeptides and Copolymers (Polyglutamic Acid).- ?) The Apparent pH of Human Skin and the Effects of Washing With Soap.- ?) The Skin Disinfectant Properties of Lactic Acid.- ?) Potentiometric Titrations of the Extracts of Skin Shavings/Scrapings, and Synthetic Skin Eluates.- ?) Potentiometrie Titrations of Lactic Acid, 1–5-Pyrrolidone Carboxylic Acid. Synthetic Skin Eluates, and Glycocoll-Ribose Condensates.- ?) Potentiometrie Titrations of Lactic Acid and Mandelic Acid and its Derivatives.- ?) Potentiometrie Titrations of Lactic Acid and Mandelic Acid and its Derivatives.- ?) Potentiometrie Titrations of Di- and Tripeptides and Mixtures of the Amino Acids of Group A (Asp/Glu), Group B (Arg/Lys), and Group C (Citrulline): the Net Charges, Charge Distribution, and Charge Density.- 5. Synthetic Skin Eluate.- III. The Horny Layer and Epidermal Proteins — The Isolation and Physical and Chemical Properties of Horny Layer Proteins.- 1. Introduction.- a) Earlier Findings and Current Problems.- 2. The Differences in the Amino Acid Composition of Horny Layer (“Soft”) and Hair (“Hard”) Keratins.- a) Analytical Errors.- b) Analytical Results.- c) The Charged Side Chains of the Proteins.- d) The Hydroxy Amino Acids of the Proteins.- 3. The Similarity Between the Amino Acid Compositions of Pooled Callus and Whole Epidermis Proteins (pH 5.5 Fractions).- 4. Comparative Analyses of Skin Proteins by Different Laboratories.- a) Analysis Characteristics.- 5. The Isolation and Refining of Large Amounts of Native Skin Protein (Dialysis and Freeze-Drying): the 5.5 Fraction.- a) Procedure of Solubilization.- b) Procedures of Isolating and Refining the pH 5.5 Fraction of Callus Material.- c) Additional Observations.- 6. The Freeze Dried Skin Protein.- 7. The Lamella Micro Structure of Freeze Dried Skin Proteins.- 8. Solution Properties, Precipitation Characteristics, and pH-Dependent Aggregation Phenomena.- 9. The Polymeric Properties of Skin Proteins.- 10. Polyacrylamide Gel Electrophoresis.- 11. Sephadex Gel Filtration.- 12. Immunological and Immuno Fluorescence Essays.- 13. Survey of the Results.- 14. Schematic Formula of a Hypothetical Skin Peptide Unit in Relationship With the Amino Acid Analyses, Charge Distribution and Potentiometrie Titration of Skin Proteins.- 15. Potentiometrie Titrations of Skin Proteins and Similar Polyampholytes (Synthetic Substitutes).- a) Titration of the Completely Dissolved Skin Protein (Molecular Destruction by Drastic Alkali Treatment).- b) Titration Curves of Britton-Robinson Buffer Solutions.- c) Titration Curves of Amino Acid (Skin Protein Components), Dipeptides, Polyglutamic Acid, and Imino Diacetic Acid (Chelex 100).- d) Titration Curves of Skin Protein: the Effect of Lactic Acid.- e) Titration of Different Batches of Skin Protein Solutions.- f) Titration of Skin Protein Flocculated at pH ZERO (Strong Hydrochloric Acid) in Comparison to a Protein Dialysate (pH 4.2).- g) Cu++ Chelation by Skin Proteins (Folin Ciocalteu).- h) Titration of Skin Protein Suspension Dialyzed for Eight Days (The Milky Turbid Flocculate: Artificial Protein “Necrosis”).- ?) The Effects of Na+ Ions and Urea on Flocculation.- i) Titration of Dialyzed Skin Protein Solution (4 Days Dialysis).- j) The Effect of Urea and Urea/Glycerol on the Skin Protein.- k) Survey of the pH-Dependent Charge Distribution and Charge Density of Skin Proteins.- l) Radio Caesium: pH-Dependent Permeation and Ion Exchange Behaviour in Relationship With the Charge Density of Skin Proteins of Mammalian Origin.