En Amérique du Nord, Mycoplasma bovis est le plus pathogène des mycoplasmes retrouvés chez les bovins. Les principales maladies qu’on lui associe (maladies respiratoires, mammites, arthrites septiques et otites moyennes et/ou internes) constituent un défi à l’industrie laitière à cause de la difficulté à les traiter et à les prévenir par une vaccination. L’objectif principal de ce projet était d’étudier l’excrétion nasale et la réponse sérologique à M. bovis chez les génisses de remplacement, entre la naissance et 7 mois d’âge, dans 4 troupeaux laitiers au Québec. Quatre-vingt-trois paires mère/génisse provenant de 4 cohortes de bovins laitiers étaient prélevées mensuellement (génisses : 0 à 7 mois ; mères : 0, 1 et 5 mois après vêlage). Écouvillons nasaux et échantillons de lait étaient analysés par culture bactériologique et par immunofluorescence indirecte. Les anticorps circulants étaient détectés par le test ELISA. À la naissance, la prévalence sérologique des génisses était supérieure à celle des mères (P = 0,01). La transmission de M. bovis aux génisses par le lait et par l’excrétion nasale des mères était faible. L’âge moyen (jour) d’une génisse à sa 1ère excrétion nasale et sa 1ère séroconversion à M. bovis était loin de la période néonatale: 77,5 ± 11,2 (n = 22) et 96,8 ± 7,4 (n = 36) respectivement. Conclusion, les vaches adultes n’ont constitué qu’une voie mineure de transmission de M. bovis aux génisses, la principale voie de transmission était fort probablement le contact direct ou indirect avec d’autres génisses excrétrices nasales de M. bovis. / In North America, Mycoplasma bovis is the most pathogenic mycoplasma found in cattle. The main diseases associated with it (respiratory disease, mastitis, septic arthritis and otitis median and/or internal) are a challenge to the dairy industry because of the difficulty to treat them and to prevent them by vaccination. The principal objective of this project was to study nasal shedding and serological response to M. bovis in replacement heifers, between birth and 7 months of age, in four dairy herds in Quebec. Eighty three pairs cow/heifer in 4 cohorts of dairy cattle were sampled monthly (heifers: 0 to 7 months; cows: 0, 1 and 5 months after calving). Nasal swabs and milk samples were analyzed by bacteriological culture and by indirect immunofluorescence. Circulating antibodies were detected by ELISA test. At birth, the serologic prevalence of heifers was significantly higher than the serologic prevalence of cows (P = 0,01). Transmission of M. bovis to heifers in milk and nasal shedding from cows was low. The average age (days) of a heifer for first nasal shedding and first seroconversion to M. bovis was far from the neonatal period: 77,5 ± 11,2 days (n = 22) and 96,8 ± 7,4 days (n = 36) respectively. Conclusion, cows were only a minor route of transmission of M. bovis to heifers, the main route of transmission was most likely the direct or indirect contact with other heifers shedding M. bovis in their upper respiratory tract.

Title Physiotherapy after arthroplasty procedures for rheumatic patients. Defining the problem The main problem this thesis solves is to find and compare findings on the practice of physiotherapy in rheumatic patients, patients with rheumatoid arthritis (RA) who have undergone surgery, joint replacement of lower limb arthroplasty, with a focus on the ankle joint. It will be a comparison of the approaches used in the workplace catchment for the Czech Republic, Institute of Rheumatology (RU) in Prague and the world. Aim The aim is to create a comprehensive overview and comparison of physiotherapy procedures used in rheumatic patients who underwent joint replacement legs, zjm. ankle joint, in the CR is in the hands, and in the world and see whether these practices vary significantly, or are identical. The method of solution The work is prepared by comparing the findings relating to the care of patients with available literature. The findings are grouped and arranged tables are created with recording procedures. The work is written in the form of research. Key worlds revmatoidní artritida totální náhrada hlezenního kloubu (TEP) hlezenní kloub fyzioterapie

Autism is a complex disorder with possible genetic, epigenetic and environmental components. As the etiology remains uncertain and an increase in incidence is suspected, the involvement of possible environmental risk factors has gained increasing attention. With this thesis, I aim to provide tools for assessing such risk factors. Firstly, I aim to construct a questionnaire for the analysis of an environmental component in the etiology of autism. Secondly, I aim to assess the importance of prenatal exposure to metals in certain diseases and thirdly I aim to construct a methodology enabling the analysis of the mitochondrial epigenome, which is especially interesting in relation to autism as mitochondrial diseases occur more frequently in an autistic population than in the general population. For the creation of the questionnaire the scientific literature was reviewed. The resulting questionnaire contains general, prenatal, neonatal and paternal risk factors. The metal analysis was conducted on the cord blood of patients who later developed autism, antinuclear antibodies positive rheumatoid arthritis or diabetes, which were then compared to healthy control subjects. My findings propose a link between elevated levels of cord blood cadmium or aluminum and rheumatic arthritis. In addition, elevated aluminum levels might be associated with autism. In regards to the analysis of the mitochondrial epigenome, to my knowledge, no standard protocol exists with frozen human whole blood as a source. In this thesis, I succeeded in creating the basis for such a protocol, however still needing several small modifications for an increased overall yield.

