No description available.

Skin cancer is a major health problem worldwide. It is the most common cancer in the United States and poses a significant healthcare burden. Excessive UVR exposure is the most common cause of skin cancer. Despite various precautionary measures to avoid direct UVR exposure, the incidence of skin cancer and mortality related to it remains high. Furthermore, the current treatment options are expensive and have side effects including toxicity to normal cells. Thus, a safe and effective approach is needed to prevent and treat skin cancer. Chemopreventive strategy using naturally occurring compounds, such as resveratrol, is a promising approach to reduce the incidence of UVR-induced skin cancer and delay its progression. This review highlights the current body of evidence related to chemopreventive role of resveratrol and its molecular mechanisms in UVR-induced skin carcinogenesis.

Afin de comprendre, caractériser et prédire l’évolution des cycles biogéochimiques océaniques face au changement climatique global, il est nécessaire d’appréhender au mieux la dynamique de la matière organique (MO) au niveau des interfaces « terre/océan ». Dans ce contexte, l’objectif général de cette thèse était d’améliorer les connaissances sur la dynamique de la fraction dissoute chromophorique de la MO (CDOM) des eaux de surface côtières méditerranéennes et arctiques, et d’en déterminer l’impact sur l’atténuation du rayonnement UV (UVR) et visible (PAR) sous-marin. Pour cela, l’étude des propriétés optiques d’absorbance et de fluorescence de la CDOM, couplée à des mesures radiométriques atmosphériques et sous-marines, ont été réalisées lors d’un cycle saisonnier en Baie de Marseille (station SOFCOM), et lors d’une mission océanographique en Mer de Beaufort durant l’été 2009. La Baie de Marseille est caractérisée par des quantités de CDOM faibles (aCDOM(350) = 0,10 ± 0,02 m-1), particulièrement à la fin de la période estivale de stratification, à cause de l’intensité de l’éclairement solaire, enrichi en UVR-B, qui dégrade et blanchie cette CDOM (SCDOM = 0,023 ± 0,003 nm-1). Dans cette zone côtière fortement urbanisée, la dynamique de la CDOM est pilotée par des processus biotiques (production biologique in situ et induite par les intrusions épisodiques du panache du Rhône) et abiotiques (photo-blanchiment et brassage). La CDOM est essentiellement d’origine autochtone, même lors d’événements d’intrusion du panache du Rhône (photo-dégradation de la CDOM terrestre durant son transit). Lors des périodes d’efflorescences algales, la CDOM se compose principalement de matériel récent, de type protéique (pic T), qui absorbe préférentiellement les courts UVR. Ces pulses de CDOM récente se superposent à un persistent signal de fond de CDOM composé majoritairement de matériel âgé, de type humique (pics M et C), qui absorbe les UVR et également le PAR. Au niveau du plateau Canadien de la Mer de Beaufort, la CDOM est très abondante (aCDOMmax(350) = 6,36 m-1), fortement influencée par les apports allochtones du Mackenzie (pics A-C et M) et décroit de manière conservatrice avec la salinité. Dans les eaux marines (salinité >25), la CDOM, qui présente de plus faibles concentrations (aCDOM(350) = 0,21 ± 0,13 m-1), provient d’une production biologique in situ récente favorisée par des upwellings ainsi que d’injections de CDOM (pics B-T et M) lors de la formation/fonte de la glace de mer. Etonnamment, la source principale du composé « humique marin » (pic M) n’est pas autochtone. Elle est issue d’apports allochtones provenant du Mackenzie. Celui-ci draine en effet de nombreux lacs qui sont le siège d’une intense activité biologique, et il est proposé dans cette thèse que les macrophytes qui s’y développent seraient à l’origine du pic M. Cette source de CDOM biologique allochtone, couplée aux processus de photo-blanchiment et d’absorption sur les particules de la CDOM terrestre, pourraient expliquer les valeurs élevées de SCDOM (≈ 0,020 nm-1) du Mackenzie en été. / To understand, characterize, and predict the evolution of oceanic biogeochemical cycles in relation to the global climate change, it is necessary to better understand the dynamics of organic matter (OM). In this context, the overall objective of this thesis was to get more insights chromophoric dissolved fraction of OM (CDOM) dynamics in surface Mediterranean and Arctic coastal waters and to determine the impact on attenuation of ultraviolet (UVR) and visible (PAR) underwater radiation. For this, the study of optical properties of absorbance and fluorescence of CDOM, coupled with atmospheric and underwater radiometric measurements, were made during a seasonal cycle in the Bay of Marseille (SOFCOM station), and in the Beaufort Sea during summer 2009. The Bay of Marseilles is characterized by low amounts of CDOM (aCDOM(350) = 0.10 ± 0.02 m-1), particularly in end summer stratification period due to the intensity of the solar irradiance, enriched in UVR-B, which degrades and bleaches CDOM (SCDOM = 0.023 ± 0.003 nm-1). In this highly urbanized coastal area, the dynamics of CDOM are driven by biotic processes (in situ biological production and within the Rhône River plume) and abiotic (photo-bleaching and mixing). Our results showed that CDOM is mostly of autochthonous origin, even during Rhône plume intrusion events (photo-degradation of terrestrial CDOM during the transit). During bloom periods, the CDOM consists mainly of a recent type protein (peak T), which preferentially absorbs in the short UVR. These pulses of recent CDOM are superimposed on a persistent background of CDOM mainly composed of aged material, humic-type (peaks M and C), which absorbs UVR and PAR. Over the Canadian shelf of the Beaufort Sea, CDOM is highly abundant (aCDOMmax (350) = 6.36 m-1) and strongly influenced by allochthonous inputs from the Mackenzie (peaks A-C and M) decreasing conservatively with salinity. In marine waters (salinity> 25), CDOM had lower concentrations (aCDOM(350) = 0.21 ± 0.13 m-1) and originated from a recent in situ biological production favored by upwelling and brine injections (peaks B-T and M). Surprisingly, the main source of the marine humic-like component (peak M) was not autochthonous. This material originates from allochthonous inputs from the Mackenzie River, which traverses numerous lakes where intense biological activity occurs. We suggest that this activity is mainly due to the macrophytes development, which may in part explain the origin of the peak M. This source of organic allochthonous CDOM coupled to other processes such as photobleaching and absorption on the particles of terrestrial CDOM, could explain the high values of SCDOM (≈ 0.020 nm-1) recorded in the Mackenzie during summertime.

