Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 133-156). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Orientador: Lizeti Toledo de Oliveira Ramalho / Banca: Rita de Cássia Loiola Cordeiro / Banca: Wilson Roberto Poi / Resumo: O objetivo deste trabalho foi avaliar a compatibilidade biológica in vivo de materiais odontológicos para remoção químico-mecânica do tecido cariado. Para isto, foram utilizados 32 camundongos que receberam no tecido conjuntivo subcutâneo o implante de tubos de polietileno preenchidos com Carisolv, Papacárie® e base de gel. Os animais foram sacrificados 3, 7, 20 e 30 dias após a cirurgia de implante, sendo os espécimes obtidos processados e submetidos à análise histológica. Os resultados mostraram que o Carisolv provocou uma inativação do metabolismo celular no período inicial, seguida de resposta inflamatória no período final. O grupo do Papacárie® manteve uma inflamação moderada até os 20 dias, que diminuiu de intensidade aos 30 dias e a base do gel provocou reação inflamatória discreta inicial, que aumentou aos 30 dias. Pôde-se concluir que o Carisolv, o Papacárie® e a base de gel são biocompatíveis com o tecido conjuntivo, porém as alterações provocadas por estes materiais são estatisticamente diferentes. / Abstract: The aim of this work was evaluate biological compatibility in vivo of dental materials to chemo-mechanical removal of caries. This study was conducted to observe in thirty-two mice subcutaneous connective tissue reaction to the implanted polyethylene tubes filled with Carisolv, Papacárie® and gel base. The animals were sacrificed 3, 7, 20 and 30 days after the implantation procedure. The implant sites were excised and prepared for histological evaluation. The results showed that Carisolv inactivated the cellular metabolism in the initial period, followed by inflammatory response in the final period. The group of Papacárie® maintained moderate inflammation until 20 days, that reduced the intensity in 30 days and the gel base provoked initial discrete inflammatory reaction, that increased in 30 days. Carisolv, Papacárie® and gel base are biocompatible with connective tissue, although alterations caused for these materials are statistically different. / Mestre

Made available in DSpace on 2014-06-11T19:24:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-03-25Bitstream added on 2014-06-13T19:51:21Z : No. of bitstreams: 1 boaventura_jmc_me_arafo.pdf: 4140317 bytes, checksum: af588edb33c7ed7c016ce9297335cbb1 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O cimento de ionômero de vidro representa um marco dentro da Odontologia, pois veio agregar propriedades físicas e biológicas favoráveis que não eram obtidas com outros materiais. Uma de suas propriedades, a biocompatibilidade, foi o tema do nosso trabalho, que teve como objetivo avaliar, comparativamente, em tecido conjuntivo subcutâneo de ratos o potencial irritativo em nível I de um cimento de ionômero de vidro em fase experimental e o resultado da associação do pó experimental com o líquido de cimentos de ionômero de vidro já disponíveis comercialmente. Foram utilizados 60 ratos (Rattus norvegicus, Albinus, Holtzman), divididos em 5 grupos de 3 animais cada, para os períodos de 7,15, 30 e 60 dias. Os materiais utilizados foram: Vitrebond (Grupo I), Ionomaster F (Grupo II), Pó experimental + Líquido do Cimento de Ionômero de vidro Vitrebond (Grupo III), Pó experimental + Líquido do Cimento de Ionômero de vidro do Ionomaster F (Grupo IV) e Pó experimental + Líquido experimental (Grupo V). Pó e liquido experimentais foram desenvolvidos pelo Instituto de Química de Araraquara – UNESP/Brasil. O Vitrebond e Ionomaster F agiram como controle e todos foram veiculados em tubos de polietileno e implantados no tecido conjuntivo subcutâneo dos ratos. Decorridos os períodos experimentais, os tubos foram removidos e encaminhados para tramitação laboratorial. Os cortes foram avaliados em microscopia óptica comum para análise descritiva do quadro reacional. Considerando-se cada evento histopatológico foi apresentada a estatística descritiva