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Background: Barrier creams are applied to the surface of the skin to form a barrier that aims to prevent the penetration of irritants and allergens through the skin surface. Several inconsistencies and controversies exist in literature regarding the effect that barrier creams may have on skin barrier function. Various skin surface parameters are used to evaluate the effect that the barrier creams have on skin barrier function. These parameters include transepidermal water loss (TEWL), skin hydration and skin surface pH. Total skin thickness may be assessed as a variable on its own. Differences may exist in skin surface parameters when comparing African participants with Caucasian participants. Aim: The specific aim of this research was to evaluate the short-term1 effects of selected barrier creams on skin barrier function. Note 1: The words short-term are used in this study as each barrier cream is only tested over a period of 8 hours and not tested over a long term period of months or years. Method: Forty two non-smoking participants were included and tested in this study, of which 21 were African and the rest Caucasian. TEWL, skin hydration and skin surface pH were used to evaluate the differences in the effect of two different barrier creams (Reinol Solvgard and Momar Chex) on skin barrier function. TEWL was measured by making use of a closed chamber Vapometer (Deflin Technology Ltd., Kuopio, Finland), skin hydration using a Corneometer® CM 825 and skin surface pH using a pH meter probe (Courage and Khazaka Electronic Kӧln, Germany). A micro-pipette was used to drip a standard volume of 20 μl of ultrapure water on the skin surface before the researcher placed the pH meter probe onto the skin surface. Total skin thickness was measured by making use of ultrasound (Ultrascan 22 - TBS0061B) (Courage and Khazaka Electronic Kӧln, Germany). Three consecutive measurements were taken on the mid-forearm and the palm of the experimental arm. After baseline values were measured, 5 ml of the selected barrier cream was applied to the experimental arm. The barrier cream (selected for the day) was reapplied after 2, 4 and 6 hours and measurements were taken every 2, 4, 6 and 8 hours. The total skin thickness was measured at time zero and at 8 hours. Results: TEWL: For both barrier creams, statistical significant differences (p ≤ 0.05) were found between TEWL on the palms of African participants and Caucasian participants. Skin hydration: Statistically significant differences (p ≤ 0.05) were obtained with regard to mid-forearm skin hydration when comparing Reinol Solvgard with Momar Chex (this was applicable to both racial groups). A statistically significant difference (p ≤ 0.05) was obtained with regard to mid-forearm skin hydration when comparing African participants with Caucasian participants (this was only applicable to Reinol Solvgard). Statistical significant differences (p ≤ 0.05) were obtained with regard to skin hydration palm when comparing Reinol Solvgard with Momar Chex (this was applicable to both racial groups). Statistically significant differences (p ≤ 0.05) were obtained with regards to skin hydration palm when comparing African participants with Caucasian participants (this was applicable to both barrier creams). Skin surface pH: A statistically significant difference (p ≤ 0.05) was obtained with regard to pH of the mid-forearm when comparing Reinol Solvgard with Momar Chex (this was applicable to only the African participants). A statistical significance (p ≤ 0.05) was obtained with regards to skin surface pH mid-forearm when comparing African participants with Caucasian participants (this was applicable to Momar Chex barrier cream only). A statistically significant difference (p ≤ 0.05) was obtained with regards to the pH of the palm when comparing Reinol Solvgard with Momar Chex (this was only applicable to the African racial group). Conclusion: Using skin surface parameters, it can be concluded that Momar Chex barrier cream elicited more positive effects on skin barrier function than Reinol Solvgard barrier cream. This may be ascribed to the fact that both barrier creams lowered TEWL (positive effect), Reinol Solvgard lowered skin hydration (negative effect) whereas, Momar Chex increased the skin hydration (positive effect) and both barrier creams increased skin surface pH (negative effect). Furthermore, the objectives of this study were reached as (a) short-term effects on skin surface parameters were identified between African versus Caucasian participants, (b) significances were observed between the two barrier creams (Momar Chex and Reinol Solvgard) by making use of skin surface parameters and (c) general increases and or decreases were observed in skin surface parameters over a short term period of 8 hours. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

