La carence en vitamine B12 est fréquente chez les sujets âgés et produit un vieillissement cérébral par des mécanismes malconnus. La vitamine B12 joue un rôle majeur dans les régulations épigénomiques dépendantes de la S-adénosyl méthionine (SAM). Nous avons établi un modèle de cellules neuronales dopaminergiques NIE115 carencé en vitamine B12 par l'expression stable d'une protéine chimère : la transcobalamine-oléosine (TO) réduisant la disponibilité cellulaire en B12, la SAM et la prolifération cellulaire. La protéine chimère oléosine-transcobalamine (OT) ne lie pas la B12 et constitue un contrôle. Les cellules TO ont une diminution B12-dépendante de la déacétylase SIRT1 (sirtuin1) et un stress du réticulum endoplasmique (RE) avec une augmentation des transducteurs transmembranaires, une diminution des protéines chaperonnes et une augmentation des marqueurs pro-apoptotiques. La diminution de l'expression de SIRT1 déclenche le stress du RE en réponse au stress nutritionnel. Cette diminution produit une augmentation de HSF1 acétylé diminuant l'expression des protéines chaperons. L'ajout de B12, des activateurs de SIRT1 et HSF1, la surexpression de SIRT1 et HSF1 réduisent le stress du RE. Dans les cellules contrôles, le traitement par la thapsigargin, l'inhibition de SIRT1 et HSF1 induisent également un stress du RE réversible en présence de B12. Le traitement des cellules OT par Adox (inhibiteur des méthyltransférases) induit les mêmes effets que la carence. En conclusion, la carence en B12 induit un stress du RE via la diminution de SIRT1 et l'augmentation de HSF1 acétylé, l'ajout de B12 induit des effets neuro-protecteurs sur les cellules soumises à un stress du RE. Ces résultats suggèrent d'évaluer les effets des agonistes de SIRT1 sur les complications cérébrales de la carence / Vitamin B12 deficiency is common in elderly population and produces neurodegenerative disorders by elusive mechanisms. B12 is a key determinant for the S-adenosyl methionine-dependent epigenomic regulations. We have established a B12-deficient cell model via the stable expression of transcobalamin-oleosin chimera (TO), which impairs cellular availability of vitamin B12, reduces SAM level and cell proliferation. Since the expression of oleosin transcobalamin chimera (OT) does not modify the phenotype of the transfected cells, these cells serve as control cells. TO cells present a B12-dependant decrease of deacetylase SIRT1 (sirtuin1) and an endoplasmic reticulum stress (ER stress) reflected by the increased expression of ER stress tranducers, decreased chaperon proteins and increased pro-apoptotic markers. We propose that the decreased expression of SIRT1 triggers cell response to nutritional stress through ER stress. This decrease results in a greater acetylation of heat-shock factor protein 1 (HSF1) and thus reducing the expression of heat shock proteins (HSP). Adding B12, SIRT1, or HSF1 activators as well as overexpressing SIRT1 or HSF1 reduce ER stress. In OT cells, thapsigargin treatment or impairing SIRT1 and HSF1 leads to B12-reversible ER stress. Treating OT cells with AdoX, an inhibitor of methyltransferase activities, produces effects similar to those observed in cells with decreased B12 availability.In summary, the impaired cellular availability of vitamin B12 induces ER stress by increasing HSF1 acetylation through a decreased SIRT1 expression and adding vitamin B12 produces neuro-protective effects in cells subjected to prior ER stress. These results suggest evaluating the effects of SIRT1 agonists on cerebral complications due to a B12 deficiency

No description available.

O objetivo deste estudo foi avaliar a resistência à microtração de adesivos autocondicionantes em dentina desmineralizada de dentes decíduos após a irradiação com laser de Er: YAG. Oitenta e dois molares decíduos tiveram a porção oclusal seccionada transversalmente e os espécimes foram desgastados com lixas de carbeto de silício de granulações 360 e 600 até expor a dentina. Os 60 espécimes utilizados no teste de microtração foram preenchidos com resina composta fotopolimerizável na região correspondente à câmara pulpar, isolados com esmalte cosmético mantendo a superfície dentinária exposta e, em seguida imersos em solução desmineralizante por seis dias em estufa a 37° C para indução de lesão de cárie artificial em dentina. Após a desmineralização, os espécimes foram preparados com laser de Er: YAG (n=30) com os parâmetros de 260 mJ, 3 Hz, 47 J/cm2, 0,81W e com broca de aço esférica em baixa rotação (n=30). Sobre as superfícies preparadas foram aplicados três sistemas adesivos autocondicionantes Clearfil SE Bond (Kuraray); Adper™ Easy One (3M ESPE) e Adper™ SE Plus (3M ESPE) e, em seguida foram confeccionados platôs de resina composta Z 250. Após termociclagem (500 ciclos), os corpos de prova foram seccionados produzindo palitos de aproximadamente 1 mm2 de área transversal, que foram submetidos ao teste de microtração e os valores obtidos foram analisados estatisticamente através de ANOVA e teste de Duncan (5%). A análise qualitativa dos tipos de fraturas foi realizada por meio de lupa estereoscópica (aumento de 40X) e da interface adesiva por meio de MEV. Para a análise química da dentina através de espectroscopia no infravermelho por transformada de Fourier (FTIR), foram utilizados discos de dentina após o preparo superficial com a broca (n=5) e com o laser (n=5), e comparadas com as análises de tecido dentinário sadio e desmineralizado obtidas dos mesmos espécimes. Os resultados foram submetidos ao teste estatístico t−Student (5%). O teste