INTRODUÇÃO: Artrite reumatoide é uma doença autoimune que causa inflamação nas membranas sinoviais de articulações chamadas diartroses. As articulações da orelha média podem estar sujeitas às mesmas lesões reumáticas que as outras articulações do corpo. Perdas auditivas neurossensoriais e condutivas foram observadas na literatura, assim como o envolvimento da artrite reumatoide na orelha média, mas os resultados não estão em concordância. A imitância acústica de banda larga pode fornecer maior sensibilidade a mudanças sutis nas articulações dos ossículos. OBJETIVO: avaliar o efeito da artrite reumatoide no sistema auditivo com enfoque na avaliação da orelha média. MÉTODOS: O delineamento desta pesquisa é estudo de casos comparando três diferentes grupos: dois grupos de indivíduos com artrite reumatoide e um grupo controle pareado por gênero e idade. Foram incluídos 39 participantes com idades entre 26 e 51 anos, de ambos os gêneros. O grupo estudo foi separado em dois: AR1, com 15 participantes (artrite reumatoide há dez anos ou mais); e AR2, com 9 participantes (artrite reumatoide há cinco anos ou menos). Estes grupos foram recrutados do ambulatório de reumatologia do Hospital das Clínicas da FMUSP e o grupo controle com 15 participantes, foi composto por voluntários, usuários do Centro de Docência e Pesquisa da FMUSP. Os procedimentos utilizados foram: Imitanciometria com sonda de 226 Hz, audiometria tonal liminar, audiometria de altas frequências e imitância acústica de banda larga, cujos dados foram extraídos como bandas de 1/3 de oitava para reflectância de energia em um documento de extensão Excel. Para análise dos dados, utilizaram-se estatística descritiva, análise de variância, teste quiquadrado e Kruskal-Wallis. RESULTADOS: As médias de idade para AR1, AR2 e controle foram de 41,1, 38,6 e 39,9 anos, respectivamente, e não houve diferença significante entre grupos. As medidas de imitanciometria 226 Hz (timpanometria e reflexos acústicos ipsilaterais) e reflectância de energia não demonstraram diferença significante entre os grupos. Foram encontradas diferenças na comparação entre os grupos AR1 e AR2 e grupo controle para os testes audiometria tonal liminar, e AR1 com o grupo controle para audiometria de altas frequências e reflexos acústicos contralaterais. Não foi observada diferença entre os resultados da orelha direita e da esquerda. CONCLUSÕES: Os grupos de artrite reumatoide apresentaram o mesmo padrão de resposta para as avaliações de orelha média do grupo controle, levantando a possibilidade de apresentarem um mesmo comportamento de sistema ou de que as ferramentas utilizadas para avaliação não são sensíveis para detectar as mudanças sutis. Foi possível observar mudança nos limiares audiométricos e de altas frequências dos grupos com artrite reumatoide em comparação com o grupo controle, mostrando a importância de monitorização auditiva nessa população / BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of synovial membranes of the diarthrodial joints. Middle ear joints may be subject to the same rheumatic lesions as other joints in the body. Sensorineural and conductive hearing loss have been reported, as well as middle ear involvement, but the results are not in agreement. Wideband acoustic immittance (WAI) may provide better sensitivity to subtle changes in the ossicular joint. PURPOSE: To evaluate the effect of RA in the auditory system focusing on the middle ear assessment with WAI. METHODS: This was a cross-sectional study comparing audiological behavior of 3 different groups: two groups of individuals with rheumatoid arthritis and a normal control (NC) group matched 1:1 based on age and gender. Thirty-nine participants, raging age from 26-51 years old, male and female. The study groups were pooled into two groups: RA1 with 15 participants (patients who had had RA for more than ten years) and RA2 with nine participants (those who had had RA for less than five years). The study groups were recruited from rheumatology clinic of Hospital das Clinicas (FMUSP) and were compared with 15 normal control, which consisted in volunteer students or employees from Centro de Docencia e Pesquisa (FMUSP). Standard 226 Hz probe tone tympanometry, pure-tone audiometry, extended high-frequency audiometry and WAI were performed in all subjects. The results from WAI were extracted as 1/3 octave bands for energy reflectance as an Excel file. Descriptive statistics, chi-square test, mixed model ANOVA and Kruskal-Wallis test were used to investigate the differences in all performed tests across the three groups. RESULTS: Mean ages for RA1, RA2 and NC were 41.1, 38.6 and 39.9 years old respectively and the difference between groups was not statistically significant. Comparison of standard immittance measures (such as 226 Hz probe tone tympanometry and ipsilateral acoustic reflex) and 1/3 octave band energy reflectance did not reveal significant difference between groups. This study found difference in standard audiometry thresholds comparing RA1 and RA2 to NC group, extended high-frequency audiometry and contralateral acoustic reflex comparing RA1 group to NC group. There was no significant difference between right and left ears. CONCLUSIONS: RA groups showed the same middle ear response pattern than the NC group, there was either no significant difference between the middle ears of RA patients and healthy individuals, or WAI is not appropriate for differentiating these two groups. Pure-tone audiometry and extended high-frequency audiometry showed different behaviors between the three groups. The actual incidence of hearing loss in RA remains to be defined. The results showed the importance of monitoring potential audiological manifestations in patients with RA

