Abstract During DNA replication cells accurately copy their DNA to transfer the genetic information to daughter cells. DNA polymerases synthesise the new DNA strand using the old strand as a template. Other functions of DNA polymerases are recombination linked and DNA iamage repair linked DNA synthesis, regulation of replication complex formation and regulation of transcription – a process in which the genetic information is transformed into an RNA sequence needed to guide protein synthesis. In this study, the TopBP1 protein was shown to associate with DNA polymerase epsilon. TopBP1 contains eight BRCT domains mediating interactions between phosphorylated proteins and is a human homolog of bakers yeast Dpb11 and fission yeast Cut5. These yeast proteins act on DNA replication and cell cycle arrest after DNA damage. TopBP1 was found to be phosphorylated and expressed in elevated amounts during S phase suggesting an involvement in DNA replication. This was directly demonstrated by DNA synthesis inhibition by a competing TopBP1 fragment and by an antibody targeted to block TopBP1. Ultraviolet irradiation damages DNA and decreases the amount of TopBP1 in the nucleus. The transcription factor Miz-1 was found to associate with TopBP1 and was released from this interaction after UV damage. Free Miz-1 activated the expression of the cell cycle arresting proteins p15 and p21 cooperatively with other transcription factors and allowed extra time for DNA damage repair. TopBP1 was also found to interact with the breast cancer susceptibility protein 1 and both proteins localised together to arrested DNA synthesis apparatuses. The interaction of TopBP1 with the damage recognition and processing protein Rad9 is still further evidence of a link between TopBP1 and DNA damage. DNA polymerase epsilon forms a complex with Cdc45, a protein involved in DNA replication initiation and elongation. This complex does not interact with Cdc45 complexed with DNA polymerase delta, suggesting that these complexes synthesise DNA independently of each other. Our results are in agreement with the view that polymerase epsilon synthesises the first strand of DNA and polymerase delta the other. Finally,DNA polymerase epsilon binds to the RNA synthesising form of RNA polymerase II and nascent transcripts. The physiological meaning of this interaction needs to be determined.

Die Untersuchung von Gewaltopfern und die Dokumentation von Verletzungen gehört zur Routinetätigkeit in der Klinischen Rechtsmedizin. Am häufigsten werden Folgen stumpfer Gewalteinwirkung festgestellt. Diese Untersuchungen geraten an ihre Grenzen, wenn z.B. Hautunterblutungen (noch) nicht oder bereits nicht mehr sichtbar sind. Die vorliegende Arbeit belegt den Nutzen von ultravioletter (UV) Strahlung zur Sichtbarmachung verblasster und mit bloßem Auge nicht erkennbare Hämatome. Die durch UV-Strahlung hervorgerufene Fluoreszenz von gesundem im Vergleich zu geschädigtem Gewebe kann teils noch bis zu Monate nach einer Verletzung Unterschiede aufweisen. Somit stellt das hier untersuchte Verfahren eine kostengünstige, schnelle und zuverlässige Alternative des Methodenspektrums rechtsmedizinischer Untersuchungstechniken dar.:1. Bibliographische Beschreibung 2. Introduction 3. Background 3.1. Hematoma 3.2. Electromagnetic radiation 3.3. Fluorescence 3.4. UV radiation 3.5. UV-induced fluorescence 3.6. Hematoma fluorescence 3.7. UV-photography 3.8. Alternative non-invasive 4. Motivation & Purpose of this Thesis 5. Publication 6. Summary & Conclusion 6.1. Background 6.2. Aim 6.3. Material and Method 6.4. Results 6.5. Thesis 6.6. Conclusion 7. Appendix 7.1. Bibliography 7.2. Core Data 7.3. Declaration of Independence 7.4. Curriculum vitae 7.5. Publications 7.6. Acknowledgements / Identification and age determination of hematomas is daily work in forensic medicine. Following blunt trauma, a hematoma may be visible between a few hours and up to three