Orientador: Dirceu Barnabé Ravelli / Resumo: Objetivo: avaliar as alterações dentárias que ocorrem após tratamento realizado com os aparelhos de Herbst e Bionator em pacientes com má oclusão de classe II, divisão 1, na fase da dentadura mista. Metodologia: este é um estudo retrospectivo. A amostra foi composta por 114 modelos de estudo de 57 pacientes classe II divisão 1 de Angle divididos em três grupos de estudo: 22 pacientes tratados com o aparelho de Herbst (GH), 20 pacientes tratados com o aparelho Bionator de Balters (GB) e 15 pacientes do grupo controle (GC), que não receberam tratamento ortodôntico. Foram realizadas mensurações nos modelos iniciais (T0) e ao final do tratamento/ acompanhamento (T1) dos três grupos. As mensurações nos modelos digitais foram realizadas através do software VistaDent® 3D Pro, Versão 2.1 (Dentsply, GAC). Foram avaliadas a relação de molares, overjet, overbite, distância intermolares e intercaninos, perímetro e comprimento do arco, e inclinação anteroposterior dos incisivos. As comparações intergrupos foram realizadas utilizando a Análise de variância à um fator seguido do pós teste de Tukey (α=5%). Resultados: não foram observadas diferenças estatísticas entre os grupos para as distâncias intercaninos, intermolares, overbite, comprimento do arco, perímetro do arco e inclinações dos incisivos. O GH apresentou maior redução (p=0,005) na relação molar (2,42mm ± 2,35) do que o GB (1,25mm ± 0,73) e o GC (0,57mm ± 1,30). O overjet teve uma maior correção (p<0,001) nos pacientes do GH (-3,8... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: to assess the dental changes induced by Bionator and Herbst appliances in the treatment of class II, division I patients in mixed dentition phase. Materials and Methods: this is a retrospective study. The sample included 114 cast models of 57 subjects class II, division 1 malocclusion divided into three groups: 22 patients treated with Herbst appliance (HG), 20 treated with Bionator (BG) and Control group, included 15 individuals who received no treatment (CG). Digital models before (T0) and after treatment (T1) were used to evaluate the dental changes by VistaDent® 3D Pro software, Version 2.1 (Dentsply, GAC). Molar relationship, overjet, overbite, dental arch widths, arch perimeter, arch length and incisors inclination were compared. The differences among groups were evaluated by one-way analysis of variance and the Tukey post-hoc test (p<0,05). Results: the results showed no statistical difference for overbite, perimeter, arch length, arch widths and incisors inclination. The molar relationship showed a greater decrease in HG (2.42mm ± 2.35, p=0.005) than BG (1.25mm ± 0.73) and CG (0.57mm ± 1.30). Overjet decrease significantly (p<0.001) in patients of the GH (-3.81mm ± 2.30) followed by BG (-2.04mm ± 1.69) and CG (- 0.30mm ± 0.86). Conclusion: The improvement in molar relationship and overjet were better in Herbst appliance than Bionator and Control group. / Mestre

O objetivo deste estudo longitudinal foi comparar as alterações dentoesqueléticas e tegumentares de jovens com má oclusão de Classe II não tratados e tratados com distalizador First Class em ancoragem convencional ou esquelética, ou com o aparelho extrabucal cervical (AEB), seguidos do aparelho fixo. A amostra foi composta por 44 pacientes com má oclusão de classe II e divididos em quatro grupos de 11 cada: pacientes tratados com distalizador First Class com ancoragem convencional no botão de Nance (G1), tratados com distalizador First Class com ancoragem esquelética apoiado em 2 mini-implantes no palato (G2), tratados com o aparelho extrabucal (AEB) (G3) e o grupo controle, com pacientes não tratados (G0). Foram obtidas as telerradiografias ao início (Ti) e final (Tf) do tratamento para a realização das análises cefalométricas e avaliação das alterações dentárias, esqueléticas e tegumentares e compará-los com o grupo controle (G0). A análise estatística foi realizada pelo teste t pareado com a finalidade de verificar as alterações ocorridas dentro de um mesmo grupo e pelo teste ANOVA a um critério e teste de Tukey para verificar as diferenças entre os grupos. Observou-se restrição e redirecionamento do crescimento maxilar ao final do tratamento no G1 e G3. Os efeitos esqueléticos na mandíbula só foram significantes no G0. As medidas da relação maxilomandibular diminuíram significantemente no G1 e G3 com significante diminuição das medidas que avaliaram o perfil tegumentar. Quanto ao componente vertical todas as medidas aumentaram no G3. Os primeiros molares superiores angularam distalmente no G2 e os inferiores mesialmente no G3. Os quatro grupos apresentaram extrusão dos dentes superiores e inferiores. Os três grupos experimentais apresentaram diminuição significante nas relações dentárias (relação molar, trespasse horizontal e vertical). Conclui-se que os grupos experimentais corrigiram a má colusão de Classe II de maneira satisfatória, sendo que o uso do AEB mostrou