Copper exposure is known to be a rare cause of skin irritation and allergic reactions and according to our knowledge occupational dermal exposure to copper sulphate has not yet been characterised. As a result, the objectives of this study were to assess the dermal exposure of workers at a chemical industry to copper sulphate and to characterise the change in the their skin barrier function from before to the end of the work shift, as the skin’s barrier function can greatly influence the permeation of chemical substances. Methods: The change in skin barrier function of reactor workers, crystal and powder packaging workers at the chemical industry were assessed by measuring their dominant hand’s palm, back and wrist as well as their foreheads’ skin hydration, transepidermal water loss (TEWL) and skin surface pH before and at the end of the work shift. Commercial GhostwipesTM were used to collect dermal exposure samples from the same four anatomical areas before and at the end of the shift. Additional dermal exposure samples were collected from the palm and back of hand, prior to breaks 1 and 2. Surface wipe sampling was also conducted at several work and recreational areas of the chemical industry. Wipe samples were analysed by an accredited analytical laboratory, according to NIOSH method 9102 by means of Inductively Coupled Plasma-Atomic Emission Spectrometry. Results: Changes in skin hydration of the workers and anatomical areas at the end of the work shift were highly variable, while in general TEWL increased and skin surface pH decreased. Copper was collected from the skin of all workers before the shift commenced, and dermal exposure increased throughout the work shift. All of the work and recreational areas from which surface samples were taken, were contaminated with copper. Conclusion: As a result of intermittent use of inadequate protective gloves and secondary skin contact with contaminated surfaces and work clothing, workers at the chemical industry are exposed to copper sulphate via the dermal exposure route. The decrease in the workers’ skin barrier function (increased TEWL) and skin surface pH is most likely the result of their dermal exposure to sulphuric acid, and may lead to enhanced dermal penetration. The low account of skin irritation or reaction incidences among these workers is contributed to their ethnicity as well as to the low sensitisation potential of copper. Recommendations on how to lower dermal exposure and improve workers’ skin barrier function are made. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2014

Background: Barrier creams are applied to the surface of the skin to form a barrier that aims to prevent the penetration of irritants and allergens through the skin surface. Several inconsistencies and controversies exist in literature regarding the effect that barrier creams may have on skin barrier function. Various skin surface parameters are used to evaluate the effect that the barrier creams have on skin barrier function. These parameters include transepidermal water loss (TEWL), skin hydration and skin surface pH. Total skin thickness may be assessed as a variable on its own. Differences may exist in skin surface parameters when comparing African participants with Caucasian participants. Aim: The specific aim of this research was to evaluate the short-term1 effects of selected barrier creams on skin barrier function. Note 1: The words short-term are used in this study as each barrier cream is only tested over a period of 8 hours and not tested over a long term period of months or years. Method: Forty two non-smoking participants were included and tested in this study, of which 21 were African and the rest Caucasian. TEWL, skin hydration and skin surface pH were used to evaluate the differences in the effect of two different barrier creams (Reinol Solvgard and Momar Chex) on skin barrier function. TEWL was measured by making use of a closed chamber Vapometer (Deflin Technology Ltd., Kuopio, Finland), skin hydration using a Corneometer® CM 825 and skin surface pH using a pH meter probe (Courage and Khazaka Electronic Kӧln, Germany). A micro-pipette was used to drip a standard volume of 20 μl of ultrapure water on the skin surface before the researcher placed the pH meter probe onto the skin surface. Total skin thickness was measured by making use of ultrasound (Ultrascan 22 - TBS0061B) (Courage and Khazaka Electronic Kӧln, Germany). Three consecutive measurements were taken on the mid-forearm and the palm of the experimental arm. After baseline values were measured, 5 ml of the selected barrier cream was applied to the experimental arm. The barrier cream (selected for the day) was reapplied after 2, 4 and 6 hours and measurements were taken every 2, 4, 6 and 8 hours. The total skin thickness was measured at time zero and at 8 hours. Results: TEWL: For both barrier creams, statistical significant differences (p ≤ 0.05) were found between TEWL on the palms of African participants and Caucasian participants. Skin hydration: Statistically significant differences (p ≤ 0.05) were obtained with regard to mid-forearm skin hydration when comparing Reinol Solvgard with Momar Chex (this was applicable to both racial groups). A statistically significant difference (p ≤ 0.05) was obtained with regard to mid-forearm skin hydration when comparing African participants with Caucasian participants (this was only