La fonction de barrière de l'endothélium vasculaire est affectée par des modifications de la cadhérine des cellules endothéliales (VE-cadhérine) telles que la phosphorylation sur tyrosine dans son domaine cytoplasmique et le clivage de son domaine extracellulaire (sVE). Ce travail s'est articulé en deux parties : 1- Etude de ces modifications dans le contexte de la polyarthrite rhumatoïde (PR), et les mécanismes sous-tendus. Ce travail a permis de montrer que la VE-cadhérine est une cible du TNFα, une cytokine essentielle dans la PR, qui induit de la libération de sVE de façon dépendante de l'activité kinase de Src, suggérant l'implication d'un mécanisme de phosphorylation sur tyrosine dans ce processus. De plus, la VE-cadhérine est aussi la cible des protéases de la matrice extracellulaire telles que MMP-2. L'application de ces données fondamentales à la clinique a permis de montrer que sVE était retrouvée dans le sang de patients PR (n=63) et que son taux était corrélé à l'activité de la maladie. Ainsi, le dosage de sVE est d'intérêt dans la prise en charge des patients. 2-Etude de la phosphorylation de la VE-cadhérine dans un contexte d'angiogenèse hormono-régulée au cours du cycle ovarien chez la souris. Les résultats ont montré que le site Y685 de la VE-cadhérine est phosphorylé dans l'ovaire et l'utérus de souris de façon régulée pendant le cycle, ce qui permet de proposer ce modèle physiologique pour étudier la phosphorylation de la VE-cadhérine in vivo. L'analyse de souris knock-in Y685F de la VE-cadhérine (VE-Y685F) a montré que l'absence du site confère une perméabilité accrue dans l'ovaire et l'utérus mais aussi dans les petits capillaires de la peau. De plus, dans deux modèles d'induction d'arthrite, les souris VE-Y685F ont présenté un taux de sVE plus élevé que les contrôles. Au total, sVE et la phosphorylation de la VE-cadhérine ont un vaste champ d'application dans le traitement de la PR ainsi que pour le développement de nouvelles thérapies pouvant s'étendre à d'autres pathologies vasculaires. / The vascular endothelium barrier function is influenced by vascular endothelial cadherin (VE-cadherin) modifications such as its cytoplasmic tail tyrosine phosphorylation and its ecto-domain cleavage (sVE). The work reported herein was divided into two parts: 1- Study of VE-cadherin modifications and the mechanisms underlying these ones in the rheumatoid arthritis context. This work demonstrated that VE-cadherin is a target of TNFα, a highly important cytokine in rheumatoid arthritis (RA) pathogenesis. We found TNFα to induce sVE shedding in a Src kinase dependent manner, suggesting the involvement of phosphorylation mechanism in this process. In addition, this VE-cadherin cleavage requires matrix metalloproteinase activities such as that of MMP-2. Applying these fundamental data to clinical study showed that sVE was detected in sera of 63 RA patients and its titer was correlated with the disease activity. This finding suggests an obvious interest for assaying sVE in RA therapies. 2- Study of VE-cadherin tyrosine phosphorylation in a context of hormones-regulated angiogenesis during mouse estrous cycle. The results showed VE-cadherin phosphorylation at Y685 that was regulated along mouse estrous cycle allowing to proposing mouse estrous cycle as a physiological model for studying VE-cadherin phosphorylation in vivo. The analysis of VE-cadherin Y685F knock-in mice (VE-Y685F) showed that these mice exhibit a higher vascular permeability in uterus and ovaries and the skin small capillaries compared to wild-type animals. Moreover, VE-Y685F mice presented higher levels of soluble VE-cadherin compared to wild-type counterparts in two induced arthritis model. Altogether, sVE and VE-cadherin phosphorylation present an array of interests for RA therapies as well as developing new therapeutic tools in RA and other vascular diseases.

