Submitted by Edineia Teixeira (edineia.teixeira@unioeste.br) on 2019-03-11T19:27:48Z No. of bitstreams: 2 Jaqueline_Denardin_2019.pdf: 2478888 bytes, checksum: 2bb64c3784018b2b204f8ce144d0c297 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2019-03-11T19:27:48Z (GMT). No. of bitstreams: 2 Jaqueline_Denardin_2019.pdf: 2478888 bytes, checksum: 2bb64c3784018b2b204f8ce144d0c297 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2019-02-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / From the theorical perspective of the Discourse Analysis (PÊCHEUX, 1969, 1975), attached to the gender studies (BEAUVOIR 1967, 1970; BENTO 2008; BUTLER 2003,2011), this work aims to analyze the series “Quem sou eu?” (Who am I?), which has passed on Fantástico, a program broadcasted by GLOBO Television Network. Being released in four episodes, on four consecutive Sundays, between March and April of 2017, the series approached transsexuality and its relevant demands attached to the transsexual individual, such as: the “choices” of whom was born in a “wrong” body, the impact in the person’s school and academic life due to the fact of being transsexual, the issue of self-medication and treatment(s), the sex reassignment surgery and the relationships in the “transgender world” regarding to familial affection, affection issues and sexual desire. The main goal is to analyze how the series, which is metaphorically narrated inspired by the popular child story “Alice no País das Maravilhas” (Alice in Wonderland) , brings out the topic in a way to start talking about transsexuality, in order to analyze the ideological functioning that permeates the discussions on this topic. Transsexuality has been facing a lot of discussions in the contemporary world covered by intense social impact that justifies the necessity of approaching transsexuality in the scientific production field, so that the conceptions related to this topic will not be mostly based on common sense, allowing the epistemological construction of knowledge on transsexuality. Therefore, this work intends to understand how the experienced effects are sustained – mentioned and not mentioned – in produced discourses – by the media, journalistic discourse, and even to notice the current ideologies in the transsexual individuals’ discourse, as a sense effect – inspired by the topic approached by the series, transsexuality. / Neste trabalho, a partir da perspectiva teórica da Análise de Discurso (PÊCHEUX, 1969, 1975), articulada aos estudos do gênero (BEAUVOIR, 1967,1970; BENTO 2008; BUTLER 2003, 2011), pretendemos analisar a série “Quem sou eu?”, transmitida pelo programa televisivo da Rede Globo de Televisão Fantástico. Realizada em quatro episódios, com circulação em quatro domingos consecutivos, entre os meses de março e abril de 2017, a série abordou o tema da transexualidade e as demandas pertinentes e “inerentes” ao sujeito transexual, tais como: as “escolhas” de quem nasceu no corpo “errado”; a repercussão na vida escolar e acadêmica por ser um sujeito trans; a questão da automedicação e tratamento(s); a cirurgia de transgenitalização e os relacionamentos no “mundo transgênero”, tanto em relação às questões de afeto familiar quanto às questões de desejo sexual. O objetivo principal é analisar como a série, que é narrada, metaforicamente, ancorada na história infantil “Alice no País das Maravilhas”, traz o(s) dizer(es) como um modo de fazer falar o tema da transexualidade. Nossa dissertação tem como intuito analisar o funcionamento ideológico que permeia as discussões feitas pelo programa televisivo acerca desse tema – assunto que tem sido pivô de várias discussões na contemporaneidade com repercussão social intensa, o que justifica cientificamente a nossa pesquisa e a necessidade de abordar a transexualidade no espaço de produção científica, para que não tenha, como dito, somente o que é produzido pelo senso comum, possibilitando, assim, uma construção epistemológica do conhecimento e saberes sobre a transexualidade. Portanto, este trabalho teve a intenção de compreender como se sustentam efeitos de sentidos – ditos e não ditos – em dizeres produzidos pelo discurso televisivo de tal programa; ademais, analisou como os sujeitos trans se dizem e são ditos nessa série sobre sua transexualidade.

