Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-10-06T18:08:43Z No. of bitstreams: 2 Dissertação - Thaíza Carvalho da Rocha - 2012.pdf: 1513291 bytes, checksum: 5cdef676b716525fc5590bddb862c72f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-10-06T19:16:52Z (GMT) No. of bitstreams: 2 Dissertação - Thaíza Carvalho da Rocha - 2012.pdf: 1513291 bytes, checksum: 5cdef676b716525fc5590bddb862c72f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-10-06T19:16:52Z (GMT). No. of bitstreams: 2 Dissertação - Thaíza Carvalho da Rocha - 2012.pdf: 1513291 bytes, checksum: 5cdef676b716525fc5590bddb862c72f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-05-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Thermal analysis techniques have been very useful to study the pre-formulations since it consists in techniques that can provide quick and reliable results. This study evaluated the thermoanalytical profiles of psoralen and bergapten, compounds used in the treatment of vitiligo, and their interactions with excipients. We also evaluated the thermal profile of the plant extract Brosimum gaudichaudii Trécul (Moraceae) and a medicine containing the same extract. The results showed that psoralen and bergapten are substances with decomposition and have only one melting step at 162 ° C and 190 respectively. The compounds psoralen and bergapten interact with each other, but the results by XRD clearly show that the crystal structures of the compounds are not affected by these interactions. Furthermore, the results of thermal analysis showed that there was no interaction with the excipients of these compounds under study. All results were confirmed by FT-IR, used as a complementary technique. The plant extract showed an endothermic event which can be attributed to the fusion of these assets. The DSC curve profile of the drug trade allowed the detection of lactose in their composition, whose presence is not included in the package leaflet. / As técnicas de análise térmica tem se mostrado muito úteis no estudo de pré-formulações visto que consiste em técnicas que apresentam resultados rápidos e seguros. Neste trabalho foram avaliados os perfis termoanalíticos do psoraleno e bergapteno, compostos utilizados no tratamento de vitiligo, e suas interações com excipientes. Avaliou-se também o perfil térmico do extrato da planta Brosimum gaudichaudii Trécul (Moraceae) e de um medicamento contendo o mesmo extrato. Os resultados mostraram que psoraleno e bergapteno são substâncias que possuem decomposição em apenas uma etapa e apresentam fusão em 162 e 190 °C, respectivamente. Os compostos psoraleno e bergapteno interagem entre si, mas os resultados através de DRX deixam claro que as estruturas cristalinas dos compostos não são afetadas por essas interações. Além disso, os resultados obtidos com a análise térmica evidenciam que não ocorreu nenhuma interação destes compostos com os excipientes em estudo. Todos os resultados foram confirmados por FT-IR, utilizada como técnica complementar. O extrato da planta mostrou um evento endotérmico que pode ser atribuído à fusão dos ativos presentes. O perfil da curva DSC do medicamento comercial possibilitou a detecção da lactose em sua composição, cuja presença não consta na bula do medicamento.

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Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2018. / Submitted by Raquel Almeida (raquel.df13@gmail.com) on 2018-05-02T18:43:13Z No. of bitstreams: 1 2018_WanessadeSouzaCardosoQuintão.pdf: 2735530 bytes, checksum: 9642af8380e33a37bcee80efcf354c2e (MD5) / Approved for entry into archive by Raquel Viana (raquelviana@bce.unb.br) on 2018-05-28T16:57:38Z (GMT) No. of bitstreams: 1 2018_WanessadeSouzaCardosoQuintão.pdf: 2735530 bytes, checksum: 9642af8380e33a37bcee80efcf354c2e (MD5) / Made available in DSpace on 2018-05-28T16:57:38Z (GMT). No. of bitstreams: 1 2018_WanessadeSouzaCardosoQuintão.pdf: 2735530 bytes, checksum: 9642af8380e33a37bcee80efcf354c2e (MD5) Previous issue date: 2018-05-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). / Brosimum gaudichaudii é uma planta do Cerrado brasileiro que possui furanocumarinas com potencial terapêutico para tratamento do vitiligo, com destaque ao bergapteno e psoraleno. Nesse sentido, este trabalho teve como objetivo desenvolver nanoemulsões, formulações