INTRODUÇÃO: A utilização dos anti-TNF no tratamento da artrite reumatoide é uma realidade cada vez mais frequente. Estudos de eficácia e efetividade têm trazido resultados de grande valor clínico. No entanto, a maneira como os diferentes desenhos de estudos são conduzidos pode mostrar resultados conflitantes. OBJETIVO: Avaliar o uso dos anti-TNF no tratamento da artrite reumatoide, comparando estudos de eficácia e efetividade. MÉTODOS: Rever sistematicamente a literatura sobre o assunto com as seguintes etapas: 1) Busca na base de dados eletrônica Pubmed; 2) Armazenamento e avaliação por título e resumo dos estudos selecionados com auxílio do aplicativo ZOTERO, versão 3.0.8; 3) Avaliação da qualidade de 39 estudos de eficácia e 06 de efetividade, utilizando a ferramenta GRADE; 4) Extração dos dados referentes aos desfechos ACR50, ACR70 e DAS28; 5) Análise dos dados extraídos. RESULTADOS: Para todos os desfechos analisados, em ambos os tipos de estudo, a síntese metaanalítica demonstrou que a terapia associada dos biológicos com MTX ou outro DMARD beneficiou o tratamento da doença. Nos estudos de eficácia, as sínteses meta-analíticas foram: ACR50: 1,64 (IC95% 1,57 a 1,72); ACR70: 1,92 (IC95% 1,80 a 2,06); remissão pelo DAS28: 1,78 (IC95% 1,67 a 1,90). Nos estudos de efetividade: ACR50: 1,29 (IC95% 1,04 a 1,59); ACR70: 1,27 (IC95% 1,05 a 1,52); remissão pelo DAS28: 1,36 (IC95% 1,18 a 1,57). Na comparação indireta dos três biológicos entre si, os valores das sínteses meta-analíticas dos riscos relativos aos DMARDs apresentou sobreposição dos intervalos de confiança, sugerindo que a magnitude do benefício é semelhante entre os anti-TNF. A análise de sensibilidade mostrou, que os estudos com cegamento placebo, com melhor qualidade, com pacientes em fase mais adiantada da doença e com menor tempo de acompanhamento dos pacientes, apresentaram valores maiores de benefício dos biológicos. CONCLUSÃO: Este estudo permitiu observar que o benefício dos biológicos está presente tanto nos estudos de eficácia quanto nos de efetividade. Entretanto, as diferenças observadas sugerem que, no mundo real da assistência ao paciente, o benefício dos anti-TNF seja menor do que o sugerido nos ensaios randomizados / INTRODUCTION: The use of anti-TNF in the treatment of rheumatoid arthritis is an increasingly common reality. Efficacy and effectiveness studies has brought results of great clinical value, but how different study designs are conducted can show conflicting results. OBJECTIVE: Evaluate the use of anti-TNF in the treatment of rheumatoid arthritis, comparing studies of efficacy and effectiveness. METHODS: Systematically review the literature about the subject, with the following steps: 1) Searching electronic databases of Pubmed; 2) Storage and evaluation by title and summary of selected studieds with aid of the Zotero version 3.0.8 application software; 3) Evaluation of quality of 39 studies of efficacy and 06 studies of effectiveness, using the GRADE tool; 4) Data extraction of ACR50, ACR70 and DAS28 outcomes; 5) Analysis of the extracted data. RESULTS: For all analyzed outcomes in both types of studies, a meta-analytic synthesis demonstrated that the associated therapy of the biologicals agents with MTX or other DMARD benefited the treatment of disease. In efficacy studies, the metaanalytic syntheses were: ACR50: 1.64 (CI95% 1.57 to 1.72); ACR70: 1.92 (CI95% 1.80 to 2.06); DAS28 remission: 1.78 (CI95% 1.67 to 1.90). In effectiveness studies: ACR50: 1.29 (CI95%1.04 to 1.59); ACR70: 1.27 (CI95%1.05 to 1.52); DAS28 remission: 1.36 (CI95%1.18 to 1.57). In the sensitivity analysis of RCTs for indirect comparison of the three biological agents each other, the values of the meta-analytic synthesis of the relative risks to DMARDs had