Enquête sur le fer(II) noyau transition de spin centrée métal coordonner avec des ligands photo-actif (isomérisation tran / cis) et l'étude de la lumière induite par le changement de spin conduit ligand (LD-LISC) propriétés en fer(II) fonctionnalisé complexes sous la forme de nanoparticules dispersées dans des films minces transparents. Pour cette étude, nous avons choisi un ensemble de complexes mononucléaires incorporant un ligand bipyridine substitué soit par un groupe méthyle (de la fonction électronique et de la structure) ou un groupe styryle (fonction photoactivable). L'introduction dans la sphère de trois de coordination (forte cas ligand-domaine) ou deux (intermédiaire force ligand-domaine) des ligands bipyridine (avec NCSe- co-ligands) a permis à la modulation de la résistance au ligand champ subi par l'ion métallique dans des systèmes différents. Propriétés de commutation optiques et thermiques des solides ont été étudiés dans les poudres polycristallines et de la dispersion des objets de taille réduite (micro, nanoparticules). Nous avons présenté l'élaboration et l'étude des micro- et nano-particules, complexes Fe(II) mononuclées non-ioniques, y compris ligand bidenté (4,4-méthyl-2,2 'bipyridine, Me₂-bpy) ont été sélectionnés. La synthèse de nano-et micro-objets a nécessité l'adaptation de la méthode (précipitation rapide anti-solvant). Il a été réalisé avec ionique [Fe(L)₃](NCSe)₂ précurseurs en jouant avec l'équilibre chimique pour induire la précipitation de connexes neutre Fe(L)₂(NCSe)₂ espèces. Nano et micro-cristaux de Fe(Me₂-bpy)₂(NCSe)₂ avec des tailles de 56 à 1200 nm ont été caractérisés et très dilués dans des films minces polymères pour optimiser l'absorption de la lumière et de l'étude des processus photocommutation. Fe (Me₂-bpy)₂(NCSe)₂ sous la forme de nano-et micro-particules, traitées dans des films polymères minces ont montré à spin-croisé thermique centrée à des températures supérieures à la température ambiante; pas d'effet significatif de l'environnement a été détectée. Nous avons étudié la réactivité photochimique de la precusors ioniques [Fe(msbpy)₃](NCSe)₂ (msbpy = trans et cis-isomères de 4-méthyl-4'-styryl-2,2 '-bipyridine), a été d'abord sondé en solution. Il a été établi que les cis isomérisation trans de 4-méthyl-4'-styryle 2,2 bipyidine a lieu d'une manière quantitative lorsque le complexe Fe(II) diamagnétique a été exposé à une lumière bleue (405 nm); cette réaction peut être partiellement inversée par une excitation UV. Nous avons élaboré des nanoparticules dérivées croisées sur la base du Fe(II) sont décrits; la commutation de ces particules (60nm) embarqués dans des films minces de PMMA et l'effet LD-LISC sont étudiés. Dans l'environnement très confiné de nanoparticules, la Feᴵᴵ(t-msbpy)₂(NCSe)₂ complexe réagit aussi lors de l'irradiation. La combinaison des UV-Vis, Raman et mesures photomagnétiques des matériaux hautement diluées nous a permis d'analyser l'effet de l'irradiation de lumière et le comportement de commutation état de spin. L'étude de Feᴵᴵ(t-msbpy)₂(NCSe)₂a montré la présence à la température ambiante des différents processus en fonction de la longueur d'onde d'excitation: un procédé de ligand centrée (trans à cis isomérisation, 365 nm) et un métal un centré (entraînant un changement MLCT, 405 nm). / Investigation of the iron(II) metal-centered spin-crossover core coordinate with photo-active ligands (tran / cis isomerization) and study of the ligand-driven light-induced spin change (LD-LISC) properties with functionalized iron(II) complexes in the form of nanoparticles dispersed in transparent thin films. For this investigation, we have selected a set of mononuclear complexes incorporating a bipyridine ligand substituted either with a methyl group (electronic and structural function) or a styryl group (photoactivable function). The introduction in the coordination sphere of three (strong ligand-field case) or two (intermediate ligand-field strength) bipyridine ligands (with NCSe- co-ligands) has allowed the modulation of the ligand-field strength experienced by the metal ion in different systems. Optical and thermal switching properties of solids have been investigated in polycrystalline powders and in dispersion of size-reduced objects (micro-, nano-particles).We have presented elaboration and study of micro- and nanoparticles, non-ionic mononuclear FeII complexes including bidentate ligand (4,4’-methyl-2,2’-bipyridine, Me2-bpy) have been selected. The synthesis of nano- and micro-objects has required the adaptation of the method (sudden precipitation in antisolvent). It was achieved with ionic [Fe(L)3](NCSe)2 precursors by playing with chemical equilibrium for inducing the precipitation of related neutral Fe(L)2(NCSe)2 species. Nano- and micro-crystals of Fe(Me2-bpy)2(NCSe)2 with sizes 56-1200 nm were characterized and then highly diluted in polymeric thin films for optimizing light absorption and investigating photoswitching processes. Fe(Me2-bpy)2(NCSe)2) in the form of nano-and micro-particles, processed in thin polymeric films were shown to exhibit thermal spin-crossover centered at temperatures higher than room temperature; no significant effect of environment was detected.We have studied the photochemical reactivity of the ionic precusors [Fe(msbpy)3](NCSe)2 (msbpy = trans- and cis-isomers of 4-methyl-4’-styryl-2,2’-bipyridine,) was first probed in solution. It has been established that the cis to trans isomerization of 4-methyl-4’-styryl-2,2’-bipyidine takes place in a quantitative way when the diamagnetic FeII complex was exposed to a blue light (405 nm); this reaction can be partly reversed with a UV excitation.We have elaborated spin-crossover nanoparticles based on the Fe(II) complexes are described; the switching of these particles (60nm) embedded in PMMA thin films and the LD-LISC effect are investigated. In the highly confined environment of nanoparticles, the FeII(t-msbpy)2(NCSe)2 complex also reacts upon irradiation. The combination of UV-Vis, Raman and photomagnetic measurements of the highly diluted materials has allowed us to analyze the effect of light irradiation and the spin-state switching behavior. The study of FeII(t-msbpy)2(NCSe)2 has shown the occurrence at room temperature of different processes depending on the excitation wavelength: a ligand-centered process (trans-to-cis isomerization, 365 nm) and a metal-centered one (resulting in a MLCT change, 405 nm).