- m) The Percentage Ionizable Beta-Carboxyl and Zeta-Amino Groups at the Side Chains of Macromolecular Protein Structures.- n) Polyglutamic Acid (PGA): Titration and Conformational Transition.- o) A Comparison Between Skin Protein and Synthetic Copolymers Provided With COOH and NH3+ Groups.- IV. Solution Properties of Skin Proteins.- 1. The Viscosity of Skin Protein Solutions and Gels.- a) General Observations.- b) The Unique Property of Skin Protein: Dilatency.- c) Protein Gelformation and Hydroxy Amino Acids.- d) The Effects of Natural Skin Lipids and “Synthetic Lipoidal Compounds” on Gel Viscosity.- e) The Effects of Na+ Ions on Skin Protein Viscosity.- f) Ordered and Disordered Protein Structures.- 2. Ultracentrifugation Experiments With Skin Protein Solutions and Gels: Sedimentation by Acceleration.- a) The “Enmeshed” Water of Skin Protein Gels (Pseudo Solutions).- b) The Glycerol Absorption by Skin Protein.- 3. A Skin Protein Philosophy.- 4. Photographic Documentation of Skin Protein Gel Behaviour.- 5. The Properties of Acid and Alkali Skin Protein Films.- 6. Experiments With Skin Protein Films and Horny Layer Sheets.- a) The Water Content of the Horny Layer.- b) Simulation Experiments.- c) Hysteresis Phenomena.- d) Structural Conversions and D2O Exchange.- e) Infra-Red Spectra of Skin Protein and Excised Skin Specimens.- V. The Optical Activity of Skin Proteins and Skin Protein Substitutes (Synthetic Copolymers).- 1. The Optical Activity of Proteins and the Fundamentals of Optical Rotatory Dispersion and Circular Dichroism.- 2. The Ordered and Disordered Structures of Proteins.- 3. The Stabilization of the pH of Stock Solutions of Skin Protein and Synthetic Copolymers.- 4. A Comparison of ORD and CD Curves of Skin Protein Solutions Adjusted to Different pH’s.- a) Room Temperature Conditions.- b) Heated Protein Solutions.- c) Sonication of the Skin Protein Solutions.- 5. The Stabilization of the Na+ Ion Concentration.- 6. The Possible Effect of Lactic Acid on Skin Protein Conformation.- 7. The Effects of pH, Temperature, Na+ Concentration, Lactic Acid, and Organic Solvents on the Conformation of Polyglutamic Acid (PGA).- a) ph Effect.- b) Temperature Effect.- c) Na+ Ion Concentration.- d) Lactic Acid.- e) Solvent Addition.- f) Impurities of Dialysis Tubes.- 8. The Polyelectrolyte Properties of Skin Protein, Polylysine (PL), Polyglutamic Acid (PGA) and Copoly-Lysine-Glutamic Acid.- a) Conformational Transitions.- b) The Formation of Beta-Extended Structures.- ?) PGA + PL (1:1) Mixture (Non Polymerized).- ?) Skin Protein + PGA (Equimolar Concentration).- ?) Skin Protein + PL (Equimolar Concentration).- ?) Röntgen Diffraction Analysis of Skin Protein Films.- 9. Additional Comments.- a) The Molecular Weights of the Copolymer PGA.- 10. Structural Arrangement and Water Binding.- VI. Review of the Data Related to the Water Binding by Proteins and the Multicomponent System of the Horny Layer (Hydration and Dehydration) and the Possible Role of the Constituents of the Exudation of the Sweat Gland.- 1. The Concepts of Water Sorption by Globular and Fibrillar Proteins.- a) The Water-Polymer Interface of Proteins.- b) The “Enmeshed” Water of Skin Protein Gels.- c) The Water Contents of Skin Protein Gels/Sols, Skin Protein-Lipid Films and Isolated Horny Layer Specimen.- ?) Skin Protein Gels/Sols.- ?) Skin Protein and Skin Protein-Lipid Films.