applicable to Reinol Solvgard). Statistical significant differences (p ≤ 0.05) were obtained with regard to skin hydration palm when comparing Reinol Solvgard with Momar Chex (this was applicable to both racial groups). Statistically significant differences (p ≤ 0.05) were obtained with regards to skin hydration palm when comparing African participants with Caucasian participants (this was applicable to both barrier creams). Skin surface pH: A statistically significant difference (p ≤ 0.05) was obtained with regard to pH of the mid-forearm when comparing Reinol Solvgard with Momar Chex (this was applicable to only the African participants). A statistical significance (p ≤ 0.05) was obtained with regards to skin surface pH mid-forearm when comparing African participants with Caucasian participants (this was applicable to Momar Chex barrier cream only). A statistically significant difference (p ≤ 0.05) was obtained with regards to the pH of the palm when comparing Reinol Solvgard with Momar Chex (this was only applicable to the African racial group). Conclusion: Using skin surface parameters, it can be concluded that Momar Chex barrier cream elicited more positive effects on skin barrier function than Reinol Solvgard barrier cream. This may be ascribed to the fact that both barrier creams lowered TEWL (positive effect), Reinol Solvgard lowered skin hydration (negative effect) whereas, Momar Chex increased the skin hydration (positive effect) and both barrier creams increased skin surface pH (negative effect). Furthermore, the objectives of this study were reached as (a) short-term effects on skin surface parameters were identified between African versus Caucasian participants, (b) significances were observed between the two barrier creams (Momar Chex and Reinol Solvgard) by making use of skin surface parameters and (c) general increases and or decreases were observed in skin surface parameters over a short term period of 8 hours. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

Copper exposure is known to be a rare cause of skin irritation and allergic reactions and according to our knowledge occupational dermal exposure to copper sulphate has not yet been characterised. As a result, the objectives of this study were to assess the dermal exposure of workers at a chemical industry to copper sulphate and to characterise the change in the their skin barrier function from before to the end of the work shift, as the skin’s barrier function can greatly influence the permeation of chemical substances. Methods: The change in skin barrier function of reactor workers, crystal and powder packaging workers at the chemical industry were assessed by measuring their dominant hand’s palm, back and wrist as well as their foreheads’ skin hydration, transepidermal water loss (TEWL) and skin surface pH before and at the end of the work shift. Commercial GhostwipesTM were used to collect dermal exposure samples from the same four anatomical areas before and at the end of the shift. Additional dermal exposure samples were collected from the palm and back of hand, prior to breaks 1 and 2. Surface wipe sampling was also conducted at several work and recreational areas of the chemical industry. Wipe samples were analysed by an accredited analytical laboratory, according to NIOSH method 9102 by means of Inductively Coupled Plasma-Atomic Emission Spectrometry. Results: Changes in skin hydration of the workers and anatomical areas at the end of the work shift were highly variable, while in general TEWL increased and skin surface pH decreased. Copper was collected from the skin of all workers before the shift commenced, and dermal exposure increased throughout the work shift. All of the work and recreational areas from which surface samples were taken, were contaminated with copper. Conclusion: As a result of intermittent use of inadequate protective gloves and secondary skin contact with contaminated surfaces and work clothing, workers at the chemical industry are exposed to copper sulphate via the dermal exposure route. The decrease in the workers’ skin barrier function (increased TEWL) and skin surface pH is most likely the result of their dermal exposure to sulphuric acid, and may lead to enhanced dermal penetration. The low account of skin irritation or reaction incidences among these workers is contributed to their ethnicity as well as to the low sensitisation potential of copper. Recommendations on how to lower dermal exposure and improve workers’ skin barrier function are made. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2014