de cada grupo. A avaliação de diferença significativa entre os materiais, considerando os períodos experimentais e os escores atribuídos aos eventos histopatológicos em estudo, foi realizada pelo teste de Kruskal – Wallis. Adicionalmente, foram efetuadas comparações múltiplas de postos médios pelo teste de Dunn. / Glass ionomer cement represents a hallmark in the Dentistry Science, since it aggregates favorable physical and biological properties, which were not obtained by the other cements. Biocompatibility, one of its properties, was the aim of this study, which was to evaluate, comparably, in the subcutaneous tissue of rats, the level I aggravation potential of glass ionomer cement in experimental phase and the result between the association of the experimental powder and the liquid from commercially available glass ionomer cements. Sixty rats were used (Rattus novergicus, Albinus, Holtzman), divided into 5 groups of 3 animals each, in the following time periods of 7, 15, 30 and 60 days. Commercial materials used were: Vitrebond (Group I), Ionomaster F (Group II), Experimental powder + Liquid of Glass Ionomer Cement Vitrebond (Group III), Experimental powder + Liquid of Glass Ionomer Cement Ionomaster F (Group IV), and Experimental powder + Experimental Liquid (Group V). Experimental powder and liquid were developed by Chemical Institute of Araraquara – UNESP/Brasil. Vitrebond and Ionomaster F were utilized as control and every group were carried within poly (ethylene) tubes and implanted in the subcutaneous connective tissue of the rats. Tubes were removed after the appropriate experimental times and were taken to laboratory processing. Cuts were evaluated under optical light microscopy to obtain descriptive analyze of the reaction overview. According to each histopathological event, descriptive statistics were presented to each group. The significant difference evaluation among materials, considering experimental times and scores attributed to the histopathological events studied, was performed by Kruskal-Wallis test. Besides this, multiple comparisons were effectuated of mean points by Dunn test.

Made available in DSpace on 2014-06-11T19:24:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-05-30Bitstream added on 2014-06-13T20:31:49Z : No. of bitstreams: 1 lima_rkp_me_arafo.pdf: 1114536 bytes, checksum: 168f29b7a36e3e5efcd89c839651e545 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O objetivo deste estudo foi o de avaliar, in vivo, a biocompatibilidade e a influência da infiltração, no sentido coroa/ápice, na reparação dos tecidos apicais e periapicais pós-tratamento endodôntico, utilizando dois diferentes materiais obturadores: o cimento Sealapex e um sistema resinoso de obturação de canal radicular denominado de sistema Epiphany/Resilon. Os resultados mostraram que o sistema Epiphany/Resilon apresentou resposta tecidual apical e periapical melhor que o cimento Sealapex, independente da presença ou não de restauração coronária, em todos os aspectos estudados. O sistema Epiphany/Resilon com restauração coronária apresentou melhores resultados que o mesmo sistema sem restauração coronária. O cimento Sealapex sofreu influência da infiltração coronária, apresentando, em todas as variáveis estudadas, os piores resultados, quando exposto ao meio bucal. / The objective of this study was to evaluate, in vivo, the biocompatibility and the leakage influence, in the crown-apex direction, in the endodontic post-treatment repairing of apical and periapical tissues, using two different filling materials: Sealapex sealer and a resinous cement of root canal filling - Epiphany/Resilon. The results showed that Epiphany/Resilon system presented apical and periapical tissue response better than Sealapex independent of presence or no of the coronary restoration, in all studied aspects. Epiphany/Resilon system, with coronary restoration presented better results than of the same system without coronary restoration. Sealapex was influenced by the coronary exposition to oral environment, presenting the worst results in all studied variables.

