Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro.

BACKGROUND: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood. AIM: The present study was designed to examine the influence of macrolide antibiotics on effector cell functions responsible for inflammation through the choice of roxithromycin (RXM) and mast cell. METHODS: Mast cells were induced by long-term culture of splenocytes from BALB/c mice. RXM was added to the cultures at seeding and then every 4-5 days, when the culture medium was replaced with a fresh one. The influence of RXM on mast cell growth was evaluated by counting the number of cells grown on the 16th day. We also examined the influence of RXM on mast cell activation by examining histamine release and inflammatory cytokine secretion. RESULTS AND CONCLUSION: RXM could not inhibit mast cell growth, even when splenocytes were exposed to 100 microg/ml of RXM throughout the entire culture periods. RXM also could not suppress histamine release from cultured mast cells in response to non-immunological and immunological stimulations. However, RXM could suppress inflammatory cytokine, interleukin-1beta, interleukin-6, granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, secretions induced by concanavalin A stimulation at a concentration of as little as 0.5 microg/ml. These results may suggest that RXM modulated the ability of mast cells to secrete inflammatory cytokines and results in improvement of clinical condition of chronic inflammatory diseases

Suppressive activity of a macrolide antibiotic, roxithromycin, on pro-inflammatory cytokine production in vitro and in vivo.

This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes. The monocytes were cultured in the presence of various doses of the agent. After 24 h, the culture supernatants were obtained and assayed for IL-1beta and TNF-alpha contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1beta and TNF-alpha in response to LPS stimulation. This was dose dependent and first noted at a concentration of as little as 0.05 microg/ml, which is much lower than therapeutic blood levels. In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1beta and TNF-alpha in mouse lung extract induced by LPS inhalation. RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts. Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1beta and TNF-alpha in aqueous lung extracts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts

Inhibition of Angiogenic Factor Production from Murine Mast Cells by an Antiallergic Agent (Epinastine Hydrochloride) In Vitro

Angiogenesis is an important event both in the development of allergic inflammatory responses and in the pathophysiology of tissue remodeling in allergic diseases. In the present study, therefore, we examined the influence of antihistamines on angiogenesis through the choice of epinastine hydrochloride (EP) and murine mast cells in vitro. Mast cells (5 × 105 cells/mL) presensitized with murine IgE specific for ovalbumin (OVA) were stimulated with 10 ng/mL OVA in the presence of various concentrations of EP for 4 hours. The levels of angiogenesis factors, keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF), and vascular endothelial growth factor (VEGF) in culture supernatants, were examined by ELISA. We also examined mRNA expression for the angiogenesis factors by RT-PCR. EP significantly inhibited the production of KC, TNF, and VEGF induced by IgE-dependent mechanism at more than 25 ng/mL. Semiquantitative analysis using RT-PCR showed that EP also significantly reduced mRNA expressions for KC, TNF, and VEGF. These results strongly suggest that EP suppresses angiogenesis factor production through the inhibition of mRNA expression in mast cells and results in favorable modification of clinical conditions of allergic diseases

Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro.

The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 microg/ml haemocyanin and various concentrations of the agents. Low concentrations (<1.5 x 10(-4)M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 x 10(-4) M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the agents and the expression of molecules were examined by flow cytometer 24h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro

Extended Generalized Feistel Networks using Matrix Representation

International audienceWhile Generalized Feistel Networks have been widely studied in the literature as a building block of a block cipher, we propose in this paper a unified vision to easily represent them through a matrix representation. We then propose a new class of such schemes called Extended Generalized Feistel Networks well suited for cryptographic applications. We instantiate those proposals into two particular constructions and we finally analyze their security

High-resolution measurement of the time-modulated orbital electron capture and of the β+\beta^+ decay of hydrogen-like 142^{142}Pm60+^{60+} ions

The periodic time modulations, found recently in the two-body orbital electron-capture (EC) decay of both, hydrogen-like $^{140}$Pr$^{58+}$ and $^{142}$Pm$^{60+}$ ions, with periods near to 7s and amplitudes of about 20%, were re-investigated for the case of $^{142}$Pm$^{60+}$ by using a 245 MHz resonator cavity with a much improved sensitivity and time resolution. We observed that the exponential EC decay is modulated with a period $T = 7.11(11)$s, in accordance with a modulation period $T = 7.12(11)$ s as obtained from simultaneous observations with a capacitive pick-up, employed also in the previous experiments. The modulation amplitudes amount to $a_R = 0.107(24)$ and $a_P = 0.134(27)$ for the 245 MHz resonator and the capacitive pick-up, respectively. These new results corroborate for both detectors {\it exactly} our previous findings of modulation periods near to 7s, though with {\it distinctly smaller} amplitudes. Also the three-body $\beta^+$ decays have been analyzed. For a supposed modulation period near to 7s we found an amplitude $a = 0.027(27)$, compatible with $a = 0$ and in agreement with the preliminary result $a = 0.030(30)$ of our previous experiment. These observations could point at weak interaction as origin of the observed 7s-modulation of the EC decay. Furthermore, the data suggest that interference terms occur in the two-body EC decay, although the neutrinos are not directly observed.Comment: In memoriam of Prof. Paul Kienle, 9 pages, 1 table, 5 figures Phys. Lett. B (2013) onlin

First application of mass measurement with the Rare-RI Ring reveals the solar r-process abundance trend at A=122 and A=123

The Rare-RI Ring (R3) is a recently commissioned cyclotron-like storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF, $^{127}$Sn, $^{126}$In, $^{125}$Cd, $^{124}$Ag, $^{123}$Pd, were injected in R3. Masses of $^{126}$In, $^{125}$Cd, and $^{123}$Pd were measured whereby the mass uncertainty of $^{123}$Pd was improved. This is the first reported measurement with a new storage ring mass spectrometery technique realized at a heavy-ion cyclotron and employing individual injection of the pre-identified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new $^{123}$Pd result on the solar $r$-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction $Y_e$. It is found that the neutron capture cross section on $^{123}$Pd increases by a factor of 2.2 and $\beta$-delayed neutron emission probability, $P_\mathrm{1n}$, of $^{123}$Rh increases by 14\%. The neutron capture cross section on $^{122}$Pd decreases by a factor of 2.6 leading to pileup of material at $A=122$, thus reproducing the trend of the solar $r$-process abundances. The trend of the two-neutron separation energies (S$_\mathrm{2n}$) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S$_\mathrm{2n}$ value at $N=77$. Such large increase of the S$_\mathrm{2n}$ values before $N=82$ was proposed as an alternative to the quenching of the $N=82$ shell gap to reproduce $r$-process abundances in the mass region of $A=112-124$

Bringing Japanese Continuous Improvement Approaches to U.S. Manufacturing: The Roles of Process Orientation and Communications *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71419/1/j.1540-5915.1995.tb01442.x.pd