No / This work investigated the effect of electroporation on human epidermal penetration of a model neutral lipophilic compound (estradiol) from saturated aqueous solution and when encapsulated in ultradeformable liposomes. Total amount penetrated and skin deposition were compared with values obtained from passive diffusion. The effect of electrical pulsing on liposome size was investigated. The action of phosphatidylcholine on skin that was structurally altered by such pulses was determined. Electroporation did not affect liposome size. Skin pulsing considerably increased estradiol penetration and skin deposition from solution, relative to passive delivery, with subsequent partial recovery of skin resistance to molecular penetration. Surprisingly, with liposomes, electroporation did not markedly affect estradiol skin penetration. Importantly, liposomal phosphatidylcholine applied during or after pulsing accelerated skin barrier repair, i.e. provided an anti-enhancer or retardant effect.

No / Background Generation and accumulation of reactive oxygen/nitrogen species in the epidermis of patients with vitiligo has been widely documented. Moreover, semiquinone radical-mediated sensitivity has been shown in blood lymphocytes of these patients. Objectives To determine the possible mechanism behind Q10-induced facial vitiligo. Methods This was a clinical assessment supported by in vivo Fourier transform–Raman spectroscopy and repigmentation. Results Topical Q10 application generated hydrogen peroxide (H2O2) leading in turn to facial vitiligo in susceptible individuals. Proof of the basic result stemmed from reduction of epidermal H2O2 by using narrowband ultraviolet B-activated propseudocatalase PC-KUS in association with cessation of depigmentation and repigmentation of the lost skin colour. Conclusions Over-the-counter availability of Q10-containing topical formulations can be harmful to individuals susceptible to vitiligo.

Thesis (M.S.W.)--Smith College School for Social Work, Northampton, Mass., 2009. / Includes bibliographical references (p. 137-146).

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Deon van der Merwe / 1,4-Dioxane is a potentially carcinogenic solvent. It is a problematic groundwater contaminant because of its unique physical-chemical properties. It is found in a wide range of consumer products as a by-product contaminant. This research aimed to investigate contaminant properties and behavior of dioxane in the environment and also in the human body. The dioxane ability to decontamination by adsorption processes was evaluated with four adsorbents. The adsorption efficiencies of activated carbon (AC), metal oxide nanomaterials (TiO[subscript]2 and MgO), and diatomaceous earth (DE) were assessed in aqueous and vapor phases using infrared spectroscopy. AC showed the highest adsorptive capacity for dioxane at equilibrium in both phases. The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to dioxane. For this purpose, a new flow through diffusion system (FTDS) was developed by modifying a Bronaugh flow through diffusion cell with flow capacity in both the donor and receptor compartments and using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) as the analytical technique. FTDS can provide ‘real time’ quantitative high-density permeation data over time and is characterized by the simplicity of its use and the low cost of test samples. The in vitro dermal absorption study of dioxane across human skin showed that the absorption parameters of dioxane were 1.16 ± 0.22 hr, 5.7 X 10[superscript]-4 ± (0.62) cm/hr, 0.286 ± 0.035 mg/cm2/hr, 4.8 X 10-5 (± 0.32) cm[superscript]2/hr, and 1.99 ± 0.086 mg for lag time, permeability, steady-state flux, diffusivity, and total amount absorbed over 8 hr, respectively. The study of the effect of the surfactant sodium lauryl sulphate and solvent systems water, ethanol, propylene glycol, and ethyl acetate on permeation profiles revealed that these solvents and surfactants increased the permeation of dioxane significantly. The FT-IR spectra of stratum corneum treated with solvents showed that there was broadening of the CH[subscript]2 asymmetric stretching vibration of the CH[subscript]2 peak near 2920 cm[superscript]-1 only in samples treated with ethanol. The lipid extract precipitates were detected and were mostly composed of the stratum corneum lipid part.

Creating realistic-looking skin is one of the holy grails of computer graphics and is still an active area of research. The problem is challenging due to the inherent complexity of skin and its variations, not only across individuals but also spatially and temporally among one. Skin appearance and reflectance vary spatially in one individual depending on its location on the human body, but also vary temporally with the aging process and the body state. Emotions, health, physical activity, and cosmetics for example can all affect the appearance of skin. The spatially varying reflectance of skin is due to many parameters, such as skin micro- and meso-geometry, thickness, oiliness, and pigmentation. It is therefore a daunting task to derive a model that will include all these parameters to produce realistic-looking skin. The problem is also compounded by the fact that we are very well accustomed to the appearance of skin and especially sensitive to facial appearances and expressions. Skin modelling and rendering is crucial for many applications such as games, virtual reality, films, and the beauty industry, to name a few. Realistic-looking skin improves the believability and realism of applications. The complexity of skin makes the topic of skin modelling and rendering for computer graphics a very difficult, but highly stimulating one. Skin deformations and biomechanics is a vast topic that we will not address in this dissertation. We rather focus our attention on skin optics and present a simple model for the reflectance of human skin along with a system to support skin modelling and rendering.