overlapping confidence intervals, suggesting that the magnitude of benefit is similar between anti-TNF. The sensitivity analysis showed that studies with blinded placebo, studies with better quality, studies in patients with more advanced stage of the disease and studies with shorter follow-up of patients showed higher values of biological benefit. CONCLUSION: This study lead to the observation that the benefit of biologics is present in both studies of efficacy and effectiveness. However, suggests that in the real world, patient care benefit of the anti-TNF is smaller than suggested by randomized trials

Introdução: A artrite reumatóide (AR) é uma artropatia autoimune, de caráter inflamatório, com prevalência em torno de 1% da população. O tabagismo é considerado o principal fator de risco para o desenvolvimento da AR. O receptor de hidrocarbonetos de arila (AhR), um fator de transcrição intracelular ativado por hidrocarbonetos aromáticos componentes da fumaça do cigarro, foi identificado como alvo de regulação da diferenciação de células Th17. Objetivos: Avaliar se os polimorfismos genéticos do AhR estariam associados ao desenvolvimento da AR , e se este receptor estaria mais expresso em pacientes com AR. Pacientes e Métodos: Nós analisamos sete polimorfismos genéticos por mudança de única base (SNP) por PCR em tempo real utilizando sondas TaqMan em 138 pacientes com AR e 129 indivíduos saudáveis. A quantificação da expressão do mRNA do AhR em células mononucleares isoladas de pacientes com AR e indivíduos saudáveis foi realizada por PCR em tempo real. Resultados: Identificamos que haplótipos formados por SNPs no AhR estariam associados com desenvolvimento da AR, podendo ser fator protetor ou de risco para a doença. Em adição, os pacientes com haplótipos de risco apresentavam doença com índice de atividade elevado, principalmente quando o tabagismo estava presente. De fato, pacientes com AR apresentaram aumento na expressão de AhR (mRNA) em relação a indivíduos saudáveis. Conclusões: Em conjunto estes resultados sugerem que o AhR possui um papel importante para o desenvolvimento da artrite reumatóide. Possivelmente mutações neste receptor podem estar relacionadas com alterações na sua atividade e conseqüentemente na diferenciação de células Th17 e a susceptibilidade a AR. / Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune arthropaty with inflammatory characteristics and prevalence around 1% in the population. Tabagism is the main risk factor to RA development. The aryl hydrocarbon receptor (AhR) is an intracellular transcription factor activated by aromatic hydrocarbons present in smoking, whichwas identified to be a target of regulation of Th17 differentiation. Purpose: Study the relationship of genetic polymorphisms in AhR with RA development, and if this receptor expression is upregulated in RA patients. Patients and Methods: We analyzed seven genetic single nucleotide polymorphisms by Real-Time PCR using TaqMan probes in 138 patients with Rheumatoid Arthritis and 129 healthy controls. The AhR mRNA quantization in mononuclear cells isolated from AR patients and healthy controls has been done by Realt-Time PCR. Results: We identified that AhR haplotypes were associated with RA development and that they could be protector or risk factors to disease. In addition, patients with risk haplotypes showed higher disease activity index, mainly when smoking was present. Indeed, patients with RA showed upregulation in the AhR expression (mRNA) when compared with healthy controls. Conclusions: These results suggest that AhR has an important role in AR development. Probably, mutations in this receptor could be related with alterations in its activity and consequently in the differentiation of Th17 cells and RA susceptibility.