capazes de incorporar ativos vegetais e modular a permeação através da pele, a partir de extratos de Brosimum gaudichaudii, para tratamento tópico do vitiligo. Os compostos bergapteno e psoraleno foram quantificados por Cromatógrafo Líquido de Alta Eficiência (HPLC). Extratos etanólicos do pó (EXT1) e da casca da raiz (EXT2) de Brosimum gaudichaudii foram preparados e caracterizados por triagem fotoquímica. Apresentaram poucas diferenças na detecção de compostos, mas houve formação de diferentes cristais. Nanoemulsões óleo-em-água (O/A) de cada extrato foram preparadas utilizando Labrasol® e Plurol® para incorporar o EXT1 e o EXT2, obtendo NE1 e NE2. O tamanho de gotícula, o potencial zeta, pH e teor de ativos nas nanoemulsões foram avaliados. Os efeitos dos extratos e padrões sobre a viabilidade, migração e proliferação celular foram analisados em melanócitos e queratinócitos humanos. Além disso, o potencial de irritabilidade das nanoemulsões foi avaliado por ensaio de HET-CAM. No estudo de estabilidade, as nanoemulsões apresentaram pH em torno 4,0. As nanoemulsões apresentaram tamanho de gotícula tamanho ideal, entre 50 e 200 nm. Houve aumento do tamanho de gotícula das nanoemulsões armazenadas em câmara climática, o que pode ser atribuído ao aumento da temperatura. O potencial zeta das nanoemulsões foi negativo, menor que -10 mV. Nos estudos de permeação in vitro, as nanoemulsões reduziram a permeação dos ativos bergapteno e psoraleno. Os extratos demonstraram certa citotoxicidade em melanócitos e queratinócitos, mas estimularam migração celular. As duas nanoemulsões foram classificadas como irritantes leves nos ensaios de HET-CAM e adequadas para uso tópico. As nanoemulsões desenvolvidas nesse trabalho, portanto, apresentaram-se estáveis, com aspectos físicos e características organolépticas adequadas para aplicação tópica, e foram capazes de concentrar os ativos na pele, reduzindo a permeação através da pele, o que poderia causar um impacto negativo na segurança do tratamento do vitiligo. / Brosimum gaudichaudii is a Brazilian Cerrado plant which has furanocumarinas with therapeutic potential for vitiligo treatment, like bergapteno and psoralen. Considering its therapeutic potential, this work aimed to develop nanoemulsions, which are formulations capable of incorporating plant compounds and regulate the permeation through the skin, using Brosimum gaudichaudii extracts, for topical treatment of vitiligo. Bergapteno and psoralen compounds were quantified by high efficiency liquid chromatograph (HPLC). Ethanolics extracts of the Powder (EXT1) and the root bark (EXT2) of Brosimum gaudichaudii were prepared and characterized by photochemical screening. They showed few differences in the detection of compounds, but they produced different crystals conformations. Oil-in-water nanoemulsions (O/A) of each extract were prepared using Labrasol ® and Plurol ® to incorporate EXT1 and EXT2, obtaining NE1 and NE2. The droplet size, the zeta potential, pH and contente of bergapten and psoralen in the nanoemulsions were evaluated. The effects of the extracts and standards on the viability, migration and cellular proliferation were analyzed in human melanocytes and keratinocytes. In addition, the irritability potential of the nanoemulsions was evaluated by HET-CAM assay. In the stability study, the nanoemulsions presented PH around 4.0. The nanoemulsions presented an optimal droplet size between 50 and 200 nm. There was an increase in the droplet size of the nanoemulsions stored in the climate chamber, which can be attributed to the increase in temperature. The nanoemulsions’ zeta potential was negative, less than -10 mV. In the in vitro permeation studies, nanoemulsions reduced the permeation of bergapteno and psoralen compounds. The extracts demonstrated a certain cytotoxicity in melanocytes and keratinocytes, but they stimulated cellular migration. The nanoemulsions were classified as mild irritants in the HET-CAM assay and suitable for topical use. The nanoemulsions developed in this work, therefore, were stable, with physical aspects and organoleptic characteristics suitable for topical application, and were able to concentrate the compounds on the skin, reducing the permeation through the skin, the That could cause a negative impact on the safety of vitiligo treatment.