efeitos esqueléticos e dentários na correção e os grupos com distalizadores somente efeitos dentários. O tempo de tratamento no grupo com AEB foi significantemente menor. / The aim of this prospective study was to compare the dental, skeletal and soft tissue changes in youngsters with Class II malocclusion untreated and treated with First Class distalizer in conventional or skeletal achorage or with cervical headgear followed by fixed orthodontic appliances. The sample consisted of 44 patients with Class II malocclusion and divided into four groups of 11: patients treated with First Class distalizer with conventional anchorage (Nance button)(G1), treated with First Class distalizer with skeletal anchorage supported in two palatal mini-implants (G2), treated with cervical headgear (G3) and follow-up group with untreated patients (G0). Lateral cephalometrics radiographs were taken before treatment and after treatment in order to cephalometric analysis and evaluate the dental, skeletal and soft tissue changes and to compare with follow-up group (G0). Statistical analysis was performed by dependent t test to verify the changes occurred in the same group and by one-way ANOVA and Tukey test to verify the changes occurred between the groups. It was observed restriction and redirection of maxillary growth after treatment in G1 and G3. Mandibular skeletal effects were significant in G0. The values of skeletal maxilomandibular relationship decreased significantly in G1 and G3 with significant decrease of measurements that evaluated soft facial profile. All measurements of vertical component increased in G3. Maxillary first molars were distal tipping in G2 and lower first molars were mesial tipping in G3. The four groups showed extrusion in the upper and lower teeth. The three experimental groups showed significant decreased in the molar relationship, overjet and overbite. It concluded that experimental groups corrected the Class II malocclusion efficiently, cervical headgear showed skeletal and dental effects and the groups with distalizers showed only dental effects. The mean treatment period was significant lower with cervical headgear.

O objetivo deste estudo foi comparar as alterações cefalométricas de pacientes com má oclusão de Classe II divisão 1 tratados com o distalizador Jones jig e com extrações dos primeiros pré-molares superiores. A amostra foi constituída por 88 telerradiografias em norma lateral de 44 pacientes, os quais foram divididos em 2 grupos. O grupo Jones jig consistiu de 21 pacientes tratados com o aparelho Jones jig, com idade média inicial de 12,88 ± 1,23 anos e final de 17,18 ± 1,37 anos, e tempo médio de tratamento de 4,29 anos. O grupo extrações dos primeiros prémolares superiores foi composto por 23 pacientes, tratados com extrações dos primeiros pré-molares superiores, com idade média inicial de 13,59 ± 1,91 anos e final de 16,39 ± 1,97 anos, e tempo médio de tratamento de 2,8 anos. As comparações intergrupos foram realizadas por meio do teste t independente e Mann-Whitney. A correção da Classe II no grupo extrações dos primeiros prémolares superiores apresentou maiores alterações esqueléticas com redução do SNA, ANB e NAP. Houve um aumento da altura facial ântero-inferior, suave protrusão e extrusão dos incisivos superiores no grupo Jones jig. Os primeiros molares superiores mostraram significante inclinação mesial e mesialização em ambos os grupos, e o trespasse horizontal foi mais eficientemente corrigido no grupo extrações dos primeiros pré-molares superiores. Por outro lado, os primeiros molares inferiores apresentaram uma extrusão significantemente maior no grupo Jones jig. / The aim of this study was to compare the cephalometric changes of Class II division 1 malocclusion patients treated with Jones jig appliance and with 2 maxillary first premolar extractions. The sample consisted of 88 lateral cephalograms of 44 patients, divided into 2 groups. Jones jig group consisted of 21 patients treated with the Jones jig appliance, with mean initial age 12,88 ± 1,23 years and final mean age 17,18 ± 1,37 years, and a mean treatment time of 4,29 years. Maxillary first premolar extractions group comprised 23 patients treated with maxillary first premolar extractions, with initial mean age 13,59 ± 1,91 years and final mean age 16,39 ± 1,97 years, and a mean treatment time of 2,8 years. Intergroup treatment changes were compared with independent t and Mann-Whitney tests. Class II correction in maxillary first premolar extractions group had greater skeletal effect with reduction of SNA, ANB and NAP. There was an increase of anterior face height, mild protrusion and extrusion of the maxillary incisors in Jones jig group. The maxillary first molars showed greater mesial tipping and mesialization in both of groups and overjet was more efficiently corrected in maxillary first premolar extractions group. On the order hand, the mandibular first molars showed extrusion in the Jones jig group.