- ?) Horny Layer Specimens.- 2. Water Binding by Proteins and Polysaccharides.- 3. The Pathology of the Horny Layer. Spontaneous and Experimental Pathology: Dehydration Phenomena and Structural Collpase of the Horny Layer.- a) Spontaneous Pathology.- b) Experimental Pathology.- ?) Structural (Protein) Necrosis by Alkali.- ?) Structural (Protein) Necrosis by Chloroform-Methanol (Folch’s Solvent) and Isoparaffins.- c) Simulation of Dehydration and Rehydration of Horny Layer Proteins by in vitro and in vivo Experiments.- ?) In vitro Experiments.- ?) In vivo Experiments.- ?) Studies of Skin Hydration in vitro and in vivo.- d) The Evaporation of Water from Hydrophobic and Hydrophylic Surfaces and the Water Sorption by the Skin and/or the Sweat Glands (Proposals for Studying Skin Hydration in vivo).- ?) The Half Lives of Evaporation of Natural Moisturizing Factor Compositions.- 4. Literature Data and Theoretical Aspects: the Solvent Effects of Urea, Lactic Acid, and the Possible Role of Na+ Ions on the Conformational Stability of Protein Structures.- a) Skin Protein.- 5. The Possible Role of Urea, Na+, Organic Acids, Polyols, and Lipids in Favouring the Conformational Stability of Skin Protein (Lipid) Lattices by Simultaneous Water Binding.- a) The Components of Acid Creams (pH 3.25–4.5).- b) Lipids.- ?) Metabolism.- ?) Protective Function and Lubrication.- ?) Functional Properties.- 6. The “Polygamous” Function of the Sweat Gland.- 7. Descriptive Model of the Horny Layer.- References.- Pharmacology of the Microvasculature of the Skin.- Foreword.- I. Introduction.- II. Functional Morphology of the Skin Microvasculature.- 1. Structural Data of the Microvasculature.- a) Arterioles.- b) Precapillaries.- c) Capillaries.- d) Venules.- 2. Structural Features of Arterial and Venous Segments of the Skin Capillaries.- 3. Contractility and Surface Change of Endothelial Cells.- III. Methods of Investigation of the Function of Microvasculature.- 1. Direct Methods.- a) Transillumination Method.- b) Surface Illumination Method, Capillary Microscopy.- c) Intracapillary Pressure Measurement.- d) Microphotoelectric Plethysmography (MPPG).- e) The Laser-Doppler Flowmeter.- 2. Indirect Methods.- 3. Measurement of Nutritient Blood Flow.- a) Transcutaneous Measurement of Partial Oxygen Pressure (tcpO2) as a Parameter of Erythrocyte Flow Through Terminal Vessels of the Skin.- ?) Principles of tcp O2 Measurement.- IV. Functional Data on the Skin Microcirculation.- 1. Regulation of Skin Blood Flow.- a) Neurogenic Regulation of the Microcirculation by Efferent Nerves of the Autonomic Nervous System.- b) The Topographical Relationship Between Nerves and Microvasculature.- V. Blood Coagulation and Microcirculation.- a) Morphokinetics of Thrombus-Formation.- VI. The Fibrinolytic System and Microcirculation.- VII. Rheology and Microcirculation.- 1. Erythrocyte Aggregation.- VIII. The Permeability of the Microvasculature.- 1. Leucodiapedesis.- 2. Capillary Resistance Test.- a) Topically Applied Substances with Pharmacodynamic Effects on CR.- IX. Lymph Flow and Microcirculation.- a) Development of Lymph Edema.- X. Reactivity of the Microvasculature.- 1. Reactive Changes in the Capillary Structure.- 2. Changes in Blood Flow and Vascular Permeability due to External Influences on the Skin Surface.- a) Dermographism.- b) The Axon Reflex.- c) The Mechanisms of the Flare Reaction in Human Skin.- d) Cold Vasodilatation (Hunting-Reaction, Lewis, 1930).