Comprehensive in vitro modelling of inflammatory human skin conditions is an essential first step in the development and assessment of potential therapeutic approaches. Mouse models or monolayer keratinocyte cultures come with distinct limitations which might be complimented or overcome by the use of human-specific organotypic 3D culture models. Over the course of this thesis, an organotypic culture system, based on patientderived immortalised keratinocyte cell lines on a dermal equivalent collagen 1 gel, was established and used to recapitulate phenotypical features for two hereditary skin diseases, Harlequin ichthyosis and Tylosis with oesophageal cancer. Small molecular compounds, supplied via the medium, or RNA interference were used to modulate disease-specific changes in histology and marker expression of the skin equivalent. Since hyperproliferative skin conditions can be associated with an aberrant wound healing phenotype, the organotypic system was manipulated to obtain a basic in vitro wound healing model. This model displays typical features of re-epithelialisation over time (both normal and disease-specific) which can further be manipulated via shRNAmediated knockdown or the exogenous supply of compounds. In parallel, a non-disease model was used to assess the topical application of novel nanopolymeric drug delivery systems in regard to their ability to penetrate across the permeability barrier. Penetrance profiles for the organotypic model (in dependence of co-application with chemical enhancers) showed a similar pattern as for topical applications performed in parallel on explant skin. In conclusion, a highly adaptable human organotypic keratinocyte culture model was developed and used to recapitulate (and manipulate) skin disease phenotypes and epidermal wound healing in vitro, as well as perform first essential assessments of novel drug delivery systems.

Creating realistic-looking skin is one of the holy grails of computer graphics and is still an active area of research. The problem is challenging due to the inherent complexity of skin and its variations, not only across individuals but also spatially and temporally among one. Skin appearance and reflectance vary spatially in one individual depending on its location on the human body, but also vary temporally with the aging process and the body state. Emotions, health, physical activity, and cosmetics for example can all affect the appearance of skin. The spatially varying reflectance of skin is due to many parameters, such as skin micro- and meso-geometry, thickness, oiliness, and pigmentation. It is therefore a daunting task to derive a model that will include all these parameters to produce realistic-looking skin. The problem is also compounded by the fact that we are very well accustomed to the appearance of skin and especially sensitive to facial appearances and expressions. Skin modelling and rendering is crucial for many applications such as games, virtual reality, films, and the beauty industry, to name a few. Realistic-looking skin improves the believability and realism of applications. The complexity of skin makes the topic of skin modelling and rendering for computer graphics a very difficult, but highly stimulating one. Skin deformations and biomechanics is a vast topic that we will not address in this dissertation. We rather focus our attention on skin optics and present a simple model for the reflectance of human skin along with a system to support skin modelling and rendering.

A viable <i>in vitro</i> excised human skin model was developed to accurately assess cutaneous delivery and metabolism of two ester type compounds; tetracaine (TC) and methyl salicylate (MS). This model could maintain the viability of fresh skin in diffusion cells for 24 hours. Skin viability was assessed using two methods; oxygen consumption measurement and confocal laser scanning microscopy. Two fluorescent probes, calcein AM and ethidium homodimer-1, were used as live and dead markers, respectively. General morphology and localization of nonspecific esterase activity in the skin samples from diffusion cell were checked histologically. Cutaneous delivery and metabolism of MS was evaluated with this viable skin model and compared to human skin homogenate model. A sensitive high performance liquid chromatography (HPLC) assay using reversed phase ion pair was developed/refined to simultaneously analyze TC and its metabolite (4-BABA). Several factors affecting this HPLC system were identified. The limit of detection for TC and 4-BABA was 0.3 ng and 0.5 ng, respectively. The limit of quantitation for TC and 4-BABA was 10 ng and 5 ng, respectively. Linearity was in the range of 10-120 ng for TC and 5-60 ng for 4-BABA. MS was hydrolyzed to salicylic acid (SA) during absorption through fall thickness human breast skin in diffusion cells. The extent of MS hydrolysis was significantly higher in viable skin than in non viable. The extent of absorption of SA through viable and non viable skins was similar. In human skin homogenate, MS was hydrolyzed at the rate of 72.31 nmol/h/[mu]g protein while the hydrolysis in phosphate buffered saline was very low. TC hydrolysis in human skin homogenate was not extensive due to substrate inhibition. From the kinetic study of TC hydrolysis in human skin homogenate, Km was in the 11-28 [mu]M range and Vmax was in the 2.0-2.8 [mu]mol/h/[mu]g protein range. Temperature over 60°C substantially reduced esterase activity in both models therefore caution must be taken during preparation and handling of tissue samples to preserve esterase activity. The viable <i>in vitro</i> excised skin model will provide more accurate quantitation of skin metabolism and absorption of xenobiotics.

