IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Renin-angiotensin system molecules are associated with subclinical atherosclerosis and disease activity in rheumatoid arthritis.

OBJECTIVES: To compare serum levels of RAS components in women with RA versus healthy females and to investigate the association between these molecules and subclinical atherosclerosis. METHODS: A cross-sectional study involving female RA patients without ischemic CVD. Disease activity was assessed using the DAS28 and the CDAI. IMT of the common carotid artery was evaluated by ultrasonography. Serum levels of Ang II, Ang-(1-7), ACE and ACE2 were determined by enzyme immunoassay. RESULTS: Fifty women with RA, mean 48.2 (7.3) years, were compared to 30 healthy women, paired by age. RA patients had higher plasma levels of Ang II (p < .01), Ang-(1-7) (p < .01), and ACE (p < .01) than controls. The ratios of ACE to ACE2 were higher in RA patients, whereas Ang II/Ang-(1-7) ratios were lower in RA patients. The presence of hypertension and the treatment with ACE inhibitors did not significantly modify serum levels of Ang II, Ang-(1-7), ACE and ACE2 in patients with RA. Seven RA patients had altered IMT, and eight patients exhibited atherosclerotic plaque. There was a negative correlation between ACE2 levels and IMT (p = .041). IMT positively correlated with age (p = .022), disease duration (p = .012) and overall Framingham risk score (p = .008). Ang II concentrations positively correlated with DAS28 (p = .034) and CDAI (p = .040). CONCLUSION: Patients with RA had an activation of the RAS, suggesting an association with disease activity and cardiovascular risk. Rheumatological key messages Imbalance of both RAS axes may be associated with cardiovascular risk and disease activity in rheumatoid arthritis. Ultrasonography of the carotid arteries can identify early, subclinical atherosclerotic disease in rheumatoid arthritis patients. Angiotensin-converting enzyme inhibition or angiotensin 1 receptor blockade may be beneficial for rheumatoid arthritis patients.

Longitudinal assessment of clinical and inflammatory markers in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate potential associations between clinical features and inflammatory markers in patients with amyotrophic lateral sclerosis (ALS). METHODS: A consecutive series of 68 patients (39 males and 29 females) with sporadic ALS were subjected to a comprehensive clinical assessment and blood draw. A subset of these patients underwent a new assessment within 6-12 months after the baseline visit. In addition, a group of 62 subjects composed by age and sex-matched healthy subjects (38 males and 24 females) was enrolled in this study. Peripheral blood was drawn and plasma levels of chemokines and cytokines were measured by cytometric bead array and enzyme-linked immunosorbent assay. RESULTS: Our sample was composed by patients with ALS with an average age of 58 (±12.3) years old and 3 (±2.7) years of disease length at the baseline visit. Patients with ALS presented increased plasma levels of interleukin (IL)-6 and IL-8 in comparison with controls. After multivariate analysis, higher levels of IL-6 and lower levels of IL-2 were significantly associated with increased likelihood of ALS diagnosis. When evaluating the subset of patients assessed longitudinally, we did not find any significant difference in the levels of inflammatory markers between the two time points. Older age at ALS onset was the only factor associated with a faster rate of disease progression. CONCLUSIONS: IL-6 levels could discriminate between ALS and controls and may be regarded as a potential biomarker of ALS diagnosis. An increase in IL-2 levels was associated with a protective effect on the odds of ALS diagnosis. Older age at ALS onset predicted a fast rate of disease progression.

Eficácia do Nintendo Wii em desfechos funcionais e de saúde de indivíduos com doença de Parkinson: uma revisão sistemática / Eficacia del Nintendo Wii en resultados funcionales y de salud de individuos con enfermedad de Parkinson: una revisión sistemática / Effectiveness of Nintendo Wii in functional and health outcomes of individuals with Parkinson's disease: a systematic review