Introdução: A comprovação da eficiência de formulações hidratantes deve ser criteriosa e analisada com métodos adequados. Objetivo: O objetivo principal do trabalho foi avaliar in vivo a eficácia hidratante de formulações contendo diferentes componentes ativos por capacitância elétrica e perda de água transepidérmica. Compararam-se os desempenhos entre Corneometer® e Moisturemeter® e entre o Vapometer® e Tewlmeter®. Verificou-se o comportamento in vitro das alterações causadas pelas substâncias hidratantes, em modelo de estrato córneo alternativo. Material e Métodos: Os compostos ativos selecionados (4% p/p) para incorporação nos géis à base de carbômero foram: uréia, extrato vegetal de Imperata cylindrica; complexo contendo fatores de hidratação natural; e os derivados do açúcar, sacarídeo isomerato e a mistura de xilitilglicosídeo e anidroxilitilglicosídeo. A avaliação in vivo da eficácia hidratante teve o delineamento experimental baseado no projeto fatorial ANOVA three way. Os tempos estudados foram: após a aplicação e 30, 60, 120; 240 e 360 minutos. O estudo de estabilidade acelerada das formulações envolveu condições drásticas de armazenamento (temperatura, umidade e luminosidade) durante 90 dias. Na avaliação in vitro do comportamento das substâncias hidratantes utilizou-se a espectroscopia Raman com transformada de Fourier (FT-Raman) e Calorimetria exploratória diferencial (DSC). Resultados: A análise estatística da capacitânia elétrica obtida por Corneometer® e do Moisturemeter® mostraram que houve diferenças significativas entre os géis e o tempo de aplicação. Com relação às medidas de perda de água transepidérmica, os resultados obtidos por Vapometer® e Tewlmeter® não apresentaram concordância. As bandas encontradas nos espectros FT-Raman mostraram que os ativos hidratantes não provocaram alterações na estrutura conformacional do estrato córneo alternativo. A análise da calorimetria (DSC) mostrou que o gel de uréia aumentou o conteúdo hídrico da membrana. Conclusão: Os géis contendo 4% (p/p) de uréia e de 4% (p/p) de derivado de açúcar apresentaram melhor eficácia hidratante in vivo, capacitância elétrica quando analisado por Corneometer® e Moisturemeter®. Em relação à perda de água transepidérmica, o gel base sem ativo obteve o melhor resultado. Com relação às medidas de capacitância, o Corneometer® e o Moisturemeter® mostraram-se estaticamente semelhantes. Comparando-se as medidas de perda de água transepidérmica, a análise estatística indicou que o Vapometer® tem precisão inferior comparada com o Tewlmeter®. A avaliação do comportamento in vitro das substâncias hidratantes sugeriram que as mesmas são seguras. / Introduction: Hydration of the corneal layer varies according to the amount of water present; the transportation of water from the lower layers; evaporation speed and quantity and composition of epicutaneous emulsion. Proof of moisturizer formula efficiency must be prudent and analyzed using appropriate methods. Objective: The studys main objective was to assess the in vivo efficacy of moisturizer formulas with different active components by means of electrical capacitance and transepidermal water loss. The accelerated stability of the referred to formulas was also observed and assessed. Performances between Corneometer® and Moisturemeter® and between Vapometer® and Tewlmeter® were compared. In vitro behavior of alterations caused by moisturizing substances was verified in an alternative corneal stratum model. Material and Methods: The active compounds selected (4% p/p) for use in carbomer-based gels were: urea, Imperata cylindrica vegetal extract; a complex with natural moisturizing factors; sugar byproducts, saccharide isomerate and the mix of xylitol glucoside and anhydro xylitol glicoside. In vivo assessment of moisturizing efficacy of the formulas by means of electrical capacitance and transepidermal water loss was designed based in ANOVA three way factorial design. The gels were applied on both arms of volunteers aged 20 to 30 and a control application (base gel) and an untreated area were used. Study times were: after application and at 30, 60, 120; 240 and 360 minutes. The accelerated stability study of the formulations involved drastic storage conditions (temperature, humidity, luminosity) over 90 days. For the in vitro assessment of moisturizing substance behavior, Raman spectroscopy was used with Fourier Transform (FT-Raman) and differential scanning calorimetry (DSC). Results: Statistical analysis of electrical capacitance using Corneometer® and Moisturemeter® revealed significant differences between the gels and application time. With regard to transepidermal water loss measures, the results obtained from Vapometer® and Tewlmeter® did not reveal concordance. The bands found in the FT-Raman spectrum revealed that the active moisturizers did not cause changes in the alternative cornea stratum conformation structure. Calorimetry (DSC) analysis showed the urea gel increased membrane water content. Conclusion: Gels containing 4% (p/p) urea and 4% (p/p) of sugar byproduct had the best in vivo moisturizing efficacy, electrical capacitance when analyzed with Corneometer® and Moisturemeter®. In relation to transepidermal water loss, the base gel without active ingredients had the best result in both Vapometer® and Tewlmeter®. The formulas were stable for a period of three months in the studied storage conditions. In relation to capacitance measures, Corneometer® and Moisturemeter® proved to be statistically similar. When comparing transepidermal water loss measures, statistical analysis indicated that Vapometer® is not as precise as Tewlmeter®. In vitro assessment of behavior of moisturizing substances suggested they are safe.

