41 research outputs found

    Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

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    The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS

    Neutrophil Extracellular Traps in Breast Cancer and Beyond: Current Perspectives on NET Stimuli, Thrombosis and Metastasis, and Clinical Utility for Diagnosis and Treatment

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    Abstract The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer

    Taxa de geração de resíduos da construção civil em edificações na cidade de João Pessoa

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    O objetivo deste trabalho foi determinar a quantidade de resíduos da construção civil (RCC) em função da área construída da edificação, para efetuar acompanhamento e fiscalização mais eficazes da geração e destinação final em dada obra. Foi escolhida uma amostra representativa das edificações em fase de construção na cidade de João Pessoa. Uma ficha para coleta das características e acompanhamento de volume de RCC descartado ao longo do cronograma de execução da construção foi fornecida aos gestores das edificações; a partir do volume descartado pelas construtoras, determinou-se a massa de RCC gerado em cada obra utilizando uma massa unitária de 1.025 kg m-3 Os resultados indicaram uma taxa média de geração de RCC classe A de 86,27 kg m-². Ainda para os RCC classe A, foram definidos os limites inferior e superior com 90% de confiança para a taxa de geração: 62,31 e 136,02 kg m-² respectivamente. A partir desses valores, o controle da geração e disposição de RCC pode ser realizado pelos órgãos competentes, dando o indicativo de quais obras podem estar infringindo a legislação vigente no tocante à destinação de tais resíduos

    Hydrothermal dolomitization in a complex geodynamic setting (Lower Palaeozoic, northern Spain)

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    Burial hydrothermal dolomitization is a common diagenetic modification in sedimentary basins with implications for oil and gas reservoir performance. Outcrop analogues represent an easily accessible source of data to refine the genetic models and assess risk in hydrocarbon exploration and production. The Palaeozoic succession of northern Spain contains numerous excellent exposures of epigenetically dolomitized limestones, particularly in the Carboniferous and Cambrian. The epigenetic dolomites in the Cambrian carbonates of the Láncara Formation are volumetrically small, but have a large aerial distribution across different tectonic units of the Variscan fold and thrust belt. Coarse crystals, abundant saddle dolomite cement, negative δ18O and fluid inclusion homogenization temperatures between 80°C and 120°C characterize these dolomites, which are petrographically and geochemically similar to the tens of kilometre-sized hydrothermal dolomites replacing the Upper Carboniferous succession in the same area. In both cases, the dolomitizing fluids are derived from highly evaporated sea water, modified to a limited degree through fluid-rock interaction. The dolomitization events affecting both Cambrian and Carboniferous strata are probably related to the same post-orogenic hydrothermal fluid flow. The formation of the post-collisional (latest Carboniferous) Cantabrian arc fostered dolomitization: the extension related to bending of the arc generated deep-reaching faults and strike-slip movements, which favoured the circulation of hot dolomitizing fluids in the outer parts of this orocline. A similar dolomitization process affected other areas of Europe after the main stages of the Variscan orogeny. Dolomitization was a continuous, uninterrupted, isochemical process. Limestone replacement resulted in a major porosity redistribution and focused the fluid flow into the newly created porous zones. Replacement was followed immediately by partial to complete cementation of the pores (including zebra fabrics and vugs) with saddle dolomite. The amount of porosity left depends on the volume of cement and therefore on the volume of fluids available
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