de microtração demonstrou que houve diferença significativa entre os adesivos, sendo que o grupo controle (Clearfil e broca) obteve o melhor desempenho comparativamente a todos os grupos avaliados. O preparo com laser de Er: YAG afetou adversamente a adesão para os sistemas adesivos Clearfil SE Bond e Adper™ Easy One em comparação com os grupos preparados com broca. Nos grupos irradiados com laser, o sistema adesivo Clearfil SE Bond foi o que proporcionou o maior valor médio de microtração. Os resultados da FTIR demonstraram que, com a irradiação da dentina desmineralizada, houve um decréscimo na quantidade de matéria orgânica e de carbonato em relação ao grupo da dentina sadia. No substrato preparado com broca, observouse aumento da matéria orgânica e redução de carbonato. Concluise que, em relação aos sistemas adesivos, o Clearfil SE Bond teve o melhor desempenho no teste de resistência à microtração em dentina de dentes decíduos. A irradiação com laser de Er: YAG afetou adversamente a adesão dos sistemas adesivos Clearfil SE Bond e Adper™ Easy One. A irradiação com laser de Er:YAG decresceu de maneira significativa a quantidade de matéria orgânica presente na dentina de dentes decíduos. / The purpose of this study was to evaluate the microtensile bond strength of three selfetch adhesives systems to demineralized dentin of primary teeth after irradiation with Er: YAG laser. Eighty two primary molars had the occlusal enamel sectioned and the specimens were grounded with silicon carbide sandpaper grits of 360 and 600 to expose the dentin. The 60 specimens used in the microtensile test were filled with composite resin in the region corresponding to the pulp chamber, insulated with nail varnish keeping the exposed dentin surface and then immersed in demineralizing solution for six days in a stove at 37 Celsius degrees in order to produce artificial carieslike lesions in dentin. After demineralization, the specimens were prepared with Er: YAG (n = 30) using as parameters 260 mJ, 3 Hz, 47 J/cm2, 0.81 W and a round steel drill at low speed (n = 30 ). On the prepared surfaces were applied three self−etch adhesives systems Clearfil SE Bond (Kuraray); Adper™ Easy One (3M ESPE) and AdperTM SE Plus (3M ESPE) and then plateaus of composite resin Z 250 were built up. After thermocycling (500 cycles), specimens were sectioned to produce multiple sticks of approximately 1 mm2 crosssectional area, which were subjected to microtensile test and the data were analyzed with ANOVA and Duncan test at a significance level of 0.05. The qualitative analysis of the types of fractures was performed using a stereomicroscope (X40 magnification) and the morphological analyses of adhesive interfaces were performed by scanning electron microscopy (SEM). Chemical analysis of the dentin by Fourier transform infrared spectroscopy (FTIR) were performed in dentin discs after surface preparation with the steel drill (n = 5) and laser (n = 5) and compared with the values previously obtained from the analysis of sound and demineralized dentin tissue in the same specimens. The results were analyzed by Student\'s t−test at a significance level of 0.05. Regarding the microtensile bond strength there was a significant difference between the adhesive systems, and the control group (Clearfil and steel drill) had the best performance compared to all groups. Er: YAG laser irradiation adversely affected bond strength to the Clearfil SE Bond and Adper™ Easy One compared with the groups prepared with steel drill. In the laser groups Clearfil SE Bond reached the highest average bond strength. Results of FTIR analysis showed that the hydration of dentin remained normal after both preparations. With laser irradiation of demineralized dentin there was a decrease in the amount of organic matter and carbonate in relation to the group of sound dentin. The analyses of substrate prepared with steel drill showed an increase in organic matter and reduction of carbonate. The conclusion in relation to adhesive systems was that Clearfil SE Bond had the best performance in microtensile bond strength in primary teeth dentin. Laser irradiation adversely affected the bond strength of Clearfil SE Bond and Adper™ Easy One selfetch adhesive systems. Laser irradiation had significantly reduced the organic matter content in dentin of deciduous teeth.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-04-24T12:41:11Z No. of bitstreams: 1 ShirleyPontesDissertacao2018.pdf: 1632850 bytes, checksum: 1119ac63b939927d264497f421422810 (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-04-24T12:41:31Z (GMT) No. of bitstreams: 1 ShirleyPontesDissertacao2018.pdf: 1632850 bytes, checksum: 1119ac63b939927d264497f421422810 (MD5) / Made available in DSpace on 2018-04-24T12:41:31Z (GMT). No. of bitstreams: 1 ShirleyPontesDissertacao2018.pdf: 1632850 bytes, checksum: 1119ac63b939927d264497f421422810 (MD5) Previous issue date: 2018-02-23 / The diagnosis and treatment of prostate cancer can cause significant changes in the life of men influencing their quality of life. The objective of this study was to evaluate the health-related quality of life of patients with prostate cancer submitted to radiotherapy. It is a descriptive cross-sectional study with non-probabilistic sampling. Subjects eligible for the study were 120 men with prostate cancer who underwent on treatments at HUB - CACON. The instruments used were EORTC QLQ-C30 and the International Index Of Erectil Function- IIEF-5. The research project was approved by the Ethics and Research Committee of the Faculty of Medicine of the