Objetivo: Avaliar as características clínicas e laboratoriais para diferenciar leucemia linfoblástica aguda (LLA) da artrite idiopática juvenil forma sistêmica (AIJs) no início da doença. Métodos: Cinquenta e sete pacientes com LLA com envolvimento musculoesquelético, sem blastos no sangue periférico e sem terapia com glucocorticoide no início da doença e 102 pacientes com AIJs (critérios ILAR) foram retrospectivamente avaliados. Foram estudadas as seguintes características: febre, exantema reumatoide, artrite, dor em membros, hepatomegalia, esplenomegalia, pericardite, miocardite, pleurite, perda de peso, sangramento, anemia, leucopenia, neutropenia, plaquetopenia, níveis séricos elevados de velocidade de hemossedimentação (VHS) e de desidrogenase lática (DHL). Resultados: A mediana da idade de início da doença foi significativamente maior em pacientes com LLA comparada com AIJs (5,8 vs. 3,8 anos, p=0,0006). As frequências de dor em membros, hepatomegalia, perda de peso e manifestações hemorrágicas foram significativamente maiores em LLA versus AIJs (70% vs. 1%, p<0,0001; 54% vs. 32%, p=0,0075; 30% vs. 8%, p=0,0005; 98% vs. 0%, p=0,0053; respectivamente). Igualmente, as frequências de anemia, leucopenia, neutropenia, plaquetopenia e DHL elevado foram significativamente maiores em LLA versus AIJs (88% vs. 57%, p<0,0001; 39% vs. 1%, p<0,0001; 60% vs. 1%, p<0,0001; 77% vs. 1%, p<0,0001; 56% vs. 14%, p<0,0001; respectivamente). Consideravelmente, a análise multivariada mostrou que dor em membros (OR=553; 95% IC=46,48-6580,42; p<0,0001) e plaquetopenia (OR=754,13; 95% IC=64,57-8806,72; p<0,0001) permaneceram como variáveis independentes que diferenciaram pacientes com LLA de pacientes com AIJs. O R2 de Nagelkerke foi de 0,91. A curva de sobrevida de Kaplan-Meier foi similar em pacientes com LLA com e sem dor em membros (p=0,8347). Conclusão: O presente estudo enfatiza a importância de investigar pacientes com LLA que apresentam manifestações musculoesqueléticas, particularmente dor em membros com plaquetopenia / Objective: To assess clinical and laboratorial features which differentiate acute lymphoblastic leukemia (ALL) from systemic onset juvenile idiopathic arthritis (SoJIA) at disease onset. Methods: Fifty seven ALL patients with musculoskeletal involvement, without blasts on peripheral blood and glucocorticoid therapy at onset of disease and 102 SoJIA patients (ILAR criteria) were retrospectively evaluated. The following features were studied: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, high erythrocyte sedimentation rate and high lactic dehydrogenase (LDH) levels. Results: The median age at disease onset was significantly higher in ALL compared to SoJIA patients (5.8 vs. 3.8years, p=0.0006). The frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in ALL versus SoJIA patients (70% vs. 1%, p<0.0001; 54% vs. 32%, p=0.0075; 30% vs. 8%, p=0.0005; 98% vs. 0%, p=0.0053; respectively). Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high LDH levels were significantly higher in ALL versus SoJIA patients (88% vs. 57%, p<0.0001; 39% vs. 1%, p<0.0001; 60% vs. 1%, p<0.0001; 77% vs. 1%, p<0.0001; 56% vs. 14%, p<0.0001; respectively). Remarkably, multivariate analysis showed that limb pain (OR=553; 95% CI=46.48-6580.42; p<0.0001) and thrombocytopenia (OR=754.13; 95% CI=64.57-8806.72; p<0.0001) remained as independent variables that differentiate ALL from SoJIA patients. The R2 of Nagelkerke was 0.91. The Kaplan-Meier survival curves were similar in ALL patients with and without limb pain (p=0.8347). Conclusion: The present study emphasizes the importance to investigate ALL patients who have musculoskeletal manifestations, particularly limb pain associated with thrombocytopenia