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting 1% of the population. The aetiology of rheumatoid arthritis is unknown, although there are multiple postulated theories. In 1950, Philip Hench won the Nobel prize for treating patients with rheumatoid arthritis with cortisone. He also treated 6 patients with adrenocorticotropic hormone (ACTH) with good results. ACTH is a melanocortin. The melanocortin system describes the five melanocortin receptors, their ligands, agonists and antagonists and the accessory proteins. The aim of this study was to explore the melanocortin receptors in rheumatoid arthritis synovium. Methods HA-tagged stable cell lines were created for MC1R, MC3R and MC5R. Multiple antibodies were tested for their utility using Western Blot, immunohistochemistry and flow cytometry. Samples of synovium from 28 patients with RA were tested using RTPCR for the presence of MC1R and MC3R. Gene expression was correlated with clinical characteristics, cytokine (RTPCR) expression and immunohistochemical score. Results The stable cell lines expressed MC1R, MC3R and MC5R respectively. Of the antibodies tested none were found to be of utility in detecting MC1R or MC3R .The MC1R RQ values in rheumatoid synovium appear to split into two groups, high and low. The medians of the two groups are significantly different (p=0.0005). There is almost a 5 cycle, or 64 fold, difference in gene expression between the medians of the two groups (1.59 v 6.23). Of note no MC3R positive samples were CD138 high (i.e. no MC3R positive samples had a significant plasma cell infiltrate) (p=0.006). Categorical analysis using Fishers Exact test revealed an association between MC1R high samples and CD68 lining high scores, (i.e. MC1R high samples also had a high macrophage score in the lining of the sample) (p=0.02). MC1R low samples were associated with not being on combination therapy, 15 this did not quite reach significance (p=0.07). Linear regression analysis confirmed these associations for MC1R. PCA analysis did not show any grouping of samples according to any of the variables tested, likely due to sample size. Conclusion MC1R and MC3R are found in human synovium. Current commercial antibodies are not of utility in detecting MC1R or MC3R. Synovial samples can be split into high and low MC1R gene expression groups. MC3R was either present or absent. High expression of MC1R was associated with a high macrophage score and MC3R expression was associated with a low plasma cell score. MC1R and MC3R expression in RA synovium could be used as biomarkers of disease state or severity as well as a target for therapy.

Sjögren's syndrome (SS) and rheumatoid arthritis (RA) are characterised by breach of self-tolerance with high affinity circulating autoantibodies and peripheral B cell disturbances in the naïve and memory B cell compartments. In addition, both SS and RA develop functional ectopic B cell follicles in the respective target organs, i.e. the salivary glands and the joint synovium, whereby autoreactive B cell undergo antigen selection and affinity maturation. However, the exact stage at which errors in B cell tolerance checkpoints accumulate is unknown. In this PhD project, I amplified and sequenced Ig VH and VL gene transcripts from single B cells which were FACS sorted either from the peripheral blood of SS patients or from the RA synovium. Healthy donors (HD) were used as controls. Subsequently, I cloned and expressed recombinant monoclonal antibodies displaying identical antigenic specificity of the original B cells. Finally, I tested the poly- and autoreactivity profile of these antibodies against SS and RA-associated autoantigens. In SS, I analysed 353 VH and 293 VL sequences and obtained 114 recombinant antibodies from circulating naïve (n=66) and memory (n=48) B cells of 4 SS patients and compared their autoreactive and polyreactive profile to 45 naïve clones from 2 HD. Analysis of the VH and VL gene usage showed no significant differences between SS and HD. Conversely, I observed accumulation of circulating autoreactive naïve B cells in SS as demonstrated by Hep-2 cells, ENA, Ro/SSA and/or La/SSB reactivity. The elevated frequency of autoreactive naïve B cells in the circulation of SS patients supports the existence of early defects in B cell tolerance checkpoints in this condition In RA, I analysed the Ig gene repertoire and the VH gene somatic mutation rate of 139 VH and 175 VL sequences of synovial CD19+ B cells which demonstrated evidence of antigen selection and hypermutated alpha > gamma > mu VH chains with presence of intra-synovial clonal diversification. Recombinant antibodies from synovial B cell clones were then screened for reactivity towards citrullinated antigens with a plan for a wider analysis using autoantigen microarrays. Overall, these results highlighted the existence of B cell abnormalities and loss of tolerance for self-antigens both in the peripheral and/or lesional compartment of SS and RA. Further analysis of the fine specificity and pathogenicity of recombinant antibodies from autoreactive B cells will be invaluable in order to dissect the mechanisms and the antigens driving the development and the persistence of autoimmunity in RA and SS.