Thesis (Ph.D.)--University of Western Australia, 2002.

Zinkoxid-Nanopartikel (ZnO-NP) finden in vielen Produkten des täglichen Verbrauchs Verwendung. Daten über die toxikologischen Eigenschaften von ZnO-NP werden kontrovers diskutiert. Die menschliche Haut ist in Bezug auf die ZnO-NP Exposition das wichtigste Kontakt-Organ. Intakte Haut stellt eine suffiziente Barriere gegenüber NP dar. Bei defekter Haut ist ein Kontakt zu den proliferierenden Stammzellen möglich, sodass diese als wichtiges toxikologische Ziel für NP darstellen. Das Ziel dieser Dissertation war die Bewertung der genotoxischen und zytotoxischen Effekte an humanen mesenchymalen Stammzellen (hMSC) durch niedrig dosierte ZnO-NP nach 24 stündiger Exposition, repetitiven Expositionen und im Langzeitversuch bis zu 6 Wochen. Zytotoxische Wirkungen von ZnO-NP wurden mit 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid-Test (MTT) gemessen. Darüber hinaus wurde die Genotoxizität durch den Comet-Assay bewertet. Zur Langzeitbeobachtung bis zu 6 Wochen wurde die Transmissionselektronenmikroskopie (TEM) verwendet. Zytotoxizität nach 24-stündiger ZnO-NP-Exposition war ab einer Konzentration von 50 µg/ml nachweisbar. Genotoxizität konnten bereits bei Konzentrationen von 1 und 10 µg/ml ZnO-NP beschrieben werden. Wiederholte Exposition verstärkte die Zyto-, aber nicht die Genotoxizität. Eine intrazelluläre NP-Akkumulation mit Penetration der Zellorganelle wurde bei einer Exposition bis zu 6 Wochen beobachtet. Die Ergebnisse deuten auf zytotoxische und genotoxisches Effekte von ZnO-NP hin. Bereits geringe Dosen von ZnO-NP können bei wiederholter Exposition toxische Wirkungen hervorrufen sowie eine langfristige Zellakkumulation. Diese Daten sollten bei der Verwendung von ZnO-NP an geschädigter Haut berücksichtigt werden. / Zinc oxide nanoparticles (ZnO-NP) are widely used in many products of daily consumption. Data on the toxicological properties of the ZnO-NP used are discussed controversially. Human skin is the most important organ in terms of ZnO-NP exposure. Intact skin has been shown to provide an adequate barrier against NPs, while defective skin allows NP contact with proliferating cells. Among proliferating cells, stem cells are the main toxicological target for NPs. Therefore, the aim of this dissertation was to evaluate the genotoxic and cytotoxic effects of human mesenchymal stem cells (hMSC) by low-dose ZnO-NP after 24 hours of exposure, repetitive exposures and in long-term experiments up to 6 weeks. Cytotoxic effects of ZnO-NP were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT). In addition, genotoxicity was assessed by the comet assay. Transmission electron microscopy (TEM) was used for long-term observation after 6 exposure periods. The results of the study show that ZnO-NP has a cytotoxic effect starting at high concentrations of 50 µg/mL and could demonstrate genotoxic effects in hMSC exposed to 1 and 10 µg/ml ZnO-NP. Repeated exposure enhanced cytotoxicity but not genotoxicity. Intracellular NP accumulation with penetration of the cell organelles was observed at exposure up to 6 weeks. The results indicate the cytotoxic and genotoxic potential of ZnO-NP. Even small doses of ZnO-NP can cause toxic effects with repeated exposure and long-term cell accumulation. These data should be considered when using ZnO-NP on damaged skin.