Orientador: Wagner Vilegas / Banca: Elfriede Marianne Bacchi / Banca: Edna Tomiko Myiake Kato / Banca: Eliana Aparecida Varanda / Banca: Mary Rosa Rodrigues de Marchi Santiago da Silva / Resumo: Brosimum gaudichaudii Trécul é uma planta medicinal utilizada na medicina tradicional no tratamento de doenças de pele, assim como o vitiligo. As furanocumarinas lineares psoraleno e bergapteno são os principais compostos responsáveis por esse efeito. O medicamento "V" produzido a partir do vegetal Brosimum gaudichaudii é usado pela população no tratamento do vitiligo, por ser alegado que o mesmo contém bergapteno. Entretanto, nada é conhecido a respeito do conteúdo de bergapteno nesse medicamento. Além disso, o uso de furanocumarinas tem sido relacionado ao aumento na incidência de câncer de pele e outras desordens assim como mutação gênica e aberrações cromossômicas em humanos. Este trabalho reporta análises qualitativas e quantitativas do vegetal B. gaudichaudii e do medicamento "V" por CLAE-DAD e CG-EM. As análises mostraram que as furanocumarinas estão presentes em maiores quantidades no córtex das raízes do vegetal, e que o medicamento "V" contém derivados de ácidos graxos e apenas pequenas quantidades de psoraleno e bergapteno. De acordo com a composição do extrato polar de B. gaudichaudii e do medicamento "V", os flavonóides 5,7,3',4'-tetraidroxi-6-C-glucopiranosilflavona e 5,7,3',4'-tetraidroxi-3-O-β-D-galactopiranosilflavonol foram identificados no extrato metanólico das folhas de B. gaudichaudii, mas estão ausentes no medicamento "V". Ensaios biológicos para mutagenicidade mostraram que os extratos aquoso e metanólico do córtex das raízes do vegetal são mutagênicos enquanto que os do medicamento não apresentam mutagenicidade...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Brosimum gaudchaudii Trécul is a medicinal plant that has been used in traditional medicine to treat skin diseases such as vitiligo. The linear furanocoumarins psoralen and bergapten are the main compounds responsible for this effect. Drug "V" produced from B. gaudichaudii has been used by the population for the treatment of vitiligo because its alleged content of bergapten. However, nothing is known about the bergapten content in drug V. Furthermore, the use of furanocoumarins has been linked to a higher incidence of skin cancer and other disorders such as gene mutations and chromosomal aberrations in humans. This work reports the qualitative and quantitative analyses of B. gaudichaudii and drug "V" by HPLC and CG-MS. The analyses showed that furanocoumarins are present in large amounts in the root bark of the plant, and that drug "V" contains fatty acid derivatives and only small amounts of psoralen and bergapten. Concerning the polar composition of B. gaudichaudii and drug V, the flavonoids 5,7,3',4'-tetrahydroxy-6-C-glucopyranosyl flavone and 5,7,3',4'- tetrahydroxy-3-O-β-galactopyranosyl flavonol were identified in the methanolic extract of B. gaudichaudii leaves, but are absent in drug "V". . Biological assays showed that the aqueous and methanolic extracts of the root bark of the plant are mutagenic, while drug "V" does not show mutagenicity. Preliminary cytotoxic assays showed that methanolic extracts of the root bark and of drug "V" are more cytotoxic than their respective aqueous extracts. In conclusion, B. gaudichaudii and drug "V" seems to present several differences not only in their chemical composition but also in the biological properties evaluated in this study. / Doutor

Orientador: Arão Rumel / Resumo : Não disponível / Abstract: Not available / Doutor

Orientador: Ana Maria Uthida Tanaka / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-01T21:43:31Z (GMT). No. of bitstreams: 1 Lombello_LucianeFaleiros_M.pdf: 18275211 bytes, checksum: 25c5d2d5b21692695693243456bc719b (MD5) Previous issue date: 2002 / Resumo: o vitiligo é uma doença adquirida, idiopática, freqüentemente associada a história familiar positiva e caracterizada por manchas acrômicas ou hipocrômicas, com dimensão e forma variáveis, sendo muitas vezes desfigurante. Afeta de 1% a 3% de todas as raças da população mundial, tendo maIor prevalência no sexo feminino; aproximadamente 50% dos pacientes desenvolvem alguma forma da doença antes dos 10 anos de idade. Alguns estudos sobre mecanismos psiconeuroimunológicos consideram o estresse emocional como parte fundamental da sua etiologia, seja como fator desencadeante ou exacerbante. Os aspectos psicossociais do vitiligo comprometem muito a auto-estima dos pacientes, passando a funcionar como fatores de "feed back" na evolução e agravamento da doença. Os objetivos do presente trabalho são: a) conhecer os aspectos clinicos e refletir sobre os aspectos