Catholic University of Brasilia under the number CAAE: 58197916.8.0000.0029.: The profile os subjects is aged between 70 and 79 years (42.3%), with elementary school (72.3%), brown (44.6%), married or had a partner (75.6%). Among the comorbidities, the highest incidence was arterial hypertension (70%) followed by Diabetes MellitusII (33.8%). The most frequent toxicities resulting from RT treatment, was dysuria (43%), followed by diarrhea (22.3%). The analysis of IIEF-5 allows to observe that 79.2% suffer from severe erectile dysfunction.. The prostate cancer treatments tend to cause negative impacts on sexual function and self-perceived quality of life. The age does not influence role performance, and isolated or simultaneous treatments proved to be important factor to erectile function score. Conclusion: The group who have undergone to RT + RP suffer more from pain and fatigue, and the group who have undergone to RT + CQ suffer more insomnia. All participants who have undergone RT + PR + CQ suffer severe erectile dysfunction. Considering the findings of this study, it confirm that the patients with prostate cancer who manage maintain erectile function moderate, mild and normal, they as well maintain their social roles as work, family relationships and marriage. They also keep their emotions balanced and control their irritability, tension, depression, and they feel less fatigue. This study allows to understand the local reality and corroborates with the findings of other studies carried out in different regions and social contexts. / O diagn??stico e o tratamento do c??ncer de pr??stata podem provocar mudan??as significativas na vida dos homens e influenciar a sua qualidade de vida. O objetivo deste estudo foi avaliar a qualidade de vida relacionada ?? sa??de e a fun????o er??til dos pacientes com c??ncer de pr??stata. Trata-se de um estudo descritivo de corte transversal com amostragem n??o probabil??stica. Os indiv??duos eleg??veis para o estudo foram 120 homens portadores de c??ncer de pr??stata, que se submeteram ?? radioterapia no HUB ??? CACON. Os instrumentos utilizados foram o EORTC QLQ-C30, e o ??ndice Internacional de Fun????o Er??til IIEF-5. O projeto de pesquisa foi aprovado pelo Comit?? de ??tica e Pesquisa da Faculdade de Medicina da Universidade Cat??lica de Bras??lia sob o n??mero CAAE: 58197916.8.0000.0029. O perfil do participante ?? idade entre 70 a 79 anos (42,3%), com ensino fundamental (72,3%), da cor parda (44,6%), casado ou tinha uma companheira (75,6%). Dentre as comorbidades a de maior incid??ncia foi hipertens??o arterial (70%) seguida de Diabetes Mellitus tipo 2 (33,8%). As toxicidades decorrentes do tratamento com RT, a mais frequente foi dis??ria (43%), seguida por diarreia (22,3%). A an??lise do IIEF- 5 permite observar o ??ndice de disfun????o er??til dos participantes, em que 79,2% dos participantes sofrem de disfun????o er??til severa. Discuss??o: Os tratamentos de c??ncer de pr??stata tendem a causar impactos negativos na fun????o sexual. E na autopercep????o da qualidade de vida. A idade n??o influencia no desempenho de papeis sociais. Os tratamentos se realizados isolados ou simultaneamente provaram ser um importante fator no escore da fun????o er??til. Conclus??o: O grupo que se submeteu a RT + RP sofre mais de dor e fadiga, o grupo que se submeteu a RT + CQ sofre mais de ins??nia e todos os participantes que se submeteram a RT + PR + CQ sofrem de disfun????o er??til severa. Considerando os achados desse estudo, se confirma que pacientes com c??ncer de pr??stata que conseguem manter a fun????o er??til entre moderada, leve e normal, tamb??m mant??m os desempenho de papeis sociais como trabalho, fam??lia, relacionamentos e o casamento. Eles tamb??m conseguem manter as emo????es mais equilibradas como controle da irritabilidade, tens??o e depress??o, e sentem menos fadiga.. Este estudo permite entender a realidade local bem como corrobora os achados de outros estudos em diferentes regi??es e contextos sociais.

Alterações visuais, histoquímicas e micromorfológicas podem ser observadas em superfícies dentais submetidas ao clareamento, desencadeando sensibilidade, menor resistência ao desgaste, maior manchamento e aderência bacteriana. Uma forma de verificar a ocorrência de danos superficiais e sub-superficiais é através da permeabilidade e da avaliação superficial por meio de microscopia eletrônica de varredura. Assim, este estudo in vitro teve por objetivo avaliar a eficácia de clareamento em dentes manchados, a permeabilidade e a morfologia superficial do esmalte dental após tratamento com diferentes técnicas de aplicação do peróxido de hidrogênio a 35% (FGM) seguido ou não da aplicação de flúor. Foram utilizados 260 incisivos bovinos, com superfícies de esmalte de 10x10 mm de área. Após, os espécimes foram casualmente distribuídos (n = 10) e submetidos ao manchamento com café, chá preto e vinho tinto por 72 horas. As medidas de cor eram realizadas com espectrofotômetro de reflexão nos tempos inicial, após o manchamento e logo após a fase de clareamento. Após o período de manchamento os fragmentos eram clareados com peróxido de hidrogênio a 35% (FGM) - convencional, ativado com LED ou laser de Er:YAG seguido ou não da aplicação de flúor (Desensibilize KF 2%, FGM). Os grupos controles eram expostos: a saliva artificial e a aplicação de flúor + saliva artificial. O tratamento clareador foi realizado de acordo com as recomendações do fabricante. No restante do período diário, os espécimes eram imersos em saliva artificial. A seguir, os fragmentos foram subdivididos