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Int. j. morphol ; 38(1): 43-47, Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056395


Rheumatoid arthritis (RA) is a disease triggered by environmental and genetic factors. Research suggests that physical exercise has benefits such as delaying functional disability. In vivo studies using experimental models of arthritis can provide useful information about these benefits. to analyze the effects that different intensities of aquatic physical exercise have on the proprieties of the bones in induced arthritis in knees of Wistar rats. Male Wistar adults rats (n=20) were divided into 5 groups: Group Control Arthritis (GCA) n=4, Group control Placebo (GCP) n=4, Group Low Physical Activity (GB) n=4, Group Moderate Physical Activity (GM) n=4 and Group Intense Physical Activity (GI) n=4. The physical activity groups got an intra-articular injection of Zymosam on the right knee; the GCA received saline solution in the right knee; the GCP was submitted to the stress of the needle. The animals were submitted to aquatic activity for 30 minutes, 4 times a week for 5 weeks, and the intensity of the exercise was determined by a weight placed on their back: GB=1 %, GM=5 %, GI=15 % of their body weight. It was observed that the group GB, and the groups that did not exercise GCA and GCP, gained more weight compared to the group GM. In relation to the bone mineral content of the tibia, there was a decrease in the GM group when compared to the GCP group, whereas in the tibial bone mineral density there was a decrease in the GM group compared to the GCP, GCA, GB. As for the area of the femur, the GI group presented an increase of it compared to the GB and GM groups. It is concluded that the high intensity exercises promote better results in bone properties.

La investigación sugiere que el ejercicio físico tiene beneficios como retrasar la discapacidad funcional de la artritis reumatoide. Los estudios in vivo que utilizan modelos experimentales de artritis pueden proporcionar información útil sobre estos beneficios. Se analizaron los efectos de las intensidades del ejercicio físico acuático sobre las propiedades de los huesos, en la artritis inducida en las rodillas de ratas Wistar. Las ratas Wistar macho adultas (n = 20) se dividieron en 5 grupos: grupo de control artritis (ACG) n = 4, grupo control placebo (CGP) n = 4, grupo de actividad física baja (GB) n = 4, grupo de actividad física moderada (GM) n = 4 y grupo de actividad física intensa (GI) n = 4. Los grupos de actividad física recibieron una inyección intraarticular de Zymosam en la rodilla derecha; el GCA recibió solución salina en la rodilla derecha; el CGP fue sometido a la tensión de una aguja. Los animales fueron sometidos a actividad acuática durante 30 minutos, 4 veces a la semana durante 5 semanas, y la intensidad del ejercicio se determinó mediante un peso colocado sobre su espalda: GB = 1 %, GM = 5 %, GI = 15 % de su peso corporal. Se observó que el grupo GB, y los grupos que no ejercitaron GCA y CGP, ganaron más peso en comparación con el grupo GM. En relación con el contenido mineral óseo de la tibia, hubo una disminución en el grupo GM en comparación con el grupo GCP, mientras que en la densidad mineral del hueso tibial hubo una disminución en el grupo GM en comparación con el GCP, GCA, GB. En cuanto al área del fémur, el grupo GI presentó un aumento en comparación con los grupos GB y GM. En conclusión el ejercicio de alta intensidad promueve mejores resultados en las propiedades óseas.

Animals , Male , Rats , Arthritis, Rheumatoid/pathology , Swimming/physiology , Tibia/pathology , Femur/pathology , Arthritis, Rheumatoid/physiopathology , Tibia/physiopathology , Body Weight , Exercise/physiology , Rats, Wistar , Disease Models, Animal , Femur/physiopathology
Braz. J. Pharm. Sci. (Online) ; 56: e18447, 2020. tab, graf
Article in English | LILACS | ID: biblio-1142492


T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Humans , Male , Female , Adolescent , Adult , Safety , Volunteers , Single Dose/drug effects , Etanercept/analogs & derivatives , Physical Examination , Arthritis, Rheumatoid/pathology , Tumor Necrosis Factor-alpha/classification , Clinical Laboratory Techniques , Asians/classification , Electrocardiography , Injection Site Reaction , Injections, Subcutaneous/classification
Braz. J. Pharm. Sci. (Online) ; 56: e18551, 2020. tab, graf
Article in English | LILACS | ID: biblio-1142487


We performed this study to measure the Tumor Necrosis Factor-alpha (TNF-α) plasma level and to survey its correlation with disease activity in the newly diagnosed Rheumatoid Arthritis (RA) patients and those who were under treatment with the combination of Disease-Modifying Anti-Rheumatic Drug (DMARD) plus Prednisolone (PSL).We enrolled 30 newly diagnosed RA patients who received no treatment regarding their disease, 30 patients under treatment with the combination of Methotrexate (MTX) + Hydroxychloroquine (HCQ) + PSL and 30 healthy subjects in this case-control study from September 2017 to December 2017. The level of plasma TNF-α was measured by enzyme-linked immunosorbent assay (ELISA) in each group. For assessment of disease severity, we used Disease Activity Score-28 (DAS-28) formula, and regarding DAS-28, we divided patients into four groups, including remission, low, moderate and high disease activity. There were no significant differences in the plasma level of TNF-α between the newly diagnosed RA patients and subjects who received MTX + HCQ + PSL, as well as healthy controls (p>0.05). There was a significant correlation between plasma levels of TNF-α and DAS-28 in the newly diagnosed patients with RA (r = 0.594, P = 0.001). Targeting TNF-α at the early stage of RA could have more beneficial effects on the amelioration of disease activity

Patients/classification , Arthritis, Rheumatoid/pathology , Lymphotoxin-alpha/pharmacology , Antirheumatic Agents/administration & dosage , Enzyme-Linked Immunosorbent Assay , Tumor Necrosis Factor-alpha/pharmacology , Antirheumatic Agents
Rev. Hosp. Clin. Univ. Chile ; 29(2): 97-108, 2018. tab
Article in Spanish | LILACS | ID: biblio-986659


