Immunomodulatory Effect of Linezolid on Methicillin-Resistant Staphylococcus aureus Supernatant-Induced MUC5AC Overexpression in Human Airway Epithelial Cells

Linezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methi-cillin- resistant Staphylococcus aureus (MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the effect of linezolid on MRSA-induced MUC5AC overexpression in airway epithelial cells. In this study, an MRSA supernatant was used to avoid the direct effect of linezolid on MRSA. MUC5AC protein production was significantly increased with a 40-fold dilution of MRSA supernatant. At the mRNA level, MUC5AC gene expression was significantly increased 6 and 9 h after stimulation. In an inhibition study, linezolid significantly reduced MRSA-induced MUC5AC protein and mRNA overexpression at concentrations of 5 and 20 μg/ml, which were the same as the trough and peak concentrations in human epithelial lining fluid. In an analysis of cell signaling, among the mitogen-activated protein kinase inhibitors, only the extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor reduced the MUC5AC protein production to the same level as that of the control; on Western blot analysis, only ERK1/2 was phosphorylated by the MRSA supernatant. In addition, the ERK1/2 phosphorylation was inhibited by linezolid. MUC5AC and MUC5B are the major barrier that traps inhaled microbial organisms, particulates, and foreign irritants. However, in patients with chronic respiratory diseases, pathogen-induced MUC5AC overexpression causes many problems, and control of the overexpression is important. Thus, this study revealed that linezolid showed a direct immunomodulatory effect in airway epithelial cells

Prevotella intermedia Induces Severe Bacteremic Pneumococcal Pneumonia in Mice with Upregulated Platelet-Activating Factor Receptor Expression

Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells

Response of plasma toroidal flow to the transition between nested and stochastic magnetic field in LHD

Response of the plasma toroidal flow to the forward and backward transition between the nested and the stochastic magnetic field is studied using the charge exchange spectroscopy in the large helical device (LHD). Abrupt damping of toroidal flow associated with a transition from nested magnetic flux surface to a stochastic magnetic field is observed when the magnetic shear at the rational surface decreases to 0.5 after the exchange of the neutral beam injection (NBI) direction from co- to counter-direction in LHD. The stochastization of magnetic field occurs only in a narrow range of magnetic shear near 0.5 and spontaneousback-transition from stochastic to nested magnetic field (healing) is observed in the steady-state phase of magnetic shear. When the NBI direction is changed from counter- to co-direction, the healing of magnetic field occurs associated with the increase of magnetic shear

Carbon impurities behavior and its impact on ion thermal confinement in high-ion-temperature deuterium discharges on the Large Helical Device

The behavior of carbon impurities in deuterium plasmas and its impact on thermal confinement were investigated in comparison with hydrogen plasmas in the Large Helical Device (LHD). Deuterium plasma experiments have been started in the LHD and high-ion-temperature plasmas with central ion temperature (T i) of 10 keV were successfully obtained. The thermal confinement improvement could be sustained for a longer time compared with hydrogen plasmas. An isotope effect was observed in the time evolution of the carbon density profiles. A transiently peaked profile was observed in the deuterium plasmas due to the smaller carbon convection velocity and diffusivity in the deuterium plasmas compared with the hydrogen plasmas. The peaked carbon density profile was strongly correlated to the ion thermal confinement improvement. The peaking of the carbon density profile will be one of the clues to clarify the unexplained mechanisms for the formations of ion internal transport barrier and impurity hole on LHD. These results could also lead to a better understanding of the isotope effect in the thermal confinement in torus plasma

Improvement of Ion Confinement in Core Electron-Root Confinement (CERC) Plasmas in Large Helical Device

An increase in ion temperature has been observed with superposition of centrally focused electron cyclotron resonance heating (ECRH) to plasmas heated by high-energy neutral beam injection (NBI) in Large Helical Device. The ion-temperature (Ti) rise is accompanied by the formation of electron internal transport barrier (ITB). A transport analysis shows that ion transport as well as electron transport is improved with the reduction of anomalous transport. A neoclassical ambipolar flux calculation shows a positive radial-electric field (Er) in the region of the Ti rise, and Er should suppress the enhancement of ripple transport due to the Ti-rise. These analyses indicate the ion transport improvement in the core electron-root confinement plasmas. Toroidal rotation is driven in the co-direction by applying ECRH, and the toroidal rotation velocity is increased with the Ti rise. A correlation between the Ti rise and toroidal rotation is suggested