Introdução: A atrite reumatoide (AR) é uma doença Inflamatória crônica de etiologia desconhecida que afeta principalmente as articulações. A evolução da doença está associada com a incapacidade funcional, aumentando o risco de doenças cardiovasculares (DCV) e disfunção endotelial e rigidez arterial. Objetivo: Avaliar os efeitos de uma única sessão de exercício aeróbico de alta intensidade na função endotelial mediada pelo fluxo (DMF), avaliar a dor no pré exercício e após uma semana de intervenção através da escala visual analógica (EVA) e rigidez arterial em pacientes 26 com AR. Métodos: Estudo quase experimento, com 22 pacientes portadores de AR leve a moderada. Foram realizados teste ergoespirométrico, ecografia braquial para determinar a dilatação mediada pelo fluxo (DMF) e a avaliação da rigidez arterial por determinação da velocidade de onda de pulso (VOP), pré, pós e uma hora após a aplicação de um protocolo de treinamento intervalado de alta intensidade (TIAI). Resultados: A média de idade dos participantes é de 59,2 + 7,6 anos e há predominância do sexo feminino (91%). Apresentaram DAS28 de 4,1+ 1,0 (atividade moderada), e HAQ de 1+ 0,6 pontos (deficiência moderada). O VO2 Máximo encontrado foi de 21,19 + 3,89 ml/Kg/min. Os valores de DMF nos três momentos foram: basal com hiperemia reativa (10,59+0,47) e com nitroglicerina spray sublingual (12,66+0,89), no pós imediato (10,69+ 0,39) e com nitroglicerina (12,93+0,58), e 1 hora após (10,93+0,29) e com o medicamento (13,20+0,46), em relação a escala analógica visual de dor (EVA) observamos no basal uma dor de (3,45+0,80) e pós uma semana de intervenção (2,50+0,51). Conclusão: Concluímos que o TIAI com portadores de AR não foi significativo em relação às porcentagens de DMF, mas quando observamos outras medidas como a VOP, Pressão Arterial, Pressão de Pulso e o Índice de Aumentação, e os pacientes não apresentaram dor após uma semana de intervenção, sendo assim o exercício parece ser eficiente, sugerindo que pode ser uma estratégia útil para a prevenção de DCV em pacientes com AR. / Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology that mainly affects the joints. The evolution of the disease is associated with functional disability, increasing the risk of cardiovascular diseases (CVD) and endothelial dysfunction and arterial stiffness. Objective: To evaluate the effects of a single high-intensity aerobic exercise session on flow-mediated endothelial function (DMF), evaluate pain in pre-exercise and after one week of intervention using visual analogue scale (VAS) and arterial stiffness in patients with AR. Methods: Almost experimental study with 22 patients with mild to moderate RA. An ergospirometric test, brachial ultrasound was performed to determine the flow-mediated dilatation (FMD) and the evaluation of arterial 53 stiffness by determination of the pulse wave velocity (VOP), pre, post and one hour after the application of an interval training protocol high intensity (TIAI). Resultados: A média de idade dos participantes é de 59.2 + 7.6 anos e há predominância do sexo feminino (91%). Apresentaram DAS28 de 4.1+ 1.0 (atividade moderada), e HAQ de 1+ 0.6 pontos (deficiência moderada). O VO2 Máximo encontrado foi de 21.19 + 3.89 ml/Kg/min. Os valores de DMF nos três momentos foram: basal com hiperemia reativa (10.59+0.47) e com nitroglicerina spray sublingual (12.66+0.89), no pós imediato (10.69+ 0.39) e com nitroglicerina (12.93+0.58), e 1 hora após (10.93+0.29) e com o medicamento (13.20+0.46), em relação a escala analógica visual de dor (EVA) observamos no basal uma dor de (3.45+0.80) e pós uma semana de intervenção (2.50+0.51). Conclusion: We conclude that the TIAI with RA patients was not significant in relation to DMF percentages, but when we observed other measures such as OPV, Blood Pressure, Pulse Pressure and Increasing Index, and patients did not present pain after one week the exercise appears to be efficient, suggesting that it may be a useful strategy for the prevention of CVD in patients with RA.

