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Background: Children with B-cell acute lymphoblastic leukemia (B-ALL) have an immune imbalance that is marked by remodeling of the hematopoietic compartment, with effects on peripheral blood (PB). Although the bone marrow (BM) is the main maintenance site of malignancy, the frequency with which immune cells and molecules can be monitored is limited, thus the identification of biomarkers in PB becomes an alternative for monitoring the evolution of the disease. Methods: Here, we characterize the systemic immunological profile in children undergoing treatment for B-ALL, and evaluate the performance of cell populations, chemokines and cytokines as potential biomarkers during clinical follow-up. For this purpose, PB samples from 20 patients with B-ALL were collected on diagnosis (D0) and during induction therapy (days 8, 15 and 35). In addition, samples from 28 children were used as a control group (CG). The cellular profile (NK and NKT-cells, Treg, CD3+ T, CD4+ T and CD8+ T cells) and soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL- 4, IL-10 and IL-2) were evaluated via flow cytometry immunophenotyping and cytometric bead array assay. Results: On D0, B-ALL patients showed reduction in the frequency of cell populations, except for CD4+ T and CD8+ T cells, which together with CCL2, CXCL9, CXCL10, IL-6 and IL-10 were elevated in relation to the patients of the CG. On D8 and D15, the patients presented a transition in the immunological profile. While, on D35, they already presented an opposite profile to D0, with an increase in NKT, CD3+ T, CD4+ T and Treg cells, along with CCL5, and a decrease in the levels of CXCL9, CXCL10 and IL-10, thus demonstrating that B-ALL patients present a complex and dynamic immune network during induction therapy. Furthermore, we identified that many immunological mediators could be used to classify the therapeutic response based on currently used parameters. Conclusion: Finally, it is noted that the systemic immunological profile after remission induction still differs significantly when compared to the GC and that multiple immunological mediators performed well as serum biomarkers.
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Abstract INTRODUCTION: Immunological control of Mycobacterium tuberculosis infection is dependent on the cellular immune response, mediated predominantly by Th1 type CD4+ T cells. Polarization of the immune response to Th2 can inhibit the host immune protection against pathogens. Patients with tuberculosis coinfected with helminths demonstrate more severe pulmonary symptoms, a deficiency in the immune response against tuberculosis, and an impaired response to anti-tuberculosis therapy. METHODS: We evaluated the cellular immune response and the impact of the presence of Ascaris lumbricoides on the immune and clinical response in pulmonary tuberculosis patients. Ninety-one individuals were included in the study: 38 tuberculosis patients, 11 tuberculosis patients coinfected with Ascaris lumbricoides and other helminths, 10 Ascaris lumbricoides patients, and 34 non-infected control individuals. Clinical evolution of pulmonary tuberculosis was studied on 0, 30, 60, and 90 days post-diagnosis of Mycobacterium tuberculosis and Ascaris lumbricoides. Furthermore, immune cells and plasma cytokine profiles were examined in mono/coinfection by Mycobacterium tuberculosis and Ascaris lumbricoides using flow cytometry. RESULTS: There were no statistical differences in any of the evaluated parameters and the results indicated that Ascaris lumbricoides infection does not lead to significant clinical repercussions in the presentation and evolution of pulmonary tuberculosis. CONCLUSIONS: The association with Ascaris lumbricoides did not influence the Th1, Th2, and Th17 type responses, or the proportions of T lymphocyte subpopulations. However, higher serum levels of IL-6 in tuberculosis patients may explain the pulmonary parenchymal damage.
Assuntos
Humanos , Animais , Masculino , Feminino , Adulto , Adulto Jovem , Ascaríase/imunologia , Tuberculose Pulmonar/imunologia , Interleucina-6/sangue , Ascaris lumbricoides , Ascaríase/complicações , Fatores de Tempo , Tuberculose Pulmonar/complicações , Anticorpos Anti-Helmínticos/sangue , Estudos de Casos e Controles , Citocinas/imunologia , Citocinas/sangue , Interleucina-6/imunologia , Progressão da Doença , Coinfecção , Citometria de Fluxo , Pessoa de Meia-IdadeRESUMO
Abstract Introduction: Aging is understood as the sum of all biological, psychological and social changes that occur over the years. Associated with aging we list up the changes of morphological and functional order of the immune system: Immunosenescence. Objective This study's objective was to characterize the effect of a brief exercise program on the profile of cytokines and peripheral blood mononuclear cells of elderly individuals in Manaus, AM, Brazil. Materials and methods: Twelve subjects aged 66.8 (± 3.7) years old on average engaged in three weekly sessions of exercises for 16 weeks and, seven subjects aged 66.1 (± 6.7) years on average, who practiced only recreational activities, composed the control group. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and INF-γ were measured using the CBA technique (cytometric Bead Array) and the count of subpopulations of lymphocytes - B, B1, T/CD4, T/CD8, Treg, NK and NKT - was performed using flow cytometry. Results: The relative number of B lymphocytes, T/CD4+ and NKT (CD3+/CD16 +/CD56+) increased significantly (p <0.05) after physical activity, compared to the pre-exercise phase and the control group. In another analysis, each individual in the test group was classified either as major or minor producer of each cytokine; i.e., their values were above or below the cut-off point defined by the median of all measurements of that cytokine. Patterns of cytokine production were observed in the post-exercise group, which allowed defining sets ("signatures") of cytokines that were associated with the practice of short-term physical exercises. Conclusion: Our work showed that exercise induces changes in the count of immune cells, which allows us to infer that it can be used as an alternative to reverse or mitigate the implications of immunosenescence.