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

Stability and Confinement Studies of High-Performance NBI Plasmas in the Large Helical Device Toward a Steady-State Helical Fusion Reactor

Recent progress in plasma performance and the understanding of the related physics in the Large Helical Device is overviewed. The volume-averaged beta value is increased with an increase in the neutral beam injection (NBI) heating power, and it reached 5.0% of the reactor-relevant value. In high-β plasmas, the plasma aspect ratio should be controlled so that the Shafranov shift would be reduced, mainly to suppress transport degradation and the deterioration of the NBI heating efficiency. The operational regime of a high-density plasma with an internal diffusion barrier (IDB) has been extended, and the IDB, which was originally found using the local island divertor, has been realized in the helical divertor configuration. The central density was recorded as high as 1 × 1021 m-3, and the central pressure reached 130 kPa. Based on these high-density plasmas with the IDB, a new ignition scenario has been proposed. This should be a scenario specific to the helical fusion reactor, in which the helical ripple transport would be mitigated. A low-energy positive-NBI system was newly installed for an increase in the direct ion heating power. As a result, the ion temperature (Ti) exceeded 5.2 keV at a density of 1.2 × 1019 m-3 in a hydrogen plasma. Transport analysis shows improvement of ion transport, and the Ti-increase tends to be accompanied by a large toroidal rotation velocity of the order of 50 km/s in the core region. The plasma properties in the extended operational regime are discussed from the perspective of a steady-state helical fusion reactor

Development of miracle medicines from sialic acids

Sialic acids are electronegatively charged C9-sugars and are considered to play important roles in higher animals and some microorganisms. Denoting their significance, understanding and exploiting the complexity of the sialic acids has been referred to as the “the third language of life”. In essence, “sialic acid derivatives possess a harmonious shape and good balance between two opposing hydrophilic and hydrophobic parts, meaning that they should display various kinds of potentially unique and possibly conflicting physiological activities (glycolipoids)”. Consequently, there are good omens that unprecedented ‘miracle’ medicines could be developed from sialic acid derivatives. In this review, the first problem, the preparation of sialic acids, is covered, the synthesis of sialic acid derivatives and confirmation of their structures obviously being of critical significance. In addition we needed to confirm their precise stereochemistry and a hydrolysis method has been developed for confirmation of the anomeric position. Several of the compounds have already demonstrated interesting bioactivity

Influence of antimicrobial regimen on decreased in-hospital mortality of patients with MRSA bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causes of bacteremia. Recently, several epidemiological and microbiological changes have become evident in MRSA infections. The purposes of this study were to assess clinical characteristics of patients with MRSA bacteremia and microbiological changes in MRSA. We conducted a retrospective observational study on patients with MRSA bacteremia who were hospitalized between 2008 and 2011. We used univariate and multivariate analysis to evaluate the predictors associated with 30-day mortality. The 7-day and 30-day mortality rates were 12.0% and 25.3%, respectively. According to multivariate analysis, the independent predictors that associated with 30-day mortality were leukopenia, low serum albumin, high sequential organ failure assessment (SOFA) score, and quinolone use within 30 days. Compared to previous data (2003-2007), the SOFA score of the new data set remained unchanged, but in-hospital mortality decreased significantly. In particular, the mortality associated with use of vancomycin (VCM) was significantly lower. Although the minimuminhibitory concentration of VCM required to inhibit the growth of 90% of organisms (MIC90) had not changed, the trough value of VCM changed significantly; a VCM trough value of 10 or greater was significantly higher compared to previous data. Of the staphylococcal cassette chromosome mec (SCCmec) types, SCCmec II values decreased significantly, and SCCmec I and IV values increased significantly. Our results indicate that changes in VCM usage might contribute to decreased in-hospital mortality