Rheumatoid arthritis (RA) is a systemic inflammatory disease that primarily affects the joints causing varying degrees of disability. Non-pharmacological management is increasing evidence of its usefulness impacting functionality. Objectives: To characterize the clinical / functional profile of patients with rheumatoid arthritis derived physiatrist assessment in the Clinical Hospital University of Chile. Methods: We reviewed the clinical records of patients with RA derivatives Physical Medicine, extraction demographics, medical history, physical examination and functionality. Statisticians analysis of central tendency, dispersion, absolute and relative frequencies. Results: 85 medical records were analyzed. 88.2% were women with an average age of 54.05 ± 11.42 years. 38.8% have at least one comorbidity. 34.1% of patients takes between 6 and 15 years of disease. The average drug related AR is 5.6 per patient, being more Disease Modifying Antirheumatic Drugs (DMARDs) found. 35.2% presented falls in the past year. Pain is a symptom found in the history and physical examination with a VAE (venous air embolism) 4.4 ± 2.43 at the time of consultation and 6.7 ± 3.3 in crisis. 20% received kinesic therapy and only 7% occupational therapy. 45.3% of patients having a value of HAQ (health assesment questionnaire) who scored as moderate disability, even if their selfperception of independence reaches 65.9%. Conclusion: The analysis allows us to perform a demographic, clinical and functional profile that allows us to guide rehabilitation actions. (AU)

Humans , Male , Female , Adult , Middle Aged , Aged , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/rehabilitation , Arthritis, Rheumatoid/therapy , Chile/epidemiology
Rev. bras. reumatol ; 57(2): 122-128, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-844222


Abstract Rheumatoid arthritis (RA) is a well and widely recognized cause of carpal tunnel syndrome (CTS). In the rheumatoid wrist, synovial expansion, joint erosions and ligamentous laxity result in compression of the median nerve due to increased intracarpal pressure. We evaluated the published studies to determine the prevalence of CTS and the characteristics of the median nerve in RA and its association with clinical parameters such as disease activity, disease duration and seropositivity. A total of 13 studies met the eligibility criteria. Pooled data from 8 studies with random selection of RA patients revealed that 86 out of 1561 (5.5%) subjects had CTS. Subclinical CTS, on the other hand, had a pooled prevalence of 14.0% (30/215). The cross sectional area of the median nerve of the RA patients without CTS were similar to the healthy controls. The vast majority of the studies (8/13) disclosed no significant relationship between the median nerve findings and the clinical or laboratory parameters in RA. The link between RA and the median nerve abnormalities has been overemphasized throughout the literature. The prevalence of CTS in RA is similar to the general population without any correlation between the median nerve characteristics and the clinical parameters of RA.

Resumo A artrite reumatoide (AR) é uma causa bem e amplamente reconhecida de síndrome do túnel do carpo (STC). No punho acometido pela artrite reumatoide, a expansão sinovial, as erosões articulares e a frouxidão ligamentar resultam em compressão do nervo mediano decorrente do aumento da pressão intracarpal. Avaliaram-se os estudos publicados para determinar a prevalência de STC e as características do nervo mediano na AR e sua associação com parâmetros clínicos, como a atividade e duração da doença e a soropositividade. Preencheram os critérios de elegibilidade 13 estudos. Os dados agrupados dos oito estudos com seleção aleatória de pacientes com AR revelaram que 86 de 1.561 (5,5%) indivíduos tinham STC. Por outro lado, a STC subclínica teve uma prevalência combinada de 14% (30/215). A área de seção transversa do nervo mediano dos pacientes com AR sem STC foi semelhante à de controles saudáveis. A grande maioria dos estudos (8/13) não apresentou relação significativa entre os achados no nervo mediano e os parâmetros clínicos ou laboratoriais na AR. A ligação entre a AR e as anormalidades do nervo mediano foi excessivamente valorizada em toda a literatura. A prevalência de STC na AR é semelhante à da população em geral, sem qualquer correlação entre as características do nervo mediano e os parâmetros clínicos da AR.

Humans , Arthritis, Rheumatoid/pathology , Wrist Joint/pathology , Carpal Tunnel Syndrome/pathology , Median Nerve/pathology , Arthritis, Rheumatoid/complications , Carpal Tunnel Syndrome/etiology , Incidence , Prevalence
Rev. bras. reumatol ; 56(5): 451-457, Sept.-Oct. 2016. tab
Article in English | LILACS | ID: lil-798098


ABSTRACT A better understanding of the inflammatory mechanisms of rheumatoid arthritis and the development of biological therapy revolutionized its treatment, enabling an interference in the synovitis – structural damage – functional disability cycle. Interleukin 33 was recently described as a new member of the interleukin-1 family, whose common feature is its pro-inflammatory activity. Its involvement in the pathogenesis of a variety of diseases, including autoimmune diseases, raises the interest in the possible relationship with rheumatoid arthritis. Its action has been evaluated in experimental models of arthritis as well as in serum, synovial fluid and membrane of patients with rheumatoid arthritis. It has been shown that the administration of interleukin-33 exacerbates collagen-induced arthritis in experimental models, and a positive correlation between cytokine concentrations in serum and synovial fluid of patients with rheumatoid arthritis and disease activity was found. This review discusses evidence for the role of interleukin-33 with a focus on rheumatoid arthritis.