INTRODUÇÃO: A diminuição da massa óssea e mudanças na composição corporal são comuns em pacientes com artrite reumatóide, particularmente nos usuários de glicocorticóide (GC). OBJETIVO: Analisar o comprometimento dos componentes da composição corporal e densidade mineral óssea (DMO) na artrite reumatóide (AR) e seus aspectos clínicos. MÉTODOS: 83 mulheres com AR realizaram densitometria óssea para análise de massa óssea total e regional e estudo da composição corporal (CC). Além disso, foram submetidas à realização laboratorial de provas inflamatórias, dosagem de fator reumatóide e aplicados questionários para avaliação da atividade da doença, classe funcional, atividade física, e inquérito alimentar. RESULTADOS: A prevalência de osteoporose nas pacientes menopausadas foi de 21,4%, 46,4% com osteopenia e 32,1% com valores normais e ocorreu de forma semelhante em coluna lombar e colo do fêmur. As mulheres na pré-menopausa apresentaram maiores valores nas médias de DMO. A idade teve efeito negativo nas medidas DMO e de CC enquanto que o índice de massa corpórea (IMC) mostrou efeito positivo nestas variáveis. A atividade física apresentou efeito positivo na DMO de fêmur total. A duração da AR teve efeito negativo na DMO de coluna lombar. O GC foi o determinante negativo na massa magra total e aumentou o percentual de gordura. CONCLUSÕES: O achado de valores reduzidos de DMO sugere que devam ser aplicadas medidas para a prevenção e tratamento de osteoporose. A doença (AR) também influenciou negativamente a DMO nestas pacientes e a utilização de GC modificou a CC, reduzindo a massa muscular e aumentando o percentual de gordura. A preservação da massa muscular é importante ao equilíbrio das pacientes, com conseqüente diminuição de quedas e futuras fraturas. / INTRODUCTION: The reduction of bone mass and changes in body compositions are usual in patients with rheumatoid arthritis specialty in users of glucocorticoid (GC). OBJECTIVE: To evaluate the bone mineral density (BMD) and body composition (BC) including its correlation to factors of rheumatoid arthritis (RA) and clinics concerns. METHODS: BMD and body composition (total and regional) were measured by densitometry in 83 patients with RA. Furthermore, it was performed laboratory exams (rheumatoid factor, inflammatory exams) and activity of disease, functional class, physical activity and alimentary data were colleted by specific questionnaires. RESULTS: The prevalence of osteoporosis in menopausal patients was 21,4%, 46,4% of osteopenia and 32,1% were normal and osteoporosis was similar in lumbar spine and femoral neck. Premenopausal women had the biggest values of BMD medias. Dose of GC was negative determinant of total lean mass and made positive effect in total fat percentual. Age made negative effect in BMD and body composition. BMI showed positive effect in all CC variables. The physical activity made positive effect in BMD in total femur. The RA duration had negative effect in BMD in lumbar spine. CONCLUSIONS: The finding of low BMD suggests a better approach to prevention and treatment. The disease (RA) also made a negative influence in BMD in these patients and the use of GC cause changes in body composition, with reduction in lean mass and improvement of total fat percentual. Recommendations to preservation of lean mass are important to reduction of falls and consequent diminution of fractures.