No / Acute exposure of human skin to the ultraviolet radiation (UVR) in sunlight results in the sunburn response. This is mediated in part by pro-inflammatory eicosanoids and other bioactive lipids, which are in turn produced via mechanisms including UVR-induction of oxidative stress, cell signalling and gene expression. Sunburn is a self-limiting inflammation offering a convenient and accessible system for the study of human cutaneous lipid metabolism. Recent lipidomic applications have revealed that a wider diversity of eicosanoids may be involved in the sunburn response than previously appreciated. This article reviews the effects of UVR on cutaneous lipids and examines the contribution of bioactive lipid mediators in the development of sunburn. Since human skin is an active site of polyunsaturated fatty acid (PUFA) metabolism, and these macronutrients can influence the production of eicosanoids/bioactive lipids, as well as modulate cell signalling, gene expression and oxidative stress, the application of PUFA as potential photoprotective agents is also considered.

No description available.

No description available.

Erythema is a hallmark skin response to excessive ultraviolet radiation (UVR) and is associated with cutaneous inflammation. Both are mediated by inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2) and chemoattractants such as 12-hydroxyeicosatetraenoic acid (12-HETE) leading to vasodilation and increased leukocyte infiltration. The erythematous response is more pronounced in individuals with low basal melanin levels or who fail to respond to UVR with a robust up-regulation of melanogenesis. While melanin production is a key function of melanocytes, these cells can also produce NO and PGE2, and are located in close proximity to the dermal vasculature. It has been hypothesized that melanocytes with poor melanogenic capacity may participate in the inflammatory response to UVR. The aim of this project was to investigate the inflammatory response in the skin of individuals with either skin phototype (SPT) 1 or 4 to UVR. Sixteen normal healthy individuals were selected for study (8 SPT-1 & 8 SPT-4). Buttock skin was investigated by immunohistochemistry for leukocyte subtypes, eicosanoid producing enzymes and NO synthases under basal and UVR-stimulated conditions. In addition primary cultures of epidermal melanocytes (EM) were established from 16 individuals (8 SPT-1 & 8 SPT-4) and assessed for the presence of eicosanoid-producing enzymes, melanogenic enzymes and NO synthases, by immunocytochemistry, Polymerase Chain Reaction and Western Blotting and for the production of the main pro-inflammatory eicosanoid PGE2 by ELISA and Mass Spectrometry. Moreover, the fatty acid composition of cultured melanocytes was assessed by Gas Chromatography. Results showed that individuals with SPT-1 had significantly greater neutrophil infiltration into the epidermis than those with SPT-4 at 24 hrs post-UVR. Moreover, CD3+ lymphocyte infiltration into the dermis was significantly greater in individuals with SPT-4 than those with SPT-1 at 24 and 72 hrs post-UVR. NOS-1, NOS-3, 12-LOX and COX-2 expression were significantly increased in SPT-1 skin, while NOS-2 and 15-LOX were significantly increased in SPT-4 skin. As 12-LOX and COX-2 products are chemoattractive (for neutrophils) and pro-inflammatory respectively these data could explain the greater observed neutrophil infiltration in SPT-1. The 15-LOX product (15-HETE) is anti-inflammatory and may suggest that 15-LOX up-regulation in SPT-4 skin may aid resolution of the sunburn response, which in part may be mediated by CD3+ lymphocytes and a class-switch in eicosanoid production from COX to LOX products. Melanocyte primary cultures surprisingly showed that SPT was not correlated with melanin content or melanogenic enzyme expression/activity suggesting that all melanocytes in vitro contained the necessary cellular machinery to produce melanin. This finding may reflect also their equal treatment under these enriched culture conditions, which may or may not be available to these cells in situ. Moreover, all melanocytes expressed the necessary machinery (PLA2, COX-1, cPGES) to produce PGE2. However, only some cultures did so at baseline and in response to UVR, and this was not correlated with SPT. A positive correlation was found however between expression level of dopachrome tautomerase (DCT) and protection against PGE2 production in response to UVR, which may suggest a novel role for DCT unrelated to melanogenesis. In summary this research project has generated data that highlights differences between the skin of individuals with SPT-1 and those with SPT-4, and may provide evidence that the keratinocyte partner contributes significantly to the SPT-associated response. This research may also suggest DCT as a novel therapeutic target to protect EM from participation in the UVR-associated inflammatory response in skin.