A doença de Chagas é considerada a terceira doença parasitária tropical de maior incidência no mundo, só superada pela malária e esquistossomose, e seu agente causador é o protozoário flagelado Trypanosoma cruzi. O parasita expressa uma enzima de superfície denominada trans-sialidase de Trypanosoma cruzi (TcTS), responsável pela transferência do ácidos siálicos de células do hospedeiro para moléculas de ?-galactose terminais presentes em glicoproteínas de sua superfície. As moléculas de glicoproteína sialiladas estão envolvidas na adesão e subsequente penetração do parasita em células hospedeiras. O papel fundamental da TcTS no reconhecimento e na invasão de células hospedeiras, bem como sua ausência em seres humanos, torna esta enzima um alvo potencial a ser estudado. A TcTS é específica em catalisar, preferencialmente, a transferência de ácido siálico para moléculas de mucina, originando ligações ?-2,3 com unidades de ?-galactose aceptoras na superfície do parasita. Considerando a importância da unidade de galactose e da função carboxila do ácido siálico para interações no sítio ativo de TcTS, priorizamos na síntese de derivados galactosil-triazolo-benzenossulfonamidas com diferentes substituintes, visto que o grupo sulfonamida é bioisóstero do ácido carboxílico, na busca de potenciais inibidores de TcTS. Os derivados galactosiltriazolo- benzenossulfonamidas 45-51 foram preparados via estratégia de click chemistry, por reação de ciclo-adição azido-alcino catalisada por Cu(I) (CuAAC), a partir do intermediário de galactose contento função amino terminal 30 e os derivados aril azidas 38-44. Após etapa de desacetilação, os produtos obtidos 52-58 foram testado em TcTS por ensaio fluorimétrico in vitro para avaliação de sua atividade inibitória. Os resultados obtidos são interessantes e bastante promissores, principalmente com os obtidos com o produto 58 (contendo o grupo galactosiltriazólico ligado a sulfapiridina), que apresentou atividade inibitória promissora (81%) na concentração de 1,0 mM, abrindo perspectivas para a síntese de um maior número de derivados galactosil-triazolo-benzenossulfonamidas com diferentes substituintes em R, para o estabelecimento de estudos de relação estruturaatividade. Adicionalmente, os compostos 53-55 foram testados em ensaios in vitro para avaliação de sua atividade tripanocida e citotóxica, e apresentaram atividade tripanocida máxima de 50%, normalmente nas concentrações de 500 a 250 ?M, com destaque para o derivado 55, contendo o grupo galactosil-triazólico ligado a sulfamerazina, que apresentou atividade moderada, mas superior ao benznidazol nas concentrações mais baixas (15,0 - 1,9 ?mol.L-1). Por outro lado, de acordo com os resultados do ensaio de citotoxicidade, a atividade citotóxica foi observada apenas nas concentrações mais elevadas, similar ao benznidazol. / Chagas disease is considered the third most common tropical parasitic disease worldwide, after malaria and schistosomiasis, and its causer is the flagellate protozoan, Trypanosoma cruzi. The parasite expresses a surface enzyme known as Trypanosoma cruzi trans-sialidase (TcTS), responsible for the transference of sialic acid from host cell to ?-galactose terminal molecules present in surface glycoproteins. Sialylated glycoproteins molecules are involved in adhesion and further penetration of parasite in host cell. Due to TcTS primordial role in recognizing and invasion of host cells, as well as its absence in humans, this enzyme becomes a potential target to be investigated. TcTS is specific on catalyzing, specially, transference of sialic acid to mucin molecule giving ?-2,3 bond with ?-galactose moiety in parasite surface. Considering the importance of the galactose moiety and the function of carboxylic in sialic acid for interactions in TcTS enzyme, we prioritized the synthesis of galactosyl-triazol-benzenesulfonamides derivatives with different substituents since sulfonamide group is bioisoster of carboxylic acid, in attempt to produce potential inhibitors of TcTS. The galactosyl-triazol-benzenesulfonamides derivatives 45-51 were prepared via click chemistry reaction (Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)) from galactose intermediate with terminal amino group 30 and aril azides derivatives 38-44. After removing acetyl group, the inhibiting activity of products 52-58 were evaluated in TcTS fluorimetric in vitro assay. We found very promising results, specially with 58 (containing galactosyl-triazolic group bonded to sulfapyridine), wich showed 81% of inhibitory activity in 1,0mM solution, bringing expectations for synthesis of greater number of galactosyl-triazolbenzenesulfonamides derivatives with different substituents in R, to establish studies of structure relationship activity. Additionally, trypanocidal and cytotoxic activity of compounds 53-55 were tested and showed maximum activity of 50%, commonly in concentrations of 500 to 250 ?M, specially compound 55, containing galactosyltriazolic group bonded to sulfamerazine, with showed moderate activity, but higher then benznidazol in lower concentrations (15,0 - 1,9 ?mol.L-1). On the other hand, according to cytotoxicity results, activity were observed only in higher concentrations, as for benznidazol.