Atopic eczema is an incurable disorder of the skin. Sufferers are afflicted with hypersensitivity to environmental agents such as soaps (detergents), animal dander, pollen, specific foods and sometimes even water. Genetic mutations in atopic eczema compromise the development of the stratum corneum resulting in xerotic skin that is prone to cracking and increased permeability which leads to irritation due to the influx of exogenous material through the skin. The causes of atopic eczema are due to a combination of genetic and environmental factors and it is, therefore, a difficult disease to manage. Emollients and topical corticosteroids are the mainstay treatments for eczema. However, they do not treat the underlying cause of the flare-ups frequently seen in the condition; the damaged skin barrier. Defects in the skin barrier arise from premature desquamation of the stratum corneum. The main contributors to barrier breakdown are the up-regulation of skin proteases that are located in the skin. Since zinc is a known protease inhibitor, it would thus follow that a topical treatment for skin barrier repair should be developed. Therefore, the main objectives of this thesis are to successfully incorporate zinc into a formulation to develop a novel class of treatment for eczema and to assess the delivery of the element into the skin. In this thesis, methods to assess and characterise changes to skin barrier function and to extract and quantify zinc in the stratum corneum have been established. The development of two novel topically applied formulations containing zinc lactate as the active ingredient (1% w/w zinc lactate cream and a 2% w/v zinc lactate formulation) has been achieved and the uptake of zinc from the preparations in vitro determined. Further, the in vitro percutaneous penetration of zinc from three commercially available preparations has been investigated and compared to that recovered from the stratum corneum after passive diffusion with the novel zinc formulations. Additionally, in vivo uptake of zinc into human stratum corneum from Sudocremis ® reported. Scanning electron microscopy has revealed the distribution of zinc on the surface of skin treated with various formulations and has also allowed the efficiency of two cleaning procedures to be ascertained. The delivery of zinc from the novel topical formulation; 1% w/w zinc lactate cream, was more efficient than that the three commercial formulations and shows promise as a new approach to treat atopic eczema.

Introdução: A comprovação da eficiência de formulações hidratantes deve ser criteriosa e analisada com métodos adequados. Objetivo: O objetivo principal do trabalho foi avaliar in vivo a eficácia hidratante de formulações contendo diferentes componentes ativos por capacitância elétrica e perda de água transepidérmica. Compararam-se os desempenhos entre Corneometer® e Moisturemeter® e entre o Vapometer® e Tewlmeter®. Verificou-se o comportamento in vitro das alterações causadas pelas substâncias hidratantes, em modelo de estrato córneo alternativo. Material e Métodos: Os compostos ativos selecionados (4% p/p) para incorporação nos géis à base de carbômero foram: uréia, extrato vegetal de Imperata cylindrica; complexo contendo fatores de hidratação natural; e os derivados do açúcar, sacarídeo isomerato e a mistura de xilitilglicosídeo e anidroxilitilglicosídeo. A avaliação in vivo da eficácia hidratante teve o delineamento experimental baseado no projeto fatorial ANOVA three way. Os tempos estudados foram: após a aplicação e 30, 60, 120; 240 e 360 minutos. O estudo de estabilidade acelerada das formulações envolveu condições drásticas de armazenamento (temperatura, umidade e luminosidade) durante 90 dias. Na avaliação in vitro do comportamento das substâncias hidratantes utilizou-se a espectroscopia Raman com transformada de Fourier (FT-Raman) e Calorimetria exploratória diferencial (DSC). Resultados: A análise estatística da capacitânia elétrica obtida por Corneometer® e do Moisturemeter® mostraram que houve diferenças significativas entre os géis e o tempo de aplicação. Com relação às medidas de