Efeito da acupuntura na variabilidade da frequência cardíaca em indivíduos com esclerose múltipla: um protocolo para ensaio randomizado controlado duplo cego

Backgroung: the growing of patients with multiple sclerosis seeking acupuncture treatment is based on clinical reports of improvements in symptoms. Considering that autonomic impairment, including cardiovascular autonomic dysfunction, is not uncommon in patients with MS, neuromodulation with acupuncture could be an interesting tool to change heart rate variability in this population. Objective: to evaluate heart rate variability in patients with multiple sclerosis, during the application of acupuncture, in order to analyze the behavior of the autonomic nervous system before, during and after therapy and changes in condition after a longitudinal intervention. Methods: a double-blinded randomized sham-controlled crossover trial with a 1:1 allocation ratio will be conducted, with 40 individuals without a previous illness, who will constitute the control group, and 40 individuals with Multiple Sclerosis, who will constitute the experimental group, paired by age and sex. All participants will undertake active or sham acupuncture sessions. Discussion: according to the studies found, cardiovascular autonomic dysfunction is expected, with alterations in heart rate variability. Although neuromodulation with acupuncture can control pain and inflammation, there are still difficulties in affirming whether the balance between the sympathetic and parasympathetic systems can be changed by acupuncture. Trial registration: We registered this trial on ClinicalTrials.gov, ID: NCT05523466Introdução: o crescimento de pacientes com esclerose múltipla que procuram tratamento com acupuntura é baseado em relatos clínicos de melhora dos sintomas. Considerando que o comprometimento autonômico, incluindo a disfunção autonômica cardiovascular, não é incomum em pacientes com EM a neuromodulação com acupuntura pode ser uma ferramenta interessante para alterar a variabilidade da frequência cardíaca nessa população. Objetivo: avaliar a variabilidade da frequência cardíaca em pacientes com esclerose múltipla, durante a aplicação da Acupuntura, a fim de analisar o comportamento do sistema nervoso autônomo antes, durante e após a terapia e as mudanças na condição após uma intervenção longitudinal. Métodos: será realizado um ensaio clínico cruzado, randomizado, placebo-controlado, duplo-cego, com proporção de alocação de 1:1, com 40 indivíduos sem doença prévia, que constituirão o grupo controle, e 40 indivíduos com Esclerose Múltipla, que constituirão o grupo experimental. grupo, pareado por idade e sexo. Todos os participantes realizarão sessões de acupuntura ativas ou simuladas. Discussão: de acordo com os estudos encontrados, é esperada disfunção autonômica cardiovascular, com alterações na variabilidade da frequência cardíaca. Embora a neuromodulação com acupuntura possa controlar a dor e a inflamação, ainda há dificuldades em afirmar se o equilíbrio entre os sistemas simpático e parassimpático pode ser alterado pela acupuntura. Registro do estudo: registramos este estudo em ClinicalTrials.gov, ID: NCT0552346

MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy

International audienceno abstrac

Corrigendum: Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy

International audienc

Matrix Metalloproteinase 2 and 9 Enzymatic Activities are Selectively Increased in the Myocardium of Chronic Chagas Disease Cardiomyopathy Patients: Role of TIMPs

International audienceChronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients

Myocardial Infarction-Associated Transcript, a Long Noncoding RNA, Is Overexpressed During Dilated Cardiomyopathy Due to Chronic Chagas Disease

International audienceno abstrac

Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy

International audienceChagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence of T. cruzi infection, while the others remain asymptomatic (ASY). IFN-γ and IFN-γ-producing Th1-type T cells are increased in peripheral blood and CCC myocardium as compared to ASY patients, while the Th1-antagonizing cytokine IL-10 is more expressed in ASY patients. Importantly IFN-γ-producing Th1-type T cells are the most frequent cytokine-producing T cell subset in CCC myocardium, while expression of Th1-antagonizing cytokines IL-10 and IL-4 is unaltered. The control of IFN-γ production by Th1-type T cells may be a key event for progression toward CCC. A genetic component to disease progression was suggested by the familial aggregation of cases and the association of gene polymorphisms with CCC development. We here investigate the role of gene polymorphisms (SNPs) in several genes involved in the control of IFN-γ production and Th1 T cell differentiation in CCC development

Sensibilizar para o desperdício alimentar : guião do professor

Background: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC

Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy

International audienceAimsChagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis.Methods and ResultsWe conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5’ region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful.ConclusionsGenetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions

<i>In silico</i> analysis predicted differential binding patterns for rs640249 and rs641563 polymorphisms. Gel shift experiment has confirmed this differential binding for rs640249 polymorphism.

<p>The probability of these polymorphisms creating or altering DNA–protein interaction was determined by in silico analysis (<a href="http://www.gene-regulation.com/cgi-bin/pub/programs/match/bin/match.cgi" target="_blank"><u>http://www.gene-regulation.com/cgi-bin/pub/programs/match/bin/match.cgi</u></a>). An 75% threshold score (similarity matrix) was used. For each polymorphism (A, rs1800925; B, rs641563) putative bindings are described. The similarity matrix score is indicated in brackets. <b>C</b>: Electrophoretic mobility shift assays were performed in vitro as described in Materials and Methods. A differential binding pattern was detected for the rs640249A allele. </p