emocionais apresentados pelas crianças, b) avaliar eventuais diferenças entre as respostas ao tratamento em 18 crianças com vitiligo, fazendo uso da mesma medicação e associando psicoterapia de grupo em 9 destas crianças. Nove crianças com vitiligo, de idades entre 8 e 12 anos participaram de psicoterapia de grupo; as sessões foram quinzenais, com duração de uma hora, e simultâneas às realizadas com o grupo de pais ou responsáveis destes pacientes. Foram realizadas 30 sessões no período de um ano e meio. A avaliação dermatológica foi trimestral e as crianças fizeram uso de medicação específica (Viticromin@)associada à fototerapia. Foram observadas mudanças no comportamento das crianças submetidas à psicoterapia tais como: melhora no desempenho escolar, desinibição, fortalecimento dos vínculos familiares e, em relação ao vitiligo, este grupo apresentou repigmentação da maioria ou do total das lesões. A diferença foi estatisticamente significativa em relação aos resultados obtidos com o grupo acompanhado sem psicoterapia. Estes resultados preliminares permitem recomendar a psicoterapia de grupo como tratamento coadjuvante do vitiligo / Abstract: Vitiligo is an acquired, idiopathic disease that is often associated with a positive familial history and it is characterized by achromic or hypochromic patches of different shapes and sizes, that often disfigure the individual. It affects between 1% t03% ofthe human race, is more prevalent in the female sex and approxirnately 50% of these patients develop some kind of disease by the age of 10 years. Some studies on psychoneuroirnrnunological mechanisms consider emotional estresse a fundamental part of its etiology ~ither as a catalyst or an aggravator (8). The psychosocial aspects of vitiligo great1y affect the patient's self-esteem and act as feedback factors in the evolution and aggravation ofthe disease (33). The objectives ofthis study are to: a) assess the eventual differences in the response to treatment of 18 children with vitiligo who used the same medication but, in of 9 of these patients, it was applied group psychotherapy; b) the second objective recognize and understand the emotional aspects presented by children with vitiligo. Nine children with vitiligo between 8 years to 12 years old participated in analytical group psychotherapy. These sessions, which lasted for an hour, were held fortnight1yand the group of parents or individuaIs responsible for the children participated sirnultaneously in similar sessions. Thirty sessions were conducted over a year and six months and the children were assessed montWy. They were treated with specific medication (Viticromin@) in combination with phototherapy. These children presented behavioral changes such as: better performance at school, redution of inhibition, stronger family ties, repigmentation of all or a great majority of the lesions. These results showed a statistical difference with the results of the group of children that did not have submitted to psychotherapy. It would be better to associate analytical group psychotherapy for vitiligo in the treatment of vitiligo in children / Mestrado / Mestre em Clinica Medica

The entire epidermis of patients with vitiligo exhibits accumulation of up to 10-3M concentrations of hydrogen peroxide (H2O2) (Schallreuter, Moore et al. 1999). Over the last decade our group and others have focused on the effect of H2O2-mediated oxidative stress on the function of many proteins and peptides due to oxidation of target amino acid residues in their structure including L-methionine, L-tryptophan, L-cysteine and seleno cysteine (Rokos, Beazley et al. 2002; Gillbro, Marles et al. 2004; Hasse, Kothari et al. 2005; Schallreuter, Chavan et al. 2005; Spencer, Chavan et al. 2005; Chavan, Gillbro et al. 2006; Elwary, Chavan et al. 2006; Gibbons, Wood et al. 2006; Schallreuter, Bahadoran et al. 2008; Shalbaf, Gibbons et al. 2008; Wood, Decker et al. 2009). Moreover, it was shown that patients with vitiligo possess up regulated wild type functioning p53 protein in their skin (Schallreuter, Behrens- Williams et al. 2003). The reason behind this up regulation has remained unclear (Schallreuter, Behrens-Williams et al. 2003). Therefore the aim of this thesis was to get a better understanding of these puzzling data. Along this project different techniques have been used including Western blot, dot blot, immuno precipitation, immuno fluorescence, EMSA and computer modelling. In this thesis we confirmed the previous result on up regulation of p53 in vitiligo and we showed that p90MDM2, the master regulator for p53 protein is not different in patients and healthy controls. Therefore we decided to test for expression of p76MDM2 which mediates the inhibition