Erythema is a hallmark skin response to excessive ultraviolet radiation (UVR) and is associated with cutaneous inflammation. Both are mediated by inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2) and chemoattractants such as 12-hydroxyeicosatetraenoic acid (12-HETE) leading to vasodilation and increased leukocyte infiltration. The erythematous response is more pronounced in individuals with low basal melanin levels or who fail to respond to UVR with a robust up-regulation of melanogenesis. While melanin production is a key function of melanocytes, these cells can also produce NO and PGE2, and are located in close proximity to the dermal vasculature. It has been hypothesized that melanocytes with poor melanogenic capacity may participate in the inflammatory response to UVR. The aim of this project was to investigate the inflammatory response in the skin of individuals with either skin phototype (SPT) 1 or 4 to UVR. Sixteen normal healthy individuals were selected for study (8 SPT-1 & 8 SPT-4). Buttock skin was investigated by immunohistochemistry for leukocyte subtypes, eicosanoid producing enzymes and NO synthases under basal and UVR-stimulated conditions. In addition primary cultures of epidermal melanocytes (EM) were established from 16 individuals (8 SPT-1 & 8 SPT-4) and assessed for the presence of eicosanoid-producing enzymes, melanogenic enzymes and NO synthases, by immunocytochemistry, Polymerase Chain Reaction and Western Blotting and for the production of the main pro-inflammatory eicosanoid PGE2 by ELISA and Mass Spectrometry. Moreover, the fatty acid composition of cultured melanocytes was assessed by Gas Chromatography. Results showed that individuals with SPT-1 had significantly greater neutrophil infiltration into the epidermis than those with SPT-4 at 24 hrs post-UVR. Moreover, CD3+ lymphocyte infiltration into the dermis was significantly greater in individuals with SPT-4 than those with SPT-1 at 24 and 72 hrs post-UVR. NOS-1, NOS-3, 12-LOX and COX-2 expression were significantly increased in SPT-1 skin, while NOS-2 and 15-LOX were significantly increased in SPT-4 skin. As 12-LOX and COX-2 products are chemoattractive (for neutrophils) and pro-inflammatory respectively these data could explain the greater observed neutrophil infiltration in SPT-1. The 15-LOX product (15-HETE) is anti-inflammatory and may suggest that 15-LOX up-regulation in SPT-4 skin may aid resolution of the sunburn response, which in part may be mediated by CD3+ lymphocytes and a class-switch in eicosanoid production from COX to LOX products. Melanocyte primary cultures surprisingly showed that SPT was not correlated with melanin content or melanogenic enzyme expression/activity suggesting that all melanocytes in vitro contained the necessary cellular machinery to produce melanin. This finding may reflect also their equal treatment under these enriched culture conditions, which may or may not be available to these cells in situ. Moreover, all melanocytes expressed the necessary machinery (PLA2, COX-1, cPGES) to produce PGE2. However, only some cultures did so at baseline and in response to UVR, and this was not correlated with SPT. A positive correlation was found however between expression level of dopachrome tautomerase (DCT) and protection against PGE2 production in response to UVR, which may suggest a novel role for DCT unrelated to melanogenesis. In summary this research project has generated data that highlights differences between the skin of individuals with SPT-1 and those with SPT-4, and may provide evidence that the keratinocyte partner contributes significantly to the SPT-associated response. This research may also suggest DCT as a novel therapeutic target to protect EM from participation in the UVR-associated inflammatory response in skin. / Wellcome Trust