Introduction: Glycoproteins of the major histocompatibility complex (MHC) are an irreplaceable part of immune response regulation and immune homeostasis maintenance. The regulation of the expression plays an important role in adaptive immune response. Recently, DNA methylation in regulatory areas, crucial for DNA availability to transcription factors, is one of the most researched mechanisms of this type of regulation. The DNA methylation is, among others, related to the aging processes. Increased predisposition age-related immunosenescence in higher age could result from the changes in methylation status of regulatory areas of MHC class II genes. Aims: The aim of this thesis is to analyze the methylation status of regulatory areas of DQB1 gene and to compare the differences between generations and specific alleles. The differences in the levels of DQB1 gene mRNA transcription between generations and specific alleles is also compared. Methods: Both DNA and RNA were isolated from blood samples obtained from donors of three different age groups. DNA was genotypized and modified by bisulfite conversion. The regulatory areas of DQB1 genes were then amplified and subcloned into bacteria. The positive clones were selected and subjected to DNA methylation analysis. RNA was reverse transcribed into cDNA...

Introduction: Recent findings about the pathogenesis of glaucoma have already demonstrated the presence of some specific autoimmune mechanisms. It has also been shown that autoimmune diseases often manifest in co-occurrence, such as celiac disease and type 1 diabetes mellitus or psoriasis. This association can be explained by sharing some of the risk variants of HLA molecules class II. Considering glaucoma an autoimmune disease, the question raises how the glaucoma genetic risk factors affect the phenotype of another autoimmune disease or vice versa, whether genetic risk variants associated for example with celiac disease can affect the glaucoma phenotype. Aims: The aims of this study were to i) identify possible genetic risk markers associated with the development of glaucoma, based on the available literature, and to map their occurrence among members of a three-generation family suffering from glaucoma and multiple autoimmune diseases, ii) find carriers of HLA-DQ2/DQ8 among the members of the same family, iii) verify whether an individual's genotype correlates with his/her phenotype, and iv) determine the potential effect of specific HLA alleles on the glaucoma phenotype. Material and methods: This study used DNA samples derived from 34 members of a three-generation family, in which coeliac...