RESUMO A melhor compreensão dos mecanismos inflamatórios da artrite reumatoide e o desenvolvimento da terapia biológica revolucionaram o tratamento da doença, permitindo uma interferência no ciclo sinovite–dano estrutural–incapacidade funcional. A interleucina 33 foi recentemente descrita como um novo membro da família da interleucina 1, cuja característica comum é a atividade pró-inflamatória. Por estar envolvida na patogênese de uma grande variedade de doenças, incluindo doenças autoimunes, a interleucina 33 começa a ser estudada na doença reumatoide. Ela tem sido avaliada em modelos experimentais de artrite, no soro, no líquido e membrana sinoviais de pacientes com artrite reumatoide. Demonstrou-se que a administração da interleucina 33 exacerba a artrite induzida por colágeno em modelos experimentais, e concentrações dessa citocina no soro e no líquido sinovial de pacientes com artrite reumatoide correlacionaram-se positivamente com a atividade da doença. Esse manuscrito apresenta a interleucina 33 e discute as evidências do seu papel em diferentes doenças, com ênfase na artrite reumatoide.

Humans , Animals , Arthritis, Experimental/immunology , Arthritis, Rheumatoid/pathology , Interleukin-33/immunology , Interleukin-33/blood , Arthritis, Experimental/pathology , Arthritis, Experimental/blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Synovial Fluid , Synovitis , Interleukins
An. bras. dermatol ; 91(4): 500-502, July-Aug. 2016. graf
Article in English | LILACS | ID: lil-792454


Abstract: A 54 year-old woman with a 3-year history of rheumatoid arthritis (RA) consulted us because of weight loss, fever and skin eruption. On physical examination, erythematous plaques with a pseudo-vesicular appearance were seen on the back of both shoulders. Histological examination was consistent with rheumatoid neutrophilic dermatosis (RND). After 3 days of prednisone treatment, the skin eruption resolved. RND is a rare cutaneous manifestation of seropositive RA, characterized by asymptomatic, symmetrical erythematous plaques with a pseudo-vesicular appearance. Histology characteristically reveals a dense, neutrophilic infiltrate with leucocitoclasis but without other signs of vasculitis. Lesions may resolve spontaneously or with RA treatment. This case illustrates an uncommon skin manifestation of active rheumatoid arthritis.

Humans , Female , Middle Aged , Arthritis, Rheumatoid/pathology , Skin Diseases, Vesiculobullous/pathology , Skin/pathology , Biopsy , Erythema/pathology , Neutrophils/pathology
Arq. bras. oftalmol ; 78(4): 236-240, July-Aug. 2015. tab
Article in English | LILACS | ID: lil-759255


ABSTRACTPurpose:To evaluate central corneal thickness (CCT) and peripheral corneal thickness (PCT) in patients with rheumatoid arthritis (RA) and to assess the relationships among the corneal parameters, dry eye disease, and clinical variables of RA.Methods:A total of 58 RA patients and 58 control subjects participated in this study. A detailed ophthalmological examination was performed on each subject. Dry eye evaluation was performed using Schirmer’s test, tear break-up time (TBUT), corneal fluorescein staining, and Ocular Surface Disease Index (OSDI). Corneal thickness at the apex point, the center of the pupil, the thinnest point, and PCT (3 mm from the apex to the superior, inferior, nasal, and temporal locations) were evaluated using Scheimpflug imaging (Pentacam®). Additionally, the relative peripheral index (RPI) was calculated by dividing the PCT by the CCT. The disease severity and quality of life were evaluated with DAS28 and HAQ, respectively. The laboratory evaluation comprised ESR and CRP.Results:The mean corneal thicknesses at the apex point, the center of the pupil, the thinnest point, and the superior, inferior, nasal, and temporal points were significantly thinner in RA patients than controls. Schirmer’s test scores and TBUT were significantly lower, and corneal staining and OSDI scores were significantly higher in RA patients. There were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests.Conclusion:The CCT and PCT were thinner in RA patients compared to those in control subjects. However, there were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests.

RESUMOObjetivo:Avaliar da espessura central da córnea (CCT) e espessura corneana periférica (PCT) em pacientes com artrite reumatoide (RA). O segundo objetivo foi avaliar as relações entre os parâmetros de córnea, doença do olho seco e variáveis clínicas da RA.Método:Um total de 58 pacientes com RA e 58 indivíduos do grupo controle participaram deste estudo. Exame oftalmológico detalhado foi realizado para cada indivíduo. Avaliação do olho seco foi realizada por meio do teste de Schirmer, tempo de ruptura do filme lacrimal (TBUT), coloração com fluoresceína da córnea e do índice de doença da superfície ocular (OSDI). Espessura da córnea no ápice, centro da pupila e ponto mais fino, assim como PCT (três milímetros do ápice para localização superior, inferior, nasal e temporal) foram avaliadas por meio de imagens Scheimpflug (Pentacam®). Além disso, o índice periférico relativo (RPI) foi calculado dividindo-se a PCT pela CCT. A gravidade da doença e qualidade de vida foram avaliados com DAS28 e HAQ respectivamente. A avaliação laboratorial foi composta por VHS e PCR.Resultados:As espessuras de córnea médias no ápice, centro da pupila, ponto mais fino, assim como nos pontos superior, inferior, nasal e temporal foram significativamente mais finas em pacientes com RA do que nos controles. Os resultados dos testes de Schirmer e TBUT foram significativamente menores e a coloração por fluoresceína e o OSDI foram significativamente maiores em pacientes com RA. Não houve correlações significativas entre os parâmetros da córnea e variáveis clínicas da RA ou testes de olho seco.Conclusões:A espessura corneana central e periférica foram mais finas em pacientes com RA em comparação com indivíduos controle. Não houve correlações significativas entre os parâmetros da córnea e variáveis clínicas da AR ou testes de olho seco.