weeks. Patients presenting their injuries outside of that timeframe usually miss visual signs. Various studies indicate that ultraviolet radiation (UVR) can aid the process of hematoma identification, when visible signs are vague or even absent. In this thesis hematoma identification using UV- induced fluorescence is discussed as simple, economic and convenient method.:1. Bibliographische Beschreibung 2. Introduction 3. Background 3.1. Hematoma 3.2. Electromagnetic radiation 3.3. Fluorescence 3.4. UV radiation 3.5. UV-induced fluorescence 3.6. Hematoma fluorescence 3.7. UV-photography 3.8. Alternative non-invasive 4. Motivation & Purpose of this Thesis 5. Publication 6. Summary & Conclusion 6.1. Background 6.2. Aim 6.3. Material and Method 6.4. Results 6.5. Thesis 6.6. Conclusion 7. Appendix 7.1. Bibliography 7.2. Core Data 7.3. Declaration of Independence 7.4. Curriculum vitae 7.5. Publications 7.6. Acknowledgements

Jusqu’à présent, la metformine a principalement été employée comme médicament contrôlant l’hyperglycémie des personnes atteintes de diabète de type II. Des études épidémiologiques ont démontré que les personnes, prenant de la metformine, développent moins de cancers. Par exemple, la prise de metformine réduit respectivement de 78% et de 46% les chances de développer un cancer hépatique ou pancréatique. Récemment, il a été montré que la metformine permet de réduire le développement de tumeur au niveau de la peau, suite à l’exposition à des rayons UVB. Dans cette étude, j’ai démontré que la présence de metformine permet une meilleure survie de la levure Saccharomyces cerevisiae suite à l’exposition à des rayons UVC ou UVA. De plus, j’ai démontré que la présence de metformine augmente le recrutement de l’histone Htz1 à la chromatine. Pour une souche htz1Δ, le niveau de survie suite à l’exposition aux rayons UVA est considérablement diminué. Htz1 permet le recrutement de Rad14 au site de dommages à l’ADN faits par les rayons UV. Htz1 est donc important pour la détection de ces sites. Enfin, le recrutement nucléaire de Rad14 en présence de metformine a considérablement augmenté. En absence de Rad14, le niveau de survie suite à l’exposition aux rayons UVA diminue significativement. Donc, Htz1 et Rad14 sont deux protéines clés dans la protection contre les rayons UV apportés par la metformine. En conclusion, avec les différents résultats de cette étude, il est possible de dire que la metformine permet une forme de protection contre les rayons UVC et UVA. / Recently, metformin has been widely used to treat hyperglycemia of humans that have type II diabetes mellitus. Recently, some epidemiological studies have showed that populations of individuals being treated with metformin showed lower incidence of cancer. For example, there is a 78 % and 46 % reduction in the incidences of liver and pancreatic cancers, respectively. It has also been demonstrated that metformin protects against skin cancers caused by ultraviolet radiation-B (UVB) DNA damage. In this study, I have demonstrated that metformin significantly protects the budding yeast Saccharomyces cerevisiae from ultraviolet radiation-C (UVC) and from ultraviolet radiation-A (UVA)-induced death. I also showed that metformin increases the recruitment of the histone Htz1 linked to chromatin. In an htz1Δ strain, the metformin protection from UVAinduced death is significantly reduced. Htz1 is important for the recruitment of Rad14 to sites of DNA damage, important for the detection of these sites. Furthermore, nuclear recruitment of Rad14 was significantly increased in cells previously treated with metformin. In the absence of Htz1, the survival rate to UVA exposure in presence of metformin drops significantly. So, Htz1 and Rad14 are two key proteins involved in the protection by metformin against UV DNA damage. With all the results of this study, it was shown that metformin can confer some protection against UVC and UVA for yeast.