em dois fragmentos de aproximadamente 5x5 mm de área, sendo um submetido à avaliação da permeabilidade e o outro a avaliação da superfície do esmalte através de microscopia eletrônica de varredura. O método de coloração histoquímica foi utilizado para evidenciar a extensão da permeabilidade no esmalte. Do esmalte eram obtidos três cortes avaliados em microscopia óptica, através de um software de digitalização de imagem (Axion Vision 3.1) verificando a penetração dos íons cobre em relação à espessura total do esmalte. As fotomicrografias eletrônicas de varredura das superfícies vestibulares do esmalte, com aumento de 2000X, foram digitalizadas e avaliadas. Para as análises estatísticas, foi considerado o valor de alteração de cor de cada fragmento nos diferentes tempos de observação e a média das três secções de um mesmo dente para a avaliação da permeabilidade. Em relação à MEV observou-se que em relação aos processos de clareamento, foi encontrado diferenças quando comparadas aos grupos controles. Os grupos controles apresentaram superfícies dentais lisas e regulares. Já os grupos tratados com PH35% e PH 35% + LED apresentaram superfícies dentais marcadas pela presença dos prismas de esmalte suavemente esboçados em meio a um esmalte interprísmático de textura lisa. A aplicação do Er:YAG promoveu a remoção da camada aprismática e exposição clara dos prismas de esmalte, depressões, tornando a superfície porosa e irregular. Nos grupos em que se aplicou o flúor, independente do tipo de clareamento realizado, observou-se superfícies relativamente cobertas por um precipitado fusiforme. Em relação à permeabilidade, os resultados demonstraram não haver diferença significativa. Já em relação à alteração de cor foi encontrada diferença estatística ente o agente aplicado ativado pelo Er:YAG, o método a alcançar as tonalidades de cor mais claras, quando comparado aos métodos convencional e ativado pelo LED. Concluímos que novos estudos são necessários para que se estabeleçam parâmetros adequados e seguros para a aplicação do laser. Isso fará com que se consiga não só melhor tonalidade de cor, mas menores efeitos deletérios na morfologia superficial do esmalte clareado. / Visual changes, micromorphological and histochemical can be observed in areas subjected to dental bleaching, triggering sensitivity, lower wear resistance, increased staining and bacterial adhesion. One way to check the damage to surface and subsurface is through the permeability and surface evaluation by scanning electron microscopy. Thus, this in vitro study was to evaluate the effectiveness of whitening stained teeth, permeability and morphology of enamel after treatment with different techniques of application of hydrogen peroxide 35% (FGM) whether or not the application of fluoride . We used 260 bovine incisors with enamel surfaces of 10x10 mm in size. After, the specimens were randomly distributed (n = 10) and subjected to staining with coffee, black tea and red wine for 72 hours. The color measurements were made at a reflection spectrophotometer in early times, after staining and after the bleaching stage. After the period of staining the fragments were bleached with hydrogen peroxide 35% (FGM) - conventional activated LED or laser Er:YAG whether or not the application of fluoride (KF Desensibilize 2%, FGM). Control groups were exposed: the artificial saliva and fluoride application + artificial saliva. The bleaching treatment was performed according to the manufacturer\'s recommendations. The rest of the daily period, the specimens were immersed in artificial saliva. Next, the fragments were divided into two fragments of approximately 5x5 mm in size, being submitted to an evaluation of the permeability and the other to evaluate the enamel surface by scanning electron microscopy. The histochemical staining method was used to show the extent of the permeability of enamel. Enamel were obtained from three sections evaluated with optical microscopy, using a software image scanning (Axion Vision 3.1) verifying the penetration of copper ions in relation to the total thickness of enamel. The images of scanning electron photomicrographs of the vestibular enamel, an increase of 2000X were scanned and evaluated. For statistical analysis, we considered the color change of each fragment in different observation times and the average of three sections of the same tooth for assessing permeability. Regarding the SEM showed that in relation to the bleaching procedure, we found differences when compared to control groups. The control groups showed tooth surfaces smooth and regular. Since the groups treated with PH35% and 35% PH + LED tooth surfaces showed marked by the presence of enamel rods gently outlined in the midst of an enamel interprismatic smooth texture. The application of Er:YAG promoted the removal of the layer aprismatic and clear statement of the enamel prisms, depressions, making the surface porous and irregular. In groups that applied fluoride, regardless of the type of bleaching done, it was observed on surfaces covered by a precipitate fusiform. In relation to permeability, the results showed no significant difference. In relation to the color change was statistical difference between individual agents used and the Er:YAG method to achieve the color shades lighter when compared to PH35 and PH35% + LED. We conclude that further studies are needed to find themselves safe and appropriate parameters for the laser application. This will make you not only get better color tone, but less deleterious effects on enamel surface morphology cleared.