Resumo Introdução: O envelhecimento é compreendido como a soma de todas as alterações biológicas, psicológicas e sociais que ocorrem com o passar dos anos. Associadas ao envelhecimento elencam-se as alterações de ordem morfológica e funcional do sistema imunológico: Imunossenescência. Objetivo: Caracterizar o efeito do condicionamento físico breve sobre o perfil de citocinas e células mononucleares do sangue periférico de idosos na cidade de Manaus, AM. Materiais e métodos: Doze indivíduos com idade média de 66,8±3,7 anos realizaram 3 sessões semanais de exercícios físicos por 16 semanas e sete indivíduos com idade média de 66,1±6,7 anos, praticantes de atividades lúdicas, formaram um grupo controle. Os níveis séricos de IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α e INF-γ foram medidos pela técnica CBA (Cytometric Bead Array) e as contagens de subpopulações de linfócitos B, B1, T/CD4, T/CD8, TReg, NK e NKT foram realizadas por citometria de fluxo. Resultados: Observou-se que, após a atividade física, houve aumento significativo (p < 0,05) no número de linfócitos B, T/CD4 + e NKT (CD3 + /CD16 + /CD56 + ), quando comparados à fase pré-treinamento e ao grupo controle. Em outro modelo de análise, qualificando-se cada indivíduo do grupo teste como alto produtor ou baixo produtor das citocinas, observaram-se padrões na fase pós-treinamento que permitiram definir conjuntos ("assinaturas") de citocinas que se expressam associadas ao exercício. Conclusão: Nosso trabalho evidenciou que o exercício induz alterações na contagem de células imunes, o que nos permite inferir que pode ser usado como alternativa para reverter ou atenuar as implicações da imunossenescência.
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Vivemos um momento de transição radical na área da saúde. Com novos modelos de saúde, a atenção é entregue por equipes, avaliada pelos resultados e adquirida como pacotes. Nesta nova configuração, mídias digitais e sociais tornam-se uma fonte cada vez mais importante de valor. As pessoa estão sendo capacitadas a participar mais ativamente de sua própria saúde, fornecendo novas ferramentas para gerenciar as condições crônicas e aliviar a carga sobre os sobrecarregados sistemas de saúde. A saúde é prestada, tradicionalmente, em três espaços: domicílios, clínicas e hospitais. As mídias digitais criaram o quarto espaço, o espaço digital, que inclui: canal digital para saúde, inovação digital e iniciativas digitais de impacto social. No canal digital para saúde, os profissionais de saúde estão implantando mídia digital e social no sistema de saúde tradicional para, por exemplo, consulta de acompanhamento por e-mail e acesso on-line para os resultados de laboratório. Na área de inovação digital para consumidores, mídia digital e social oferecem maneiras novas e melhores para pacientes e cuidadores gerirem doença e saúde e compartilharem experiências com comunidade on-line. Nas iniciativas digitais de impacto social, as organizações dos setores público e privado usam inovações digitais para facilitar comunicações interativas, a fim de prevenir a doença e promover a saúde. Concluindo, o uso das estratégias digitais na área da saúde está cada vez mais presente e, certamente, contribui e contribuirá para a melhoria da prática clínica, porém, ainda se sugere a necessidade de novos estudos bem planejados e de qualidade sobre este novo método.
We are living a moment of a radical transition in the health area. Health care is proportioned by a team, evaluated by results and acquired like packets. In this new way of health care the digital and social media become na important source of value. People are being capable of taking part actively of their own health, providing tools to manage chronic conditions in order to relieve "overburdened" health system. The health traditionally contains three spaces: homes, ambulatories and hospitals. The digital media created the fourth space, the digital space that includes: digital channel for health, digital innovation and digital initiatives of social impact. In the digital channel for health, the health professional are implanting digital and social media in the traditional health system to make the follow up of patients by e-mail, or to have online access of laboratory results. In the digital innovation for consumers social and digital media provide new and better ways for patients and caregivers to manage disease and health and share experiences with online community. In the digital initiatives of social impact, the private and public organizations to prevent disease and promote health. Concluding, the use of digital strategies in the health area is more and more presente and certainly contributes and will contribute to improve clinical practice, however we suggest the need of well-planned new studies for the use of this strategy.