Apresenta-se, nesta tese, a síntese total do alcaloide marinho (+)-trans-triquentrina A. Três abordagens foram investigadas como estratégias sintéticas: uma adição conjugada assimétrica, um acoplamento arílico com um complexo de ferro e uma resolução cinética enzimática. Esta última permitiu finalizar a síntese do produto natural em 20 etapas e com 0,6% de rendimento global. A síntese tem como etapas-chave a resolução cinética de um éster racêmico, mediada pela lipase da Pseudomonas cepacia - que forneceu o (S)-ácido correspondente em excelente excesso enantiomérico - e a contração de anel de um ciclo-hexeno substituído promovida por um sal de tálio(III), fornecendo seletivamente o composto trans-1,3-dimetilciclopentano correspondente. Efetuaram-se testes visando à síntese total da (+)-cis-triquentrina A a partir de um intermediário obtido da etapa de resolução cinética enzimática, que seria comum à síntese das duas moléculas-alvo. Investigou-se a atividade antiproliferativa da (+)-trans-triquentrina A, bem como a de intermediários da síntese e de produtos relacionados. Estes estudos permitiram descobrir compostos com atividade potente frente a linhagens de células tumorais humanas de ovário (GI50=0,31-0,42 µg.mL-1) e de cólon (GI50=0,25 µg.mL-1). / The total synthesis of marine alkaloid (+)-trans-trikentrin A is presented in this thesis. Three approaches were investigated as synthetic strategies: an asymmetric conjugate addition, an aryl coupling with an iron complex and an enzymatic kinetic resolution. The latter allowed the synthesis of the natural product to be achieved in 20 steps and 0.6% overall yield. The synthesis features as key steps a kinetic resolution of a racemic ester, which was mediated by the lipase from Pseudomonas cepacia, leading to the corresponding (S)-acid in excellent enantiomeric excess, as well as a thallium(III)-mediated ring contraction of a cyclohexene derivative that selectively afforded the corresponding trans-1,3- dimethylcyclopentanic compound. Studies toward the total synthesis of (+)-cis-trikentrin A were performed aiming to achieve both natural products from a common intermediate, obtained from the enzymatic kinetic resolution. The antiproliferative activity of (+)-trans-trikentrin A as well as that of intermediates and related products was investigated. Compounds with potent activity against ovarian (GI50=0.31- 0.42 µg.mL-1) and colon (GI50=0.25 µg.mL-1) tumor cell lines were discovered during these studies.