Artrite reumatóide (AR) é uma doença crônica e multisistêmica, que afeta o indivíduo como um todo. De etiologia desconhecida, possui como característica uma inflamação sinovial, efeitos periarticulares, simétricas e cumulativas. Os principais sinais e sintomas apresentados na fase aguda são as dores nas articulações, edemas e rigidez matinal. E em 75% dos casos acometem membro superiores, com um grande impacto nas habilidades funcionais. Nas mãos, as deformidades podem atingir todas as articulações causando subluxações e deformidades em metacarpofalangenas (MF), interfalangeanas (IF) e punhos. Quando há a destruição dos ligamentos e cartilagens do punho as forças musculares e fatores anatômicos causam o colapso do punho em desvio radial e as articulações MF, como consequência a essas forças anatômicas, também entram em colapso e favorecem o desvio ulnar dessas articulações. Há diferentes recursos utilizados no tratamento desta patologia, sendo um deles o uso de órtese. Assim, este estudo tem por objetivo projetar e desenvolver uma órtese, articulada e original, com função de corrigir a deformidade em desvio ulnar dos dedos e favorecer a funcionalidade. Para tanto os procedimentos metodológicos foram divididos em: Reconhecimento de Necessidades; Especificação e Conceito. Após levantamento Bibliográfico, estudo antropométrico chegou-se ao esboço e ao conceito do projeto. Como resultado obteve-se o primeiro protótipo em material disponível e utilizando o programa CAD solid edge Insight foi proposto um protótipo digitalizado da órtese, definindo as propostas e requisitos necessários para o desenvolvimento da órtese. Como resultados obteve-se dois desenhos digitalizados do protótipo e quatro protótipos em materiais diferentes entre si, compostos por 9 peças (2 hastes laterais, 1 bloqueio ulnar, 3 pulseiras e 3 anéis), que montadas mostram uma órtese articulada. Observou-se que houve bloqueio do desvio ulnar mesmo em pacientes com deformidades mais graves dos dedos. A mesma permitia a flexão e extensão de MFs e punho. Houveram ajustes nos desenhos com o decorrer do estudo, após realização dos testes de bancada. Verificou-se que a órtese poderá ser utilizada bilateralmente, com uso dorsal da haste redonda em mão direita e uso ventral em mão esquerda. A órtese permite a função da mão e possui fácil colocação e manuseio. / Rheumatoid arthritis (RA) is a chronic, multisystem, which affects the individual as a whole. Of unknown etiology, is characterized as a synovial inflammation, periarticular effects, and cumulative symmetrical. The main signs and symptoms in the acute phase are joint pain, swelling and stiffness. And 75% of cases involve upper limb, with a great impact on functional abilities. Deformities in the hands can reach all the joints causing deformities and subluxations metacarpophalangeal (MF), interphalangeal (IF) and wrists. When there is destruction of cartilage and ligaments of the wrist muscle forces and anatomical factors cause the collapse of the wrist in radial deviation and MP joints, the effect of these anatomical forces also favor collapse and ulnar deviation of these joints. There are different resources used in the treatment of this pathology, one being the use of bracing. Thus, this study aims to design and develop a bracing, articulate and original, with the function to correct the deformity in ulnar deviation of fingers and promote functionality. For both methodological procedures were divided into: Recognition of Needs; Specification and Concept. After Bibliographic survey, anthropometric study came to the sketch and the concept of the project. As a result we obtained the first prototype in material available and using the CAD program Solid Edge Insight has been proposed a prototype scanned of the orthosis, setting out proposals and requirements for the development of bracing. The results we obtained two scanned drawings of the prototype and four prototypes in different materials, composed of nine parts (two lateral branches, an ulnar block, three bracelets and three rings), which show a stent mounted articulated. It was observed that the blockade of Ulnar deviation of fingers and allow flexion and extension and the MF\'s wrist. There were adjustments to the drawings in the course of the study, after completion of bench testing. We also found that the orthosis can be used bilaterally, using dorsal round rod in his right hand and left hand use ventral. The stent allows the function of the hand and has easy handling and placement.

