O potencial uso do riluzole no tratamento do câncer: revisão sistemática

Riluzole is a medication that has been used in the treatment of amyotrophic lateral sclerosis (ALS). Experimental studies have shown inhibitory effects on tumor growth with its administration. The aim of this systematic review was to analyze the potential of the treatment of canceres with the use of riluzole. The databases Web of Science, Scopus and PubMed were screened for published studies between 2007 and 2021 using the keywords cancer and riluzole. In the discussion section not only the relation between glutamate and cancer is examined but also how riluzole acts as an important signaling inhibitor of this component in regard to the growth rate and invasiveness of specific types of cancer. Most of the studies in vitro, in vivo and in humans report that riluzole has presented itself as a promising medication in the treatment of specific types of cancer. However, further researches are made necessary before making definite conclusions on the use of this drug in such cases. Keywords: Neoplasms; Riluzole.O riluzole tem sido usado para o tratamento da Esclerose Lateral Amiotrófica (ELA). Estudos experimentais têm mostrado inibição do crescimento tumoral com riluzole. O objetivo desta revisão sistemática foi analisar as potencialidades do tratamento de cânceres com uso de riluzole. Foram investigadas publicações científicas nas bases Web of Science, Scopus e Pubmed de 2007 a 2021 com os termos câncer e riluzole. A discussão mostra a relação do glutamato com o câncer e como o riluzole atua como um importante inibidor da sinalização deste componente relacionado com a taxa de crescimento e invasibilidade de tipos específicos de câncer. A maioria dos diferentes estudos in vitro, in vivo ou em humanos relata que o riluzole tem se apresentado como uma droga promissora no tratamento de tipos específicos de câncer. No entanto, mais pesquisas tornam-se necessárias antes de conclusões definitivas sobre o uso de riluzole para diversos tipos de câncer. Palavras-chave: Neoplasias; Riluzole

A influência do isolamento social na incidência de positividade nos testes de covid-19 em região metropolitana de São Paulo, Brasil

Introduction: With the arrival of the SARS-CoV-2 (Coronavirus 2 of severe acute respiratory syndrome) pandemic in Brazil, especially in the city of São Paulo, there was a need to apply social isolation policies associated with testing, covering all municipalities. The Clinical Analysis Laboratory of Centro Universitário FMABC was one of the first laboratories to receive certification and qualification to perform RT-PCR (reverse transcriptase reaction followed by polymerase chain reaction) tests in the metropolitan region of São Paulo. Objective: Aim to analyze the influence of adopting social isolation on the incidence of positivity in COVID-19 tests in the metropolitan region of São Paulo, Brazil. Methods: a descriptive study carried out from March to May 2020, epidemiological data were collected from each unit served and organized by the data controllership team of the Clinical Analysis Laboratory of FMABC. Epidemiological, demographic, and laboratory data were extracted from the Matrix® outpatient data management system. Clinically suspected cases and confirmed by laboratory tests (RT-PCR and serological tests) were entered. The tests were divided into serological tests using the RT-PCR molecular test, on samples of nasopharyngeal mucosal scrapings collected with sterile Swab. Results: It were evaluated PCR test and antibody presence (IgA, IgM and IgG) in blood samples of 16.297 patients. 22.718 tests were performed for the diagnosis of COVID-19, both RT-PCR (10.410 tests) and serological tests to detect anti-SARS-CoV-2 antibodies, IgA, IgM and IgG, a total of 16.297 patients were assessed, 63% women and 37% men. It was observed that the social isolation policies adopted during this period contained the massive expansion of contamination, at least while the social isolation rates were above 55%. Conclusion: The data of this study demonstrated the effectiveness of social isolation in containing the positive contamination of SARS-CoV-2 in the metropolitan region of São Paulo, at least for the first three months.Introdução: com a chegada da pandemia de SARS-CoV-2 (Coronavirus 2 da síndrome respiratória aguda grave) ao Brasil, especialmente na cidade de São Paulo, houve a necessidade de aplicar medidas de distanciamento social associado a testagem, que abrangesse todos os municípios. A região metropolitana de São Paulo compreende 39 municípios e possui uma rede de laboratórios habilitados a realizar a testagem para a detecção do coronavírus, tanto testes sorológicos quanto moleculares. O Laboratório de Análises Clínicas do Centro Universitário ABC/FMABC foi um dos primeiros laboratórios a receber a certificação e habilitação para realizar os testes RT-PCR (reação da transcriptase reversa seguida pela reação em cadeia da polimerase) na região metropolitana de São Paulo. Objetivo: analisar a influência da adoção do isolamento social na incidência de positividade nos testes de COVID-19 em região metropolitana de São Paulo, Brasil. Método: estudo descritivo realizado no período de março a maio de 2020, os dados epidemiológicos foram coletados de cada unidade atendida e organizada pela equipe de controladoria de dados do Laboratório de Análises Clínicas da FMABC. Os dados epidemiológicos, demográficos e laboratoriais foram extraídos do sistema Matrix® de gerenciamento de dados ambulatoriais. Foram inseridos os casos clinicamente suspeitos e confirmados por testes de laboratório (RT-PCR e testes sorológicos). Os testes foram divididos em testes sorológicos no teste molecular RT-PCR, em amostras de raspado de mucosa nasofaríngea coletada com Swab estéril. Resultados: foram avaliados o teste de RT-PCR e a presença de anticorpos (IgA, IgM e IgG) em amostras de sangue de 16.297 pacientes. Foram realizados 22.718 testes para o diagnóstico de COVID-19, tanto RT-PCR (10.410 testes), quanto testes sorológicos para detecção de anticorpos anti-SARS-CoV-2, IgA, IgM e IgG, um total de 16.297 pacientes foram avaliados, 63% mulheres e 37% homens. Observou-se que as políticas de isolamento social adotadas nesse período continham a expansão massiva da contaminação, pelo menos enquanto as taxas de isolamento social eram superiores a 55%. Conclusão: nossos dados demonstraram a efetividade do isolamento social na retenção da positividade da contaminação do SARS-CoV-2 nas cidades contempladas pelo serviço de testagem do Centro Universitário Saúde ABC, pelo menos nos três primeiros meses