Chez les patients souffrant d'insuffisance rénale chronique, les calcifications vasculaires représentent la première cause de mortalité. Elles résultent de la trans-différenciation des cellules musculaires lisses (CMLs) en cellules de type ostéoblastique et/ou chondrocytaire, en réponse à des cytokines inflammatoires ou à une hyperphosphatémie. Les CMLs forment alors des cristaux par l'activité de la phosphatase alcaline non-spécifique du tissu (TNAP). A la lumière de résultats récents, nous avons émis l'hypothèse que la TNAP module la trans différenciation des CMLs. Nos objectifs étaient donc de déterminer l'effet de la TNAP dans la trans-différenciation des CMLs, et d'étudier les mécanismes impliqués dans son induction, avec un intérêt particulier pour les microRNAs. Nous avons observé que l'ajout de phosphatase alcaline purifiée ou la surexpression de TNAP stimule l'expression de marqueurs chondrocytaires en culture de CMLs et de cellules souches mésenchymateuses. De plus, l'inhibition de la TNAP bloque la maturation de chondrocytes primaires. Nous excluons un rôle des cristaux formés par la TNAP, puisque l'ajout de cristaux seuls ou associés à une matrice collagénique n'a pas reproduit les effets de la TNAP. Nous suspectons que la TNAP agit en hydrolysant le pyrophosphate inorganique (PPi). En effet, c'est la TNAP qui hydrolyse le PPi en culture de CMLs et de chondrocytes, et le PPi mime les effets de l'inhibition de TNAP en culture de chondrocytes. Enfin, nous rapportons le profil de microRNA des artères cultivées en conditions hyperphosphatémiques. Ces résultats pourraient être particulièrement importants dans le développement de nouvelles approches thérapeutiques / In patients with chronic kidney disease (CKD), vascular calcification represents the main cause of mortality. Vascular calcification results from the trans-differentiation of vascular smooth muscle cells (VSMCs) into cells similar to osteoblasts and/or chondrocytes, in response to inflammatory cytokines or hyperphosphatemia. Calcifying VSMCs form calcium phosphate crystals through the activity of tissue nonspecific alkaline phosphatase (TNAP). In light of recent findings, we hypothesized that TNAP also modulates VSMC trans-differentiation. Our objectives were therefore to determine the effect of TNAP activity on VSMC trans-differentiation, and secondly to investigate the molecular mechanisms involved in TNAP expression in aortas, with a particular interest in microRNAs. We first observed that addition of purified alkaline phosphatase or TNAP over-expression stimulates the expression of chondrocyte markers in culture of the mouse and rat VSMC lines, and of mesenchymal stem cells. Moreover, TNAP inhibition blocks the maturation of mouse primary chondrocytes and reduces mineralization. We exclude a role for crystals in TNAP effects, since addition of crystals alone or associated to a collagenous matrix fails to mimic TNAP effects. We rather suspect that TNAP acts through the hydrolysis of inorganic pyrophosphate (PPi). Indeed, PPi is hydrolyzed by TNAP in VSMCs and chondrocytes and addition of PPi mimics the effects of TNAP inhibition on chondrocyte maturation. Finally, we report microRNA signature of aortic explants treated under hyperphosphatemic conditions that induce vascular calcification. These results could be of particular importance in patients with CKD

The major sorting station of biosynthetic material destined for the cell surface or secretion is the trans Golgi Network, TGN. This organelle sorts proteins and lipids into vesicular transport carriers that are targeted via different pathways to distinct membrane compartments of the cell. The molecular principles that operate in cargo sorting at the TGN are still not very well understood. Especially, we know very little about the sorting of lipids. It was postulated that a sorting mechanism based on clustering of lipid rafts, dynamic membrane domains enriched in sphingolipids and sterols, could be an important part of the picture. My thesis study dealt with the elucidation of the molecular sorting principles at the TGN and their exploitation for cell surface polarity in the yeast Saccharomyces cerevisiae. To this end, we conducted a genome wide screen that identified yeast mutants defective in cell surface delivery of the model cargo protein FusMid-GFP. The most striking result of this screen was that mutant strains with defects in ergosterol (the major yeast sterol) and sphingolipid biosynthesis lost sorting competence. To elucidate a direct role for sphingolipids and ergosterol in cargo sorting and secretion we sought to characterize the lipid composition of secretory vesicles. Hence, we established a vesicle purification protocol based on an immunoisolation strategy. Additionally, in collaboration with the group of A. Shevchenko, we developed a mass spectrometry methodology that allows the comprehensive and quantitative lipid analysis of subcellular organelles. Preliminary results corroborate our genetic evidence. The data show that the vesicles are enriched in sphingolipids and decreased in phosphatidylcholine indicating a role for raft clustering in cargo sorting at the TGN. The studies of cell polarity during yeast mating also unraveled a role for raft clustering. We could identify that the lipid bilayer at the tip of the mating projection was more ordered than at the plasma membrane enclosing the cell body and that this was dependent on sphingolipid synthesis. The results of my thesis suggest that in the yeast Saccharomyces cerevisiae fundamental cell biological processes such as cargo sorting and vesicle formation at the TGN as well as cell surface polarity during mating employ raft clustering mechanisms.