Female , Humans , Male , Middle Aged , Arthritis, Rheumatoid/pathology , Cornea/pathology , Corneal Topography/methods , Dry Eye Syndromes/diagnosis , Arthritis, Rheumatoid/physiopathology , Case-Control Studies , Cornea/physiopathology , Diagnostic Techniques, Ophthalmological , Dry Eye Syndromes/physiopathology
Rev. bras. anestesiol ; 65(3): 217-221, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-748919


RATIONALE: The changes in body position can cause changes in lung function, and it is necessary to understand them, especially in the postoperative upper abdominal surgery, since these patients are susceptible to postoperative pulmonary complications. OBJECTIVE: To assess the vital capacity in the supine position (head at 0° and 45°), sitting and standing positions in patients in the postoperative upper abdominal surgery. METHODS: A cross-sectional study conducted between August 2008 and January 2009 in a hospital in Salvador/BA. The instrument used to measure vital capacity was analogic spirometer, the choice of the sequence of positions followed a random order obtained from the draw of the four positions. Secondary data were collected from the medical records of each patient. RESULTS: The sample consisted of 30 subjects with a mean age of 45.2 ± 11.2 years, BMI 20.2 ± 1.0 kg/m2. The position on orthostasis showed higher values of vital capacity regarding standing (mean change: 0.15 ± 0.03 L; p = 0.001), the supine to 45 (average difference: 0.32 ± 0.04 L; p = 0.001) and 0° (0.50 ± 0.05 L; p = 0.001). There was a positive trend between the values of forced vital capacity supine to upright posture (1.68 ± 0.47; 1.86 ± 0.48; 2.02 ± 0.48 and 2.18 ± 0.52 L; respectively). CONCLUSION: Body position affects the values of vital capacity in patients in the postoperative upper abdominal surgery, increasing in postures where the chest is vertical. .

JUSTIFICATIVA: As alterações no posicionamento corporal podem ocasionar mudanças na função respiratória e é necessário compreendê-las, principalmente no pós-operatório abdominal superior, já que os pacientes estão suscetíveis a complicações pulmonares pós-operatórias. OBJETIVO: Verificar a capacidade vital nas posições de decúbito dorsal (cabeceira a 0° e 45°), sentado e em ortostase em pacientes no pós-operatório de cirurgia abdominal superior. MÉTODOS: Estudo transversal, feito entre agosto de 2008 e janeiro de 2009, em um hospital na cidade de Salvador (BA). O instrumento usado para mensuração da capacidade vital (CV) foi o ventilômetro analógico e a escolha da sequência das posições seguiu uma ordem aleatória obtida a partir de sorteio das quatro posições. Os dados secundários foram colhidos nos prontuários de cada paciente. RESULTADOS: A amostra foi composta por 30 indivíduos com idade média de 45,2 ± 11,2 anos e IMC 20,2 ± 1,0 kg/m2. A posição em ortostase apresentou valores maiores da CV em relação à sedestração (média das diferenças: 0,15 ± 0,03 litros; p = 0,001), ao decúbito dorsal a 45° (média das diferenças: 0,32 ± 0,04 litros; p = 0,001) e 0° (0,50 ± 0,05 litros; p = 0,001). Houve um aumento positivo entre os valores de CVF do decúbito dorsal para a postura ortostática (1,68 ± 0,47; 1,86 ± 0,48; 2,02 ± 0,48 e 2,18 ± 0,52 litros; respectivamente). CONCLUSÃO: A posição do corpo afeta os valores da CV em pacientes no pós-operatório de cirurgia abdominal superior, com aumento nas posturas em que o tórax encontra-se verticalizado. .

JUSTIFICACIÓN: Las alteraciones en el posicionamiento corporal pueden ocasionar cambios en la función respiratoria y es necesario comprenderlas, principalmente en el postoperatorio abdominal superior, ya que los pacientes son susceptibles a complicaciones pulmonares postoperatorias. OBJETIVO: Verificar la capacidad vital en las posiciones de decúbito dorsal (cabeza a 0° y 45°), sentado y en ortostasis en pacientes en el postoperatorio de cirugía abdominal superior. MÉTODOS: Estudio transversal realizado entre agosto de 2008 y enero de 2009, en un hospital en la ciudad de Salvador (BA). El instrumento usado para la medición de la capacidad vital (CV) fue el espirómetro analógico y la elección de la secuencia de las posiciones siguió un orden aleatorio que se obtuvo a partir de un sorteo de las 4 posiciones. Los datos secundarios fueron extraídos de las historias clínicas de cada paciente. RESULTADOS: La muestra se compuso de 30 individuos con edades medias de 45,2 ± 11,2 años e IMC de 20,2 ± 1 kg/m2. La posición en ortostasis presentó valores mayores de CV con relación a la posición sedente (media de las diferencias: 0,15 ± 0,03 L; p = 0,001), al decúbito dorsal a 45° (media de las diferencias: 0,32 ± 0,04 L; p = 0,001) y a 0° (0,50 ± 0,05 L; p = 0,001). Hubo un aumento positivo entre los valores de CV forzada del decúbito dorsal para la postura ortostática (1,68 ± 0,47; 1,86 ± 0,48; 2,02 ± 0,48 y 2,18 ± 0,52 L, respectivamente). CONCLUSIÓN: La posición del cuerpo afecta los valores de la CV en pacientes durante el postoperatorio de cirugía abdominal superior, con aumento en las posturas en las que el tórax está verticalizado. .