A Artrite Reumatóide (AR) é uma doença auto-imune, crônica e inflamatória cujas manifestações são notadas, principalmente, nas articulações. Um ponto de extrema importância nesta doença é a necessidade de diagnostico e início do tratamento dos pacientes o mais rápido possível, para que os danos às articulações e erosões ósseas sejam evitados, pois estes danos ocorrem no início da doença e são, muitas vezes, irreversíveis. O presente projeto teve como objetivo a construção de um sistema computacional via Web para o auxílio ao diagnóstico de pacientes portadores de artrite reumatóide, através da utilização de técnicas de inteligência artificial, como Redes Neurais Artificiais, Árvores de Decisão e Algoritmos Genéticos, e o sistema gerenciador de conteúdos Drupal. O objetivo do sistema é proporcionar um ambiente estruturado, no qual as informações clínicas e de expressão gênica de pacientes portadores de AR são cadastradas e categorizadas, para que, a partir destas informações, os algoritmos de aprendizado de máquinas possam ser treinados para selecionar características clínicas e genes relevantes para a predição da resposta dos pacientes ao tratamento com Drogas Anti-Reumáticas Modificadoras da Doença (DMARDs). Após o treinamento, os modelos gerados podem ser utilizados para a predição da resposta à DMARDs de novos pacientes. O sistema visa selecionar possíveis características que permitam identificar precocemente os pacientes que irão evoluir de forma mais agressiva e, assim, fornecer uma nova ferramenta para que os médicos possam indicar o melhor tratamento possível para cada paciente individualmente. O Sistema desenvolvido foi denominado ARIA e está disponível através do endereço http://gbi.fmrp.usp.br/artrite. Apenas médicos e colaboradores do projeto têm permissão para acessá-lo. Estão disponíveis os seguintes conteúdos: Cadastro de Pacientes, Ferramenta de Seleção de Atributos e Ferramenta de Predição da Resposta dos Pacientes à DMARDs. Além disso, o sistema disponibiliza diversas possibilidades de visualização e interação com tais conteúdos. Estão cadastrados, até o momento, 126 pacientes, sendo que 106 deles são utilizados para o treinamento da ferramenta de seleção de atributos e vinte deles para os testes da ferramenta de predição da resposta à DMARDs. / Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease, whose manifestations are observed, mainly in the joints. One point of extreme importance in this disease is the early diagnosis and the begging of the treatment as quickly as possible. These procedures try to avoid joints damage and bone erosions, since these damages are often irreversible. This project aimed to develop a computational system to aid diagnosis of rheumatoid arthritis patients. Artificial intelligence techniques, such as Artificial Neural Networks, Decision Trees and Genetic Algorithms, and the content management system Drupal were employed to the system development. The system goal is to provide a structured environment in which clinical and gene expression information about RA patients are registered and categorized. From the information stored in the system database, the machine learning algorithms can be trained to select clinical information or genes which are relevant to predicting the patients response to treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs). After the training, the generated models generated can be used for predicting the response to DMARDs of new RA patients. The system aims to select characteristics to early identify patients who might have more aggressively disease outcome and thus, it provides a new tool to physicians in the analysis of the best treatment for each patient individually. The system developed was called ARIA System and it is available at the web site http://gbi.fmrp.usp.br/artrite. Only doctors and collaborator researchers have permission to access it. The contents available in the system are the following: Patients Register, Feature Selection Tool and Prediction the Response to DMARDs Tool. Besides these contents, the system offers different kinds of displaying and interaction with the content. There are, until now, 126 patients registered in the ARIA System, 106 of them are used for training the features selection tool and twenty of them are used to test the tool for predicting patients response to DMARDs.

