Kratkotrajni učinci izloženosti niskim koncentracijama didušikova oksida u anesteziologa

The aim of this study was to assess whether a sample of 37 anaesthetists occupationally exposed only to N2O showed any deterioration in vigilance and/or mood. The anaesthetists were examined with three neurobehavioural tests (Simple Reaction Time and Colour Word Vigilance to measure the vigilance and Mood Rating Scale to evaluate the level of stress and arousal) and underwent N2O biological monitoring (to correlate the test results with the N2O exposure) on the first and on the last day of the work week, before and after work in the operating room. No significant relationship was found between the biological monitoring and the test results. The only significant statistical difference was found between the beginning and the end of each workday in the arousal level, regardless of the result of the biological monitoring.Cilj je ovoga ispitivanja bio utvrditi do kakvih promjena budnosti i raspoloženja dolazi u 37 anesteziologa profesionalno izloženih didušikovu oksidu. Promjene u budnosti ispitane su s pomoću zadatka jednostavnog vremena reagiranja i zadatka pozornosti, a promjene u raspoloženju s pomoću skale procjene različitih raspoloženja. Mjerenja su izvršena na početku i na kraju prvog i zadnjeg radnog dana u tjednu, a mjerenja didušikova oksida u urinu izvršena su samo na kraju radnog vremena prvoga i posljednjeg radnog dana u tjednu. Nije utvrđena povezanost između rezultata biološkog monitoringa i psihologijskog ispitivanja. Konzistentne statistički značajne razlike utvrđene su jedino u subjektivnim procjenama budnosti na početku i na kraju radnog dana

Role of Plasma Membrane Caveolae/Lipid Rafts in VEGF-Induced Redox Signaling in Human Leukemia Cells

Caveolae/lipid rafts are membrane-rich cholesterol domains endowed with several functions in signal transduction and caveolin-1 (Cav-1) has been reported to be implicated in regulating multiple cancer-associated processes, ranging from tumor growth to multidrug resistance and angiogenesis. Vascular endothelial growth factor receptor-2 (VEGFR-2) and Cav-1 are frequently colocalized, suggesting an important role played by this interaction on cancer cell survival and proliferation. Thus, our attention was directed to a leukemia cell line (B1647) that constitutively produces VEGF and expresses the tyrosine-kinase receptor VEGFR-2. We investigated the presence of VEGFR-2 in caveolae/lipid rafts, focusing on the correlation between reactive oxygen species (ROS) production and glucose transport modulation induced by VEGF, peculiar features of tumor proliferation. In order to better understand the involvement of VEGF/VEGFR-2 in the redox signal transduction, we evaluated the effect of different compounds able to inhibit VEGF interaction with its receptor by different mechanisms, corroborating the obtained results by immunoprecipitation and fluorescence techniques. Results here reported showed that, in B1647 leukemia cells, VEGFR-2 is present in caveolae through association with Cav-1, demonstrating that caveolae/lipid rafts act as platforms for negative modulation of VEGF redox signal transduction cascades leading to glucose uptake and cell proliferation, suggesting therefore novel potential targets

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

Occupational relevance of subclavian vein thrombosis in association with thoracic outlet syndrome

OBJECTIVES: Primary subclavian vein thrombosis ("effort thrombosis") is not generally recognized as a work-related disorder, and more knowledge is required on the particular biomechanical risks. An extensive biomechanical risk analysis was performed for a possible work-related case. CASE REPORT: A hard-working 43-year-old race-course farrier received successful surgical treatment for subclavian vein thrombosis. No congenital abnormalities were apparent. At work, the farrier spent 75% of his time with his back bent (generally at > 70 degrees) with his right shoulder flexed and abducted, a position that thereby increased the pressure on the subclavian vein. High average (and peak) stress ratings for the neck and shoulder postures are accompanied by high levels of force and considerable repetitiveness. CONCLUSIONS: Taken together, these forms of biomechanical overload suggest that the leading cause of the subclavian thrombosis suffered by this farrier could have been occupational. Case-control studies on this neglected topic are needed to investigate possible associations between subclavian vein thrombosis and specific occupational activitiesObjectives: Primary subclavian vein thrombosis ("effort thrombosis") is not generally recognized as a work-related disorder, and more knowledge is required on the particular biomechanical risks. An extensive biomechanical risk analysis was performed for a possible work-related case. Case report: A hard-working 43-year-old race-course farrier received successful surgical treatment for subclavian vein thrombosis. No congenital abnormalities were apparent. At work, the farrier spent 75% of his time with his back bent (generally at >70 degrees) with his right shoulder flexed and abducted, a position that thereby increased the pressure on the subclavian vein. High average (and peak) stress ratings for the neck and shoulder postures are accompanied by high levels of force and considerable repetitiveness. Conclusions: Taken together, these forms of biomechanical overload suggest that the leading cause of the subclavian thrombosis suffered by this farrier could have been occupational. Case-control studies on this neglected topic are needed to investigate possible associations between subclavian vein thrombosis and specific occupational activities