Humans , Arthritis, Rheumatoid/drug therapy , Computer Simulation , Cartilage, Articular/drug effects , Extracellular Matrix/drug effects , Models, Biological , Osteoarthritis/drug therapy , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Interleukin-1/pharmacology , Interleukin-1/therapeutic use , Oncostatin M/pharmacology , Oncostatin M/therapeutic use , Osteoarthritis/metabolism , Osteoarthritis/pathology , Signal Transduction
São Paulo; s.n; s.n; abr. 2014. 119 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-836920


A artrite reumatoide (AR) é uma doença inflamatória crônica, caracterizada por inflamação das articulações e se manifesta por inchaço e incapacidade funcional das mesmas. A patologia da doença envolve a produção excessiva de radicais livres pelos neutrófilos ativados, podendo induzir à peroxidação lipídica nas membranas celulares o que leva ao aumento da inflamação. Nesse sentido, o selênio (principal fonte é a castanha-do-brasil) é um importante fator por diminuir a atividade dos hidroperóxidos por meio da ação da enzima antioxidante glutationa peroxidase (GPx). No entanto, estudos que avaliem a associação do estado nutricional relativo ao selênio em pacientes com AR com os biomarcadores do estresse oxidativo e de inflamação são escassos na literatura. Desse modo, a avaliação do efeito potencial in vivo da suplementação com castanha-do-brasil, como fonte de selênio, sobre os parâmetros descritos anteriormente e sua relação com o polimorfismo Pro198Leu no gene da GPx1, em pacientes com artrite reumatoide (AR), vêm a suprir essa lacuna. Inicialmente foi realizada a caracterização da castanha-do-brasil quanto à composição de macronutrientes e teor de selênio. O estudo em pacientes com artrite reumatoide foi de natureza longitudinal. Foram avaliados 46 pacientes com AR, com idade média de 55,2 ± 10,9 anos, atendidos no Setor de Reumatologia da Universidade Federal de São Paulo. O estudo foi dividido em duas fases: antes (T0) e após a suplementação (T1) com 1 nóz de castanha-do-brasil. Foi realizada a avaliação da composição corporal e do consumo alimentar. Além disso, foram avaliados parâmetros bioquímicos relativos ao status de selênio por espectrofotometria de absorção atômica por geração de hidretos; atividades da GPx e SOD com uso de kits comerciais; concentração da GPx1 por kits comerciais, sua expressão gênica (qRT-PCR) e genotipagem do Pro198Leu no referido gene por PCR em tempo real; determinação de 8-isoprostanos por kit comercial, assim como níveis circulantes de fibrinogênio, proteína C reativa, IL-6, IL-10, TNF-α, IL-1ß, IL-2, VCAM, ICAM, PAI-1 e sE-selectina pelo ensaio ELISA. O genótipo selvagem (Pro/Pro) foi observado em 57,63% das participantes; 35,59% para as heterozigotas para o alelo variante (Pro/Leu) e 6,78% apresentaram os dois alelos variantes. As pacientes com artrite reumatoide apresentaram baixa ingestão de selênio e, após a intervenção, o consumo aumentou significantemente. Em relação ao status de selênio, houve um aumento em sua concentração no plasma e eritrócitos após o período de intervenção com castanha-do-brasil, assim como na atividade da GPx, na concentração da GPx1 e em sua expressão gênica. Níveis urinários reduzidos de 8-isoprostano e nenhuma alteração quanto à capacidade antioxidante total plasmática e quanto aos marcadores inflamatórios foram observados após o período de intervenção. Por outro lado, houve um aumento nas concentrações séricas das moléculas de adesão celulares. Portanto, pode-se concluir que a suplementação com castanha-do-brasil mostrou-se efetiva em melhorar o estado nutricional relativo ao selênio dos pacientes e os marcadores de estresse oxidativo, todavia a ingestão de 350 µgSe/dia não foi suficiente para promover uma melhora do quadro inflamatório. Além disso, a presença do polimorfismo Pro198Leu modificou as respostas dos indivíduos CT e TT em relação à suplementação, sendo inferior à dos indivíduos CC

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, manifested by swelling and joint impairment. These pathology involves excessive free radicals production by activated neutrophils leading to lipid peroxidation in cell membranes and increased inflammation. Accordingly, selenium (Brazil-nut as main source) is an important factor reducing hydroperoxides through the improvement of glutathione peroxidase (GPx) activity. However, studies evaluating their association with oxidative stress biomarkers and inflammation in RA patients are scarce. Thus, the assessment of the in vivo potential Brazil nut supplementation on the parameters described above and its relationship to the polymorphism Pro198Leu in GPx1 gene in patients with rheumatoid arthritis, come to fill this gap. First of all, we analysed macronutrients and selenium content in Brazil nut. This is a longitudinal study with 46 RA patients attending rheumatologic treatment at Federal University of São Paulo and whose mean age were 55.2 ± 10.9 years. The present study was carried out by two phases, before and after one Brazil ingestion. We evaluated selenium status by spectrophotometry absorption with hydride generation; body composition, SOD, GPx activites, GPx1 concentration and 8- isoprostane levels, using commercial Kits; gene expression by RT-PCR and genotyping using real time PCR. Besides, inflamatory biomarkers were performed (fibrinogen, C reactive protein, IL-6, IL-10, TNF-α, IL-1ß, IL-2, VCAM, ICAM, PAI-1 e sE-selectin by ELISA. The wild genotype (Pro/Pro) was observed in 57.63% of the participants, 35.59% were heterozygote for variant allele (Pro/Leu) and 6.78% had two variant alleles. Patients with rheumatoid arthritis had low selenium intake and after the intervention, consumption of this element increased significantly. Selenium status increased significantely after Brazil nut ingestion, as well as GPx activity, GPx1concentration and its gene expression. Reduced urinary levels of 8-isoprostane and no change for total plasma antioxidant capacity and markers for inflammation were observed after the intervention period. On the other hand, there was an increase in serum concentrations of cell adhesion molecules. Therefore, it can be concluded that Brazil-nut supplementation proved to be effective in improving selenium status and markers of oxidative stress in RA patients, however ingestion of 350 µgSe/day wasn't enough to ameliorate inflammation. Besides, the presence of Pro198Leu polymorphisms interfere in supllementation response in CT and TT groups, being less responsive than CC ones

Humans , Male , Female , Arthritis, Rheumatoid/pathology , Cytokines/adverse effects , Polymorphism, Genetic , Selenium/administration & dosage , Bertholletia/metabolism , Glutathione Peroxidase/adverse effects , Inflammation/classification , Oxidative Stress
Biol. Res ; 47: 1-8, 2014. graf
Article in English | LILACS | ID: biblio-950737


