Altered expression of microRNAs and B lymphocytes during Natalizumab therapy in multiple sclerosis.

MicroRNAs (miRNAs) are a family of non-translated small ribonucleic acids (RNAs) measuring 21-25 nucleotides in length that play various roles in multiple sclerosis (MS). By regulating gene expression via either mediating translational repression or cleavage of the target RNA, miRNAs can alter the expression of transcripts in different cells, such as B lymphocytes, also known as B cells. They are crucial in the pathogenesis of MS; however, they have not been extensively studied during the treatment of some drugs such as natalizumab (NTZ). NTZ is a humanized immunoglobulin G4 antibody antagonist for integrin alpha 4 (α4) used in the treatment of MS. The drug reduces the homing of lymphocytes to inflammation sites. Integrin α4 expression on the cell surface of B cells is related to MS severity, indicating a critical component in the pathogenesis of the disease. NTZ plays an important role in modifying the gene expression in B cells and the levels of miRNAs in the treatment of MS. In this review, we have described changes in gene expression in B cells and the levels of miRNAs during NTZ therapy in MS and its relapse. Studies using the experimental autoimmune encephalomyelitis (EAE) model and those involving patients with MS have described changes in the levels of microRNAs in the regulation of proteins affected by specific miRNAs, gene expression in B cells, and certain functions of B cells as well as their subpopulations. Therefore, there is a possibility that some miRNAs could be studied at different stages of MS during NTZ treatment, and these specific miRNAs can be tested as markers of therapeutic response to this drug in future studies. Physiopathology, gene expression in B cells and their subpopulations can help understand this complex puzzle involving miRNAs and the therapeutic response of patients with MS.

Mast cells: A key component in the pathogenesis of Neuromyelitis Optica Spectrum Disorder?

Neuromyelitis Optica Spectrum Disorder (NMOSD) is characterized as an autoimmune, inflammatory and demyelinating disease of the Central Nervous System (CNS). Its pathogenesis is due to the presence of anti-aquaporin 4 immunoglobulin G1 antibodies (anti-AQP4IgG), with presence of lymphocytes T Helper 1 and 17 (TH1 and TH17), in addition to previous neuroinflammation. The Mast cell (MC) is a granular cell present in all vascularized tissues, close to vessels, nerves, and meninges. In CNS, MCs are in the area postrema, choroid plexus, thalamus and hypothalamus. MC has ability to transmigrate between the nervous tissue and the lymphoid organs, interacting with the cells of both systems. These cells reach the CNS during development through vessel migration. Most MCs reside on the abluminal side of the vessels, where it can communicate with neurons, glial cells, endothelial cells and the extracellular matrix. Considering the role of MCs in neurodegenerative diseases has been extensively discussed, we hypothesized MCs participate in the pathogenesis of NMOSD. This cell represents an innate and adaptive immune response regulator, capable of faster responses than microglial cells. The study of MCs in NMOSD can help to elucidate the pathogenesis of this disease and guide new research for the treatment of patients in the future. We believe this cell is an important component in the cascade of NMOSD neuroinflammation.

Uso de anticoagulantes em pacientes com fibrilação atrial em primeiro evento de AVC e em recidivas / Use of anticoagulants in patients with atrial fibrillation in the first event of AVC and in recidivas

Introdução: A fibrilação atrial (FA) é a causa mais comum de AVC cardioembólico. Esse artigo científico pretende quantificar o número total de pacientes com acidente vascular cerebral cardioembólico portadores de fibrilação atrial prévia, o seguimento do tratamento e a taxa de recorrência. Métodos: estudo retrospectivo (de abril de 2014 a abril de 2015) cujos dados foram extraídos da base JOINVASC e organizados em uma tabela no programa Excel®. Os dados registrados incluíram o total de pacientes que apresentaram AVC cardioembólico inicial ou recorrência de AVC que eram portadores de FA e o uso de medicação anticoagulante ou não. Resultados e conclusões: 49 pacientes com FA conhecida foram encontrados. Desses, 46 receberam anticoagulante após AVC e apenas 3 não receberam tratamento anticoagulante. Entre os pacientes que receberam anticoagulação, 27 usaram varfarina, 3 usaram apixabana, 3 rivaroxabana, 2 dabigatrana e 1 femprocumona. Durante 2 anos, o controle de seguimento foi realizado com os 49 pacientes com FA conhecida, os 3 que não receberam tratamento anticoagulante não sofreram recidiva de AVC ou apresentaram outra comorbidade associada a causas vasculares. Estudo com número maior de sujeitos faz-se necessário para esclarecer o achado de desfecho favorável nos pacientes que não receberam medicação anticoagulante.

Introduction: Atrial fibrillation is the most commonly cause of cardioembolic stroke. This article aim to quantify the total number of patients with cardioembolic stroke that had preview atrial fibrillation, the outcoming of the treatment and if had any recurrence. Methods: It's a retrospective study (April 2014 through April 2015), the data will be registered in a table in the Excel® program, extracted from the data collected from the JOINVASC study of patients who had an initial cardioembolic stroke or recurrence of stroke who had AF and data from the medical record, recording the use or not of anticoagulant and which class. Results and conclusions: In a total of 49 patients with known AF, 46 received anticoagulant after stroke, and only 3 did not receive anticoagulant treatment. Among patients who received anticoagulation, 27 used warfarin, 3 used apixaban, 3 rivaroxaban, 2 dabigatran and 1 phenprocoumon. For 2 years follow-up control was performed with the 49 patients with known AF, the 3 who chose not to receive anticoagulant treatment, after 2 years they had not relapsed or some comorbidity associated with vascular causes. The authors suggest a new study with a larger N, since it can not be affirmed that the non-use is positive.

The advances of Deep Brain Stimulation (DBS) for treatment of Parkinson's disease (PD)

Advanced Parkinson's disease (PD) is characterized by the presence of motor fluctuations, various degrees of dyskinesia, and disability with functional impact on daily living and independence. Therapeutic management aims to extend levodopa (L-DOPA) benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. The concept of deep brain stimulation (DBS) for PD was introduced over 20 years ago, but our understanding of the nuances of this procedure continues to improve. This review aims to demonstrate the advances of DBS in the treatment of PD patients. (AU)