O objetivo deste estudo foi avaliar a resistência à microtração de adesivos autocondicionantes em dentina desmineralizada de dentes decíduos após a irradiação com laser de Er: YAG. Oitenta e dois molares decíduos tiveram a porção oclusal seccionada transversalmente e os espécimes foram desgastados com lixas de carbeto de silício de granulações 360 e 600 até expor a dentina. Os 60 espécimes utilizados no teste de microtração foram preenchidos com resina composta fotopolimerizável na região correspondente à câmara pulpar, isolados com esmalte cosmético mantendo a superfície dentinária exposta e, em seguida imersos em solução desmineralizante por seis dias em estufa a 37° C para indução de lesão de cárie artificial em dentina. Após a desmineralização, os espécimes foram preparados com laser de Er: YAG (n=30) com os parâmetros de 260 mJ, 3 Hz, 47 J/cm2, 0,81W e com broca de aço esférica em baixa rotação (n=30). Sobre as superfícies preparadas foram aplicados três sistemas adesivos autocondicionantes Clearfil SE Bond (Kuraray); Adper™ Easy One (3M ESPE) e Adper™ SE Plus (3M ESPE) e, em seguida foram confeccionados platôs de resina composta Z 250. Após termociclagem (500 ciclos), os corpos de prova foram seccionados produzindo palitos de aproximadamente 1 mm2 de área transversal, que foram submetidos ao teste de microtração e os valores obtidos foram analisados estatisticamente através de ANOVA e teste de Duncan (5%). A análise qualitativa dos tipos de fraturas foi realizada por meio de lupa estereoscópica (aumento de 40X) e da interface adesiva por meio de MEV. Para a análise química da dentina através de espectroscopia no infravermelho por transformada de Fourier (FTIR), foram utilizados discos de dentina após o preparo superficial com a broca (n=5) e com o laser (n=5), e comparadas com as análises de tecido dentinário sadio e desmineralizado obtidas dos mesmos espécimes. Os resultados foram submetidos ao teste estatístico t−Student (5%). O teste de microtração demonstrou que houve diferença significativa entre os adesivos, sendo que o grupo controle (Clearfil e broca) obteve o melhor desempenho comparativamente a todos os grupos avaliados. O preparo com laser de Er: YAG afetou adversamente a adesão para os sistemas adesivos Clearfil SE Bond e Adper™ Easy One em comparação com os grupos preparados com broca. Nos grupos irradiados com laser, o sistema adesivo Clearfil SE Bond foi o que proporcionou o maior valor médio de microtração. Os resultados da FTIR demonstraram que, com a irradiação da dentina desmineralizada, houve um decréscimo na quantidade de matéria orgânica e de carbonato em relação ao grupo da dentina sadia. No substrato preparado com broca, observouse aumento da matéria orgânica e redução de carbonato. Concluise que, em relação aos sistemas adesivos, o Clearfil SE Bond teve o melhor desempenho no teste de resistência à microtração em dentina de dentes decíduos. A irradiação com laser de Er: YAG afetou adversamente a adesão dos sistemas adesivos Clearfil SE Bond e Adper™ Easy One. A irradiação com laser de Er:YAG decresceu de maneira significativa a quantidade de matéria orgânica presente na dentina de dentes decíduos. / The purpose of this study was to evaluate the microtensile bond strength of three selfetch adhesives systems to demineralized dentin of primary teeth after irradiation with Er: YAG laser. Eighty two primary molars had the occlusal enamel sectioned and the specimens were grounded with silicon carbide sandpaper grits of 360 and 600 to expose the dentin. The 60 specimens used in the microtensile test were filled with composite resin in the region corresponding to the pulp chamber, insulated with nail varnish keeping the exposed dentin surface and then immersed in demineralizing solution for six days in a stove at 37 Celsius degrees in order to produce artificial carieslike lesions in dentin. After demineralization, the specimens were prepared with Er: YAG (n = 30) using as parameters 260 mJ, 3 Hz, 47 J/cm2, 0.81 W and a round steel drill at low speed (n = 30 ). On the prepared surfaces were applied three self−etch adhesives systems Clearfil SE Bond (Kuraray); Adper™ Easy One (3M ESPE) and AdperTM SE Plus (3M ESPE) and then plateaus of composite resin Z 250 were built up. After thermocycling (500 cycles), specimens were sectioned to produce multiple sticks of approximately 1 mm2 crosssectional area, which were subjected to microtensile test and the data were analyzed with ANOVA and Duncan test at a significance level of 0.05. The qualitative analysis of the types of fractures was performed using a stereomicroscope (X40 magnification) and the morphological analyses of adhesive interfaces were performed by scanning electron microscopy (SEM). Chemical analysis of the dentin by Fourier transform infrared spectroscopy (FTIR) were performed in dentin discs after surface preparation with the steel drill (n = 5) and laser (n = 5) and compared with the values previously obtained from the analysis of sound and demineralized dentin tissue in the same specimens. The results were analyzed by Student\'s t−test at a significance level of 0.05. Regarding the microtensile bond strength there was a significant difference between the adhesive systems, and the control group (Clearfil and steel drill) had the best performance compared to all groups. Er: YAG laser irradiation adversely affected bond strength to the Clearfil SE Bond and Adper™ Easy One compared with the groups prepared with steel drill. In the laser groups Clearfil SE Bond reached the highest average bond strength. Results of FTIR analysis showed that the hydration of dentin remained normal after both preparations. With laser irradiation of demineralized dentin there was a decrease in the amount of organic matter and carbonate in relation to the group of sound dentin. The analyses of substrate prepared with steel drill showed an increase in organic matter and reduction of carbonate. The conclusion in relation to adhesive systems was that Clearfil SE Bond had the best performance in microtensile bond strength in primary teeth dentin. Laser irradiation adversely affected the bond strength of Clearfil SE Bond and Adper™ Easy One selfetch adhesive systems. Laser irradiation had significantly reduced the organic matter content in dentin of deciduous teeth.