of p90MDM2-p53 binding. Our results show for the first time the presence and over expression of p76MDM2 protein in vitiligo compared to 3 healthy individuals. This result could provide an explanation, why up regulated p53 is not degraded in this disease. Since epidermal H2O2 accumulation has been extensively documented in vitiligo, we wanted to know whether other ROS could also contribute to the overall oxidative stress in this scenario. Therefore we turned our interest to nitric oxide (NO) and its possible effects on p53 protein. In order to elucidate this role in more detail, the expression levels of epidermal nitric oxide synthesase (iNOS) and the oxidation product of NO and O2 - i.e peroxynitrite (ONOO-) were investigated. Our data revealed over expression of iNOS and nitrated tyrosine residues, the foot print for ONOO-. Moreover, we show for the first time the presence of abundant nitration of p53 protein in vitiligo. In addition using purified p53 from E. coli strain (BL21/DE3) and mutant p53 protein from HT-29 cells (colon cancer cells), we show that nitration takes place in a dose and time dependent manner. On this basis we investigated the effect of both H2O2 and ONOO- on p53-DNA binding capacity employing EMSA, since this is the most acceptable technique to follow the binding between proteins and DNA. Our results revealed that ONOO- abrogated p53-DNA binding capacity at concentrations >300 ¿M, meanwhile oxidation of p53 protein with H2O2 at the same concentrations does not affect binding capacity. Importantly, a much higher p53- DNA binding capacity was observed after exposure to both ONOO- and H2O2. Taken together, p53 is regulated by both ROS (H2O2) and RNS (ONOO-). Next we identified the presence of phosphorylated and acetylated p53 in vitiligo. Phosphorylation of ser 9 and ser 15 residues of the protein are associated with over expressed ATM protein kinase, while acetylation of lys 373, 382 residues correlates with increased PCAF expression. We show that up regulated p53 is associated with over expressed p21 (cyclin dependent kinase inhibitor 1) and induced PCNA 4 expression. Hence, we can conclude that p53 in patients with vitiligo is up regulated, activated and functional. Finally we show up regulated BCL-2 supporting the long voiced absence of increased apoptosis in vitiligo. Given that patients with vitiligo have no increased risk for solar induced skin cancer and increased photo damage (Calanchini-Postizzi and Frenk 1987; Westerhof and Schallreuter 1997; Schallreuter, Tobin et al. 2002), despite the presence of increased DNA damage as evidenced by increased 8-oxoG levels in the skin and in the plasma, our findings suggest that both p53 and PCNA provide a powerful machinery to mediate DNA repair via hOgg1, APE1 and DNA polymerase ß (Shalbaf 2009). On this basis it is tempting to conclude that DNArepair is the overriding mechanism to combat oxidative stress in this disease. / Egyptian government; Institute for Pigmentary Disorders in association with the EM Arndt University of Greifswald, Germany.

No / It has long been appreciated in science that correlation does not imply causation. However, with any logical fallacy, simply spotting that the reasoning behind an argument is faulty does not imply that the resulting conclusion is false. Thus, I begin the tricky business of exploring the basis upon which researchers and clinicians are often tempted to conclude that two medical conditions (here alopecia areata and vitiligo), with some striking resemblances, are in fact related. This is relevant, particularly if assumptions of shared aetiology (and to some extent shared pathomechanism) encourage a common strategy to finding a treatment or cure.

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

No / Background  Vitiligo is an acquired, idiopathic, and worldwide common depigmentation disorder with an estimated prevalence from 0.1 to 8%. These numbers are based on clinical population studies and field research examining inhabitants of geographically enclosed areas. Our aim was to collect all available data on the prevalence of vitiligo in the general population, paying particular attention to children/adolescent groups and adults. Materials and methods  Screening of available literature and online databases using several key words. Results  We found more than 50 studies that used several methods and subgroups of the general population. The prevalence of vitiligo ranges from 0.06 to 2.28%, whereas this was 0.0–2.16% in children/adolescents populations. Conclusions  The often cited prevalence of 8% could not be confirmed after excluding clinical patient populations. Accordingly, the worldwide prevalence of vitiligo ranges between 0.5 and 2%.