- XI. Pharmacological Influence on the Terminal Blood Vessels of the Skin.- 1. Biogenic Vasoactive Substances and Microcirculation.- a) Histamine.- b) Serotonin.- 2. Polypeptides.- a) Kinins.- b) The Renin-Angiotensin System.- c) Neuropeptide Hormones (NPH).- 3. Prostaglandins.- 4. Neurogenic Transmitters.- a) Norepinephrine.- ?) Pharmacological Examination of the Contractile Response of Arterioles to Vasoactive Substances.- ?) Comparative Investigations of Vasoconstrictory Active Substances in a Skin Test.- b) Acetylcholine.- 5. Medicaments Exerting a Direct Effect on the Smooth Muscle of the Microcirculation.- a) Papaverine and Papaverinoid Substances.- b) Nitrites and Nitrite Derivatives.- c) Adenosine-3?-phosphate, Adenylic Acid.- d) Xanthines.- e) Nicotinic Acid, Nicotinic Acid Ester and Microcirculation.- f) Pentoxifylline.- XII. The Pharmacological Influence of Medicaments, which Interact with the Transmitter-Receptor Mechanism of the Autonomic Nervous System.- 1. The Adrenergic Nervous System.- a) Antisympathicotonics.- ?) Reserpine.- ?) Guanethidine.- ?) ?-Methyldopa.- b) ?-Sympathicolytics.- c) Sympathicolysis.- 2. Sympathicomimetics.- a) Direct-Acting Sympathicomimetics.- ?) Action of Dopamine on Skin Veins and Varicous Veins.- b) Synthetic Sympathicomimetics Primarily Affecting ?-Receptors.- c) Indirectly Acting Sympathicomimetics.- d) Parasympathicomimetics.- 3. Parasympathicolytics.- 4. Compounds Blocking and Stimulating Ganglionic Transmission in the Autonomic Nervous System.- a) The Effects of Smoking on Skin Blood Flow.- XIII. Corticosteroids and Microcirculation.- The Effect of Vasoactive Substances on the Skin in Relation to Local and Systemic Treatment With Corticosteroids.- XIV. The Human Mucosa as a Test Area for Vasoactive Substances.- References.- Skin Permeability.- I. Introduction.- 1. To the Reader.- 2. Definitions.- II. Morphologic Basis of Absorption by Human Skin.- 1. Skin Surface.- 2. Horny Layer.- 3. Epidermis.- 4. Dermis (Corium).- 5. Subcutis.- III. Methods for Measurement of Absorption.- 1. Animal Experiments.- 2. In Vitro Methods.- a) Disappearance Measurements.- b) Penetration Into the Isolated Horny Layer.- c) Diffusion Through Horny Layer and Epidermis Into Dermis.- d) Diffusion Through Horny Layer and Epidermis.- e) Diffusion Through the Total Skin Specimen.- f) Penetration Into Single Layers of the Skin.- g) Inverse Penetration.- 3. In Vivo Methods.- a) Disappearance Measurements.- b) Measurement in the Horny Layer.- c) Appearance in the Skin and Inner Organs (Autoradiography).- d) Measurement of Total Body Content.- e) Measurement of Skin Clearance.- f) Measurement in Exudates.- g) Measurement of Appearance in the Serum.- h) Radioimmunoassay.- i) Determination in the Urine.- j) Determination of Concentration in the Horny Layer, Epidermis and Dermis.- k) Determination of Appearance in the Epidermis and Dermis by Secondary Parameters.- l) Determination of Skin Reactivity.- m) Determination of Allergenic Potency.- n) Determination and Estimation of Therapeutic Efficiency.- o) Determination of Migration From the Vessels of the Underlying Tissue Into the Skin and to the Skin Surface.- 4. Prerequisites for the Measurement of Permeation Parameters With Radioactively Labelled Substances.- 5. Comparison of in Vivo and in Vitro Permeability.- 6. Compartments of Skin Permeation.- a) Skin Surface.- b) Horny Layer.- c) Percutaneous Resorption and Systemic Treatment.