The idea for this study was evoked from a number of observations that we did in relation to our personal interest for feminism and gender studies. We have noticed tendecies of identity politics in feminist web­based discussion forums, which have led to intermutual conflicts within the feminist movement. Discussions of great importance between the members of these discussion forums, have oftentimes ended up being matters of interpretative prerogative, and to whom it belongs, as well as questions about who holds authority to claim which opinion, and why one holds authority to claim any opinion at all. We read this phenomenon as a matter of power configuration ­ for even within these formed groups of people that are oppressed in the western majority culture, relations including roles with oppressing positions as well as roles with oppressed positions emerge. In this study we have chosen to focus on a certain type of identities that are frequently stressed when conflicts emerge in these web­based forums, namley transgender identities. The purpose of this paper is to bring forward the narratives of people with transgender identities, about their experienced possibilites to word in feminist web­based discussion forums, as well as analyze the discourses of power that figures in these forums. The material for this study was collected through qualitative interviews, which were made with four different respondents. All of which having experience of being transgender and members of different feminist web­based forums. The analysis in turn consists of essential recitals by the respondents, which are resolved from a discourse theoretical perspective. According to discourse theory, power configurations between people are made from a variation of factors that determine the directions of power, and are constantly reformed from one moment to another. From the recitals of our respondents we understand that there are several power discourses prevailing concurrently in the feminist web­based discussion forums, and that there is no binary and consistent divergence between the oppressing position and the oppressed position. A person whose identity validates its power in one discussion, can be totally powerless because of its identity in another.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 3 uppsatser.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A utilização da música na reabilitação de pessoas que fazem uso abusivo de substâncias psicoativas configura-se como uma incógnita epistemológica para o campo da musicoterapia. A carência de pesquisas teóricas e práticas no âmbito da musicoterapia, que atentem para a complexidade da demanda na reabilitação de pessoas acometidas pelo abuso de substâncias, é o principal motivador para a elaboração do trabalho. Sendo metodologicamente provindo de revisão bibliográfica, o escrito é divido em três momentos. O primeiro investiga de que maneira o uso abusivo de substâncias psicoativas arraigou-se como um dos principais problemas da sociedade atual e de que forma o uso de substâncias está culturalmente relacionado às artes, especificamente a música. Servirão de aporte para essa parte, os olhos da Teologia da Libertação, a qual busca no âmago do sofrimento das pessoas, o reconhecimento da dignidade inerente a todos os seres humanos. A identificação das vias rituais pelas quais acontece a trans-significação do real pelo ser humano, é executada no segundo momento. Questões relacionadas às linguagens e às formas pelas quais o ser humano sai da realidade, as quais intermediam suas buscas existenciais, são o cerne dessa parte. O terceiro e último momento avista a natureza comunicacional e organizacional da música, para uma formulação epistemológica que contemple a demanda concernente à prática clínica musicoterapêutica na reabilitação de pessoas acometidas pelo abuso de substâncias. Identifica-se nessa parte, que a sessão musicoterapêutica é uma prática salutar de trans-significação do devir humano. / The use of music in rehabilitation of people who use psychoactive substances emerges as an epistemological question to the field of Music Therapy. The lack of theoretical and practical researches in Music Therapy, which focuses on the complexity of the demand in rehabilitation of people affected by the abuse of substances, is the main motivator for the development of this work. Methodologically based on a bibliographical review, this dissertation is divided into three parts. The first investigates how the abuse of psychoactive substances rooted itself as one of the main problems of the current society and how the use of substances is culturally related to the arts, specifically music. This part has an approach of the Liberation Theology, which seeks the recognition of the dignity, common to all human beings, by looking into the suffering of the people. The second part identifies the ritual paths, in which the trans-signification of what is real happens. Issues related to language and ways the human being uses to leave reality, which mediate their existential quest, are the core of this part. The third and last part addresses the communicational and organizational nature of the music, in order to build an epistemological concept that considers the demand regarding to the clinical music therapy practice in rehabilitation of people affected by the abuse of substances. In this part, we identify that the Music Therapy session is a healthy practice of trans-signification of becoming human.