perda de água transepidérmica, os resultados obtidos por Vapometer® e Tewlmeter® não apresentaram concordância. As bandas encontradas nos espectros FT-Raman mostraram que os ativos hidratantes não provocaram alterações na estrutura conformacional do estrato córneo alternativo. A análise da calorimetria (DSC) mostrou que o gel de uréia aumentou o conteúdo hídrico da membrana. Conclusão: Os géis contendo 4% (p/p) de uréia e de 4% (p/p) de derivado de açúcar apresentaram melhor eficácia hidratante in vivo, capacitância elétrica quando analisado por Corneometer® e Moisturemeter®. Em relação à perda de água transepidérmica, o gel base sem ativo obteve o melhor resultado. Com relação às medidas de capacitância, o Corneometer® e o Moisturemeter® mostraram-se estaticamente semelhantes. Comparando-se as medidas de perda de água transepidérmica, a análise estatística indicou que o Vapometer® tem precisão inferior comparada com o Tewlmeter®. A avaliação do comportamento in vitro das substâncias hidratantes sugeriram que as mesmas são seguras. / Introduction: Hydration of the corneal layer varies according to the amount of water present; the transportation of water from the lower layers; evaporation speed and quantity and composition of epicutaneous emulsion. Proof of moisturizer formula efficiency must be prudent and analyzed using appropriate methods. Objective: The studys main objective was to assess the in vivo efficacy of moisturizer formulas with different active components by means of electrical capacitance and transepidermal water loss. The accelerated stability of the referred to formulas was also observed and assessed. Performances between Corneometer® and Moisturemeter® and between Vapometer® and Tewlmeter® were compared. In vitro behavior of alterations caused by moisturizing substances was verified in an alternative corneal stratum model. Material and Methods: The active compounds selected (4% p/p) for use in carbomer-based gels were: urea, Imperata cylindrica vegetal extract; a complex with natural moisturizing factors; sugar byproducts, saccharide isomerate and the mix of xylitol glucoside and anhydro xylitol glicoside. In vivo assessment of moisturizing efficacy of the formulas by means of electrical capacitance and transepidermal water loss was designed based in ANOVA three way factorial design. The gels were applied on both arms of volunteers aged 20 to 30 and a control application (base gel) and an untreated area were used. Study times were: after application and at 30, 60, 120; 240 and 360 minutes. The accelerated stability study of the formulations involved drastic storage conditions (temperature, humidity, luminosity) over 90 days. For the in vitro assessment of moisturizing substance behavior, Raman spectroscopy was used with Fourier Transform (FT-Raman) and differential scanning calorimetry (DSC). Results: Statistical analysis of electrical capacitance using Corneometer® and Moisturemeter® revealed significant differences between the gels and application time. With regard to transepidermal water loss measures, the results obtained from Vapometer® and Tewlmeter® did not reveal concordance. The bands found in the FT-Raman spectrum revealed that the active moisturizers did not cause changes in the alternative cornea stratum conformation structure. Calorimetry (DSC) analysis showed the urea gel increased membrane water content. Conclusion: Gels containing 4% (p/p) urea and 4% (p/p) of sugar byproduct had the best in vivo moisturizing efficacy, electrical capacitance when analyzed with Corneometer® and Moisturemeter®. In relation to transepidermal water loss, the base gel without active ingredients had the best result in both Vapometer® and Tewlmeter®. The formulas were stable for a period of three months in the studied storage conditions. In relation to capacitance measures, Corneometer® and Moisturemeter® proved to be statistically similar. When comparing transepidermal water loss measures, statistical analysis indicated that Vapometer® is not as precise as Tewlmeter®. In vitro assessment of behavior of moisturizing substances suggested they are safe.