A exposição à radiação ultravioleta (RUV) pode provocar desequilíbrio no balanço oxidante/antioxidante da pele, causando prejuízos à sua integridade e levando a diversas alterações, entre as quais o envelhecimento precoce e o câncer de pele. Considerando a estreita relação entre o aumento do estresse oxidativo e os efeitos danosos causados pela RUV na pele, aliado ao fato de que estudos epidemiológicos demonstram que o uso de protetores ou bloqueadores solares não é completamente efetivo na prevenção dos diversos malefícios causados pela exposição à RUV, o uso de antioxidantes aparece como importante alternativa nas terapias de fotoproteção. A administração tópica de antioxidantes, como a quercetina, poderia afetar as alterações moleculares desencadeadas pela RUV e conseqüentemente as seqüelas biológicas e clínicas resultantes das mesmas. Desta forma, na presente pesquisa, sistema microemulsionado para a liberação cutânea de quercetina foi obtido, caracterizado e avaliado quanto a sua capacidade em promover maior penetração cutânea deste ativo, estabilidade, segurança e eficácia in vivo contra os danos na pele causados pela exposição à RUV. Além disso, o efeito da quercetina contra diferentes alterações moleculares induzidas pela RUV foi também avaliado, com o objetivo de investigar os possíveis mecanismos de ação fotoprotetora deste flavonóide. Os resultados demonstram que a incorporação da quercetina em sistema microemulsionado aumentou a penetração cutânea in vitro e in vivo deste flavonóide sem causar irritação, sendo, portanto, uma importante estratégia para melhorar a liberação tópica da quercetina. O estudo de estabilidade demonstra a necessidade de armazenamento deste sistema a 4°C para manutenção de sua funcionalidade. A microemulsão contendo quercetina inibiu a depleção do antioxidante endógeno GSH, assim como o aumento da atividade/secreção de proteinases e da atividade da MPO, induzidos pela exposição à RUVB. O pré-tratamento de queratinócitos com quercetina não alterou a indução pela RUV das MAP quinases, conseqüentemente não houve inibição na elevação dos níveis de c-Jun e c-Fos, assim como no aumento da produção das MMPs 1 e 3, mas por outro lado foi efetivo contra o aumento na produção das citocinas IL-1, IL-6, IL-8 e TNF-. Finalmente, demonstrou-se que a ação fotoprotetora da quercetina contra os danos na pele causados pela RUV é mediada principalmente pela inibição da via de sinalização do NF-kB, uma vez que, enquanto o pré-tratamento de queratinócitos com quercetina diminuiu a ativação deste fator de transcrição, nenhum efeito contra a indução da via de sinalização da AP-1 foi observado. Concluindo, este trabalho sugere a incorporação da quercetina em sistema microemulsionado como estratégia relevante no combate ao aparecimento de desordens cutâneas causadas pela exposição à RUV, além de contribuir para a elucidação, pelo menos em parte, do mecanismo de ação fotoprotetora da quercetina contra alterações moleculares induzidas pela RUV. / The ultraviolet radiation (UVR) exposition may lead to the skin oxidant/antioxidant imbalance injuring its integrity and leading to several disorders, such as ageing and skin cancer. Considering the close relationship between the increase in oxidative stress and UV-induced skin damages, together with the fact that epidemiological studies indicate that the use of sunscreen and sun block are not completely effective in preventing UV-induced damages, the use of antioxidants arises as an important approach to photoprotection therapies. The topical use of antioxidants, such as quercetin, would affect the molecular changes induced by UV and subsequent biological and clinical sequela. Therefore, in the present study, microemulsion system for topical delivery of quercetin was obtained, characterized and evaluated with regards to its capability to increase skin penetration of quercetin, stability, toxicity and in vivo effectiveness against UV-induced skin damages. Moreover, quercetin effect against different UV-induced molecular changes was also assessed, in order to investigate the possible photoprotective mechanisms of action of this flavonoid. The results demonstrate that the incorporation of quercetin into microemulsion increased the in vitro and in vivo skin penetration of this flavonoid without causing skin irritation, being an important strategy to improve the topical delivery of quercetin. The stability study demonstrate the necessity to storage this system at 4°C to maintain its functionality. The microemulsion containing quercetin inhibited the depletion of the endogenous antioxidant GSH, as well as the increase in proteinases activity/secretion and MPO activity induced by UVB irradiation exposure. The pretreatment of keratinocytes with quercetin had no blocking effect on UV activation of MAP kinases, consequently, there was no inhibition in the c-Jun and c-Fos levels, as well as in the induction of MMPs 1 and 3, on the other hand, it was effective against the increase in the production of cytokines IL-1, IL-6, IL-8 e TNF-. Finally, it was demonstrated that the photoprotective action of quercetin against UV-induced skin damages is mediated mainly by suppression of NF-kB signaling pathway, once, while the pretreatment of keratinocytes with quercetin suppressed the activation of this transcription factor, no effect was observed against UV-induced AP-1 activation. In conclusion, the present study suggests the incorporation of quercetin into microemulsion system as a relevant strategy to prevent UV-induced skin disorders, and contribute, at least in part, to the elucidation of quercetin photoprotective mechanism of action against UV-induced molecular changes.