RESUMO O objetivo deste estudo foi revisar sistematicamente a literatura sobre a eficácia do Nintendo Wii na melhora de desfechos funcionais e de saúde de indivíduos com doença de Parkinson. A revisão foi desenvolvida seguindo o PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), com buscas nas bases de dados MEDLINE, SciELO, LILACS e PEDro mediante estratégia de busca composta pela combinação dos termos "Wii", "Doença de Parkinson", "reabilitação" e "fisioterapia", seguida de busca manual. Os critérios de inclusão foram: estudos experimentais ou quase-experimentais relacionados a intervenções envolvendo o uso do Nintendo Wii para melhora de desfechos funcionais em indivíduos com doença de Parkinson, publicados até fevereiro de 2016, sem restrição de idioma. A qualidade metodológica dos estudos foi avaliada pela escala PEDro. Dos 701 estudos encontrados, foram selecionados sete que atenderam aos critérios de inclusão, a maioria (57,14%) apresentava qualidade metodológica ruim e era do tipo quase-experimental. Os resultados sugerem que o uso do Wii parece eficaz para melhora de desfechos funcionais (equilíbrio, mobilidade, desempenho motor e independência) e de saúde (diminuição do risco de quedas), sendo mais consistentes os resultados para melhora do equilíbrio. São necessários estudos com melhor qualidade metodológica para o estabelecimento das evidências e, ainda, padronizações sobre os tipos de jogos, intensidade e frequência adequados para cada tipo de paciente com DP.

RESUMEN El objetivo de este estudio ha sido el de revisar sistemáticamente la literatura sobre la eficacia del Nintendo Wii en la mejora de resultados funcionales y de salud de individuos con enfermedad de Parkinson. La revisión sistemática de la literatura ha sido desarrollada siguiendo el PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), con búsquedas en las bases de datos MEDLINE, SciELO, LILACS y PEDro de acuerdo con la estrategia de búsqueda compuesta por la combinación de los términos "Wii", "Enfermedad de Parkinson", "rehabilitación" y "fisioterapia", seguida de búsqueda manual. Los criterios de inclusión han sido: los estudios experimentales o casi-experimentales relacionados a las intervenciones involucrando el uso del Nintendo Wii para la mejora de resultados funcionales en los individuos con enfermedad de Parkinson, publicados hasta febrero de 2016, sin restricción de idioma. La cualidad metodológica de los estudios ha sido evaluada por la escala PEDro. De los 701 estudios encontrados, han sido incluidos siete que atendieron a los criterios de inclusión, la gran parte (el 57,14%) con cualidad metodológica mala y del tipo casi-experimental. Los resultados sugieren que el uso del Wii parece eficaz para la mejora de resultados funcionales (el equilibrio, la movilidad, el desempeño motor y la independencia) y de salud (disminución del riesgo de caídas), siendo más consistentes los resultados para la mejora del equilibrio. Son necesarios estudios con mejor cualidad metodológica para el establecimiento de las evidencias. Todavía son necesarias estandarizaciones sobre los tipos de juegos, intensidad y frecuencia adecuados para cada tipo de paciente con EP.

ABSTRACT The objective of this study was to conduct a systematic review of the literature on the effectiveness of Nintendo Wii in the improvement of functional and health outcomes of individuals with Parkinson's disease. A systematic review of the literature was developed following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), with research in MEDLINE, SciELO, LILACS, PEDro through a search strategy that combined the terms Wii, Parkinson's Disease, rehabilitation, and physical therapy, followed by manual search. Inclusion criteria were: experimental studies or quasi-experiments related to interventions involving the use of Nintendo Wii to improve functional outcomes in individuals with Parkinson's disease, published until February 2016, without language restriction. The methodological quality of the studies was assessed with the PEDro scale. Of the 701 studies found, we included seven that met the inclusion criteria - most of the articles (57.14%) had bad methodological quality and were quasi-experiments. The results suggest that the use of Wii seems effective to improve functional outcomes (balance, mobility, motor performance and independence) and health (reducing the risk of falls), being more consistent the results for the improvement of balance. Studies with better methodological quality are needed for the establishment of evidence. Standardization on the types of games, intensity and frequency suitable for each type of patient with PD are still required.