Inúmeros estudos têm demonstrado elevada prevalência de hipovitaminose D (deficiência/insuficiência de 25(OH)D) em indivíduos normais e em pacientes com e sem doença renal. Como os pacientes transplantados renais têm maior risco de desenvolver câncer de pele, são orientados a evitar exposição ao sol e usar filtro solar. A combinação de doença renal crônica (DRC) e menor exposição ao sol contribuem para que esses pacientes desenvolvam hipovitaminose D, o que pode piorar ou favorecer o desenvolvimento de doença óssea. O objetivo desse estudo foi avaliar a concentração sérica de 25(OH)D e a prevalência de hipovitaminose D em uma amostra representativa (N=149) de pacientes transplantados renais do Hospital das Clinicas da Universidade de São Paulo. Avaliamos ainda se a hipovitaminose poderia ser atribuída a menor exposição ao sol ou ingestão insuficiente de alimentos fontes. Comparamos os níveis séricos de 25(OH)D desses pacientes com o de indivíduos normais. Hipovitaminose D, definida pelos níveis séricos de 25(OH)D menores que 30 ng/ml, foi observada em 79% dos pacientes transplantados e o principal fator determinante foi a menor exposição ao sol.Os níveis séricos de creatinina e de paratormônio (PTH) foram significativamente mais elevados nos pacientes com hipovitaminose quando comparados aos com níveis normais de 25(OH)D. Observamos uma correlação inversa dos níveis séricos de 25(OH)D com os de paratormônio (r= -0,24; p<0,03). A prevalência de hipovitaminose D foi maior nos pacientes transplantados que nos indivíduos normais. Os níveis séricos de creatinina e PTH foram mais elevados nos transplantados, enquanto os de Ca, P e albumina menores que dos indivíduos normais. Em conclusão: A hipovitaminose D é freqüente nos pacientes transplantados renais e orientação dietética, exposição solar curta e regular ou mesmo a suplementação com vitamina D seriam medidas simples para assegurar níveis adequados dessa vitamina / Recent epidemiological studies have shown a high prevalence vitamin D deficiency in normal population and in patients with and without kidney diseases. In addition, kidney transplant patients are at higher risk for skin cancer, so they are advised to avoid sun and use sunscreen. Because of the combination of chronic kidney disease (CKD) and sun avoidance, kidney transplant patients are at high risk for developing hypovitaminosis D. We evaluated serum 25 vitamin D levels in a representative sample (N = 149) of kidney transplant patients from the University of São Paulo Transplant Unit. Our objectives were to determine the prevalence of hypovitaminosis D, comparing them to normal volunteers, as well as, to identify the factors that could be associated with this decrease in serum 25 vitamin D, such as sun exposure and dietary habits. Hypovitaminosis D, defined by serum levels < 30 ng/mL, was found in 79% of kidney transplant patients, and the main associated factor was low sun exposure. Patients that presented hypovitaminosis D had higher serum creatinine and parathormone (PTH) levels. Serum 25 vitamin D correlated with serum PTH (r= - 0.24; p=0.03). When compared to normal volunteers, renal transplant patients presented a higher prevalence of hypovitaminosis D, as well as low serum calcium, phosphate albumin, and higher creatinine, and PTH. Our results confirm a high prevalence of hypovitaminosis D in renal transplant patients. In conclusion, hypovitaminosis D is frequent in kidney transplant patients, therefore dietary orientation, short or regular sun exposure, and vitamin D supplementation are important determinants of vitamin D status

Submitted by GABRIELLI BRIANEZI null (gabrielli.brianezi@hotmail.com) on 2016-02-26T15:36:13Z No. of bitstreams: 1 20160224 Tese Gabrielli Brianezi.pdf: 3073309 bytes, checksum: 8fd0793265926aa1a58aea12aad689a6 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-02-26T20:04:11Z (GMT) No. of bitstreams: 1 brianezi_g_dr_bot.pdf: 3073309 bytes, checksum: 8fd0793265926aa1a58aea12aad689a6 (MD5) / Made available in DSpace on 2016-02-26T20:04:11Z (GMT). No. of bitstreams: 1 brianezi_g_dr_bot.pdf: 3073309 bytes, checksum: 8fd0793265926aa1a58aea12aad689a6 (MD5) Previous issue date: 2016-01-26 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A patogênese do melasma, especialmente o papel dos queratinócitos e fibroblastos no desenvolvimento e manutenção da doença não é bem compreendida. Alterações dérmicas como dano estrutural à zona de membrana basal, melanócitos em pêndulo, elastose solar, celularidade, proliferação vascular, além da expressão de mediadores inflamatórios, fatores de crescimento, expressão