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Diet fatty acids (FA) are fundamental to the phospholipids structure and function of cell membranes, in which long chain polyunsaturated FA (PUFA) increase its fluidity, while the trans FA (TFA) to make it more rigid. Also, the barrier function and hydration are highly dependent on the skin composition and structure, as well as the organization of lipids in the cell matrix. In recent years, the ozone layer depletion has increased human exposure to ultraviolet radiation (UVR), inducing deleterious effects on skin homeostasis. Moreover, lifestyle habits and eating patterns, especially in Western countries, has shown an increasing consumption of processed foods rich in AGT, whose cutaneous consequences do not present scientific validation. Whereas the skin health is partially related to the lipids that compose it, this study was designed to evaluate the effect of supplementation of different oils or fat in distinctlife periods of rodents on oxidative damage acute and chronic exposure to UVR-induced. Male Swiss mice weanling were supplemented daily (3g/kg, po) with soybean oil (C-SO; rich in n-6 PUFA), fish oil (FO; rich in n-3 PUFA) or hydrogenated vegetable fat (HVF; rich in TFA) until 90 days old and the dorsal skin was acutely exposed to UVR. The FO supplementation showed n-3 PUFA incorporation in mice skin, while the groups supplemented with soybean oil and HVF showed incorporation of n-6 PUFA and TFA, respectively. Such skin incorporations exerted influences on the development of UVR -induced oxidative damage in the mice skin and HVF group showed the highest protein carbonylation (PC) levels and lipid peroxidation, accompanied by larger skin thickening (edema), lower catalase (CAT) activity and cell survival. While soybean oil was associated with a partial prevention of damage observed in HVF group, FO supplementation prevented cutaneous oxidative damage UVR-induced. Sequentially, second and third experimental protocols were developed with the first and second generations offsprings born adult rats under daily supplementation of the same oils used in experiment 1 (SO, FO and HVF) and at 90 days old, each experimental group were exposed to UVR 3x/ week for 12 weeks. Animals first generation offspring (experiment 2) FO supplemented treated showed higher incorporation of n-3 FA and lower n-6/n-3 ratio in the dorsal skin, while the HVF group showed greater incorporation of TFA. Biochemical analyzes showed higher PC levels, per se, and smaller functionality of mitochondrial enzymes and decrease of some antioxidant defenses ((reduced glutathione (GSH) and vitamin C (VIT C)) in the dorsal skin HVF supplemented group. After UVR exposure, the same experimental group showed higher wrinkles scores, increased reactive species (RS) generation and PC levels, which were accompanied by decrease in GSH and VIT C skin levels. In contrast, FO group showed lower wrinkles scores and skin thickening after UVR exposure, besides lower PC levels and increased of the functionality of mitochondrial enzymes. Additionally, we observed a positive correlation between the RS generation-UVR induced and skin thickness, wrinkles and PC levels, while a negative correlation between the RS generation-UVR induced and functionality of mitochondrial enzymes, and between PC levels and GSH, SOD and VIT C.Animals of the second generation offspring (experiment 3) supplemented with FO showed higher n-3 FA incorporation and lower n-6/n-3 ratio in the dorsal skin, while TFA were incorporated only in HVF group. The latter experimental group showed biochemical changes per se: high RS generation, lower functionality of mitochondrial enzymes and increased Na+K+-ATPase activity. UVR exposure increased skin wrinkling andRS generation, besides reduced functionality of mitochondrial enzymes and GSH levels in HFV group. FO groupUVR exposure showed reduced skin thickness and PC levels, besides increase CAT activity and the preservation of Na+K+-ATPase activity. Whereas the n-3 PUFA compete with n-6 PUFA for desaturases and elongases activities, which originate from long chain n-3 or n-6 PUFA, respectively, which are incorporated into the cell membranesphospholipids.Such incorporation allows the cyclooxygenase-2 (COX-2) activity over them, originating active metabolites of the series 3 (prostaglandins (PG) and thromboxanes (TX)) or series 2 (PG and TX series 2), respectively. Series 3 metabolites are less pro-inflammatory than those of series 2, which may partly explain our findings. Moreover, to date, no study has shown the metabolites generation of AGT, even their influence on inflammation and pro-oxidant in cell membranes. How TFA have been reported to inhibit the desaturases activity, we suggest that the presence of AGT in the membranes may be inhibiting the n-3 PUFA incorporation and, thus, reduce the metabolites generation, which are known to be beneficial. Taken together, the data presented in this thesis suggest that healthy eating habits that include reduced intake of foods rich in AGT and the inclusion of n-3 PUFA, accompanied by care front sun exposure can contribute to the prevention of skin diseases and skin diseases associated with UV exposure. / Os ácidos graxos (AG) provenientes da dieta são fundamentais para a estrutura e função dos fosfolipídeos das membranas celulares, nas quais os AG poliinsaturados (AGPI) de cadeia longa aumentam