La polyarthrite rhumatoïde (PR) est une maladie inflammatoire, auto-immune, chronique et systémique avec la présence d’arthrites et synovites périphériques. Une autre conséquence sévère de la maladie et de ses traitements est la présence d’une rigidité artérielle élevée précoce, par conséquent une haute incidence de problèmes cardiovasculaires pour les sujets atteints. La pratique d'exercices physiques (EP) est reconnue comme une des thérapies non-pharmacologiques les plus efficaces pour lutter contre le risque cardiovasculaire. Cependant la population PR présente un bas niveau de pratique d’activité physique et les programmes d’EP sont rarement proposés dans la prise en charge thérapeutique de ces patients. Pour dépasser cette problématique l’association de la cryothérapie à un programme d’EP adapté semble être une stratégie intéressante. L’objectif de ce travail était de concevoir et de tester un programme d’EP associé à de la cryothérapie adapté aux patients PR afin de lutter contre le risque cardiovasculaire.A partir d’une revue systématique, nous avons montré le caractère lacunaire de la littérature en termes de programme d’EP associé à de la cryothérapie pour des patients PR, le manque de consensus sur les méthodes utilisées aussi bien pour le type d’EP à proposer que pour les méthodes de cryothérapie et les températures employées. Face à cette situation, nous avons proposé plusieurs études préliminaires afin de déterminer les modalités d’exercice et de cryothérapie les plus appropriées pour définir un programme simple, efficace et adapté aux patients PR. Ces travaux ont été réalisés d’une part avec des sujets sains et d’autre part avec des patients PR. Nous avons également entrepris de mieux définir les conditions d’utilisation de la vitesse de propagation de l’onde de pression pour traduire la rigidité artérielle, afin d’utiliser cette dernière comme un marqueur des effets de nos propositions de programme d’EP sur le risque cardiovasculaire. Enfin nous avons tenté d’évaluer quels pouvaient être les freins à la pratique d’EP pour ces patients afin de pouvoir les prendre en compte et les contourner dans la mise en place de nos propositions. Les principaux résultats de nos travaux nous ont permis de définir les caractéristiques d’un programme d’EP associé à de la cryothérapie pour des patients PR afin d’agir sur leur rigidité artérielle.Ce programme, intitulé Prexcrim, a été mise en œuvre avec un groupe de patients atteints de PR. Les premiers résultats que nous avons obtenus confirment la faisabilité de nos propositions et la bonne tolérance des patients. Aucune sortie de l’étude ou effet secondaire a été observé. A ce stade des inclusions et de l’analyse des résultats, il semble que le programme d’EP proposé permette de modifier la rigidité artérielle en particulier des patients qui présentaient une rigidité artérielle élevée au départ. Il n’a pas été observé d’aggravation de la maladie ou du syndrome inflammatoire ce qui semble renforcer l’intérêt de la méthode de cryothérapie proposée. Les inclusions qui se poursuivent permettront sans doute d’affiner ces premières interprétations.En conclusion, notre travail a permis de combler une partie des lacunes constatées dans la littérature en termes de lutte contre le risque cardiovasculaires accru constaté chez les patients PR. Notre approche a permis la réalisation d’un programme simple et facile d’EP associé à de la cryothérapie, dont les premiers résultats répondent aux attentes fixées. Les premières analyses que nous avons réalisées montrent que les principes d’individualisation et de progressivité seront certainement à améliorer pour optimiser les effets du programme. / Rheumatoid arthritis (RA) is an inflammatory, autoimmune, chronic and systemic disease with the presence of arthritis and peripheral synovitis. Another severe consequence of the disease and its treatments is the presence of early high arterial stiffness, hence a high incidence of cardiovascular problems for the subjects with RA. The practice of physical exercises (PE) is recognized as one of the most effective non-pharmacological therapies against the cardiovascular risk. However, the RA population has a low level of physical activity and PE programs are rarely offered in the therapeutic management of these patients. To overcome this problem, the association of cryotherapy to an appropriate PE program seems to be an interesting strategy. The objective of this work was to design and test a PE program associated with cryotherapy adapted to patients with RA in order to fight against the cardiovascular risk.From a systematic review, we have shown the lack of the literature in terms of PE program associated with cryotherapy for patients with RA, the lack of consensus on the methods used for both the type of PE to be proposed and the cryotherapy methods and temperatures employed. Consequently, we have proposed several preliminary studies to determine the most appropriate exercise and cryotherapy modalities for defining a simple, effective and suitable program. These works were carried out firstly in healthy subjects and after in patients with RA. We have also undertaken to better define the used conditions of the pulse wave velocity to interpret arterial stiffness and use it as a marker of effects of our PE program on cardiovascular risk. Finally, we tried to evaluate what could be the obstacles to the practice of PE for these patients, to consider and overcome them in the implementation of our proposals. The main results of our works allowed us to define the characteristics of a PE program associated with cryotherapy for patients with RA to act on their arterial stiffness.This program, entitled Prexcrim, was implemented with a group of patients with RA. The first results confirmed the feasibility of our proposals and the good tolerance of patients. No study output or side effect was observed in the patients. At this stage of inclusion and analysis of the results, it appears that the proposed PE program allows for changes in arterial stiffness, particularly for patients with high arterial stiffness. It was not observed exacerbation of the disease or inflammatory syndrome, which seems to reinforce the interest of the proposed cryotherapy method. The inclusions that continue will undoubtedly refine these first interpretations.In conclusion, our work proposes some responses about the lack in terms of the fight against the increased cardiovascular risk observed in patients with RA. Our approach allowed the realization of a simple and easy PE program associated with cryotherapy. The first results meet our expectations. The first analyzes shown that the principles of individualization and progressivity need to be improved to optimize the effects of the program.