Muscle strength and psychiatric symptoms influence health-related quality of life in patients with myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by skeletal muscle weakness which can impact motor function and, furthermore, produce negative impact on the health-related quality of life (HRQOL). OBJECTIVE: To evaluate the predictors for HRQOL in patients with MG. METHODS: Eighty patients were evaluated with the MG Foundation of America classification and the MG Composite scale. HRQOL was estimated by the MGQOL15, while anxious and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale (HAD). RESULTS: The mean age of patients was 41.9 years with mean illness duration of 13.5 years. Almost half of the patients (43.75%) had significant anxiety and more than a quarter (27.50%) had depressive symptoms. Factors that influenced the HRQOL in MG were skeletal muscle weakness and anxiety and depressive symptoms (p < .001 in logistic regression model). CONCLUSION: Anxiety and depressive symptoms, besides motor symptoms, influence HRQOL in MG. Mental health must be a clinical focus in addition to the treatment of somatic symptoms during the course of MG.

Body composition and adipokines plasma levels in patients with myasthenia gravis treated with high cumulative glucocorticoid dose.

This study aimed to evaluate changes in body composition, i.e. overweight, obesity, fat accumulation and low lean body mass and plasma levels of adipokines in patients with MG. The study enrolled 80 patients with MG, and 62 controls. Body fat mass and body lean mass was analyzed by dual-energy X-ray absorptiometry technique (DXA). Plasma levels of leptin were analyzed by Luminex® and adiponectin and resistin were analyzed by ELISA. The mean age of patients with MG was 41.9years, with 13.5years of length of illness, and mean cumulative dose of glucocorticoids 38,123mg. Our results showed that the frequency of obesity is higher in MG patients than in controls, and patients with MG presented higher body fat mass, android body adiposity and total body fat than controls. MG patients presented lower levels of resistin and higher levels of leptin in comparison with controls. There were no differences in the plasma levels of adiponectin. Higher total body fat and lower body lean mass were associated with increased severity of MG symptoms. This result points to the relevance of estimation of body composition in planning long-term care of MG patients.

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

Influence of Cytokines and Soluble Receptors in the Quality of Life and Functional Capacity of Workers Exposed to Silica.

OBJECTIVES: The aim of the study was to evaluate the plasma levels of inflammatory mediators in subjects exposed to silica, with and without silicosis compared with unexposed control group; and to check the association between inflammatory mediators with pulmonary function, quality of life, functional capacity, and dyspnea grade. METHODS: Inflammatory mediators were measured by enzyme-linked immunosorbent assay. There were 30 subjects exposed to silica and 24 control group. RESULTS: Interleukin-6 plasma levels were higher in subjects exposed to silica with and without silicosis than in the control group. There was a positive correlation between radiological severity and the quality of life, whereas there was a negative correlation between radiological severity and pulmonary function. A negative correlation between sTNFR1 plasma level and functional capacity was found. Interleukin-10 was negatively correlated with the quality of life total score and was positively correlated with the functional capacity and pulmonary function.

Association between inflammatory biomarkers in plasma, radiological severity, and duration of exposure in patients with silicosis.

OBJECTIVE: To evaluate the plasma levels of CCL2, CCL3, CCL11, CCL24, tumor necrosis factor alpha, sTNFR1, and sTNFR2 in subjects exposed to silica (SES) with and without silicosis compared with unexposed reference control group, and their associations with the radiological severity and duration of exposure to silica. METHODS: Fifty-seven SES; 36 with silicosis and 22 subjects in control group, were included in the study. RESULTS: CCL3, CCL24, sTNFR1, and sTNFR2 were increased in SES and in SES with silicosis than in controls. There were no differences in the levels of CCL2, CCL11, or tumor necrosis factor alpha. The sTNFR2 level was greater in SES with silicosis than in SES without silicosis. There was a positive correlation between sTNFR1 and sTNFR2 and the radiological severity and time of exposure to silica. sTNFR2 was associated with all categories of radiological severity. CONCLUSION: sTNFR2 is associated with silicosis severity and early exposure to silica.