epitelial de melanocortina e receptores dos hormônios sexuais; sugerem interação entre a unidade epidermo-melânica e a derme na fisiopatologia do melasma. A pigmentação melânica da pele pode ser estimulada por diferentes vias de sinalização, sendo a radiação ultravioleta, citocinas dérmicas e inflamação epidérmica, os modelos mais usuais. Neste estudo, objetivamos comparar a morfologia nuclear e a textura da cromatina entre queratinócitos basais no melasma facial e pele adjacente, investigar a ativação das diferentes vias de estímulo à pigmentação, além do envolvimento da derme, com foco na zona de membrana basal e colágeno, no melasma facial. Para a sua execução, foram coletados pares de biópsias faciais (2mm) de mulheres adultas com melasma e de pele adjacente (<2 cm). Processaram-se para coloração de PAS e picrosirius red; imunofluorescência para p53, p38, IL- 1α, αMSH, MC1R e COX2; imunoistoquímica para Melan-Acontracorada com PAS; Microscopia Eletrônica de Transmissão, além de cultura primária de fibroblastos para real-timePCR array e marcação para SA-β-gal. Foram avaliados: núcleos de queratinócitos da camada basal quanto à morfometria nuclear e textura da cromatina; quantificada a intensidade de fluorescência nos compartimentos da epiderme e derme; avaliadas organelas citoplasmáticas e zona de membrana basal; além do colágeno dérmico e densidade de melanócitos: totais e em pêndulo. Em relação à pele adjacente sem melasma: núcleos de queratinócitos basais da epiderme com melasma facial apresentaram índices morfométricos e textura da cromatina alterados; houve aumento da expressão epitelial de αMSH e MC1R, sem diferença quanto ao p53, p38, IL1α e COX2; houve maior número de organelas citoplasmáticas e melanossomas em estágios de maturação maiores nos queratinócitos e melanócitos; áreas danificadas na zona de membrana basal com presença de microvesículas adjacentes à membrana basal; maior número de melanócitos em pêndulo; colágeno dérmico desestruturado. Entre os fibroblastos, houve maior marcação para SA-β-gal e expressão alterada dos genes COL4A1, IL6, ESR2, DKK3, CCL2, WIF1, WNT3A, HGF, IL1B, MMPs 1-7-9 no melasma. As alterações encontradas nos queratinócitos, na derme e zona de membrana basal, sugerem que o fenótipo do melasma pode resultar de alterações em toda unidade epidermo-melânica, não somente de uma hipertrofia dos melanócitos, as vias inflamatórias da epiderme e dependentes de p53 não se mostraram proeminentes, além de ser identificado um possível papel do processo de reparo/dano da derme e da senescência de fibroblastos na patogênese da doença. / The melasma pathogenesis, specially the role of keratinocytes and fibroblast in the disease development and maintenance are not completely understood. Dermal alterations such as basal membrane structural damage, pendulous melanocytes, solar elastosis, cellularity, vascular proliferation, in addition to the expression of inflammatory mediators, grow factors, epithelial melanocortin and sexual hormones receptors, suggest there is an interaction between the epidermal melanin unit and dermis in melasma physiopathology. The melanin skin pigmentation can be stimulated by different signaling pathways. UVR, dermal cytokines and epidermal inflammation are the most common models. These study aims to compare the nuclear morphology and chromatin texture in basal keratinocytes between melasma and adjacent skin, to investigate the activation of different pigmentation signaling pathways, and the dermal involvement, focusing on basal membrane zone and collagen. Therefore, facial skin biopsies (2 mm) from women were taken from melasma and normal skin (<2 cm apart) and processed for PAS and picrosirius red; immunofluorescence for p53, p38, IL-1α, αMSH, MC1R and COX2, immunohistochemistry for Melan-A counterstaining with PAS, and transmission electronic microscopy. Furthermore, primary fibroblast culture for real-timePCRarray and SA-β-gal staining. The nuclei of basal keratinocytes were evaluated as nuclear morphometry and chromatin texture; the fluorescence intensity was quantified in the epidermis and dermis; cytoplasm organelles and basal membrane zone were evaluated; in addition to dermal collagen and melanocytes density: total and pendulous. Regarding adjacent healthy skin, the melasma skin showed alterations in morphometric index and chromatin texture; there was greater epithelial expression of αMSH and MC1R, but without difference for p53, p38, IL1α and COX2; cytoplasm organelles and melanossomas in higher maturity were in greater number in keratinocytes and melanocytes; there were