Cell-to-Cell Propagation of the Bacterial Toxin CNF1 via Extracellular Vesicles: Potential Impact on the Therapeutic Use of the Toxin

Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via EVs. We have herein demonstrated that eukaryotic EVs represent an additional route of cell-to-cell propagation for the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1). Our results prove that EVs from CNF1 pre-infected epithelial cells can induce cytoskeleton changes, Rac1 and NF-κB activation comparable to that triggered by CNF1. The observation that the toxin is detectable inside EVs derived from CNF1-intoxicated cells strongly supports the hypothesis that extracellular vesicles can offer to the toxin a novel route to travel from cell to cell. Since anthrax and tetanus toxins have also been reported to engage in the same process, we can hypothesize that EVs represent a common mechanism exploited by bacterial toxins to enhance their pathogenicity

Effect of plasma membrane cholesterol depletion on glucose transport regulation in leukemia cells.

GLUT1 is the predominant glucose transporter in leukemia cells, and the modulation of glucose transport activity by cytokines, oncogenes or metabolic stresses is essential for their survival and proliferation. However, the molecular mechanisms allowing to control GLUT1 trafficking and degradation are still under debate. In this study we investigated whether plasma membrane cholesterol depletion plays a role in glucose transport activity in M07e cells, a human megakaryocytic leukemia line. To this purpose, the effect of cholesterol depletion by methyl-β-cyclodextrin (MBCD) on both GLUT1 activity and trafficking was compared to that of the cytokine Stem Cell Factor (SCF). Results show that, like SCF, MBCD led to an increased glucose transport rate and caused a subcellular redistribution of GLUT1, recruiting intracellular transporter molecules to the plasma membrane. Due to the role of caveolae/lipid rafts in GLUT1 stimulation in response to many stimuli, we have also investigated the GLUT1 distribution along the fractions obtained after non ionic detergent treatment and density gradient centrifugation, which was only slightly changed upon MBCD treatment. The data suggest that MBCD exerts its action via a cholesterol-dependent mechanism that ultimately results in augmented GLUT1 translocation. Moreover, cholesterol depletion triggers GLUT1 translocation without the involvement of c-kit signalling pathway, in fact MBCD effect does not involve Akt and PLCγ phosphorylation. These data, together with the observation that the combined MBCD/SCF cell treatment caused an additive effect on glucose uptake, suggest that the action of SCF and MBCD may proceed through two distinct mechanisms, the former following a signalling pathway, and the latter possibly involving a novel cholesterol dependent mechanism

Role of Plasma Membrane Caveolae/Lipid Rafts in VEGF-Induced Redox Signaling in Human Leukemia Cells

Caveolae/lipid rafts are membrane-rich cholesterol domains endowed with several functions in signal transduction and caveolin-1 (Cav-1) has been reported to be implicated in regulating multiple cancer-associated processes, ranging from tumor growth to multidrug resistance and angiogenesis. Vascular endothelial growth factor receptor-2 (VEGFR-2) and Cav-1 are frequently colocalized, suggesting an important role played by this interaction on cancer cell survival and proliferation. Thus, our attention was directed to a leukemia cell line (B1647) that constitutively produces VEGF and expresses the tyrosine-kinase receptor VEGFR-2. We investigated the presence of VEGFR-2 in caveolae/lipid rafts, focusing on the correlation between reactive oxygen species (ROS) production and glucose transport modulation induced by VEGF, peculiar features of tumor proliferation. In order to better understand the involvement of VEGF/VEGFR-2 in the redox signal transduction, we evaluated the effect of different compounds able to inhibit VEGF interaction with its receptor by different mechanisms, corroborating the obtained results by immunoprecipitation and fluorescence techniques. Results here reported showed that, in B1647 leukemia cells, VEGFR-2 is present in caveolae through association with Cav-1, demonstrating that caveolae/lipid rafts act as platforms for negative modulation of VEGF redox signal transduction cascades leading to glucose uptake and cell proliferation, suggesting therefore novel potential targets

Dietary Phenolic Acids Act as Effective Antioxidants in Membrane Models and in Cultured Cells, Exhibiting Proapoptotic Effects in Leukaemia Cells

Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H2O2. Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL), whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach