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Briva A Vadász I Lecuona E Welch LC Chen J Dada LA Trejo HE Dumasius V Azzam ZS Myrianthefs PM Batlle D Gruenbaum Y Sznajder JI 《PloS one》2007,2(11):e1238
Background
In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes ∼40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function.Principal Findings
We found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCζ which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools.Conclusions
Our data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange. 相似文献2.
Kallinteri P Fatouros D Klepetsanis P Antimisiaris SG 《Journal of liposome research》2004,14(1-2):27-38
The use of arsenic-containing compounds in cancer therapy is currently being re-considered, after the recent approval of arsenic trioxide (Trisenox) for the treatment of relapsed promyelocytic leukemia (PML). In an attempt to prepare a carrier system to minimize the toxicity of this drug, the aim of this study is to prepare and characterize liposomes encapsulating arsenic trioxide (ATO). For this, we prepared different types of liposomes entrapping ATO: large multilamellar (MLV), sonicated (SUV) and dried reconstituted vesicles (DRV). The techniques used were: thin film hydration, sonication and the DRV method, respectively. Two lipid compositions were studied for each liposome type, EggPC/Chol (1:1) and DSPC/Chol (1:1). After liposome preparation, drug encapsulation was evaluated by measuring arsenic in liposomes. For this, energy-dispersive X-ray fluorescence spectroscopy or atomic absorption was used. In addition, the retention of the drug in the liposomes was evaluated after incubating the liposomes in buffer at 37 degrees C. The experimental results reveal that encapsulation of ATO in liposomes ranges between 0.003 and 0.506 mol/ mol of lipid, and is highest in the DRV vesicles and lowest in the small unilamellar vesicles, as anticipated. Considering the in vitro stability of ATO-encapsulating liposomes: 1) For the PC/Chol liposomes (DRV and MLV), after 24 hours of incubation, more than 70% (or 90% in some cases) of the initially encapsulated amount of ATO was released. 2) The liposomes composed of DSPC/Chol could retain substantially higher amounts of ATO, especially the DRV liposomes (54% retained after 24 h). 3) In the case of PC/Chol, temperature of incubation has no effect on the ATO release after 24 hours, but affects the rate of ATO release in the MLV liposomes, while for the DSPC/Chol liposomes there is a slight increase (statistically insignificant) of ATO release at higher temperature. 相似文献
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Vascular stents influence the post-procedural hemodynamic environment in ways that may encourage restenosis. Understanding how stents influence flow patterns may lead to more hemodynamically compatible stent designs that alleviate thrombus formation and promote endothelialization. This study employed time-resolved Digital Particle Image Velocimetry (DPIV) to compare the hemodynamic performance of two stents in a compliant vessel. The first stent was a rigid insert, representing an extreme compliance mismatch. The second stent was a commercially available nitinol stent with some flexural characteristics. DPIV showed that compliance mismatch promotes the formation of a ring vortex in the vicinity of the stent. Larger compliance mismatch increased both the size and residence time of the ring vortex, and introduced in-flow stagnation points. These results provide detailed quantitative evidence of the hemodynamic effect of stent mechanical properties. Better understanding of these characteristics will provide valuable information for modifying stent design in order to promote long-term patency. 相似文献
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Missirlis F Rahlfs S Dimopoulos N Bauer H Becker K Hilliker A Phillips JP Jäckle H 《Biological chemistry》2003,384(3):463-472
Cellular defense systems against reactive oxygen species (ROS) include thioredoxin reductase (TrxR) and glutathione reductase (GR). They generate sulfhydryl-reducing systems which are coupled to antioxidant enzymes, the thioredoxin and glutathione peroxidases (TPx and GPx). The fruit fly Drosophila lacks a functional GR, suggesting that the thioredoxin system is the major source for recycling glutathione. Whole genome in silico analysis identified two non-selenium containing putative GPx genes. We examined the biochemical characteristics of one of these gene products and found that it lacks GPx activity and functions as a TPx. Transgene-dependent overexpression of the newly identified Glutathione peroxidase homolog with thioredoxin peroxidase activity (Gtpx-1) gene increases resistance to experimentally induced oxidative stress, but does not compensate for the loss of catalase, an enzyme which, like GTPx-1, functions to eliminate hydrogen peroxide. The results suggest that GTPx-1 is part of the Drosophila Trx antioxidant defense system but acts in a genetically distinct pathway or in a different cellular compartment than catalase. 相似文献