Orientador: Alexandre Leite Rodrigues de Oliveira / Tese (doutorado) - Universidade Estadual de Campinas. Instituto de Biologia / Made available in DSpace on 2018-08-15T19:14:30Z (GMT). No. of bitstreams: 1 Emirandetti_Amanda_D.pdf: 10405230 bytes, checksum: 86b2578427126b457b8a4ebeac01a1f5 (MD5) Previous issue date: 2009 / Resumo: Após uma lesão de um nervo periférico, astrócitos e microglia tornam-se reativos, desencadeando a chamada gliose reativa. Adicionalmente, uma porcentagem significativa dos botões sinápticos em íntima relação com os motoneurônios é eliminada, sendo este mecanismo associado à ação de fagocitose das células gliais. Recentemente, a expressão de MHC I (complexo de histocompatibilidade principal classe I) tem sido relacionada com a plasticidade das sinapses e com o processo de regeneração axonal subseqüente à transecção do nervo isquiático, sendo a manipulação da expressão dessa molécula um possível alvo terapêutico. Por sua vez, a óxido nítrico sintase induzível (iNOS), parece estar envolvida com eventos pró- e anti-apoptóticos e com processos de plasticidade das sinapses após lesão do nervo periférico. Embora alguns trabalhos tenham sugerido a participação do MHC classe I nos processos de plasticidade sináptica após a lesão do Sistema Nervoso (SN), as suas funções bem como os mecanismos moleculares que estão envolvidos nesses processos permanecem obscuros. Portanto, os objetivos principais deste trabalho foram identificar a importância relativa de distintas moléculas de MHC classe I clássico (Ia) e não clássico (Ib) na reatividade astroglial e microglial após a axotomia periférica, bem como avaliar o envolvimento da iNOS em tais processos e no grau de eliminação das sinapses. Para tais fins, foram utilizados camundongos knockout para transportador associado com a apresentação de antígeno - 1 (TAP-1), microglobulina-p2 (mp2) genes K e D do MHC I (H2-Kb / Db), iNOS e camundongos controle C57BL/6J. Os animais que foram submetidos à transecção do nervo isquiático foram processados para imunohistoquímica, histoquímica, western blotting e microscopia eletrônica de transmissão (estudo in vivo). Camundongos neonatos foram utilizados para o cultivo de astrócitos (estudo in vitro). Os resultados indicam que a ausência de complexo principal de histocompatibilidade I não clássico (MHC Ib) pode influenciar o grau de reação astroglial e microglial uma e três semanas após a axotomia periférica. Ainda, animais deficientes em iNOS apresentaram menor capacidade de expressão de complexo principal de histocompatibilidade I clássico (MHC Ia) por células da microglia uma semana após a lesão. A análise quantitativa da microscopia eletrônica indica maior retração das sinapses em animais knockout para iNOS quando comparados com a linhagem selvagem C57BL/6J. O conjunto dos resultados obtidos sugere que a gliose reativa é influenciada pela expressão de MHC I não clássico e que a iNOS pode participar de mecanismos de apresentação da forma clássica na superfície celular microglial, aumentando assim a retração sináptica e contribuindo para a resposta regenerativa neuronal após a axotomia periférica. / Abstract: Following a peripheral nerve injury, microglial and astrocytic cells become reactive, triggering the so called 'reactive gliosis'. Also, a significant percentage of the synaptic buttons to the motoneurons is eliminated and such process can be associated to the activation of glial cells. Recently, major histocompatibility complex class I (MHC I) expression has been related to the synaptic plasticity and axonal regeneration process that follows sciatic nerve transection. In this sense, the modulation of MHC I expression can be, in the future, used as a therapeutic approach in several diseases and also after trauma of the nervous system. Similarly to the MHC I, inducible nitric oxide synthase (iNOS) can be involved in the synaptic plasticity process after nerve lesion. The objectives of this work were to investigate the relative importance of MHC I expression (classical / Ia and non-classical / Ib MHC I) on the microglial and astroglial reaction after axotomy and to evaluate iNOS involvement in such process and on the degree of synaptic stripping. For this purpose, knockout mice for transporter associated with antigen processing (TAP-1), P2- microglobulin (mp^) , K and D MHC I genes (H2-Kb / Db), iNOS and wild type C57BL/6J strains were subjected to unilateral sciatic nerve transection and specimens were processed for immunohistochemistry, histochemistry, Western blotting and transmission electron microscopy (in vivo study). Astrocytes from newborn mice were also investigated in