Made available in DSpace on 2015-04-14T13:39:13Z (GMT). No. of bitstreams: 1 460149.pdf: 698283 bytes, checksum: 09b1b88964bea0ea869efaf7aa5cb9e7 (MD5) Previous issue date: 2014-02-28 / The eroticism always has been present in written culture once it is an essential element of the human condition and appears even when it is absent. However, this universe is composed from elements that cause discomfort, not just pragmatic, but theoretical. This dissertation aims to enter this obscure and marginal field. So, considering the eroticism as part of the text s structure and also a representation of a social and individual phenomenon, it was analyzed the Erotica of Ana?s Nin. For this, the approach was based on the philosophical conception of Bataille, with an intersection of the concepts of body (Le Breton) and sexuality (Foucault). After, it was made a brief introduction of the eroticism in literature, in order to legitimize and consolidate the erotic literary tradition, in which is inserted the writer Ana?s Nin. Finally, the literary corpus is compound by tales of the collections Delta of Venus and Little birds, and it was analyzed from the theoretical framework developed with the thinkers above cited. / O erotismo sempre esteve presente na cultura escrita, uma vez que, sendo um elemento essencial da condi??o humana, manifesta-se mesmo na sua aus?ncia. Contudo, esse universo ? constru?do a partir de elementos que geram um desconforto, n?o apenas pragm?tico, mas te?rico. Nessa perspectiva, esta disserta??o tenciona adentrar esse campo ainda t?o obscuro e marginal. Considerando o erotismo tanto como parte da tessitura textual de uma obra liter?ria, quanto como representa??o de um fen?meno social e pessoal, objetivou-se analisar a constru??o do erotismo na literatura er?tica de Ana?s Nin. Para isso, o erotismo foi abordado atrav?s da concep??o filos?fica de Georges Bataille, em uma intersec??o com os conceitos de corpo (David Le Breton) e sexualidade (Michel Foucault). No segundo momento, realizou-se uma breve introdu??o da presen?a do erotismo na literatura, com objetivo de legitimar e consolidar a exist?ncia de uma tradi??o liter?ria er?tica, na qual se insere a escritora Ana?s Nin. Por fim, o corpus liter?rio, composto por contos selecionados das colet?neas Delta de V?nus e Passarinhos, foi analisado a partir do quadro te?rico desenvolvido com os pensadores supracitados.

MyD88 est une protéine adaptatrice clé dans la signalisation des TLRs/IL-1R qui mène à l'activation de NF-KB et des MAPK, et à la production de cytokines inflammatoires. MyD88 participe à la tumorigénèse par le biais de son activité inflammatoire dans la signalisation des TLRs/IL-1R, et également via son interaction directe avec la kinase Erk dans la cellule cancéreuse. Dans cette thèse, nous identifions de nouveaux partenaires protéiques de MyD88 et nous examinons comment leurs interactions peuvent réguler sa fonction. Nous démontrons que MyD88 interagit avec Ubc9, ce qui conduit à sa sumoylation, et que cette modification posttraductionnelle régule négativement l'inflammation dépendante de MyD88. Nos résultats montrent également que MyD88 interagit avec le récepteur nucléaire, ER-α, et que cette interaction est nécessaire pour la réponse inflammatoire. Enfin, nous avons étudié l'importance de l'interaction MyD88/Erk dans le maintien de la transformation des tumeurs dépendant de l'oncogène Ras. Ces résultats pourraient éventuellement être exploités pour cibler MyD88 et ses interactions dans le traitement des maladies inflammatoires et le cancer / MyD88 is a protein that is at the interface between inflammation and cancer. It is the key adaptor protein used by TLRs/IL-1R to mediate their downstream signaling, resulting in NF-κB and MAPK activation, and inflammatory cytokine production. MyD88 also plays a role in tumorigenesis via two mechanisms, an inflammatory one dependent on its function in TLRs/IL- 1R signaling, and an intrinsic, cell-autonomous mechanism mediated by its interaction with the kinase Erk. Based on the different roles played by MyD88, this thesis work consisted in studying how MyD88 protein-protein interactions can regulate its function. We show that MyD88 interacts with Ubc9, resulting in its sumoylation and subsequent negative regulation of MyD88- mediated inflammation. We also demonstrate that MyD88 interacts with the nuclear receptor ER-α, an interaction necessary for the inflammatory response. Finally, we have studied the importance of the MyD88/Erk interaction in the maintenance of the transformed phenotype of Ras-dependent tumors. These findings could eventually be exploited to target MyD88 and its interactions in the treatment of inflammatory disorders and cancer

Submitted by Maria Aparecida (cidazen@gmail.com) on 2017-04-26T12:29:41Z No. of bitstreams: 1 Bruno Araújo Serra Pinto.pdf: 5546725 bytes, checksum: 07839b14efcc510ac5ecfa62b980626e (MD5) / Made available in DSpace on 2017-04-26T12:29:41Z (GMT). No. of bitstreams: 1 Bruno Araújo Serra Pinto.pdf: 5546725 bytes, checksum: 07839b14efcc510ac5ecfa62b980626e (MD5) Previous issue date: 2017-04-07 / FAPEMA / Background: The epidemiological rise of metabolic syndrome (MS) is directly related to the exponential increase of added sugar consumption. Studies describes that MSmetabolic disorders, mainly insulin resistance and obesity, are related to development of oxidative stress, cognitive declines and dementias, and neuronal senescence acceleration. Even with several evidences correlating MS to neuronal damage, the molecular mechanisms involved are still unclear, and the endoplasmic reticulum stress (ER stress), in this context, could be placed like an intermediary condition that interconnects those