commoner damaged areas in basal membrane zone, presence of microvesicules adjacent to basal membrane; and higher number of pendulous melanocyte; dermal collagen was less structured. There were greater SA-β-gal staining and altered expression of COL4A1, IL6, ESR2, DKK3, CCL2, WIF1, WNT3A, HGF, IL1B, MMPs 1-7-9 genes in melasma fibroblasts.The alterations presented in keratinocytes, dermis and basal membrane zone suggest the melasma phenotype can result from alteration in entire epidermal melanin unit, not just hypertrophic melanocytes, the epidermal inflammatory pathways and p53 dependents do not show prominence, in addition to the possible role of the repair/ damage process identified at dermis and fibroblast senescence in the melasma pathogenesis. / FAPESP: 12/09233-5 / FAPESP: 12/05004-1

Submitted by Ana Cláudia Cavalcante Espósito null (anaclaudiaesposito@gmail.com) on 2017-07-27T20:34:29Z No. of bitstreams: 1 Ana Cláudia mestrado para depositar.pdf: 2933638 bytes, checksum: 3c192abd021482675fa186f4c4bba9e4 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-07-31T19:29:06Z (GMT) No. of bitstreams: 1 lemos_acce_me_bot.pdf: 2933638 bytes, checksum: 3c192abd021482675fa186f4c4bba9e4 (MD5) / Made available in DSpace on 2017-07-31T19:29:06Z (GMT). No. of bitstreams: 1 lemos_acce_me_bot.pdf: 2933638 bytes, checksum: 3c192abd021482675fa186f4c4bba9e4 (MD5) Previous issue date: 2017-07-20 / Fundo de Apoio à Dermatologia de São Paulo (FUNADERSP) / O melasma é hipermelanose crônica e adquirida decorrente de um complexo processo que envolve hipertrofia melanocítica e disfunção melanogênica. Acomete preferencialmente o sexo feminino e as lesões ocorrem nas áreas fotoexpostas, especialmente a face. Sua patogênese não é bem compreendida e os estudos clássicos avaliam apenas pele acometida e perilesional, mas pouco se sabe do comportamento da pele fotoprotegida, submetida aos mesmos fatores sistêmicos e genéticos. Neste estudo, objetivamos avaliar características histológicas, vias epidérmicas que influem na melanogênese (Wnt e ASIP) e características ultraestruturais da pele com melasma em comparação com a pele sã adjacente e retroauricular. Para a execução deste estudo transversal com controle intra-sujeito, foram coletadas três biópsias cutâneas (punch 3 mm) de onze mulheres com melasma facial. As áreas de coleta foram a pele com melasma, pele sã adjacente (distando no máximo 2 cm do limite da lesão) e pele retroauricular ipsilateral. Os fragmentos provenientes de dez participantes foram corados por hematoxilina-eosina, ácido periódico de Schiff, Fontana-Masson, picrosirius red, azul de toluidina e Verhöff; imunomarcados para CD34 e submetidos à imunofluorescência direta (IFD) de dupla marcação para proteínas Wnt1, WIF-1 e ASIP. Já os três fragmentos de uma das participantes foram processados para Microscopia Eletrônica de Transmissão (MET). Os dados obtidos foram comparados entre as topografias por modelo linear generalizado de efeitos mistos. As participantes eram fototipo III ou IV de Fitzpatrick, com idade média (desvio-padrão) de 42,9 (8,9) anos e apresentavam lesões há 16,7 (7,9) anos. Houve adelgaçamento da camada córnea na pele com melasma e na pele adjacente. Na pele com melasma houve maior compactação da córnea, maior pigmentação melânica epidérmica, maior heterogeneidade do colágeno, elastose solar, maior número de mastócitos, falhas da integridade da zona da membrana basal, melanócitos em pêndulo, bem como maior celularidade e vasos na derme superficial. IFD evidenciou maior intensidade de marcação de Wnt1 na pele com melasma em relação à pele adjacente e maior intensidade na pele retroauricular em relação à pele sã adjacente. Não houve diferença estatística significativa na intensidade de marcação de WIF-1 e ASIP entre as topografias. À MET, houve maior dano estrutural na lâmina lúcida no melasma, bem como maior número de melanossomas maduros e organelas citoplasmáticas nos melanócitos e queratinócitos basais. Tais resultados evidenciam que a pele com melasma apresenta, além da hipertrofia melanocítica, alterações na barreira epidérmica, na derme superior, zona de membrana basal e maior ativação da via Wnt, que diferem da pele fotoexposta adjacente e da retroauricular, configurando um fenótipo individualizado e não somente uma extensão do fotoenvelhecimento ou do envelhecimento intrínseco. / Melasma is a chronic and acquired hypermelanosis resulting from a complex process which involves melanocytic hypertrophy and melanogenic dysfunction. Melasma mainly affects females and lesions occur in the photoexposed areas, especially the face. Its