BACKGROUND: The root of Angelica sinensis (AS), also known as "Dang-gui," was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time. This study aimed to determine the effects of ethyl acetate fraction from Angelica sinensis (EAAS) on the interleukin-1ß (IL-1ß)-induced proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) 2, and prostaglandin E2 (PGE2), involved in articular bone and cartilage destruction, by RASFs. RESULTS: RASF proliferation was evaluated with cholecystokinin octapeptide (CCK-8) reagent in the presence of IL-1ß with/without EAAS. Expression of MMPs, tissue inhibitor of metalloproteinases-1 (TIMP-1), COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signaling molecules, including p-ERK, p-p38, p-JNK, and NF-κB, were examined using immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. EAAS inhibited IL-1ß-induced RASF proliferation; MMP-1, MMP-3, and COX-2 mRNA and protein expressions; and PGE2 production. EAAS also inhibits the phosphorylation of ERK-1/2, p38, and JNK, and activation of NF-κB by IL-1ß. CONCLUSION: EAAS might be a new therapeutic modality for rheumatoid arthritis management.

Humans , Arthritis, Rheumatoid/metabolism , Bursa, Synovial/cytology , Inflammation Mediators/metabolism , Angelica sinensis/chemistry , Cell Proliferation/drug effects , Fibroblasts/drug effects , Arthritis, Rheumatoid/pathology , Recombinant Proteins/pharmacology , Enzyme-Linked Immunosorbent Assay , Plant Extracts/pharmacology , Dinoprostone/metabolism , Immunoblotting , NF-kappa B/drug effects , Plant Roots/chemistry , Matrix Metalloproteinases/drug effects , Matrix Metalloproteinases/metabolism , Herbal Medicine , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/metabolism , Interleukin-1beta/pharmacology , Primary Cell Culture , Real-Time Polymerase Chain Reaction , Fibroblasts/cytology , Fibroblasts/metabolism , Flow Cytometry , Knee Joint/cytology , Acetates
Fisioter. pesqui ; 20(4): 336-342, out.-dez. 2013. ilus, tab
Article in Portuguese | LILACS | ID: lil-699049


Controle postural, estabilidade nos movimentos voluntários, reação às perturbações externas e propriocepção constituem elementos básicos para a manutenção do equilíbrio. Pessoas com Artrite Reumatoide (AR) têm dificuldade em manter o controle postural, prejudicando o equilíbrio nas Atividades de Vida Diárias (AVD's), tornando-se um importante fator de risco para quedas. O presente estudo teve por objetivo avaliar o equilíbrio corporal de indivíduos com AR, em função do nível de atividade da doença. Foram avaliados 24 indivíduos com 54,66±9,52 anos. Todos foram submetidos à aplicação de questionário de identificação e história clínica, avaliações antropométricas, coleta de amostra sanguínea para análise de Proteína C-Reativa (PCR), determinação do nível de atividade da doença por meio do Disease Activity Score (DAS-28) e avaliação do equilíbrio através dos testes: Escala de Equilíbrio de Berg (EEB) e Timed Up and Go (TUG). Os pacientes foram divididos em três grupos: baixa, moderada e alta atividade da doença. Os resultados dos testes de equilíbrio demonstraram que, embora a amostra tenha apresentado baixo risco para quedas, o grupo em alta atividade da doença apresentou maior distribuição de frequência (57,2%) nos escores entre 48-52 na EEB, em comparação ao grupo moderada atividade, cuja distribuição de frequência predominou nos escores entre 53 e 56 (92,3%-p<0,05). Também foi verificada diferença no tempo de execução do TUG, entre os grupos alta (11,86±4,62s) e moderada (9,71±0,90s) atividade da doença (p<0,05). Estes dados evidenciam que o nível de atividade da doença pode influenciar na realização dos testes EEB e TUG, sugerindo um aumento do risco de quedas ou até mesmo uma dependência na realização de suas AVD's em função do aumento do nível de atividade da doença...

Postural control, stability in voluntary movements in response to external disturbances and proprioception are basic elements for maintaining balance. People with Rheumatoid Arthritis (RA) have difficulty maintaining postural control, undermining the balance in the Activities of Daily Living (ADL's), making it an important risk factor for falls. The present study aimed to evaluate the body balance of individuals with RA, according to the level of disease activity. We evaluated 24 individuals with 54.66±9.52 years. All underwent a questionnaire identification and medical history, anthropometric measurements, blood sampling for analysis of C-Reactive Protein (CRP), determining the level of disease activity using the DAS-28 and equilibrium through tests: Berg Balance Scale (BBS) and TUG. Patients were divided into three groups: low, moderate and high disease activity. The results of equilibrium tests showed that, although the sample has presented low risk for falls, the group in high disease activity had higher frequency distribution (57.2%) in scores between 48-52 in the BBS compared to the moderate activity group, whose frequency distribution prevailed in the scores between 53 and 56 (92.3%-p<0.05). It was also observed differences in the time of the TUG execution between groups high (11.86±4.62 s) and moderate (9.71±0.90 s) disease activity (p<0.05). These data show that the level of disease activity can influence the achievement of the BBS and TUG tests, suggesting an increased risk of falls or even a dependency in performing their ADL's due to the increased level of disease activity...

