126 research outputs found

    Radiofrequency Ablation of Subpleural Lung Malignancy: Reduced Pain Using an Artificially Created Pneumothorax

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    One of the main issues with radiofrequency (RF) ablation of the subpleural lung malignancy is pain management during and after RF ablation. In this article, we present a case that utilized a technique to decrease the pain associated with RF ablation of a malignancy located within the subpleural lung. Under CT guidance, we created an artificial pneumothorax prior to the RF ablation, which resulted in minimizing the pain usually experienced during and after the procedure. It also decreased the amount of pain medications usually used in patients undergoing RF ablation of a subpleural lung lesion

    Light regime characterization in an airlift photobioreactor for production of microalgae with high starch content

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    The slow development of microalgal biotechnology is due to the failure in the design of large-scale photobioreactors (PBRs) where light energy is efficiently utilized. In this work, both the quality and the amount of light reaching a given point of the PBR were determined and correlated with cell density, light path length, and PBR geometry. This was made for two different geometries of the downcomer of an airlift PBR using optical fiber technology that allows to obtain information about quantitative and qualitative aspects of light patterns. This is important since the ability of microalgae to use the energy of photons is different, depending on the wavelength of the radiation. The results show that the circular geometry allows a more efficient light penetration, especially in the locations with a higher radial coordinate (r) when compared to the plane geometry; these observations were confirmed by the occurrence of a higher fraction of illuminated volume of the PBR for this geometry. An equation is proposed to correlate the relative light intensity with the penetration distance for both geometries and different microalgae cell concentrations. It was shown that the attenuation of light intensity is dependent on its wavelength, cell concentration, geometry of PBR, and the penetration distance of light.Fundação para a Ciência e a Tecnologia (FCT

    Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2

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    © 2017 The Authors. Published by Nature Publishing Group. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/cddis.2017.176Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs. Here, we report the in vitro and in vivo activity of DS in combination with copper (Cu) against CD34(+)/CD38(+) leukemia stem-like cells sorted from KG1α and Kasumi-1 AML cell lines, as well as primary CD34(+) AML samples. DS plus Cu (DS/Cu) displayed marked inhibition of proliferation, induction of apoptosis, and suppression of colony formation in cultured AML cells while sparing the normal counterparts. DS/Cu also significantly inhibited the growth of human CD34(+)/CD38(+) leukemic cell-derived xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was closely associated with activation of the stress-related ROS-JNK pathway as well as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-κB pathways. In summary, our findings indicate that DS/Cu selectively targets leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising LSC-targeted activity of this repurposed agent for treatment of relapsed and refractory AML

    Effects of ambient air pollution on functional status in patients with chronic congestive heart failure: a repeated-measures study

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    <p>Abstract</p> <p>Background</p> <p>Studies using administrative data report a positive association between ambient air pollution and the risk of hospitalization for congestive heart failure (HF). Circulating levels of B-type natriuretic peptide (BNP) are directly associated with cardiac hemodynamics and symptom severity in patients with HF and, therefore, serves as a marker of functional status. We tested the hypothesis that BNP levels would be positively associated with short-term changes in ambient pollution levels among 28 patients with chronic stable HF and impaired systolic function.</p> <p>Methods</p> <p>BNP was measured in whole blood at 0, 6, and 12 weeks. We used linear mixed models to evaluate the association between fine particulate matter (PM<sub>2.5</sub>), carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and black carbon and log(BNP). Lags of 0 to 3 days were considered in separate models. We calculated the intraclass correlation coefficient and within-subject coefficient of variation as measures of reproducibility.</p> <p>Results</p> <p>We found no association between any pollutant and measures of BNP at any lag. For example, a 10 μg/m<sup>3 </sup>increase in PM<sub>2.5 </sub>was associated with a 0.8% (95% CI: -16.4, 21.5; p = 0.94) increase in BNP on the same day. The within-subject coefficient of variation was 45% on the natural scale and 9% on the log scale.</p> <p>Conclusion</p> <p>These results suggest that serial BNP measurements are unlikely to be useful in a longitudinal study of air pollution-related acute health effects. The magnitude of expected ambient air pollution health effects appears small in relation to the considerable within-person variability in BNP levels in this population.</p

    International recommendations for glucose control in adult non diabetic critically ill patients

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    The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishedPour la Société Française d'Anesthésie-Réanimation (SFAR); Société de Réanimation de langue Française (SRLF) and the Experts grou

    Synthesis of a Dual Functional Anti-MDR Tumor Agent PH II-7 with Elucidations of Anti-Tumor Effects and Mechanisms

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    Multidrug resistance mediated by P-glycoprotein in cancer cells has been a major issue that cripples the efficacy of chemotherapy agents. Aimed for improved efficacy against resistant cancer cells, we designed and synthesized 25 oxindole derivatives based on indirubin by structure-activity relationship analysis. The most potent one was named PH II-7, which was effective against 18 cancer cell lines and 5 resistant cell lines in MTT assay. It also significantly inhibited the resistant xenograft tumor growth in mouse model. In cell cycle assay and apoptosis assay conducted with flow cytometry, PH II-7 induced S phase cell cycle arrest and apoptosis even in resistant cells. Consistently revealed by real-time PCR, it modulates the expression of genes related to the cell cycle and apoptosis in these cells, which may contributes to its efficacy against them. By side-chain modification and FITC-labeling of PH II-7, we were able to show with confocal microscopy that not only it was not pumped by P-glycoprotein, it also attenuated the efflux of Adriamycin by P-glycoprotein in MDR tumor cells. Real-time PCR and western blot analysis showed that PH II-7 down-regulated MDR1 gene via protein kinase C alpha (PKCA) pathway, with c-FOS and c-JUN as possible mediators. Taken together, PH II-7 is a dual-functional compound that features both the cytotoxicity against cancer cells and the inhibitory effect on P-gp mediated drug efflux

    Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism

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    Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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