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Submitted by Erika Demachki (erikademachki@gmail.com) on 2015-02-12T17:38:37Z No. of bitstreams: 2 Dissertação - Rafael Navarrete Fernandez - 2004.pdf: 737923 bytes, checksum: 9f9c7b498798d7f0e65f37b958ef6d70 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2015-02-12T17:38:59Z (GMT) No. of bitstreams: 2 Dissertação - Rafael Navarrete Fernandez - 2004.pdf: 737923 bytes, checksum: 9f9c7b498798d7f0e65f37b958ef6d70 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-02-12T17:39:02Z (GMT). No. of bitstreams: 2 Dissertação - Rafael Navarrete Fernandez - 2004.pdf: 737923 bytes, checksum: 9f9c7b498798d7f0e65f37b958ef6d70 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2004-04-20 / Introduction: Chlamydia trachomatis is the bacteria responsible for the most prevalent sexually transmitted disease worldwide. Most of the infections in men and women is asymptomatic and when undiagnosed and untreated may reach the joints causing not only arthritis, but also other acknowledged complications related to the female reproductive system. Objective: To investigate C. trachomatis DNA in the urine and synovial fluid from patients with spondyloarthropathies (SpA) and rheumatoid arthritis (RA) and evaluate serum anti-C. trachomatisIgG and IgM antibodies. Methods: The population consisted of 15 patients with spondyloarthropathies, being nine with undifferentiated spondyloarthropathy (US) and six with reactive arthritis (ReA) (group I), and 15 patients with rheumatoid arthritis (RA) (group II). The chlamydial DNA was assessed in synovial fluid and urine samples of all patients by Amplicor PCR. The anti-chlamydial IgG and IgM antibodies were quantified through indirect imunofluorescence (IIF), while 15 patients of group I were typed for HLA-B27 by the use of flow citometry. Social demographical data and all information on sexual behavior and presence of symptoms were collected through a (questionnaire in the form of) an interview. Results: C. trachomatis DNA was found in only one synovial fluid sample from patient with ReA (6,7%). In two patients with RA, chlamydial DNA was identified in the urine sample (13,3%). The anti-chlamydial IgG antibodies were present in eight patients of the population studied; being three patients from group I (20%), and five from group II (33,3%). The greatest titer of this antibody 1/256 was associated with the presence of chlamydial DNA in a patient from group II. The IgM antibody was not detected in any of the samples from both groups. Four individuals from group II (26,7%) were HLA-B27 positive and its presence was 16 related to sacroiliitis. Conclusion: The results in this study show that in patients with spondyloarthropathies and rheumatoid arthritis, presenting a picture of articular activity one might not exclude C. trachomatisas the triggering agent. / Introdução: A Chlamydia trachomatis é a bactéria responsável pela doença sexualmente transmissível mais prevalente no mundo. A maioria das infecções em homens e mulheres é assintomática e, quando não diagnosticada e tratada, pode alcançar as articulações e causar artrite, isto sem mencionar outras complicações conhecidas relacionadas ao aparelho reprodutor feminino. Objetivos: Pesquisar o DNA de C. trachomatis no líquido sinovial e urina, em pacientes com espondiloartropatias e artrite reumatóide (AR) e avaliar a presença de anticorpos séricos IgG e IgM anti-C. trachomatis nestes dois grupos de doenças. Identificar o antígeno HLA-B27 em pacientes com espondiloartropatias. Metodologia: A população do estudo consistiu de 15 pacientes com espondiloartropatias: nove com espondiloartropatia indiferenciada (EI) e seis com artrite reativa (ARe) (grupo I) e 15 pacientes com AR (grupo II). O DNA clamidial foi pesquisado em amostras de líquido sinovial e urina de todos eles empregandose a PCR (Amplicor Roche). Os anticorpos IgG e IgM anti-clamidiais foram quantificados por imunofluorescência indireta (IFI), enquanto o HLA-B27 foi tipado em 15 pacientes do grupo I por citometria de fluxo. Os dados sócio-demográficos, de comportamento sexual e presença de sintomas foram obtidos através de questionário na forma de entrevista. Resultados: O DNA da C. trachomatis foi evidenciado apenas em uma amostra de líquido sinovial do grupo I (6,7%), sendo o paciente portador de ARe. Em dois pacientes com AR, o DNA de clamidial foi identificado na urina (13,3%). Os anticorpos IgG anti-clamidiais estavam presentes em oito pacientes da população estudada, três do grupo I (20%) e cinco do grupo II (33,3%). O maior título desse anticorpo (1/256) associou-se com a presença do DNA clamidial na urina de um paciente do grupo II. O anticorpo IgM não foi detectado em nenhuma amostra 14 dos dois grupos. O antígeno HLA-B27 foi positivo em quatro indivíduos do grupo II (26,7%) e sua presença relacionou-se com sacroiliite. Conclusões: Os resultados desse estudo indicam que em portadores de espondiloartropatias e artrite reumatóide, com quadro articular em atividade, a C. trachomatisnão pode ser excluída como agente desencadeador.