- d) Binding to the Skin.- e) Transfollicular Absorption.- 7. Transformation and Metabolism of Drugs in the Skin.- a) Autodisintegration by Radiolysis.- b) Chemical Decomposition.- c) Passive Metabolism.- d) Microbial Transformation.- e) Active Metabolism.- f) Conclusions.- IV. Quantitative and Qualitative Aspects of Absorption.- 1. Theoretic Aspects.- a) Diffusion Through the Horny Layer.- b) Resulting Concentrations in the Epidermis and Dermis.- 2. Kinetics of Penetration, Permeation, Resorption and Excretion.- a) Theoretic and Experimental Prerequisites.- b) Concepts of Optimal Permeation Kinetics in Topical Therapy.- c) Normal Kinetics.- d) Kinetics in the Horny Layer.- e) Barrier Function of the Horny Layer.- f) Reservoir Function of the Horny Layer.- g) Shunt Diffusion.- h) Kinetics in the Epidermis.- i) Kinetics in the Dermis.- j) Percutaneous in Relation to Systemic Absorption.- k) Penetration Into the Subcutis.- l) Binding of Substances to Cutaneous Constituents.- m) Urinary Excretion.- 3. Chemical Structure and Absorption.- a) Homologous Series of Alcohols.- b) Transport Forms.- c) Steroids.- 4. The Horny Layer as Regulating and Limiting Factor.- a) Barrier and Reservoir Function of the Individual Strata of the Horny Layer.- b) Kinetics of Various Substances in the Horny Layer.- c) Surface Fat and Barrier Effect.- d) Pathologic Alterations of the Barrier Function in Diseased Skin.- e) Regeneration of Barrier Function.- f) Alteration of the Barrier Function of the Horny Layer by “Chemical Stress”.- g) Loss of Barrier Function of the Horny Layer Caused by Stripping.- V. Pharmacy of Topical Drugs.- 1. Pharmaceutical Problems of Externally Applied Drugs.- 2. Availability of Topically Applied Drugs.- 3. Drug Release Into the Stratum Corneum and Optimal Vehicle Properties.- 4. Vehicle Systems.- a) Emulsifying Agents.- b) Pharmaceutical Emulsifying Agents for External Application.- c) Ointment Bases.- ?) Hydrocarbons.- ?) Fats and Oils.- ?) Polyethylene Glycols.- ?) W/O Emulsion Ointments.- ?) O/W Emulsion Ointments.- ?) Hydrogel Ointments.- d) Transparent Gels.- ?) Transparent Oleaginous Gels.- ?) Transparent Microemulsions (“Swinging Gels”).- ?) Transparent Hydrogels.- e) Silicone Ointments.- f) Powders.- g) Solvents as Vehicles.- ?) Penetration of Solvents and Surfactants — Enhancement of Penetration.- ?) Dimethylsulfoxide (DMSO) and Other “Accelerants”.- ?) Solvent Concentration and Particle Size.- ?) Solvent Concentration in Nonvolatile Vehicles.- 5. Drug Release From Vehicles.- a) In Vitro Release Rates.- b) In Vivo Release.- 6. Intrinsic Activity of the Vehicle.- a) Penetration of Vehicle Constituents.- b) Skin Blanching by Vehicle Components.- 7. Drugs and the Accompanying “Appropriate” Vehicles.- a) Partition Coefficient.- b) Concentration of the Applied Substance.- 8. Kinetics of Substance Distribution in the Horny Layer.- a) Shorter Penetration Periods.- b) Intermediate Penetration Periods.- c) Longer Penetration Periods.- d) Horny Layer Kinetic Curves.- ?) Phase I.- ?) Phase II.- ?) Phase III.- ?) Phase IV.- 9. Kinetics of a Drug From Different Vehicles.- a) Aqueous Hydrophilic Ointments.- b) Vaseline.- c) Lipophilic W/O-Emulsion.- d) Polyethylene Glycol.- VI. Therapy and Preparation Form.- 1. Localization.- 2. Application Procedure.- 3. Application Frequency.- 4. Vehicle and Sebum.- VII. The Choice of Vehicle in Skin Diseases.- 1. Acuity of a Dermatosis.- 2. Skin Type, Physiologic Skin Status.