Biomarcadores inflamatórios na silicose pulmonar / Inflammatory biomarkers in pulmonary silicosis

A silicose representa um importante problema de saúde pública em todo o mundo, sobretudo nos países em desenvolvimento, sendo a principal causa de invalidez entre as doenças respiratórias ocupacionais. É uma pneumoconiose fibrótica, irreversível e potencialmente fatal, causada pela inalação de poeira contendo sílica cristalina. O diagnóstico é estabelecido através da história clínica e ocupacional de exposição à sílica, na presença de alterações radiológicas. Estudos experimentais e clínicos sugerem que a inalação da poeira da sílica está associada a um processo inflamatório pulmonar e sistêmico, mesmo em indivíduos que não desenvolveram silicose. Até o momento não existem exames laboratoriais específicos para o diagnóstico da doença, de modo que o conhecimento de marcadores biológicos associados à imunopatologia da silicose pode ser importante na detecção precoce da instalação e desenvolvimento da doença. O presente artigo traz uma revisão de estudos que investigaram os possíveis biomarcadores inflamatórios da doença no sangue e no lavado bronco-alveolar de humanos e de modelos experimentais.

Silicosis is an important public health problem worldwide, especially in developing countries and is the leading cause of disability among occupational respiratory diseases. It is a fibrotic disease irreversible and potentially fatal caused by inhaling dust containing crystalline silica, the most frequent type of pneumoconiosis. Diagnosis is established by clinical and occupational history of exposure to silica, in the presence of radiological changes. Experimental and clinical studies suggest that inhalation of silica dust is associated with pulmonary and systemic inflammation even in patients who did not develop silicosis. There are no specific tests for the routine laboratory diagnosis of the disease and the study of biological markers associated with the immunopathology of silicosis is important to understanding the establishment and development of silicosis. This article presents a review of studies investigating the possible inflammatory biomarkers of disease in blood and bronchoalveolar lavage from humans and experimental models.

Efeitos de um protocolo de exercícios baseados no método Pilates sobre variáveis respiratórias em umapopulação de jovens sedentários / Effects of a protocol of exercises based on the Pilates method about respiratory variables in a sedentary young population

Objetivo: Investigar os efeitos de um protocolo de exercíciosbaseados no método Pilates, sobre a força muscular respiratória, opico de fluxo expiratório e a mobilidade toracoabdominal em jovenssedentários. Métodos: Tratou-se de um estudo clínico, prospectivo,no qual as variáveis avaliadas foram comparadas antes e após umprotocolo de 12 semanas de exercícios baseados no Método Pilates.Participaram do estudo 15 universitários (9 mulheres e 6 homens)com idade média de 22 ± 2 anos. O protocolo teve duração de 12semanas ininterruptas, sendo 2 sessões semanais com duração de 60minutos cada, com progressão dos exercícios na sétima semana. Asvariáveis analisadas foram as pressões respiratórias máximas, o picode fluxo expiratório e a mobilidade toracoabdominal. Resultados:Ao comparar os valores das pressões respiratórias máximas, do picode fluxo expiratório e da mobilidade toracoabdominal, antes e apóso treinamento, observou-se que todas elas apresentaram diferençasestatisticamente significantes (p < 0,05) com melhora de todas asvariáveis analisadas. Conclusão: O protocolo de exercícios propostono presente estudo mostrou ser eficiente para promover o aumentodas pressões respiratórias máximas, do pico de fluxo expiratório e damobilidade toracoabdominal em jovens sedentários.

Objective: To investigate the effects of a protocol of exercisesbased on the Pilates method regarding the strength of respiratorymuscle, peak expiratory flow and thoracoabdominal mobility of sedentaryyoung adults. Methods: This was a prospective clinical studyin which the variables were compared before and after a protocolduring 12 weeks of exercises based on the Pilates method. The studywas composed of 15 students (9 women and 6 men) 22 ± 2 yearsold. The protocol lasted 12 weeks uninterrupted, with two weeklysessions lasting 60 minutes each, with progression of the exercises onthe seventh week. The variables analyzed were maximal respiratorypressures, peak expiratory flow and thoracoabdominal mobility.Results: When comparing the values of the maximal respiratorypressures, peak expiratory flow and thoracoabdominal mobility,before and after the training, it was observed that all of the variablesshowed significant differences (p < 0.05) with increase in all variablesanalyzed. Conclusion: The exercise protocol performed in the presentstudy showed to be efficient in promoting an increase of maximalrespiratory pressures, peak expiratory flow and thoracoabdominalmobility of sedentary young adults.