INTRODUÇÃO: A Artrite aguda do joelho é o tipo mais comum de artrite, e sua prevalência aumenta em paralelo com o aumento da idade da população. Há muitas evidências de benefícios clínicos do laser para o tratamento da osteoartrite. No entanto, existem poucos estudos abordando os efeitos de 810 nm laser. Aqui nós iremos investigar os efeitos de Laser de Baixa Potencia (infra-vermelho, 810 nm). MATERIAL E MÉTODOS: Ratos Wistar machos (230 - 250g) foram anestesiados com halotano antes da injeção de pró-inflamatórios compostos. Carragenina e Kaolin, ambos a 3%, em solução diluída em soro Fisiológico, administrado intra-articular. Os grupos tratados receberam irradiação laser no local. Após 6 horas todos os animais foram anestesiados e mortos por deslocamento cervical para coleta de cavidade articular e lavado para celulares e análise bioquímica. O tecido articular foi analisado por PCR em tempo real análise, a fim de avaliar a expressão de COX-1 e COX-2. IL-1, TNF-alfa e IL-6 e a mieloperoxidase (MPO) também foi realizada. RESULTADOS E DISCUSSÃO: A terapia com laser de baixa potência foi capaz de inibir o número total de leucócitos, atividade de mieloperoxidase, o extravasamento vascular, IL-1b, TNF-a, IL-6 e Prostaglandina E2. / Introduction. Arthritis of the knee (AK) is the most common type of osteoarthritis, and its prevalence is rising in parallel with the increasing age of the population.. Here we investigate the effects of Low Level Laser Therapy (infra-red, 810 nm) in experimentally induced rat knee osteoarthritis. Methods. Male wistar rats (150 200g) were anaesthetized with halothane 1% prior the injection of pro-inflammatory compounds. Carrageenan and Kaolin (both 3%) administered intra-articular. After 6 hours all animals were killed by decaptation and articular cavity was washed and collected. Articular Tissue was carefully removed for edema and Real-time PCR analysis in order to evaluate COX-1 and COX-2 expression. Total and differential cell account, mieloperoxidase activity, IL-b, TNF-a, IL-6 was also analysed. Results. Low Level laser therapy was able to significantly inhibit the total number of leukocytes as well as the mieloperoxidase activity, polymorphonuclear cells at the inflammatory site, vascular extravasation, IL-1, TNF-alpha, IL-6 and prostaglandin E2. Conclusions. Low Level Laser Therapy operating in 810 nm markedly reduced inflammation in carrageenan, kaolin-induced knee osteoarthritis.

Introdução: recentemente, foi descrita a ação do abatacepte (ABA) na redução nos níveis de imunoglobulinas (Ig) plasmáticas em pacientes com artrite reumatoide (AR). No entanto, a possível associação destes resultados com infecções não foi avaliada até o presente momento. Objetivos: comparar os níveis totais de Igs, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) em pacientes com AR em uso de ABA vs. agentes anti-TNF semestralmente, durante 24 meses de uso, e correlacioná-los com a presença de infecções. Método: dezoito pacientes consecutivos com AR tratados abatacepte (ABA-AR) foram comparados com 18 pacientes com AR tratados com anti-TNF (aTNF-AR). Dados clínicos, laboratoriais e dosagens de imunoglobulinas total, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) foram obtidos a cada seis meses até o tempo total de 24 meses. Foi feito screening sistemático para presença de infecções. Os critérios de exclusão foram: uso prévio de abatacepte/rituximabe e hipogamablobulinemia basal (< 0,7 g/dL). Resultados: no baseline, as medianas da idade (55 vs. 53 anos, P = 0,92), porcentagem de gênero feminino (78 vs. 78%, P = 1,0), comorbidades (28 vs. 28%, P = 1,0), DAS-28 (5,73 vs. 5,67, P = 0,93), HAQ (1,5 vs. 1,13, P = 0,1), VHS (21,5 vs. 22 mm/1ahora, P = 0,49), PCR (15,5 vs. 12 mg/dL, P = 0,43) e contagem de linfócitos (2.200 vs. 1.800/mm3, P = 0,18) foram semelhantes entre os grupos ABA-AR e aTNF-AR, assim como as medianas da gamaglobulina total (1,4 vs. 1,35 g/dL, P = 0,74), IgG (1.168 vs. 1.079 mg/dL, P = 0,46), IgM (107 vs. 113mg/dL, P = 0,38), IgA (333 vs. 322 mg/dL, P = 0,71), kappa (342 vs. 249 mg/dL, P = 0,39) e lambda (170 vs. 150 mg/dL, P = 0,20). No grupo ABA-AR, após seis meses de uso, houve uma queda dos níveis séricos de gamaglobulina total (1,4 vs. 1,05 g/dL, P < 0,001), IgG (1.168 vs. 997 mg/dL, P < 0,001), IgA (333 vs. 278 mg/dL, P < 0,001), kappa (342 vs. 257 mg/dL, P < 0,001) e lambda (170 vs. 144 mg/dL, P < 0,001). Esses níveis permaneceram estáveis dos seis meses até os 24 meses de tratamento (P > 0,05). Em contraste, no grupo aTNF-AR, não houve alteração nos níveis séricos da gamaglobulina total, suas frações e cadeias leves (P > 0,05) em nenhum momento. A variação negativa da gamaglobulina total, IgG, IgM, IgA, kappa e lambda no grupo ABA-AR foi diferente do grupo aTNF-AR (P < 0,05) em todas as avaliações. No entanto, a frequência de infecções foi semelhante entre os grupos (77,8 vs. 88,9%, P = 0,66) e não se associou às variações da gamaglobulina total, de suas frações ou das cadeias leves em nenhum dos dois grupos. Não houve infecções graves durante o período do estudo. Conclusão: o presente estudo demonstra que o abatacepte, mas não os aTNFs, induz uma queda nos níveis de imunoglobulina total, suas frações e cadeias leves nos primeiros seis meses de uso, com estabilidade nos níveis até 24 meses. No entanto, essa queda não está relacionada ao aumento da frequência de infecções nesse grupo de pacientes / Objective: to evaluate the influence of abatacept on gamma-globulin levels in comparison to anti-TNF treatment and correlate these effects with infections frequency in rheumatoid arthritis (RA) patients. Methods: eighteen consecutive RA patients undergoing abatacept (ABA-RA) were compared to 18 patients treated with anti-TNF (aTNF-RA) agents with similar ages. Clinical and laboratory data, total, specific (IgG, IgM, IgA) gamma-globulin and free light chains (FLC) levels were assessed before and every six months during biologic treatment, up to 24 months. Systematic clinical screening protocol for infection was performed. Exclusion criteria were previous abatacept/rituximab treatments and low gamma-globulin level ( < 0.7 g/dL). Results: at baseline, median age (55 vs. 53 years, P = 0.92), female gender (78 vs. 78%, P = 1.0), co morbities (28 vs. 28%, P = 1), DAS-28 (5.73 vs. 5.67, P = 0.93), HAQ (1.5 vs. 1.13, P = 0.1), ESR (21.5 vs. 22mm/1sth, P = 0.49), CRP (15.5 vs. 12mg/dL, P = 0.43) and lymphocyte count (2,200 vs. 1,800/mm3, P = 0.18) were comparable in ABA-RA and aTNF-RA. Medians of gamma-globulin (1.4 vs. 1.35g/dL, P = 0.74), IgG (1,168 vs. 1,079mg/dL, P = 0.46), IgM (107 vs. 113mg/dL, P = 0.38), IgA (333 vs. 322mg/dL, P = 0.71), kappa (342 vs. 249mg/dL, P = 0.39), lambda (170 vs. 150mg/dL, P = 0.20) were also alike. In ABA-RA, total gamma-globulin (1.4 vs. 1.05 g/dL, P < 0.001), IgG (1,168 vs. 997 mg/dL, P < 0.001), IgA (333 vs. 278 mg/dL, P < 0.001), kappa (341.5 vs. 257 mg/dL, P < 0.001), lambda (169.5 vs. 144.3 mg/dL, P < 0.001) levels decreased after six months in comparison to baseline values and persisted stable up to 24 months (P > 0.05). In contrast, in aTNF-RA no decrease in total, specific gamma-globulin levels or FLC was seen (P > 0.05). The negative variation of gamma-globulin, IgG, IgM, IgA, kappa and lambda levels in ABA-RA was different from aTNF-RA (P < 0.05) at all evaluations. However, the infection rates (77.8 vs. 88.9%, P = 0.66) were similar and not associated to variations in total or specific gamma-globulin levels in any group. No severe infection was observed. Conclusion: these comparative data demonstrate that ABA, but not the aTNF, induces a non-progressive and mild, but significant reduction in gamma-globulin levels. We further demonstrated that this alteration is not clinically relevant since it is not associated with increased infection rate