Essa pesquisa investigou e interpretou aspectos relevantes da desinfecção por radiação ultravioleta (UV) na inativação de microrganismos indicadores. O efluente sanitário foi proveniente de tratamento anaeróbio (Reator UASB), seguido de Biofiltro Aerado Submerso, em escala real. A pesquisa foi dividida em duas etapas, sendo que na primeira foi dado destaque ao estudo das características operacionais da unidade ultravioleta. Na segunda etapa da pesquisa objetivou-se o estudo da resistência de diferentes microrganismos indicadores à radiação ultravioleta e das possíveis correlações entre as variáveis testadas. Os resultados obtidos na primeira etapa da pesquisa forneceram indicativos de que a limpeza das lâmpadas emersas pode ser feita em períodos superiores a 2 meses, devendo-se levar em consideração também a fragilidade do sistema. A limpeza do canal de desinfecção não teve relação com a eficiência de desinfecção. A operação de unidades UV é relativamente simples desde que haja treinamento dos operadores e condições ergonômicas favoráveis ao trabalho dos mesmos. O custo operacional situou-se na faixa de 0,006 R$/\'M POT.3\' de esgoto desinfetado e o custo de energia elétrica foi de 0,07 R$/\'M POT.3\' de esgoto desinfetado. As eficiências máximas de desinfecção encontradas na segunda etapa da pesquisa foram de 100% para Colifagos, 99,999% para CF (Coliformes Fecais) e 99,993% para CT (Coliformes Totais), o que demonstra que a ordem decrescente de resistência desses organismos é CT > CF > Colifagos. Os resultados indicaram que houve pouca variação da eficiência de inativação para as três lâminas de esgoto testadas (3 cm, 4 cm e 5 cm) o que sugere que a unidade é capaz de atender aumentos moderados de vazão, confirmando os pressupostos adotados no seu dimensionamento. Os dados obtidos a partir do ensaio hidrodinâmico indicaram que o reator de desinfecção testado comporta-se como um sistema composto de um reator pistonado ideal com presença de curtos circuitos hidráulicos. / This research has investigated and interpreted relevant aspects of disinfection by ultraviolet radiation (UVR) in the inativation of indicator microorganisms\' inactivation. The sanitary effluent was provided by anaerobic treatment (UASB reactor), followed by aerated submerged biofilter (ASB), on a real scale. This research was divided into two stages, whereas in the first stage, operational characteristics of the ultraviolet unit studies were highlighted. The aim of the second stage of the research was the resistance of different indicator microorganisms to ultraviolet radiation study and the possible relation among variables tested. Results obtained in the first stage of the research have provided indication that the cleaning of submerged lamps may be done in periods longer than two months, however the fragility of the system must be considered. Disinfection channel cleaning should not be related to the disinfection efficiency. The operation of UV units is relatively simple, as long as the operators are trained and work under favorable ergonomic conditions. The operational cost was set at 0.006 R$/\'M POT.3\' of disinfected sewer system and the electrical energy cost was set at 0.07 R$/\'M POT.3\'. The maximum efficiency found on the disinfection of the research second stage were 100% for Coliphages, 99.999% for FC and 99.993% for TC, which demonstrates that the resistance decreasing order of these organisms is TC > FC > Coliphages. Results indicated that there was a low inactivation efficiency variation for the three tested sewer samples (3 cm, 4 cm and 5 cm), which suggests that the unit is capable of serving moderate increase of flow, confirming adopted predictions in its dimensioning. Information obtained from the hydrodynamic test indicated that the tested disinfection reactor behaves as a compound system of an ideal piston reactor with hydraulic short circuits.