primary cell cultures (in vitro study). The results indicate that nonclassical class I major histocompatibility (MHC Ib) absence may influence the microglial and astroglial reaction one and three weeks after axotomy. Also, iNOS deficient mice presented milder classical class I major histocompatibility (MHC Ia) expression by microglia one week after lesion than C57BL/6J. Quantitative transmission electron microscopy (TEM) analysis indicates greater number of synaptic elimination in the iNOS knockout mice as compared to the wild type. Overall, the present results suggest that reactive gliosis is influenced by non-classical MHC Ia expression and iNOS molecules might participate on microglial cell surface presentation of MHC I, therefore contributing to synaptic detachment and the regenerative response after axotomy. / Doutorado / Anatomia / Doutor em Biologia Celular e Estrutural

La SpA est un rhumatisme inflammatoire chronique fréquent, dont la prévalence est de 0,3% en France. Les mécanismes pathologiques qui en sont à l’origine demeurent largement incertains. Néanmoins, l’héritabilité de la maladie est élevée, impliquant de multiples facteurs génétiques, dont la région du complexe majeur d’histocompatibilité (CMH) et plus particulièrement l’allèle HLA-B27 qui y exerce un rôle prédominant. L’objectif de ce travail était d’identifier de nouvelles cibles moléculaires, en vue d’améliorer la compréhension de la physiopathologie de la SpA, par des approches génétiques et de génomiques fonctionnelles.La première partie de mon travail a consisté en l’identification de polymorphismes du CMH associés à la SpA et distinct de HLA-B27. Les études d’association portant sur les données génétiques de 3 cohortes indépendantes nous ont permis d’identifié 5 variants associés à la SpA indépendamment du HLA-B27. Les deux polymorphismes situés à proximité des gènes MICA et MAPK14 semblent particulièrement intéressants pour leur implication potentielle dans la pathogénèse de la SpA. En marge de cette étude, nous avons entrepris de déterminer la prévalence du HLA-B27 dans une cohorte française représentative de la population générale, qui était de 6,9% chez les témoins et de 74,2% chez les sujets atteints de SpA.Les études fonctionnelles conduites sur des cellules dendritiques dérivées de monocytes (MD-DCs) ont permis d’identifier un défaut de réponse proliférative des LT CD4+ stimulés par les MD-DCs de patients atteints de SpA, ainsi qu’une signature transcriptomique de 81 gènes caractéristique des MD-DCs de ces patients. Parmi les gènes validés, la surexpression d’ADAMTS15, de F13A1 et de SELL pourrait jouer un rôle dans l’inflammation liée à la pathologie, alors que la sous-régulation de CITED2 paraitrait corrélée à une dérégulation de la voie Wnt. Enfin, nos investigations sur les MD-DCS nous ont amené à identifier une corrélation entre l’haplotype d’ERAP1 prédisposant à la SpA, et un niveau accru d’expression de ce gène ainsi que de la protéine ERAP1. / Spondyloarthritis (SpA) is a frequent chronic inflammatory rheumatic disorder, with a prevalence of 0.3% in France. Pathological mechanisms leading to SpA remain largely uncertain. Nevertheless, the heritability of this disorder is high, likely involving multiple genetic factors, among which the major histocompatibility complex (MHC) region and particularly the HLA-B27 allele which plays a prominent role. The objective of this work was to achieve a better understanding of SpA physiopathology via genetic and transcriptomic approaches. The first part of my work consisted in identification of MHC polymorphisms associated with SpA, distinct of HLA-B27. Association studies based on the genetic data of 3 independent cohorts have allowed to identify 5 SNPs associated to SpA, independently of HLA-B27. Two polymorphisms localized next to MICA and MAPK14 genes seem particularly interesting for their implication in SpA pathogenesis. In parallel of this study, we characterized HLA-B27 prevalence in a French cohort corresponding to 6.9% in healthy controls and 74.2% in SpA patients. Functional studies on monocyte-derived dendritic cells (MD-DCs) revealed altered capacity to stimulate allogeneic CD4+ T cell responses by MD-DCs from SpA patients and a transcriptomic signature of 81 genes differentially expressed in those cells, as compared to those from healthy controls. Among validated genes, ADAMTS15, F13A1 and SELL could play a role in SpA inflammation, whereas CITED2 seemed to be correlated to Wnt pathway. Finally, a strong correlation between ERAP1 SpA-susceptibility haplotype and an increased expression of this gene and the ERAP1 protein has been identified.