Control postural, estabilidad en los movimientos voluntarios, reacción a las perturbaciones externas y propiocepción constituyen elementos básicos para la manutención del equilibrio. Personas con Artritis Reumatoidea (AR) tienen dificultad en mantener el control postural, perjudicando el equilibrio en las Actividades de Vida Diarias (AVD's), volviéndose un importante factor de riesgo de caídas. El presente estudio tuvo por objetivo evaluar el equilibrio corporal de individuos con AR, en función del nivel de actividad de la enfermedad. Fueron evaluados 24 individuos con 54,66±9,52 años. Todos fueron sometidos a la aplicación de cuestionario de identificación e historia clínica, evaluaciones antropométricas, colecta de muestra sanguínea para análisis de Proteína C-Reactiva (PCR), determinación del nivel de actividad de la enfermedad por medio del Disease Activity Score (DAS-28) y evaluación del equilibrio a través de los tests: Escala de Equilibrio de Berg (EEB) y Timed Up and Go (TUG). Los pacientes fueron divididos en tres grupos: baja, moderada y alta actividad de la enfermedad. Los resultados de los tests de equilibrio demostraron que, aunque la muestra haya presentado bajo riesgo de caídas, el grupo en alta actividad de la enfermedad presentó mayor distribución de frecuencia (57,2%) en los escores entre 48-52 en la EEB, en comparación con el grupo moderada actividad, cuya distribución de frecuencia predominó en los escores entre 53 y 56 (92,3%-p<0,05). También fue verificada diferencia en el tiempo de ejecución del TUG, entre los grupos alta (11,86±4,62s) y moderada (9,71±0,90s) actividad de la enfermedad (p<0,05). Estos datos evidencian que el nivel de actividad de la enfermedad puede influenciar en la realización de los tests EEB y TUG, sugiriendo un aumento del riesgo de caídas o aun una dependencia en la realización de sus AVD's en función del aumento del nivel de actividades de la enfermedad...

Humans , Male , Female , Middle Aged , Activities of Daily Living , Accidental Falls/prevention & control , Arthritis, Rheumatoid/pathology , C-Reactive Protein , Postural Balance , Joints/physiopathology , Surveys and Questionnaires , Sickness Impact Profile
Clinics ; 68(4): 475-481, abr. 2013. tab, graf
Article in English | LILACS | ID: lil-674239


OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis. METHODS: In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay. RESULTS: We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis. CONCLUSION: Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis. .

Adult , Aged , Animals , Female , Humans , Male , Mice , Middle Aged , Arthritis, Rheumatoid/metabolism , Osteoclasts/cytology , Receptors, Immunologic/physiology , /blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Bone Marrow Cells/pathology , Cell Differentiation/physiology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunohistochemistry , Osteoclasts/drug effects , Osteoprotegerin/physiology , RANK Ligand/blood , Receptors, Immunologic/analysis , Receptors, Immunologic/antagonists & inhibitors , Synovial Membrane/metabolism
Article in English | WPRIM | ID: wpr-147328


Myeloid-related protein (MRP)8/MRP14 is an endogenous Toll-like receptor 4 (TLR4) ligand and is abundant in synovial fluid (SF) of rheumatoid arthritis (RA) patients. Belonging to damage-associated molecular patterns, it amplifies proinflammatory mediators and facilitates a wide range of inflammatory and autoimmune diseases. Interleukin (IL)-17-producing T-helper (Th)17 cells have a crucial role in RA pathogenesis, and IL-6 is the key factor promoting Th17 differentiation. We investigated whether the level of MRP8/MRP14 is positively associated with IL-6 and IL-17 levels in RA SF and found that MRP8/MRP14 level had a significant correlation with IL-6 and IL-17 levels in RA SF. We also observed that MRP8-induced IL-17 production by peripheral blood mononuclear cells but MRP14 did not. Upon stimulation with MRP8, IL-6 production was enhanced by RA fibroblast-like synoviocytes (FLS) and was further elevated by coculturing RA FLS with activated CD4+ T cells. Moreover, we demonstrated that MRP8-activated IL-6 production by RA FLS promoted differentiation of Th17 cells using the coculture system consisting of CD4+ T cells and RA FLS. In addition, IL-6 blockade attenuated Th17 polarization of CD4+ T cells in the cocultures. Inhibitor studies revealed that MRP8 increased IL-6 production in RA FLS via TLR4/phosphoinositide 3-kinase/nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways. Our results show that MRP8 has a crucial role in stimulating IL-6 expression by RA FLS, and subsequently promotes Th17 differentiation in RA, suggesting that neutralizing MRP8 level in RA synovium may be an effective therapeutic strategy in RA treatment.

ATP-Binding Cassette Transporters/metabolism , Adult , Aged , Arthritis, Rheumatoid/pathology , CD4-Positive T-Lymphocytes/metabolism , Calgranulin B/metabolism , Cell Differentiation/immunology , Fibroblasts/metabolism , Humans , Inflammation Mediators/metabolism , Interleukin-17/metabolism , Interleukin-6/biosynthesis , Middle Aged , Signal Transduction/immunology , Synovial Fluid/cytology , Synovial Membrane/metabolism , Th17 Cells/pathology , Toll-Like Receptor 4/metabolism , Up-Regulation
Rev. Méd. Clín. Condes ; 23(4): 458-463, jul. 2012. tab, ilus
Article in Spanish | LILACS | ID: biblio-1145403


Las fallas en el control de las respuestas inmunes fisiológicas o en la mantención de la tolerancia a lo propio, produce enfermedades en las cuales el mecanismo patogénico primario es inmunológico. Estas respuestas inmunes descontroladas se llaman mecanismo de hipersensibilidad y serán revisadas en este artículo, basándonos en las clasificaciones de Gell y Coombs y la más reciente de los mecanismos de daño mediados por células.

Failure to control physiologic immune responses or to maintain self-tolerance leads to diseases in wich the primary pathogenic mechanism is immunologic. These uncontrolled immune reactions are called hypersensitivity responses, and are reviewed in this article, based upon the Gell and Coombs and the more recent cell-mediated hypersensitivity reactions classifications.