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We have studied the effect of interferon α (IFN-α) on MHC class II expression by human buccal epithelial cells (BEC), and mRNA expression by BEC and mucosal-associated mononuclear cells (MAMC). In 6 experiments, freshly collected BEC were suspended at a concentration of 1.0 x 105/ml in RPMI 1640 and incubated in the presence of 0-10000 IU/ml of human lymphoblastoid IFN-α (HuIFN-α). Zero and six hour samples were analyzed by single color flow cytometry using FITC-labeled murine IgG1 monoclonal antibody to HLA-DR. Preparations were also analyzed for expression of cytokine transcripts (IL-2 IL-4, IL-5, IL-6, IL-8, IFN-γ, GM-CSF) by reverse transcriptase polymerase chain reaction (RT-PCR). Increasing concentrations of IFN-α resulted in proportionate increases in the percentage of HLA-DR + BEC (r = 0.7897, p = 0.0627) and in the percentage of HLA-DR + staining at higher intensities (101 to 102 log fluorescence intensity) (LFI) (r = 0.40l0, p = 0.0424). The percentage of HLA-DR + BEC rose from a mean of 1.5% with no IFN-α to 7% with 10000 IU/ml IFN-α (p < 0.05). The percentage of HLA-DR + BEC staining at 101 to 102 LFI rose from a mean of 8.3% with no added IFN-α to 19.2% with 10000 IU/ml IFN-α (p <0.05). Unstimulated BEC constitutively expressed IL-8 and GM-CSF. IFN-α stimulated preparations also expressed IFN-γ, possibly due to the presence of MAMC, which comprised 2-9% of the total cell population. These data indicated that HuIFN-α upregulates MHC class II expression by human BEC, possibly by enhancing IFN-γ production by MAMC present in the culture preparations.

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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INTRODUCTION Une meilleure prédiction du gain esthétique réalisable par un traitement ortho-chirurgical est cruciale dans une société où la chirurgie est de plus en plus accessible et où l'importance accordée au physique est prédominante. L'objectif de cette étude est donc de tenter de définir des critères qui permettent aux cliniciens d'évaluer le potentiel d'amélioration de l’esthétisme du profil après une chirurgie d'avancement mandibulaire chez des patients hypodivergents. MÉTHODE L'échantillon est composé de 18 patients hypodivergents traités par combinaison d'orthodontie et de chirurgie d'avancement mandibulaire sans génioplastie. Des radiographies céphalométriques initiales (T1) et finales (T2) sont utilisées pour produire des silhouettes noires. Ces images sont présentées à 20 sujets sans connaissances de la médecine dentaire, 20 résidents en orthodontie et 20 orthodontistes gradué.e.s à qui on a demandé de noter l'esthétique de chaque profil sur une échelle de 1 à 10. RÉSULTATS Une corrélation négative a été trouvée entre le score esthétique initial et la différence du score esthétique. 88 % des patients de cet échantillon ont été jugés comme présentant une amélioration de l'esthétisme de leur profil en présence de valeurs initiales d'ANB ≥ 6° et/ou de G'-Sn-Pog' ≤ 160° indépendamment. Les professionnels ont été plus sensibles dans le discernement des profils et ont eu tendance à juger d’une plus grande amélioration de l'esthétisme des profils que le public général. Les résidents et orthodontistes évaluent de manière très similaire la quantité d’amélioration de l’esthétisme du profil. CONCLUSION Cette étude soutient ainsi que ces seuils peuvent être utilisés pour juger de l'amélioration esthétique potentielle du profil chez les patients hypodivergents envisageant cette chirurgie. / INTRODUCTION A better prediction of the achievable esthetic gain from ortho-surgical treatment is crucial in a society where surgery is becoming more widely accessible and where the importance attached to physical appearance is predominant. The objective of this study is to attempt to define criteria that would enable clinicians to assess the potential for improving profile aesthetics following mandibular advancement surgery in hypodivergent patients. METHOD The sample consists of 18 hypodivergent patients who had been treated with a combination of orthodontics and mandibular advancement surgery without genioplasty. Initial (T1) and final (T2) cephalometric radiographs were used to produce silhouette images. These pictures were then presented to 20 laypeople, 20 orthodontic residents and 20 orthodontists who were asked to score the aesthetics of each profile from 1-10. RESULTS A negative correlation is found between the initial esthetic score and the overall change in the esthetic score. 88% of patients in this sample are judged to show an improvement in their post-surgical profile aesthetics when initial values of ANB ≥ 6° and/or initial values of G’-Sn-Pog’ ≤ 160° were met independently. Professionals are more sensitive in discerning profiles and tend to note a greater improvement in the profile aesthetics than laypeople. Residents and orthodontists rate the amount of post-surgical improvement similarly. CONCLUSION This study supports that these thresholds can be used to judge potential profile aesthetics improvement in hypodivergent patients considering mandibular advancement surgery.