5 Abstract Products of major histocompatibility complex (MHC) plays key role in immune system of vertebrates. Prior studies on different vertebrate species show, that heterozygosity in MHC genes is linked to more efficient immune system and preferred in mate choice. Results of human studies are ambivalent, which can be due to the effect of some modulating factors like reproductive status. Therefore, our aim was to test heterozygosity related preferences in faces, odor and voice across menstrual cycle. Our sample consisted of 51 men and 52 women, from which 23 used hormonal contraception and 29 had natural cycle. They were genotyped in -A, -B and -DR alleles. All odor stimuli, face photos and voice records were rated on seven-point scale in both follicular and luteal phase. Repeated measures ANOVA was used for the analysis. Changes in ratings across the menstrual cycle and heterozygosity were most discernible on voice ratings. Voices of homozygous males were rated more attractive than voices of heterozygous males especially in follicular phase. Similar shift to higher ratings in follicular phase was manifested in ratings of homozygous male faces, but the difference between homozygous males and heterozygous males was not significant. Women with natural cycle also rated voices higher in their follicular phase...

Indiana University-Purdue University Indianapolis (IUPUI) / The function of major histocompatability complex (MHC) class II molecules is to present antigenic peptides to CD4+ T cells. Typically, MHC class II molecules present peptides derived from exogenous sources. Yet, certain endogenous antigens (Ags) have been found to be presented by class II molecules. Studies suggest that specific heat shock protein family members may play a role in Ag processing and subsequent class II presentation. The studies presented here using B lymphoblasts demonstrate the importance of HSP90α, HSP90β, and possibly HSP70 in selectively regulating MHC class II presentation. Inactivation of HSP90 function using pharmacological inhibitors inhibited class II presentation of exogenous and endogenous GAD, but did not perturb the presentation of several other intra- and extracellular Ags. Individual knockdown of HSP90 isoforms using isoform specific siRNA selectively inhibited GAD Ag presentation. These results demonstrate a requirement for HSP90α and HSP90β in regulating MHC class II presentation of select Ags. Studies to explore mechanistically the roles of HSP90α and HSP90β in regulating GAD Ag presentation were pursued. The pathways of exogenous and endogenous MHC class II presentation of GAD Ag are distinct yet converge with shared terminal processing of GAD within endosomal/lysosomal vesicles. The effect of HSP90 manipulation on various shared components of the MHC class II pathway was examined. The studies presented here suggest that HSP90α and HSP90β regulate MHC class II presentation of GAD Ag at discrete steps most likely involving HSP90 binding to GAD Ag rather than perturbing overall MHC class II function. vi Studying the role of HSP90 in MHC class II presentation in B cells revealed the potential requirement for HSP70 in the presentation of select Ags. The studies presented here demonstrate a possible role for HSP70 in the presentation of Ags such as SMA or Ig kappa by MHC class II molecules. Also included in this work is a study of a rare case of diabetes caused by type B insulin resistance due to development of insulin receptor autoantibodies during the treatment of hepatitis C with interferon alpha and ribavirin. Clinical and laboratory findings in the case are presented.

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