Evaluation of ATP-P2X7 axis during experimental asthma

Atualmente a asma é uma das doenças não transmissíveis mais disseminadas no mundo, com mais de 339 milhões de pessoas vivendo com a doença. Os sintomas relacionados à asma incluem dificuldade respiratória, produção excessiva de muco, tosse e chiado durante a respiração. Esses sintomas são intimamente relacionados às respostas imunes promovidas através do gatilho gerado pelo alérgeno. Na asma experimental, o ATP extracelular e os receptores P2X apresentam um papel importante no desenvolvimento da doença, e essas moléculas parecem contribuir para regulação da produção de anticorpos durante processos infamatórios. Nesse estudo nós investigamos o papel da sinalização através do eixo ATP-P2X7 no desenvolvimento da asma experimental. Foi observado um papel crítico da sinalização através do receptor P2X7 para o desenvolvimento de infiltrado eosinofílico, mas não para a produção de anticorpos IgE durante a asma experimental. Camundongos P2rx7-/- apresentam menor número de células CD4&#43CD44&#43 localizadas no parênquima pulmonar em comparação a camundongos C57BL/6 durante a asma experimental, e apresentam infiltrado de células CD4&#43CD44&#43GATA3&#43, similar aos camundongos não imunizados, mesmo após imunização. Além disso, o linfonodo de camundongos P2rx7-/- imunizados apresentam menor número de células comparados ao de camundongos C57BL/6. Caracterizamos o papel da administração de altas concentrações de ATP (1mM, 4,5mM e 50mM) durante desafios intranasais, demonstrando a regulação através dessas moléculas no recrutamento de eosinófilos e produção de anticorpos IgE, provavelmente através da sinalização pelo receptor P2X7, com aumento da produção de IL-4 e nenhuma alteração em células CD4&#43CD44&#43GATA3&#43. Este estudo contribui para a compreensão de como os sinais de dano afetam o desenvolvimento da asma em modelos experimentais, ressaltando o receptor P2X7 como um potencial alvo terapêutico relacionado a doença pulmonar asmática.Asthma is one of the most non-infectious widespread diseases in the world, with more than 339 million people living with the disease. Asthma-related symptoms include hardness to breath, excessive mucus production, coughing and wheezing. These symptoms are closely related to the immune responses promoted through the trigger generated by the allergen. In experimental asthma, extracellular ATP and P2X play an important role during the development of the disease, and these molecules seem to contribute to the regulation of antibody production during inflammatory processes. In this study we investigated the role of signaling through the ATP-P2X7 axis during the development of experimental asthma. It was observed a critical role of signaling through the P2X7 receptor for the development of eosinophilic infiltrate, but not for production of IgE antibodies during experimental asthma. P2rx7-/- mice showed lower number of CD4&#43CD44&#43 cells localized in the lung parenchyma compared to C57BL/6 mice during experimental asthma, as well as, these mice have CD4&#43CD44&#43GATA3&#43 cell infiltration similar to non-immunized mice, even upon immunization. In addition, mediastinal lymph node of immunized P2rx7-/- mice presented lower number of cells compared to that of C57BL/6 mice. We also characterized the role of ATP at high concentrations (1mM, 4.5mM and 50mM) during intranasal challenges, demonstrating the regulation through these molecules in the recruitment of eosinophils and production of IgE antibodies, probably through signaling by the P2X7 receptor, with increased production of IL-4 and no changes in CD4&#43CD44&#43GATA3&#43 cells. This study contributes to the understanding of how the signs of damage affect the development of asthma in experimental models, highlighting the P2X7 receptor as a potential therapeutic target related to asthmatic lung disease

Molecular and clinical epidemiological surveillance of dengue virus in Paraíba, Northeast Brazil

ABSTRACT INTRODUCTION: Despite being the most prevalent arboviral disease worldwide, dengue has been neglected lately. However, recent epidemics of arboviruses such as Zika and chikungunya in locations throughout the world have alerted health authorities to these diseases. This study evaluated the incidence pattern of dengue, its clinical characteristics, and co-circulation of serotypes from 2007 to 2015 in Paraiba State, Northeast Brazil. METHODS: Data on dengue cases from 2007 to 2015 were extracted from clinical reports of the National System for Notifiable Diseases [Sistema Nacional de Agravos de Notificação (SINAN)] of Brazil provided by the Paraiba Health Department. Reverse transcription polymerase chain reaction (RT-PCR) assays for dengue serotypes were carried out on plasma samples obtained from patients with suspected dengue. The data were analysed using descriptive statistics. RESULTS: According to clinical features, dengue fever [n = 39,083 (70.2%)] and dengue without warning signs [n = 15,365 (27.7%)] were the most common classifications of dengue. On RT-PCR, DENV 1 was the most commonly identified serotype (80.5%) in all years studied. Co-circulation of all four DENV serotypes was observed in 2013 and 2014. Furthermore, we observed an increase in dengue notifications in 2015, possibly due to the rise of Zika and chikungunya. CONCLUSIONS: Our findings support the hypothesis that co-circulation of the four DENV serotypes may be a reason for the increased prevalence of severe forms of dengue in the years studied. This study may contribute to directing research, health policy, and financial resources toward reducing poorly controlled epidemic diseases

Molecular and clinical epidemiological surveillance of dengue virus in Paraíba, Northeast Brazil

<div><p>ABSTRACT INTRODUCTION: Despite being the most prevalent arboviral disease worldwide, dengue has been neglected lately. However, recent epidemics of arboviruses such as Zika and chikungunya in locations throughout the world have alerted health authorities to these diseases. This study evaluated the incidence pattern of dengue, its clinical characteristics, and co-circulation of serotypes from 2007 to 2015 in Paraiba State, Northeast Brazil. METHODS: Data on dengue cases from 2007 to 2015 were extracted from clinical reports of the National System for Notifiable Diseases [Sistema Nacional de Agravos de Notificação (SINAN)] of Brazil provided by the Paraiba Health Department. Reverse transcription polymerase chain reaction (RT-PCR) assays for dengue serotypes were carried out on plasma samples obtained from patients with suspected dengue. The data were analysed using descriptive statistics. RESULTS: According to clinical features, dengue fever [n = 39,083 (70.2%)] and dengue without warning signs [n = 15,365 (27.7%)] were the most common classifications of dengue. On RT-PCR, DENV 1 was the most commonly identified serotype (80.5%) in all years studied. Co-circulation of all four DENV serotypes was observed in 2013 and 2014. Furthermore, we observed an increase in dengue notifications in 2015, possibly due to the rise of Zika and chikungunya. CONCLUSIONS: Our findings support the hypothesis that co-circulation of the four DENV serotypes may be a reason for the increased prevalence of severe forms of dengue in the years studied. This study may contribute to directing research, health policy, and financial resources toward reducing poorly controlled epidemic diseases.</p></div