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile

Abstract Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy—DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult—DMA—or elderly—DME and control sham adult—CSA—or control sham elderly—CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

16 janvier 19111911/01/16 (A12,N3745)

Early infiltration of p40IL12 +

INTRODUCTION: Macrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2‐related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro‐inflammatory macrophages dictates tissue scarring after injury. METHODS AND RESULTS: We first determined that tissue‐localized macrophages exhibit a pro‐inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro‐resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage. Then, we evaluated the effects of injecting macrophages differentiated in vitro in the presence of IFNγ + LPS or IL4 + IL13 or non‐differentiated macrophages (hereafter, M0) on promoting inflammation and progression of chronic injury in macrophage‐depleted mice. In addition to enhancing the expression of pro‐inflammatory cytokines, the injection of M (IFNγ + LPS), but not M (IL4 + IL13) or M0, accentuated fibrosis while augmenting levels of anti‐inflammatory molecules, increasing collagen deposition and impairing organ function. We observed a similar profile after injection of sorted CCR7(+)CD11b(+) cells and a more pronounced effect of M (IFNγ + LPS) cells originated from Stat6(−/−) mice. The injection of M (IFNγ + LPS) cells was associated with the up‐regulation of inflammation‐ and fibrosis‐related proteins (Thbs1, Mmp7, Mmp8, and Mmp13). CONCLUSIONS: Our results suggest that pro‐inflammatory macrophages promote microenvironmental changes that may lead to fibrogenesis by inducing an inflammatory milieu that alters a network of extracellular‐related genes, culminating in tissue fibrosis

Early infiltration of p40IL12(+)CCR7(+)CD11b(+) cells is critical for fibrosis development

IntroductionMacrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2-related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro-inflammatory macrophages dictates tissue scarring after injury. Methods and ResultsWe first determined that tissue-localized macrophages exhibit a pro-inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro-resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage. Then, we evaluated the effects of injecting macrophages differentiated in vitro in the presence of IFN+LPS or IL4+IL13 or non-differentiated macrophages (hereafter, M0) on promoting inflammation and progression of chronic injury in macrophage-depleted mice. In addition to enhancing the expression of pro-inflammatory cytokines, the injection of M (IFN+LPS), but not M (IL4+IL13) or M0, accentuated fibrosis while augmenting levels of anti-inflammatory molecules, increasing collagen deposition and impairing organ function. We observed a similar profile after injection of sorted CCR7(+)CD11b(+) cells and a more pronounced effect of M (IFN+LPS) cells originated from Stat6(-/-) mice. The injection of M (IFN+LPS) cells was associated with the up-regulation of inflammation- and fibrosis-related proteins (Thbs1, Mmp7, Mmp8, and Mmp13). ConclusionsOur results suggest that pro-inflammatory macrophages promote microenvironmental changes that may lead to fibrogenesis by inducing an inflammatory milieu that alters a network of extracellular-related genes, culminating in tissue fibrosis.CNPqFapesp [2012/02270-2]Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, BrazilUniv Sao Paulo, Dept Pediat, Fac Med, FMUSP, Sao Paulo, BrazilUniv Sao Paulo, Inst Biomed Sci, Dept Cellular Biol, Sao Paulo, BrazilUniv Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, BrazilUniv Sao Paulo, Renal Pathophysiol Lab LIM16, Fac Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, BrazilFAPESP:2012/02270-2Web of Scienc

Intravital microscopy: Taking a close look inside the living organisms

status: publishe