pathogenesis is not well understood, and classical studies evaluate only the affected and perilesional skin, but little is known about the behavior of the non-sun-exposed skin, subjected to the same systemic and genetic factors. In this study, we aimed to evaluate histological features, epidermal pathways that influence melanogenesis (Wnt and ASIP) and ultrastructural characteristics of the skin with melasma in comparison to healthy adjacent and retroauricular skin. For the execution of this cross-sectional study with intrasubject control, three skin biopsies (punch 3 mm) were collected from eleven women with facial melasma. The areas of collection were the skin with melasma, adjacent healthy skin and retroauricular skin. Fragments from ten participants were stained with hematoxylin-eosin, periodic acid from Schiff, Fontana-Masson, picrosirius red, toluidine blue and Verhöff; immunomarked for CD34 and subjected to double-labeled direct immunofluorescence (DIF) for Wnt1, WIF-1 and ASIP proteins. The three fragments of one of the participants were processed for Transmission Electron Microscopy (TEM). The data obtained were compared between topographies by generalized linear model of mixed effects. Participants were Fitzpatrick's phototype III or IV; the mean age (standard deviation) was 42.9 (8.9) years and they had lesions for 16.7 (7.9) years. There was thinning of the corneal layer on the skin with melasma and adjacent skin. In the skin with melasma, there was more corneal compaction, greater epidermal melanic pigmentation, greater collagen heterogeneity, solar elastosis, more mast cells, defects of the basement membrane area, pendulum melanocytes, as well as greater cellularity and vessels in the superficial dermis. DIF showed a greater intensity of Wnt1 marking in the skin with melasma in relation to the adjacent skin, and greater intensity in the retroauricular skin in relation to the adjacent healthy skin. There was no significant statistical difference in the intensity of WIF-1 and ASIP marking between topographies. At TEM, there was more structural damage to the lamina lucida in melasma, as well as more mature melanosomes and cytoplasmic organelles in melanocytes and basal keratinocytes. These results show that melasma skin presents, in addition to melanocytic hypertrophy, alterations in the epidermal barrier, upper dermis, basement membrane zone and greater activation of the Wnt pathway, which differ from adjacent and retroauricular photoexposed skin, forming an individualized phenotype and not only an extension of photoaging or intrinsic aging.

Inúmeros estudos têm demonstrado elevada prevalência de hipovitaminose D (deficiência/insuficiência de 25(OH)D) em indivíduos normais e em pacientes com e sem doença renal. Como os pacientes transplantados renais têm maior risco de desenvolver câncer de pele, são orientados a evitar exposição ao sol e usar filtro solar. A combinação de doença renal crônica (DRC) e menor exposição ao sol contribuem para que esses pacientes desenvolvam hipovitaminose D, o que pode piorar ou favorecer o desenvolvimento de doença óssea. O objetivo desse estudo foi avaliar a concentração sérica de 25(OH)D e a prevalência de hipovitaminose D em uma amostra representativa (N=149) de pacientes transplantados renais do Hospital das Clinicas da Universidade de São Paulo. Avaliamos ainda se a hipovitaminose poderia ser atribuída a menor exposição ao sol ou ingestão insuficiente de alimentos fontes. Comparamos os níveis séricos de 25(OH)D desses pacientes com o de indivíduos normais. Hipovitaminose D, definida pelos níveis séricos de 25(OH)D menores que 30 ng/ml, foi observada em 79% dos pacientes transplantados e o principal fator determinante foi a menor exposição ao sol.Os níveis séricos de creatinina e de paratormônio (PTH) foram significativamente mais elevados nos pacientes com hipovitaminose quando comparados aos com níveis normais de 25(OH)D. Observamos uma correlação inversa dos níveis séricos de 25(OH)D com os de paratormônio (r= -0,24; p<0,03). A prevalência de hipovitaminose D foi maior nos pacientes transplantados que nos indivíduos normais. Os níveis séricos de creatinina e PTH foram mais elevados nos transplantados, enquanto os de Ca, P e albumina menores que dos indivíduos normais. Em conclusão: A hipovitaminose D é freqüente nos pacientes transplantados renais e orientação dietética, exposição solar curta e regular ou mesmo a suplementação com vitamina D seriam medidas simples para assegurar níveis adequados dessa vitamina / Recent epidemiological studies have shown a high prevalence vitamin D