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Myrianthefs P Karatzas S Venetsanou K Grouzi E Evagelopoulou P Boutzouka E Fildissis G Spiliotopoulou I Baltopoulos G 《Cytokine》2003,24(6):286-292
We examined seasonal differences in whole blood cytokine production after endotoxin (LPS) stimulation in 17 healthy individuals from an urban area having normal sleep/wakefulness pattern. We used 500 pg/ml of LPS for incubation period of 4 h to stimulate 100 microl of whole blood of the same subjects in June, September, February, and March. We found no differences in the circulating total WBCs and differentials including monocytes between different seasons. We found during September (autumn) a reduced pro-inflammatory cytokine production in terms of TNF-alpha and IL-6 production compared to the other seasons. We also found a reduced anti-inflammatory cytokine production in June (summer) and September (autumn) in terms of IL-10, TNF-RI and TNF-RII compared to February (winter) and March (spring). Our results suggest that in early summer there is a predominating pro-inflammatory cytokine response which is counterbalanced early in autumn. These results may have significant implications in the determination of reference values, in exploration of immune response and inflammatory disease prevalence between different seasons, in determining LPS tolerance (immunoparalysis) and planning clinical trials and immunomodulary therapies. However, the effect of dark/light exposure differences on the circadian periodicity in the responsiveness of immune cells during different seasons should be further investigated. 相似文献
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Yu‐Kuang Liao Maël Brossard Dan‐Hua Hsieh Tzu‐Neng Lin Martin D. B. Charlton Shun‐Jen Cheng Chyong‐Hua Chen Ji‐Lin Shen Lung‐Teng Cheng Tung‐Po Hsieh Fang‐I Lai Shou‐Yi Kuo Hao‐Chung Kuo Pavlos G. Savvidis Pavlos G. Lagoudakis 《Liver Transplantation》2015,5(2)
A novel scheme for hybridizing inkjet‐printed thin film Cu(In,Ga)Se2 (CIGS) solar cells with self‐assembled clusters of nanocrystal quantum dots (NQDs), which provides a 10.9% relative enhancement of the photon conversion efficiency (PCE), is demonstrated. A non‐uniform layer of NQD aggregates is deposited between the transparent conductive oxide and a CdS/CIGS p‐n junction using low cost pulsed‐spray deposition. Hybridization significantly improves the external quantum efficiency of the hybrid devices in the absorption range of the NQDs and in the red to near‐IR parts of the spectrum. The low wavelength response enhancement is found to be induced by luminescent down‐shifting (LDS) from the NQD layer, while the increase at longer wavelengths is attributed to internal scattering from NQD aggregates. LDS is demonstrated using time‐resolved spectroscopy, and the morphology of the NQD layer is investigated in fluorescence microscopy and cross‐sectional transmission electron microscopy. The influence of the NQD dose on the PCE of the hybrid devices is investigated and an optimum value is obtained. The low costs and limited material consumptions associated with pulsed‐spray deposition make these flexible hybrid devices promising candidates to help push thin‐film photovoltaic technology towards grid parity. 相似文献
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Andrew Lucas Michaela Lucas Anette Strhyn Niamh M. Keane Elizabeth McKinnon Rebecca Pavlos Ellen M. Moran Viola Meyer-Pannwitt Silvana Gaudieri Lloyd D’Orsogna Spyros Kalams David A. Ostrov S?ren Buus Bjoern Peters Simon Mallal Elizabeth Phillips 《PloS one》2015,10(2)
BackgroundFifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population.MethodsTo determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling.ResultsAbacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells.ConclusionsWe propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection. 相似文献
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Chrysanthia A. Leontiou Michael D. Hadjidaniel Petros Mina Pavlos Antoniou Marios Ioannides Philippos C. Patsalis 《PloS one》2015,10(8)