morbidities. Objective: To investigate the deleterious effects of hippocampal ER stress about progression of cognitive, behavioral and motor declines in rats with metabolic syndrome-induced by sucrose-rich diet in different ages. Methods: Weaned Wistar rats were divided into 4 groups: two control groups (CTR, n = 7-9), fed a standard diet and followed up to 3 and 6-months-old, respectively; and two obese groups (HSD, n = 7), fed a sucrose-rich diet (25% sucrose) followed by the same periods. Was assessed in these groups: MS development; redox profile; Cognitive, behavioral and motor functions; And the hippocampal gene/protein expression of UPR sensors (Ire1α, Perk and Atf6), chaperones (Grp78, Grp94, Pdi, Calnexin and Calreticulin), neuronal plasticity (Bdnf), antioxidant defense (Nrf2), apoptosis (Bcl2, Chop and Parp-1) and senescence (p53 and p21). For aging control, rats at 20 months of age (OLD, n = 7) fed standard chow were included as aging control for gene/protein expression and neurological assessments. Results: The sucrose-rich diet was successful in establish the SM-phenotype. At 3 months, we observed central obesity even with lower energy intake, fasting and fed dysglycemia, hypertriglyceridemia, hapatic ectopic fat deposit, decreased lipolysis rates, glucose intolerance and hepatic insulin resistance. In unpublished data, we observed mild lipid peroxidation without exepressive antioxidant enzymes activity, and absence of peripheral insulin resistance. In animals with 6 months, we observed a deepening of metabolic dysfunctions encountered in 3-months-old. In addition we observed weight gain, free fatty acids, hyperinsulinemia, peripheral insulin resistance, increased lipid peroxidation, higher SOD, CAT and GPx reduction activity in 6-months-old rats. The lipolysis rate wasn't performed. Regarding the neurofunctional assessment at 3-months-old, the animals presented motor deficit and anxiogenic behavior, however without cognitive dysfunctions. In 6-months-animals, we observed anxiogenic behavior and important motor and cognitive impairments (learning and memory), similar to OLD group. Hippocampal molecular analysis revealed a different signaling between HSD groups of 3 and 6-months. In HSD at 3 months, we observed a switch-over from UPR-adaptive to pro-apoptotic signaling, marked by increased gene expression of Perk, Atf6 and Pdi A2 (adaptive), reduction of Grp78 and Bcl2, and increases of Chop and Caspase 3 (Apoptotic). In 6-months-HSD, we observed a complete failure of UPR adaptive signaling (UPR sensors and chaperones) and increased apoptotic signaling, featured by Bcl2 reduction and increased gene/protein expression of Chop. Additionally, we observed a reduction in the Bdnf gene expression and protein cleavage of Parp-1 compatible to calpain presence (necrosis/apoptosis marker). The expressions found in the 6-month-HSD were similar to OLD group, but the cell death markers (Chop and Calpain) were found only in HSD. As expected, senescence markers (p53 and p21) were increased in the OLD group and only p21 shown increased in HSD. Conclusions: Our data set supports that prolonged exposure to sucrose-rich diet promotes SM and oxidative stress, which disrupt hippocampal ER homeostasis, leading to senescence acceleration and cell death, and subsequently leads to severe cognitive, behavioral and motor impairments. / Introdução: O crescimento epidemiológico da síndrome metabólica (SM) está diretamente relacionado ao exponencial aumento do consumo de açucares de adição. Estudos descrevem que as desordens metabólicas que compõem a SM, principalmente a resistência insulínica e obesidade, estão relacionadas ao desenvolvimento de estresse oxidativo, declínios cognitivos, demências e aceleração da senescência neuronal. Mesmo com diversas evidências correlacionando a SM a danos neuronais, os mecanismos moleculares envolvidos ainda não são totalmente conhecidos. Neste contexto, o estresse do retículo endoplasmático (ERE) pode ser apontado como uma condição intermediária que interconecta estas morbidades. Objetivo: Investigar os efeitos deletérios do ERE hipocampal sobre a instalação de declínios cognitivos, comportamentais e motores em ratos com síndrome metabólica induzida por dieta rica em sacarose em diferentes faixas etárias. Métodos: Ratos Wistar com 21 dias de vida (desmame) foram divididos em 4 grupos: dois grupos controle (CTR, n = 7-9), alimentados com uma dieta padrão e acompanhados até os 3 e 6 meses de idade, respectivamente; e dois grupos obeso (HSD, n = 7), alimentados com dieta rica em sacarose (sacarose a 25%) acompanhados pelos mesmos períodos. Foi avaliado nos grupos: desenvolvimento de SM; perfil redox; funções cognitivas, comportamentais e motoras; e expressão gênica/proteica hipocampal de sensores da UPR (Ire1α, Perk e Atf6), chaperonas (Grp78, Grp94, Pdi, Calnexina e Calreticulina), plasticidade neuronal (Bdnf), defesa antioxidante (Nrf2), apoptose (Bcl2, Chop e Parp-1) e senescência (p53 e p21). Como um controle de envelhecimento, ratos com 20 meses de idade (OLD, n = 7) alimentados com dieta padrão foram incluídos aos experimentos de expressões gênica/proteica e avaliações neurológicas. Resultados: A dieta rica em sacarose teve sucesso em estabelecer o fenótipo de SM. Com 3 meses, o grupo HSD desenvolveu obesidade central mesmo com menor ingestão energética, disglicemia em estados de jejum e alimentado, hipertrigliceridemia, acúmulo de gordura ectópica hepática, diminuição da taxa de lipólise, intolerância à glicose e resistência hepática à insulina. Em dados não publicados, observamos discreta peroxidação lipídica sem expressiva atividade de enzimas antioxidantes e sem resistência insulínica periférica. Nos animais com 6 