a sua fluidez, enquanto os AG trans (AGT) a tornam mais rígida. Nos últimos anos, a diminuição da camada de ozônio tem aumentado a exposição humana à radiação ultravioleta (RUV), causando consequências deletérias sobre a homeostase cutânea. Por outro lado, os hábitos de vida e os padrões alimentares, especialmente em países ocidentais, tem apresentado um consumo crescente de alimentos processados ricos em AGT, cujas consequências cutâneas ainda não apresentam validação científica. Considerando que a saúde da pele está parcialmente relacionada aos lipídios que a compõem, este estudo foi desenvolvido para avaliar a influência da suplementação de diferentes óleos ou gordura em diferentes períodos da vida de roedores sobre os danos oxidativos induzidos pela exposição aguda e crônica à RUV. Camundongos Swiss machos recém desmamados foram diariamente suplementados (3g/kg; p.o.) com óleo de soja (rico em AGPI n-6) (grupo controle), óleo de peixe (rico em AGPI n-3) ou gordura vegetal hidrogenada (GVH; rica em AGT) até 90 dias de idade, quando a pele da região dorsal foi agudamente exposta à RUV. A suplementação com óleo de peixe foi relacionada à incorporação de AGPI n-3 no tecido cutâneo dos camundongos, enquanto os grupos suplementados com óleo de soja e GVH apresentaram incorporação de AGPI n-6 e AGT, respectivamente. Tais incorporações exerceram influências sobre o desenvolvimento de danos oxidativos induzidos pela RUV na pele dos camundongos, de modo que o grupo GVH mostrou maiores níveis de peroxidação lipídica e carbonilação protéica, acompanhados de maior espessamento da pele (edema), menor atividade da catalase (CAT) e viabilidade celular. Enquanto o óleo de soja foi associado a uma prevenção parcial dos danos observados no grupo GVH, a suplementação com óleo de peixe preveniu os danos oxidativos cutâneos. Sequencialmente, o segundo e terceiro protocolos experimentais foram desenvolvidos com a 1ª e a 2ª gerações de ratas adultas nascidas sob a suplementação diária dos mesmos óleos utilizados no experimento 1 (óleo de soja, óleo de peixe e GVH) e, aos 90 dias de idade, parte de cada grupo experimental foi exposto à RUV 3x/ semana, durante 12 semanas. Animais de 1ª geração (experimento 2) tratados com óleo de peixe apresentaram maior incorporação de n-3 FA e menor razão n-6/n-3 na pele dorsal, enquanto o grupo GVH mostrou maior incorporação de AGT. Análises bioquímicas mostraram um aumento dos níveis de proteína carbonil (PC), per se, menor funcionalidade das enzimas mitocondriais e diminuição de algumas defesas antioxidantes (glutationa reduzida (GSH) e vitamina C (VIT C)) na pele dorsal do grupo suplementado com GVH. Após exposição à RUV, este mesmo grupo experimental apresentou maior escore de rugas, maior geração de espécies reativas (ER) e níveis de PC, os quais foram acompanhados de uma diminuição dos níveis de GSH e de VIT C na pele dorsal. Contrariamente, o grupo óleo de peixe mostrou menor escore de rugas e espessamento da pele após exposição à RUV, além de apresentar menores níveis de PC e maior funcionalidade das enzimas mitocondriais. Adicionalmente, observou-se uma correlação positiva entre a geração de ER induzida pela RUV e a espessura da pele, rugas e PC, enquanto uma correlação negativa entre a geração de ER induzidas pela RUV e a funcionalidade das enzimas mitocondriais, e entre os níveis de PC e GSH, SOD e VIT C. Animais de 2ª geração (experimento 3) tratados com óleo de peixe apresentaram maior incorporação AG n-3 e menor razão n-6/n-3 na pele dorsal, enquanto que os AGT foram incorporados apenas no grupo GVH. Este último grupo experimental apresentou alterações bioquímicas per se: maior geração de ER, menor funcionalidade das enzimas mitocondriais e maior atividade da Na+K+ATPase. A exposição do grupo GVH à RUV aumentou a rugosidade da pele, aumentou a geração de ER e reduziu a funcionalidade das enzimas mitocondriais, além de diminuir os níveis de GSH. No grupo óleo de peixe, a exposição à RUV foi associada à menor espessura da pele e à redução dos níveis de PC, além do aumento da atividade da CAT e da preservação da atividade da Na+K+ATPase. Os AGPI n-3 competem com AGPI n-6 pela atividade das elongases e dessaturases, as quais originam AGPI de cadeia longa n-3 ou n-6, respectivamente, que são incorporados aos fosfolipídeos das membranas celulares. Tal incorporação permite a atividade da ciclooxigenase-2 (COX-2) sobre os mesmos, originando metabólitos ativos da série 3 (prostaglandinas (PG) e tromboxanos (TX) da série 3) ou da série 6 (PG e TX da série 2), respectivamente. Os metabólitos da série 3 são menos pró-inflamatórios que aqueles da série 2, o que pode em parte explicar nossos achados. Além disto, até o momento, nenhum estudo mostrou a geração de metabólitos de AGT, nem mesmo sua influência sobre o processo inflamatório e pró-oxidante nas membranas celulares. Como os AGT têm sido descritos por inibir a atividade das dessaturases, nós sugerimos que a presença de AGT nas membranas pode estar inibindo a incorporação de AGPI n-3 e, dessa maneira, reduzir a geração de seus metabólitos, os quais são reconhecidamente benéficos. Tomados em conjunto, os dados apresentados nesta tese sugerem que hábitos alimentares saudáveis, que inclui uma ingesta reduzida de alimentos ricos em AGT e a inclusão de AGPI n-3, acompanhado de cuidados frente à exposição solar, podem contribuir para a prevenção de afecções cutâneas e doenças de pele associadas à exposição UV.