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-12-06T20:11:07Z No. of bitstreams: 1 IonePereira.pdf: 4313615 bytes, checksum: b4b18d96e95ccf2676273520e2380e31 (MD5) / Made available in DSpace on 2017-12-06T20:11:07Z (GMT). No. of bitstreams: 1 IonePereira.pdf: 4313615 bytes, checksum: b4b18d96e95ccf2676273520e2380e31 (MD5) Previous issue date: 2017-03-09 / CAPES / FAPEMA / INCT / The transient receptor potential ankyrin 1 (TRPA1) is a non-selective Ca+2 channel expressed on neuronal and non-neuronal cells, and mediates pain and inflammation; being implicated in rheumatoid arthritis (RA). Here, we evaluated the expression of TRPA1 on peripheral blood leukocytes obtained from RA patients, as well as its correlation with pain and disability, in addtition to the immune alterations in RA patients treated or not with antirheumatic drugs: the disease-modifying angent leflunomide (LFN) and the anti-TNFα adalimumab (ADA); in comparison with healthy subjects. Peripheral blood samples were taken from 15 healthy subjects (controls), 10 RA patients not undertaking anti-rheumatic therapy (NST), 15 patients treated with LFN and 15 patients treated with ADA. C reactive protein (CRP), rheumatoid factor (FR), hydrogen peroxide (H2O2), 4-hydroxynonenal (4- HNE) and tumour necrose factor α (TNFα) levels were quantified. Also, leukocyte subpopulations, the number of red blood cells, the levels of haemoglobin and the expression of TRPA1 on peripheral blood leukocytes, were evaluated. TRPA1 expression was increased on NST leukocytes and this was correlated with pain and disability and was associated with the number of polymorphonuclear cells and the activation of CD14+ cells. It was also demonstrated that treatment with either LFN or ADA attenuates anaemia in AR, with those treatments being effective in treating both the intra- and extra-articular disease. Overall, our data showns that TRPA1 influences pain and disability in RA and that its expression is reduced in patients treated with LFN or ADA. These evidences, together with the promissing data on the anti-rheumatic therapy in reducing anaemia in RA patients suggest that these drugs are effective in treating both the intra- and extra-articular alterations of RA. / O receptor de potencial transitório anquirina 1 (TRPA1) é um canal não seletivo para Ca+2 , expresso em neurônios sensoriais e células não neuronais, o qual medeia a transdução da dor e a inflamação; tendo sido implicado na artrite reumatoide (AR). Este trabalho avaliou a expressão de TRPA1 em leucócitos de sangue periférico de pacientes com AR, bem como sua correlação com a dor e a prda de função articular, além de alterações imunes encontradas em indivíduos com AR recebendo ou não terapia anti-reumática com o modificador da doença leflunomida (LFN) e ou o anti-TNFα adalimumab (ADA); em comparação à indivíduos sadios. Amostras de sangue foram coletadas de 15 indivíduos sadíos (controle), 10 pacientes artríticos não submetidos à terapia anti-reumática específica (NST), 15 pacientes tratados com LFN e 15 pacientes tratados com ADA. Os níveis circulantes de proteína C reativa (PCR), fator reumatóide (FR), peróxido de hidrogênio (H2O2), 4-hidroxinonenal (4-HNE) e fator de necrose tumoral (TNFα) foram quantificados. Ainda, avaliou-se as populações de leucócitos, o número de hemácias, os níveis de hemoglobina e a expressão de TRPA1 em leucócitos do sangue periférico. Observou-se que a expressão de TRPA1 em leucócitos de sangue periférico está aumentada em pacientes NST, e que isto está associado ao aumento do número de células polimorfonucleares e à ativação de células CD14+ . Ainda, a expressão de TRPA1 correlaciona-se com a dor e disfunção articular, alterações estas, que encontram-se reduzidas em pacientes tratados com LFN e ADA. Demonstrou-se ainda que o tratamento com LFN ou ADA previne a anemia relacionada à AR, sendo efetivos tanto no tratamento das alterações intra quanto extra articulares decorrentes da doença.. Em conjunto, os dados demonstram que o TRPA1 influencia a resposta dolorosa e a disfunção articular da AR, e que sua expressão é reduzida pelo tratamento com LFN ou ADA. Estas evidências, aliadas com dados promissores na redução da anemia dos pacientes artríticos sugerem que o tratamento com estas drogas anti-reumáticas é efetivo no tratamento de manifestações intra- e extra-articulares da AR