Exposure to high heat and humidity can lead to serious health risks, including heat exhaustion and heat stroke. Wet Bulb Globe Temperature (WBGT) and heat index have historically been used to predict heat stress events, but individualized factors are not included in the measurement. It has been shown that there is a relationship between cardiovascular measurements and heat stress, which could be used to measure heat stress risk on an individual level. Research has been done to find relationships between cardiovascular metrics in a workplace environment, however the study did not include the use of a controlled environment as a baseline. This study provides measurements of transepidermal water loss (TEWL), heart rate, body core temperature, and blood pressure in a controlled environment when human subjects are exposed to high heat and humidity. Thirty subjects (n=17 females, 13 males) were asked to self-express their activity level (active vs. sedentary), gender, and age. The subjects performed a 30-minute moderate exercise routine on a stationary stepper machine in a heated environmental chamber (average WBGT of 26ºC). TEWL, heart rate, tympanic temperature, and blood pressure were recorded at every 10-minute increment of the exercise protocol per subject. The data was analyzed using JMP® software to find significant (P

La peau, organe le plus étendu du corps humain, réalise une barrière entre l’environnement et le milieu interne préservant ainsi l’homéostasie. De nombreuses fonctions sont assurées par le tégument telles une modulation des échanges thermiques, une barrière physique, chimique et immunitaire contre l’entrée des composés et microorganismes exogènes mais également contre la perte des substances du milieu interne. L’altération de la surface cutanée et donc de ses fonctions, engendre un processus complexe de réparation qui vise à restaurer le système. Lors de ce travail de thèse des outils biophysiques ont été expérimentés dans un premier temps afin de renseigner sur la qualité de la fonction barrière, et donc sur la qualité de la cicatrisation cutanée. La première approche consistait à quantifier la qualité de la barrière cutanée par mesure de la perte insensible en eau. Cette approche s’est révélée fructueuse et a été proposée comme standard interne dans les études de perméation cutanée ex vivo afin de permettre une comparaison plus aisée des résultats expérimentaux issus de différentes préparations de peau. Dans un second temps la mesure des paramètres du micro relief cutané a été confrontée aux résultats des mesures concomitantes des paramètres biophysiques classiques (perte insensible en eau et hydratation cutanée) afin de mettre en évidence une possible corrélation entre qualité de la fonction barrière cutanée et topologie de surface. Les résultats des deux méthodes d’investigation sont effectivement bien corrélés dans le cas d’une altération physique de la surface cutanée, suggérant les mesures des paramètres du micro relief cutané comme une méthode originale de quantification de la réépithélialisation cutanée. Une approche plus fondamentale a également été éprouvée afin d’appréhender les mesures de « pertes insensibles en oxygène » comme une mesure innovante de la qualité de la fonction barrière cutanée. Cette première approche a permis de mettre en évidence, une orientation préférentielle significative du flux d’oxygène à travers la peau.La deuxième partie de ce travail de thèse a consisté à développer une nouvelle formulation pro cicatrisante et de tester son potentiel thérapeutique in vitro. Initialement basée sur l’administration d’oxygène afin de lutter contre l’hypoxie qui accompagne souvent les lésions cutanées, cette ligne d’étude a rapidement été écartée au profit du développement d’une formulation pour l’établissement d’un stress oxydant améliorant les processus de cicatrisation. Cette théorie du stress oxydant comme promoteur de la cicatrisation découle d’observations récentes qui démontrent un retard de cicatrisation en l’absence d’un stress oxydant in vivo, et une stimulation spécifique des cellules in vitro. Les formulations développées à ce dessein ont été testées sur des cultures de kératinocytes in vitro afin d’étudier leurs effets sur la réépithélialisation : l’une des dernières étapes de la cicatrisation. / Skin, the largest organ of the human body, confers protection from the environment through several barrier functions which provide physical, immune and chemical defenses. Skin provides protection to microorganisms, exogenous compounds, shocks, radiations, temperature and out flowing of solutes or water from the body. Without an efficient system to restore skin structures and functions, skin wounding may be deleterious. Over the course of this Ph.D. work, varied biophysical parameters have been experienced as tools to investigate the cutaneous wound healing quality. Measurement of transepidermal water loss (TEWL) to quantify the barrier function quality of the skin has been successfully assessed. It has been proposed as an internal standard of skin integrity facilitating direct comparison of data issued from different skin samples. In an in vivo approach, skin micro-relief parameters have been set against TEWL and hydration values after a physical or chemical damage onto the skin. Interestingly micro-relief parameters and biophysical measurements were closely related after tape-stripping, suggesting topographical parameters as an original method to quantify skin reepithelialization. A more fundamental assay was performed suggesting oxygen flux as a new tool to investigate skin barrier quality. From our results a “transepidermal oxygen loss” development seems to be compromised but surprisingly, we pointed out a preferential oxygen delivery course through the skin from endogenous reservoir. Besides the improvement of these tools for wound healing assessment, an innovative formulation to promote skin wound healing has been developed. The challenge of this new preparation is to generate reactive oxygen species, namely hydrogen peroxide, at sub-cytotoxic levels. Indeed recent studies pointed out that down regulation of hydrogen peroxide production in vivo delayed wound healing; furthermore, in vitro stimulation of fibroblasts or keratinocytes with hydrogen peroxide induced expression of healing promoting factors. The developed formulation was therefore assayed on keratinocytes’ in vitro culture in order to evaluate their efficacy on réépithélialisation, ending wound closure. Interestingly one of the developed formulation stimulated significantly keratinocytes migration, through a mechanism which do not imply TGF-1 expression, suggesting a potential benefit in wound réépithélialisation.