deficiency in normal population and in patients with and without kidney diseases. In addition, kidney transplant patients are at higher risk for skin cancer, so they are advised to avoid sun and use sunscreen. Because of the combination of chronic kidney disease (CKD) and sun avoidance, kidney transplant patients are at high risk for developing hypovitaminosis D. We evaluated serum 25 vitamin D levels in a representative sample (N = 149) of kidney transplant patients from the University of São Paulo Transplant Unit. Our objectives were to determine the prevalence of hypovitaminosis D, comparing them to normal volunteers, as well as, to identify the factors that could be associated with this decrease in serum 25 vitamin D, such as sun exposure and dietary habits. Hypovitaminosis D, defined by serum levels < 30 ng/mL, was found in 79% of kidney transplant patients, and the main associated factor was low sun exposure. Patients that presented hypovitaminosis D had higher serum creatinine and parathormone (PTH) levels. Serum 25 vitamin D correlated with serum PTH (r= - 0.24; p=0.03). When compared to normal volunteers, renal transplant patients presented a higher prevalence of hypovitaminosis D, as well as low serum calcium, phosphate albumin, and higher creatinine, and PTH. Our results confirm a high prevalence of hypovitaminosis D in renal transplant patients. In conclusion, hypovitaminosis D is frequent in kidney transplant patients, therefore dietary orientation, short or regular sun exposure, and vitamin D supplementation are important determinants of vitamin D status

Made available in DSpace on 2014-08-20T13:58:01Z (GMT). No. of bitstreams: 1 Dissertacao_Ricardo_Lanzetta_Haack.pdf: 494944 bytes, checksum: 10807629b06e525dba3ccc9785fda779 (MD5) Previous issue date: 2006-11-16 / Objective: to evaluate the prevalence of sunburn and its risk factors among subjects aged between 10 and 29 years in urban area of Pelotas, a Southern Brazilian city. Methods: a cross-sectional population based study, using a multiple stage sampling, was carried out between October and December of 2005. Sunburn was defined as burning of the skin after sun exposure. Chi-square test was used to compare proportions and Poisson regression with design effect and robust adjustment of variance was applied in the multivariate analysis. Results: a total of 1597 household were visited and 1604 individuals aged between 10 and 29 years were interviewed, of which 1412 reported that had been exposed to the sun in the previous summer. Among those exposed to the sun, 48.7% reported sunburn in the previous year. The following variables were associated with sunburning in the multivariate analysis: white skin (RP 1,41 CI 95% 1,12-1,79), higher sensitivity of the skin to the sun (RP 1,84 CI 95% 1,64-2,06), age between 15 and 19 years (RP 1,30 CI 95% 1,12-1,50), to belong to the higher quartile of income (RP 1,20 CI 95% 1,01-1,42) and to make irregular use of sunscreen (RP 1,23 CI 95% 1,08-1,42). Conclusion: the prevalence of sunburn was high, and exposure to the sun in safe schedules and with adequate methods of protection must be stimulated. / Objetivos: determinar a prevalência de queimadura solar e fatores de risco em indivíduos com idade entre 10 e 29 anos residentes na zona urbana de Pelotas, no sul do Brasil. Métodos: estudo transversal de base populacional com amostragem em múltiplos estágios, realizado entre os meses de outubro e dezembro de 2005. Queimadura solar foi definida como ardência na pele após exposição ao sol. Para as comparações entre proporções, utilizou-se teste do qui-quadrado com correção de Yates para as tabelas 2x2, enquanto que na análise multivariada utilizou-se a regressão de Poisson com controle para efeito de delineamento e ajuste robusto da variância. Resultados: nos1597 domicílios visitados foram entrevistados 1604 pessoas com idade entre 10 e 29 anos, dos quais 1412 relataram exposição ao sol no último verão. As perdas e recusas somaram 5,5%. Queimadura solar no último ano foi relatada por 48,7% dos entrevistados. Na análise multivariada cor da pele branca (RP 1,41 IC 95% 1,12-1,79), maior sensibilidade da pele quando exposta ao sol (RP 1,84 IC 95% 1,64-2,06), idade entre 15 e 19 anos (RP 1,30 IC 95% 1,12-1,50), pertencer ao quartil de maior renda (RP 1,20 IC 95% 1,01-1,42) e fazer uso irregular de fotoprotetor (RP 1,23 IC 95% 1,08-1,42) estiveram associadas à ocorrência de queimadura. Conclusão: A prevalência de queimadura solar na população estudada é alta e a exposição solar em horários seguros e com métodos de proteção adequados deve ser estimulada.

