The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage inflicted was quantified by non-invasive measurements of transepidermal, water loss and erythema. The penetration of salicylic acid, applied in an ethanol solution in chambers glued to the skin in the barrier perturbed areas, was measured by microdialysis sampling of the drug level in the underlying dermis. At the end of the experiment, probe depth in the dermis and skin thickness were measured by ultrasound scanning. In humans and hairless rats alike, the cutaneous drug penetration was highly increased in tape stripped skin (157- and 170-fold increased, respectively, in comparison to the penetration in unmodified skin) and in skin with irritative dermatitis (46- and 80-fold increased). Delipidization by acetone led to a doubling of the penetration in humans but had no effect on penetration in hairless rats. In both studies a close correlation between the measurements of barrier perturbation by non-invasive methods and the cutaneous drug penetration in the same area was found. In th
It has been the intention of this thesis to increase the knowledge on the development of cutaneous side effects from treatment with the argon laser, the copper vapor laser, and the pulsed dye laser, which represent technical developments within laser systems used for treatment of vascular lesions. To reach that goal, the investigations focused on patient and lesional characteristics (skin pigmentation, skin redness, and epidermal thickness) and on the importance of UV irradiation before and after dermatological laser treatment. The aspect of UV irradiation was added because vascular lesions frequently involve the face and, therefore, may be exposed to sunlight in relation to laser treatment. Risk assessments were performed on clinically visible side effects in order to improve the preoperative information to the patients about their individual risks of obtaining side effects from dermatological laser treatment. The laser-induced side effects were evaluated by systematic clinical assessments, by histological and biochemical examinations, by skin reflectance measurements, optical profilometry, and ultrasonography. The term side effects is associated with both transient and permanent skin reactions such as purpura, wounds, textural changes, scars, pigmentary changes, and squamous cell carcinomas. Lightly pigmented, hairless hr/hr C3H/Tif mice, hairless, albino hr/hr MORO/Ibm mice, human, healthy volunteers, and children with port-wine stains were included in the studies. This thesis represents the first systematic and experimental approach to selected side effects from laser treatment of the skin. The argon laser (AL) and the copper vapor laser (CVL) The results from AL and CVL treatments are described together because these lasers are continuous/quasicontinuous lasers that do not meet the requirements for selective photothermolysis, which represents the most selective delivery of energy to cutaneous vessels. In normal-skinned human volunteers, the postoperative development of scars and pigmentary alterations depended on the preoperative constitutive skin pigmentation degree. Significant correlations were found between the preoperative skin pigmentation and the clinically scored pigmentary changes and scarring 1, 2, and 6 months postoperatively, indicating that dark-pigmented skin types respond with more heavy skin reactions than fair-pigmented skin types. Pigmentary changes occurred at lower intensity levels than scarring. No difference was seen between the AL and the CVL concerning the risk of inducing these side effects. In hairless, albino hr/hr MORO/Ibm mice increasing epidermal thicknesses reduced CVL-induced wounds and scars. Significant negative correlations were found between preoperative epidermal thicknesses and CVL-induced skin reactions. In lightly pigmented, hairless hr/hr C3H/Tif mice, CVL treatment induced an increase in skin pigmentation, evaluated by a semiquantitative technique. Postoperative UV irradiations with simulated s
Colophony--also called rosin--is a material obtained from coniferous trees. It is used widely in many products, particularly because of its good tackifying properties. Colophony is also used in paper sizing to increase water resistance. Colophony may cause contact allergy, and around 5% of Swedish dermatitis patients show allergic reactions to colophony at patch testing. There are many case reports of colophony in different products causing contact dermatitis. Often, however, the clinical relevance of a positive patch-test reaction to colophony is difficult to evaluate. The principal aims of the present thesis were to study the prevalence of contact allergy to colophony and of skin disease in individuals with an occupational exposure to colophony; to study the prognosis of dermatitis in colophony-sensitive subjects, and to investigate the outcome of repeated open applications of colophony, thereby trying to elucidate the clinical relevance of contact allergy to colophony. Employees of a tall-oil rosin (colophony) factory (n = 180), and of an opera company where colophony was used in dancers' rosin, mascara and wig glues (n = 132), were interviewed, examined and patch tested. 3.9% and 2% of these two groups respectively had a positive patch test to colophony. More than every fourth participant showed some kind of skin disease, but only few cases were related to work. Eighty-three patients with previously diagnosed contact allergy to colophony were followed-up 72% showed a positive patch-test reaction to colophony at re-testing. Around one third had hand eczema. There was no significant correlation between colophony exposure and current hand eczema. Adhesive bandages containing colophony and zinc oxide (ZnO), colophony and mixes of colophony and ZnO, were tested in 7 colophony-sensitive subjects to see whether addition of zinc oxide inhibited elicitation of allergic dermatitis to colophony, which has been proposed. No difference in reactivity between colophony and colophony/ZnO was seen at patch testing, and there were positive patch-test reactions to all colophony-containing bandages. Thus no inhibitory effect of ZnO was shown. Repeated open application tests were performed with cobalt chloride and colophony in sensitized guinea pigs. The animals were also patch-tested. A dose-response correlation was found with both cobalt chloride and colophony. There was a concordance between patch-test reactions and reactions at repeated open application tests, the higher the concentration of the allergen at the open test the stronger the concordance. In 13 colophony-sensitive subjects serial dilution patch tests with colophony were performed followed by repeated open application tests using colophony of different concentrations once daily for two weeks. Reactions were assessed visually, by laser Doppler flowmetry and by measurements of transepidermal water loss. Ten subjects reacted at open applications with colophony 20%. The strength of the reaction v