- 3. Localization of Dermatosis.- 4. Climatic Factors.- 5. Cosmetic Considerations.- VIII. Pharmacodynamic Activities of Locally Applied Drugs to Normal and Diseased Skin.- 1. Modification by the Dermatosis.- 2. Pharmacoanalysis.- 3. Primary Mode of Action of a Drug and Its Secondary Empiric Therapeutic Effects.- 4. Site of Primary and Secondary Pharmacologic Effects.- 5. Structure and Function in Relation to Pharmacologic Effects.- 6. Antihistamines.- 7. Corticosteroids.- 8. “Vasoconstriction” Test as Bioassay for Corticosteroids.- a) Vasoconstriction and Antiinflammatory Activity.- b) Vasoconstriction (Blanching) as Measure for Penetration.- c) Vasoconstriction and Drug Interaction.- d) Vasoconstriction and Atrophy.- e) Mechanism of Steroid-Induced Vasoconstriction.- f) Further Vasoactive Drugs.- ?) Nicotinic Acid Esters.- ?) Catecholamines.- 9. Caffeine.- 10. Heparin.- 11. Vitamins.- 12. Sex Hormones.- IX. Special Cases and Modifying Factors Related to Topical Therapy.- 1. Drug Interaction.- 2. Combinations with Salicyclic Acid and Derivatives.- 3. State of Skin and Permeation (Childhood, Diseased Skin).- 4. Skin Permeability in Infants and Young Children.- 5. Percutaneous Therapy of Systemic Diseases.- 6. The Permeability of the Vessels of Human Skin.- 7. Penetration From the Blood Into the Skin.- 8. Pharmacokinetics in the Skin (Local Versus Systemic Application).- 9. Penetration From the Undersurface of the Dermis into the Skin (Inverse Penetration).- 10. Permeability of Mucosal Surfaces.- 11. Permeability of Human Nails.- 12. Permeability of the Cornea of the Eye.- X. Factors Influencing the Penetration.- 1. Hydration of the Horny Layer.- 2. Medicinal and Mineral Baths.- 3. Occlusion.- 4. Stripping.- 5. Temperature.- 6. Depilatory Agents.- 7. pH Dependence.- 8. Surface Tension.- 9. Iontophoresis.- 10. Ultrasound (Phonophoresis).- XI. Toxicologic Aspects of Skin Permeability.- 1. Cytostatic Agents.- 2. Antibiotics.- 3. Salicylic Acid.- 4. Hexachlorophene.- 5. Pesticides, Herbicides.- 6. Solvents.- 7. Mercury.- 8. Boron.- 9. Lead.- 10. Contamination and Decontamination of the Skin.- 11. Surfactants, Soaps.- XII. Special Problems Encountered in Penetration.- 1. Permeation of Gases.- a) Permanent Gases.- b) Nonpermanent Gases.- 2. Penetration of Solid Particles.- 3. Water Movement Through the Skin.- 4. Penetration of Electrolytes.- 5. Glucocorticosteroids.- a) Hydrocortisone.- b) Further Literature on Hydrocortisone (HC).- c) Hydrocortisone-17-butyrate (HCB).- d) Betamethasone-17-valerate, Bethamethasone.- e) Desoximetasone (DOM).- f) Fluocinolone (F), Fluocinolone Acetonide (FA), Fluocinolone Acetonide Acetate (FAA).- g) Triamcinolone, Triamcinolone Acetonide (TA).- h) Fluprednylidene-21-acetate.- i) Corticosteroids: Conclusions.- 6. Mineralocorticoids.- 7. Androgens, Antiandrogens and Estrogens.- a) Androgens.- b) Antiandrogens.- c) Estrogens.- d) Conclusions.- 8. Vitamin A Acid and Derivatives.- 9. Psoralens.- a) In Vitro Experiments.- ?) Effects of Different 8-MOP Concentrations on Penetration.- ?) Effects of Solvents on Penetration.- ?) Effects of UV Irradiation on 8-MOP Binding.- b) In Vivo Experiments.- ?) Oral Administration.- ?) Topical Application.- ?) Conclusions Concerning the Photochemotherapy With 8-MOP.- 10. Dithranol (= Anthralin = Cignolin).- 11. Methotrexate (MTX).- XIII. Flux.- XIV. General Rules.- XV. Substances Investigated in Penetration and Related Fields.- References.- Index of Names.