Made available in DSpace on 2014-08-20T13:58:01Z (GMT). No. of bitstreams: 1 RODRIGO_PEREIRA_DUQUIA_tese.pdf: 673344 bytes, checksum: ae25f96b35c9d6357bf3d184433ebb25 (MD5) Previous issue date: 2006-10-26 / Background: Sunscreen use is important for the prevention of skin cancer, but population-based information about the prevalence and its associated factors are scarce in Brazil. Objective: To evaluate the prevalence and associated factors with sunscreen use among Brazilian adults. Methods: We conducted a cross-sectional population-based study with a representative sample of adults aged 20 years or older living in the urban area of the city of Pelotas, Southern Brazil. We evaluated sunscreen use at the beach, at work, and during outdoor sports, for at least 20 minutes between 10 a.m. and 4 p.m., from December 2004 to March 2005. The outcome measure was dichotomized in subjects who never used sunscreen, and those who used sunscreen, regardless of frequency. Results: Prevalence of sunscreen use at the beach, work, and outdoor sports was 60.8% (CI95% 55.6 - 66.0), 13.7% (CI95% 10.7 - 16.6%), and 30.2% (CI95% 24.1 - 36.3), respectively. At work, the median number of days of exposure was 70 days, while at the beach it was 10 and, for sport it was 16. Females, whites, those with higher educational achievement, and with higher income were more likely to use sunscreen. Limitations: No data on adequacy of sunscreen use was gathered Conclusion: Our data show that the subjects most exposed to sunlight are those that use sunscreen the least. Interventions targeting this group are required, since this is also the population with the lowest socioeconomic level. / Diversos estudos já comprovaram que ficar exposto ao sol acarreta prejuízos para a pele. Pessoas que se protegem do sol têm menor chance de desenvolver câncer de pele. Além disso, a proteção contra os raios solares retarda o aparecimento de rugas e manchas, preservando, desta forma, a pele das pessoas. Apesar deste conhecimento, muitas pessoas preferem expor-se ao sol para ficarem bronzeadas ao invés da preservação de uma pele jovem e saudável. Este assunto tem despertado o interesse de diversos pesquisadores na área da saúde. O médico dermatologista Rodrigo Pereira Duquia realizou uma pesquisa com adultos da cidade de Pelotas para avaliar o comportamento da população com relação à utilização de fotoprotetores (creme protetor solar) durante o verão. O trabalho foi realizado durante os meses de outubro a dezembro de 2005, sendo entrevistadas 3136 pessoas com 20 anos ou mais de idade. Entre os achados mais importantes do estudo destaca-se que 23% dos entrevistados trabalhavam em média 65 dias no verão expostos ao sol, no período das 10:00 às 16:00h, considerado o de maior risco para o desenvolvimento do câncer de pele. Mais preocupante ainda foi o achado de que apenas cerca de 14% dessas pessoas utilizavam fotoprotetor. O estudo também demonstrou que a freqüência do uso do protetor solar foi muito maior na praia. Mais campanhas são necessárias para que a população saiba os malefícios da exposição ao sol e utilize medidas preventivas, como o uso do fotoprotetor, com o objetivo de 106 diminuir as taxas de câncer de pele e retardar o envelhecimento da pele. Atenção especial deve ser dirigida aos trabalhadores expostos ao sol, já que este é o grupo que menos usa o fotoprotetor solar e que permanece maior número de dias exposto ao sol.

Transfer of the melanocyte-specific and lysosome-related organelle, the melanosome, from melanocytes to keratinocytes is crucial for the protection of the skin against harmful ultraviolet radiation (UVR)--our main physiological cutaneous stressor. However, this commonplace event remains a most enigmatic process despite several early hypotheses. Recently, we and others have proposed a role for filopodia in melanin transfer, although conclusive experimental proof remained elusive. Using known filopodial markers (MyoX/Cdc42) and the filopodial disrupter, low-dose cytochalasin-B, we demonstrate here a requirement for filopodia in melanosome transfer from melanocytes to keratinocytes and also, unexpectedly, between keratinocytes. Melanin distribution throughout the skin represents the key phenotypic event in skin pigmentation. Melanocyte filopodia were also necessary for UVR-stimulated melanosome transfer, as this was also inhibited by MyoX knockdown and low-dose cytochalasin-B. Knockdown of keratinocyte MyoX protein, in its capacity as a phagocytosis effector, resulted in the inhibition of melanin uptake by keratinocytes. This indicates a central role for phagocytosis by keratinocytes of melanocyte filopodia. In summary, we propose a new model for the regulation of pigmentation in human skin cells under both constitutive and facultative (post-UVR) conditions, which we call the "filopodial-phagocytosis model." This model also provides a unique and highly accessible way to study lysosome-related organelle movement between mammalian cells.