Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.

Hallazgos radiológicos de la enfermedad pulmonar en pacientes Colombianos con esclerodermia

La esclerosis sistémica (ES) es una enfermedad autoinmune multisistémica que afecta principalmente la piel, los pulmones, el tracto gastrointestinal, el corazón y los riñones. La enfermedad pulmonar, presente en casi el 100% de los casos, es el factor con mayor influencia en la mortalidad. El propósito de este estudio es realizar un análisis detallado de la enfermedad pulmonar por tomografía computarizada de alta resolución(TCAR) en pacientes Colombianos con ES, para lo cual se realizó un estudio de prevalencia analítica en 44 pacientes con ES valorados en el Hospital Universitario Mayor Méderi en los últimos 7 años. Los resultados mostraron características demográficas y clínicas similares a las previamente descritas. La prevalencia de enfermedad pulmonar intersticial fue alta, y los hallazgos de fibrosis pulmonar como vidrio esmerilado y panal de abejas se asociaron con la presencia del autoanticuerpo antiSCL70. La medida del diámetro esofágico por TCAR fue mayor en los pacientes con disfagia, antiSCL 70 y linfopenia, los cuales son marcadores de mal pronóstico.

Arterial disease and thrombosis in the antiphospholipid syndrome (APS): A pathogenic role for endothelin-1 (ET-1)

Objective To explore a possible correlation between endothelin 1 (ET-1), the most potent endothelium-derived contracting factor that modulates vascular smooth muscle tone, and arterial disease in patients with the antiphospholipid syndrome (APS). Methods Plasma levels of ET-1 were measured in APS patients with (n = 16) and without (n = 11) arterial thrombosis and in non-APS patients with arterial thrombosis (n = 9). In addition, steady-state prepro-ET-1 messenger RNA (mRNA) levels were determined in endothelial cells treated with a range of human monoclonal anticardiolipin antibodies (aCL) (as anti-β2-glycoprotein I antibodies) by semiquantitative 32P-dCTP-labeled reverse transcription-polymerase chain reaction. Results Compared with healthy controls, markedly increased plasma levels of ET-1 were found in APS patients with arterial thrombosis (2.00 ± 0.87 versus 0.96 ± 0.37 pg/ml; P = 0.0001) but not in other groups. Three human monoclonal aCL induced prepro-ET-1 mRNA levels significantly more than did control monoclonal antibody lacking aCL activity. Conclusion Plasma ET-1 levels correlated significantly with a history of arterial thrombosis in patients with APS. Prepro-ET-1 mRNA was induced by human monoclonal aCL in the in vitro experimental system. The induction of ET-1 by antiphospholipid antibodies might contribute to increased arterial tone, leading to vasospasm and, ultimately, to arterial occlusion.

Capacidade antioxidante in vitro e avaliação da toxicidade aguda in vivo de extratos de folhas de Licania rígida Benth., Licania tomentosa (Benth.) Fritsch e Couepia impressa Prance (Chrysobalanaceae)

Licania rigida Benth., Licania tomentosa (Benth.) Fritsch, and Couepia impressa Prance (Chrysobalanaceae family) plants have long been used medicinally by the people from Northeastern Brazil. Crude extracts and infusions of these plants have been applied in the treatment of several conditions such as diabetes and rheumatism, degenerative diseases with involvement of reactive oxygen species (ROS). The aim of this study was to evaluate the aqueous, ethanolic, and hydroethanolic leaves extracts antioxidant capacity of these species, using several in vitro assay systems (reducing power, DPPH● scavenging, the β-carotene linoleate model system and lipid peroxidation inhibition in rat brain homogenate, using thiobarbituric acid reactive substances - TBARS). The oral acute toxicity of aqueous extracts was also evaluated in vivo. Results revealed that these extracts possess a potent reducing power and DPPH scavenging ability, as well as the ability to prevent TBARS formation in rat brain homogenate in a concentration-dependent manner. Regarding in vivo oral acute toxicity of the aqueous species extracts, no toxic effects were observed upon evaluating physiological, hematological and biochemical parameters. The presence of high levels of phenolics and flavonoids was determined mainly in the ethanol extract. However, the C. impressa hydroethanolic extract, fractionated with hexane, chloroform and ethyl acetate for analysis by NMR 1H, showed more efficient results than the reference antioxidant Carduus marianus. The classes of organics compounds were determined were phenolics in the fraction of ethyl acetate and terpenes in chloroform and hexane fractions. The ethil acetate fraction had the highest content of flavonoids and increased scavenging capacity of DPPH●, possibly by the presence of phenolic compounds. Therefore, a detailed investigation of the phytochemical composition and in vivo study of the C. impressa hydroethanolic extract is suggested to characterize the active compounds of the species

Genotoxicity assessment of Garcinia achachairu Rusby (Clusiaceae) extract in mammalian cells in vivo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

Objective. We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study.Methods. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >= 21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008.Results. of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.Conclusion. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Macrophage Activation Syndrome in Juvenile Systemic Lupus Erythematosus A Multinational Multicenter Study of Thirty-Eight Patients

Objective. To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE).Methods. Cases of juvenile SLE-associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve.Results. The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed.Conclusion. Our findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.

Tumor Necrosis Factor alpha and Interleukin-1 beta Modulate Calcium and Nitric Oxide Signaling in Mechanically Stimulated Osteocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antinociceptive and anti-inflammatory activities of ethanolic extracts of Lychnophora species

Extracts from Lychnophora species are traditionally used in Brazil as anti-inflammatory, and to treat bruise, pain and rheumatism. The ethanolic extract of aerial parts of five species of Lychnophoras and one specie of Lychnophoriopsis were examined for the antinociceptive (hot-plate and writhing tests) and anti-inflammatory (carrageenan-induced paw oedema test) activity in mice, by oral and topical routes, respectively. In the hot-plate test, the Lychnophora pinaster (0.75 g/kg) and Lychnophora ericoides (1.50 g/kg) extracts significantly increased the time for licking of the paws. The species Lychnophora passerina, Lychnophoriopsis candelabrum and Lychnophora pinaster, using the dose of 0.75 g/kg, and Lychnophora ericoides and Lychnophora trichocarpha in both doses evaluated (0.75 and 1.50 g/kg) significantly reduced the number of writhes induced by acetic acid. The administration of Lychnophora pinaster and Lychnophora trichocarpha ointments, in both concentrations evaluated (5 and 10%, w/w), and Lychnophora passerina and Lychnophoriopsis candelabrum, in the concentration of 10%, significantly reduced the paw oedema measured 3 h after carrageenan administration, suggesting, for the first time, an anti-inflammatory activity upon topical administration of these species. The present work comparatively demonstrated the antinociceptive and anti-inflammatory activities of some Brazilian Lychnophoras. (C) 2007 Elsevier B.V. All rights reserved.

Caracterização anatômica, química e antibacteriana de folhas de Brunfelsia uniflora (manacá) presentes na Mata Atlântica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Uso medicinal da pimenta malagueta (Capsicum frutescens L.) em uma comunidade de várzea à margem do rio Amazonas, Santarém, Pará, Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Pediatric Rheumatology International Trials Organization American-College-of-Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: Prospective validation of the definition of improvement

Objective. To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).Methods. Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.Results. The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.Conclusion. PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.