Aspirin is a unique nonsteroidal anti-inflammatory drug; at high doses (aspirinhigh, 1g), it is anti-inflammatory stemming from the inhibition of cyclooxygenase and proinflammatory signaling pathways including NF-κB, but is cardioprotective at lower doses (aspirinlow, 75 mg). The latter arises from the inhibition of thromboxane (Tx) B2, a prothrombotic eicosanoid also implicated in polymorphonuclear leukocyte trafficking. As a result, aspirinlow is widely used as a primary and secondary preventative against vascular disease. Despite this and its ability to synthesize proresolution 15-epi-lipoxin A4 it is not known whether aspirinlow is anti-inflammatory in humans. To address this, we generated skin blisters by topically applying cantharidin on the forearm of healthy male volunteers, causing an acute inflammatory response including dermal edema formation and leukocyte trafficking. Although not affecting blister fluid volume, aspirinlow (75 mg, oral, once daily/10 days) reduced polymorphonuclear leukocyte and macrophage accumulation independent of NF-κB-regulated gene expression and inhibition of conventional prostanoids. However, aspirinlow triggered 15-epi-lipoxin A4 synthesis and up-regulated its receptor (FPRL1, ALX). From complimentary in vitro experiments, we propose that 15-epi-lipoxin A4 exerts its protective effects by triggering antiadhesive NO, thereby dampening leukocyte/endothelial cell interaction and subsequent extravascular leukocyte migration. Since similar findings were obtained from murine zymosan-induced peritonitis, we suggest that aspirinlow possesses the ability to inhibit mammalian innate immune-mediated responses. This highlights 15-epi-lipoxin A4 as a novel anti-inflammatory working through a defined receptor and suggests that mimicking its mode of action represents a new approach to treating inflammation-driven diseases.

Endothelin-1 (ET-1) is a potent vasoconstrictor and co-mitogen for vascular smooth muscle and is implicated in pulmonary vascular remodeling and the development of pulmonary arterial hypertension. Vascular smooth muscle is an important source of ET-1. Here we demonstrate synergistic induction of preproET-1 message RNA and release of mature peptide by a combination of tumor necrosis factor ␣ (TNF␣) and interferon ␥ (IFN␥) in primary human pulmonary artery smooth muscle cells. This induction was prevented by pretreatment with the histone acetyltransferase inhibitor anacardic acid. TNF␣ induced a rapid and prolonged pattern of nuclear factor (NF)-B p65 subunit activation and binding to the native preproET-1 promoter. In contrast, IFN␥ induced a delayed activation of interferon regulatory factor-1 without any effect on NF-B p65 nuclear localization or consensus DNA binding. However, we found cooperative p65 binding and histone H4 acetylation at distinct B sites in the preproET-1 promoter after stimulation with both TNF␣ and IFN␥. This was associated with enhanced recruitment of RNA polymerase II to the ATG start site and read-through of the ET-1 coding region. Understanding such mechanisms is crucial in determining the key control points in ET-1 release. This has particular relevance to developing novel treatments targeted at the inflammatory component of pulmonary vascular remodeling.Endothelin-1 is a 21-amino acid peptide which is known to be both a potent vasoconstrictor and mitogen for vascular smooth muscle (1, 2). It is released as a 38-amino acid precursor (Big ET- 1 2 ) before cleavage to the mature ET-1 form. As such it has been implicated in the pathogenesis of vascular disease and is particularly associated with pulmonary arterial hypertension (3). Indeed, several endothelin receptor antagonists are now approved for the treatment of pulmonary arterial hypertension (4). However, endothelin receptor antagonists as a class are associated with potentially serious side effects (4), making new treatments aimed at blocking ET-1 synthesis an attractive alternative.Although endothelial cells are thought to be the main source of ET-1 release, several groups including our own have shown that ET-1 can be released from the more numerous vascular smooth muscle cells (5-10). The vascular pathology observed in pulmonary arterial hypertension is propagated by inflammation, and circulating levels of cytokines including tumor necrosis factor ␣ (TNF␣) are elevated in patients with pulmonary arterial hypertension (11-15). In many cell types cytokines mediate their biological effects at least in part by the activation of the nuclear factor B (NF-B) pathway (16), and a role for NF-B in pulmonary arterial hypertension has been proposed (17). In addition, we have shown previously that a combination of TNF␣ and interferon ␥ (IFN␥) stimulates human pulmonary artery smooth muscle (HPASM) cells to release ET-1 (18). However, the mechanisms underlying this effect are unknown.The preproET-1 promoter region has been shown experimental...

The increased EMMPRIN expression in COPD is reflected by an increased release from bronchial EC, which are one of the main source of EMMPRIN. EMMPRIN regulates MMP-9 expression in COPD.

Objective: to compare the entrepreneurial tendency between beginner and graduating students from undergraduate Nursing courses. Method: this is a cross-sectional and quantitative research study. Data was collected from 377 Nursing students from four undergraduate Nursing courses in different Brazilian regions, 162 of them in first year and 215 in last year. Data was collected by means of a social and academic characterization form and the General Entrepreneurial Tendency Test. Data analysis was conducted by means of descriptive and inferential statistics. Results: the scores of the beginner students were below the mean in all dimensions of the instrument. The senior year students were above the test mean in the Impulse and determination dimension. A statistically significant difference was identified in relation to the course period and to the entrepreneurial tendency in the following dimensions: Need for achievement (p=0.001) and Impulse and determination (p=0.000). Conclusion: the results indicate the importance of investment by universities in the development of an entrepreneurial culture in higher education in Nursing.

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A Inteligência Artificial (IA) tem sido amplamente usada para aprimorar a experiência do usuário (UX) em diferentes sistemas computacionais. Neste contexto, este artigo tem como objetivo analisar a IA usada na Netflix e verificar os sentimentos hedônicos proporcionados a seus usuários. Para atingir o objetivo, são utilizadas diferentes técnicas de avaliação oriundas da áreas de Interação Humano-Computador (IHC). Os resultados demonstram que a combinação das técnicas de avaliação podem contribuir para identificar os sentimentos dispertados pelo sistema de recomendação

Este artigo, considerando a importancia do descarte correto dos resíduos eletrônicos, nos leva a um novo olhar de forma colaborativa para a reflexão dos atores organizacionais, visando a consientização e redução do impacto do descarte incorreto dos resíduos eletrônicos. Desta forma, este artigo tem como objetivo geral, analisar de que forma ocorre o descarte de resíduos eletrônicos urbanos. Os objetivos específicos são verificar quais ferramentas são utilizadas para gerir a destinação dos resíduos, descrevendo sobre conceitos e impactos; e analisar a legislação, quanto ao descarte correto de resúdos eletrônicos. A pesquisa bibliográfica, viabilizou a confirmação da hipótese de que a ausência de informação acarreta na disposição incorreta dos resíduos eletrônicos . Os resultados obtidos com a pesquisa atenderam aos objetivos propostos e confirmaram a hipótese deste artigo.

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