meses, observamos um aprofundamento das disfunções metabólicas dos animais de 3 meses. Adicionalmente, observamos ganho de peso, ácidos graxos livres, hiperinsulinemia, resistência insulínica periférica, maior peroxidação lipídica, maior atividade das enzimas SOD, CAT e redução da GPx. No que se refere à avaliação neurofuncional, aos 3 meses de idade, o grupo HSD apresentou déficit motor e comportamento ansiogênico, no entanto sem disfunções cognitivas. Contudo, nos animais de 6 meses observamos comportamento ansiogênico e importantes prejuízos motores e cognitivos (aprendizado e memória), semelhantes ao grupo OLD. A análise molecular hipocampal evidenciou uma sinalização diferente entre os grupos HSD de 3 e 6 meses. No HSD com 3 meses, observamos uma transição da sinalização adaptativa da UPR para a pró-apoptótica, marcada pelo aumento das expressões gênicas de Perk, Atf6 e Pdi A2 (adaptativa), redução da Grp78 e aumento da Chop e Caspase 3 (apoptótica). No HSD de 6 meses, observamos uma falência total da sinalização adaptativa da UPR (sensores da UPR e chaperonas), e aumento da sinalização apoptótica, caracterizada pela redução do Bcl2 e aumento da expressão gênica/proteica de Chop. Adicionalmente, observamos também redução da expressão gênica do Bdnf, redução da expressão proteica de Grp94 e clivagem proteica do Parp-1 compatível com a presença de Calpaína (marcador de necrose/apoptose). As expressões encontradas no HSD de 6 meses foram semelhante as alterações observadas no grupo OLD, mas os fatores de morte celular (Chop e Calpaína) foram encontrados apenas no HSD. Como esperado, os marcadores de senescência (p53 e p21) estavam aumentados no grupo OLD e apenas o p21 se mostrou aumentado no HSD. Conclusões: Nosso conjunto de dados apoia que a exposição prolongada à dieta rica em sacarose promove SM e estresse oxidativo, que perturba a homeostase do RE hipocampal, acarretando aceleração da senescência e morte celular, e subsequentes prejuízos cognitivos, comportamentais e motores.

Obesity-associated metabolic disorders are amongst the most prevalent causes of death worldwide. Understanding how obesity leads to the development of the Metabolic Syndrome (MetS) and cardiovascular disease (CVD) will enable the development of novel therapies that dissociate obesity from its cardiometabolic complications. Our laboratory views the functional capacity of white adipose tissue (WAT), the organ designed for safe lipid storage, as a key factor in the development of MetS and CVD. At a genetically-defined stage of the aberrant WAT expansion that occurs during obesity, adipocytes undergo a functional failure, resulting in an impaired control of serum free fatty acid (FFA) concentration. In such setting, FFAs and their metabolic derivatives accumulate in other organs, where they cause lipotoxicity, leading to the development of insulin resistance and CVD. We therefore aim to understand the pathophysiological mechanisms that induce adipocyte dysfunction. The past two decades of research have established the immune system as an important regulator of WAT function. The number of adipose tissue macrophages (ATMs), the most abundant immune cell type in WAT, increases during obesity, resulting in WAT inflammation. Multiple genetic and pharmacological intervention studies of murine models of obesity have assigned a causal link between ATM pro-inflammatory activation and WAT dysfunction. However, while the propagation of inflammation in ATMs during obesity has been extensively studied, factors triggering ATM inflammatory activation are less clear. Recently, our lab has observed lipid accumulation in the ATMs isolated from obese mice. Lipid-laden ATMs were pro-inflammatory, leading us to hypothesise that aberrant lipid build-up in macrophages triggers WAT inflammation during obesity. This thesis expands on the initial findings from our lab and describes two novel mechanisms that potentially contribute to lipid-induced inflammatory activation of ATMs. In chapter 3, the role of de novo phosphatidylcholine (PC) synthesis pathway during lipotoxicity in macrophages is addressed. The first part of the chapter demonstrates that lipotoxic environment increased de novo PC synthesis rate in bone marrow-derived macrophages (BMDMs) and ATMs, and that loss of rate-limiting enzyme in de novo PC synthesis pathway, CTP:phosphocholine cytidylyltransferase a (CCTa) diminished saturated FFA-induced inflammation in BMDMs. In the second part, I show that macrophage-specific CCTa deletion did not impact on the development of WAT inflammation or systemic insulin resistance, but had a minor benefitial effect on hepatic gene transcription during obesity. Chapter 4 develops on recent observations of interactions between sympathetic nerves and macrophages in WAT. In the first part of the chapter, I demonstrate that stimulating B2-adrenergic receptor (B2AR), the main receptor for sympathetic neurotransmitter norepinephrine in macrophages, enhanced intracellular triglyceride storage by up-regulating diacylglycerol O-acyltransferase 1 (Dgat1) gene expression in BMDMs. The second part of the chapter shows that macrophage-specific B2AR deletion did not modulate systemic glucose and lipid metabolism during obesity, but mice lacking B2ARs in macrophages demonstrated augmented hepatic glucose production on a chow diet. Furthermore, systemic B2AR blockade or macrophage-specific B2AR deletion in mice did not affect the thermogenic response to cold exposure. Chapter 5 includes the characterisation of B2AR stimulation-induced changes to the global cellular proteome of BMDMs, and a subsequent validation of the role of candidate transcription factors in regulating B2AR agonism-induced gene expression in BMDMs.