Humans , Hypersensitivity/pathology , Immune System Diseases/immunology , Immune System Diseases/pathology , Arthritis, Rheumatoid/pathology
Article in Korean | WPRIM | ID: wpr-175984


PURPOSE: The purpose of this predictive study was to identify factors affecting health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA). METHODS: The participants in this study were 131 patients with RA who were recruited from the outpatient clinic of a university hospital in Seoul. Disease activity in rheumatoid arthritis was evaluated by calculating the Disease Activity Score 28. Disability in activities of daily living (ADL) was assessed with the Korean Health Assessment Questionnaire, and depression with The Center for Epidemiologic Studies Depression Scale. HRQoL was evaluated using The Short Form 36 Health Survey. Data were analyzed using descriptive statistics, correlation, and hierarchical multiple regression. RESULTS: Pain, disability in ADL, disease activity, and depression correlated negatively with physical and mental dimensions of HRQoL. But hierachical multiple regression analysis revealed that disability in ADL and depression were the only variables negatively influencing physical and mental QoL after adjustment for influences of sociodemographic variables. CONCLUSION: Results of this study suggest that disability in ADL and depression, rather than disease activity and pain have profound effects on HRQoL in patients with RA. Further studies are needed to assess the predictive ability of disease activity and pain on HRQoL in this population.

Activities of Daily Living , Adaptation, Psychological , Adult , Aged , Arthritis, Rheumatoid/pathology , Depression , Female , Health Status , Hospitals, University , Humans , Male , Middle Aged , Pain , Quality of Life , Surveys and Questionnaires , Republic of Korea
Rev. venez. cir. ortop. traumatol ; 43(2): 16-20, dic. 2011. ilus
Article in Spanish | LILACS | ID: lil-654076


Diversos tipos de fijación han sido utilizados para la artrodesis Tibiotalocalcánea. El propósito de este estudio es analizar retrospectivamente el uso de la placa bloqueada de humero proximal para la fijación de esta artrodesis. Entre Julio 2007 y Julio 2010 se realizaron 12 artrodesis tibiotalocalcánea en 12 pacientes con placa bloqueada de húmero proximal a través de un abordaje lateral extendido previa resección del Peroné distal. Los pacientes presentaban como diagnóstico preoperatorio: artrítis reumatoidea, artropatía de Charcot y osteoartrosis postraumática. Los pacientes fueron seguidos por un periodo de 7 meses y 3 años (media de 19 meses). Todos los pacientes obtuvieron fusión de sus artrodesis en un periodo de 3 a 6 meses. Este estudio demuestra que el uso de placa humeral bloqueada para la fijación de artrodesis tibiotalocalcánea es una excelente opción por la alta incidencia de fusión de la artrodesis y facilidad la lograr correcta alineación del retropié por su forma

There are many options for Tibiotalocalcaneal arthrodesis. The aim of this study is to retrospectively review the role of the inverted proximal humeral locking plate to fix this arthrodesis. Between July 2007 and July 2010, 12 tibiotalocalcaneal arthrodesis were performed in 12 patients with the inverted proximal humeral locking plate thru an extended lateral ankle approach resecting the distal fibula. Patients preoperative diagnosis were : rheumathoid arthritis, Charcot arthropaty and posttraumatic osteoarthrosis. Patients were followed for a period between 7 months and 3 years (19 months). All the patients fused they arthrodesis in a period of 3 to 6 months. This study showed that the inverted proximal humeral locking plate is an excellent option for tibiotalocalcaneal arthrodesis because of the high fusion rate and the facility for correct hindfoot alignment because of the plate shape

Humans , Male , Adult , Female , Middle Aged , Arthrodesis , Arthritis, Rheumatoid/pathology , Arthrodesis/methods , Arthropathy, Neurogenic/pathology , Bone Plates , Humeral Fractures/surgery , Humeral Fractures , Osteoarthritis/pathology , Rheumatology
Rev. bras. reumatol ; 51(6): 635-641, dez. 2011. ilus, tab
Article in Portuguese | LILACS | ID: lil-624864


A artrite reumatoide (AR) é uma poliartrite inflamatória crônica que frequentemente causa progressiva destruição articular. O tratamento e o manejo da AR têm se baseado na identificação e na intervenção precoce da doença com medicamentos modificadores da doença (DMARDs). As alterações no tratamento têm resultado em melhora significativa para os pacientes, incluindo redução dos sintomas e dos sinais da doença, preservação articular e redução da progressão de lesões. Métodos de avaliação de resposta ao tratamento e predição do curso da doença são necessários. Em relação ao diagnóstico precoce da AR, estudos longitudinais demonstraram que a imagem por ressonância magnética (IRM) é mais sensível que a radiografia (RX) para demonstrar presença e progressão de erosões ósseas. Por outro lado, muitos fatores de pior prognóstico têm sido relacionados à AR, incluindo fatores demográficos, genéticos, clínicos, imunológicos e radiográficos. Este artigo apresenta a IRM na AR em relação ao seu valor no diagnóstico, no monitoramento e no prognóstico da doença.

Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis that often leads to progressive joint destruction and disability. The treatment and management of RA has been based on early identification of the disease and intervention with disease-modifying antirheumatic drugs (DMARDs). Changes in management have resulted in significant improvements for patients with RA, including reduction of signs and symptoms of disease, joint preservation, and reduction of structural damage progression. In addition, sensitive methods to assess treatment response and predict the course of disease are required. Regarding early diagnosis of RA, longitudinal studies have demonstrated that magnetic resonance imaging (MRI) is more sensitive than X-rays to demonstrate the presence and progression of bone erosions. On the other hand, many factors of poor prognostics have been linked to RA, including demographic, genetic, environmental, clinical, immunological, and radiographic. This paper presents considerations on the use of MRI in RA regarding diagnose, monitoring, and prognostic of disease.

Humans , Arthritis, Rheumatoid/pathology , Magnetic Resonance Imaging