Inhibition of the production of mediators of inflammation by corticosteroids is a glucocorticoid receptor-mediated process

In order to find an explanation for corticosteroid resistance we assessed whether inhibition by dexamethasone (DEX) of the stimulated production of TNF-∝, IL-6, PGE2 and LTB4 by peripheral blood mononuclear cells (MNC) depends on binding to the glucocorticoid receptor (GR), and whether it is determined by the number or the affinity of the GR of these cells. GR number and affinity of MNC were determined by means of a whole cell DEX binding assay. MNC were incubated with DEX and LPS or A23187 in the absence or presence of RU486, a potent steroid antagonist. DEX caused a concentration dependent inhibition of TNF-∝, IL-6 and PGE2 production but had no effect on LTB4 production. RU486 significantly blocked the effect of DEX, but no correlations were found between the inhibition of mediator release and the Kd or receptor number

Water in massive star-forming regions: HIFI observations of W3 IRS5

We present Herschel observations of the water molecule in the massive star-forming region W3 IRS5. The o-H17O 110-101, p-H18O 111-000, p-H2O 22 202-111, p-H2O 111-000, o-H2O 221-212, and o-H2O 212-101 lines, covering a frequency range from 552 up to 1669 GHz, have been detected at high spectral resolution with HIFI. The water lines in W3 IRS5 show well-defined high-velocity wings that indicate a clear contribution by outflows. Moreover, the systematically blue-shifted absorption in the H2O lines suggests expansion, presumably driven by the outflow. No infall signatures are detected. The p-H2O 111-000 and o-H2O 212-101 lines show absorption from the cold material (T ~ 10 K) in which the high-mass protostellar envelope is embedded. One-dimensional radiative transfer models are used to estimate water abundances and to further study the kinematics of the region. We show that the emission in the rare isotopologues comes directly from the inner parts of the envelope (T > 100 K) where water ices in the dust mantles evaporate and the gas-phase abundance increases. The resulting jump in the water abundance (with a constant inner abundance of 10^{-4}) is needed to reproduce the o-H17O 110-101 and p-H18O 111-000 spectra in our models. We estimate water abundances of 10^{-8} to 10^{-9} in the outer parts of the envelope (T < 100 K). The possibility of two protostellar objects contributing to the emission is discussed.Comment: Accepted for publication in the A&A HIFI special issu

Changes in Eicosanoid and Tumour Necrosis Factor-α Production by Rat Peritoneal Macrophages During Carrageenin-Induced Peritonitis

Changes and correlations in cytokine and eicosanoid production by blood monocytes, non-purified and purified peritoneal cells during a carrageenin-induced peritonitis were investigated for a period of ten days. The cells were isolated and stimulated in vitro. Cytokine and eicosanoid production of the non-purified fraction increased steadily during peritonitis. During the whole episode of peritonitis the production capacity of granulocytes was very low and hardly any effect on the production capacity of macrophages (Mϕ) was observed. Cytokine and eicosanoid production of the non-purified fraction was mainly due to the presence of Mϕ. The production capacity of the peripheral blood monocytes was not similar to that of the peritoneal Mϕ

Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis.

FRom several in vitro and in vivo studies involvement of somatostatin (SMS) in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 microg daily) or octreotide (3 microg daily) subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS) 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin-1beta (IL-1beta), IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity

Expression of lipocortins in human bronchial epithelial cells: effects of IL-1β , TNF-α, LPS and dexamethasone

In this study, we investigated the expression of lipocortin I and II (annexin I and I in the human bronchial epithelium, both in vivo and in vitro. A clear expression of lipocortin I and II protein was found in the epithelium in sections of bronchial tissue. In cultured human bronchial epithelial cells we demonstrated the expression of lipocortin I and II mRNA and protein using Northern blotting, FACScan analysis and ELISA. No induction of lipocortin I or II mRNA or protein was observed after incubation with dexamethasone. Stimulation of bronchial epithelial cells with IL-1β, TNF-α or LPS for 24 h did not affect the lipocortin I or II mRNA or protein expression, although PGE2 and 6-keto-PGF1α production was significantly increased. This IL-1β- and LPS-mediated increase in eicosanoids could be reduced by dexamethasone, but was not accompanied by an increase in lipocortin I or II expression. In human bronchial epithelial cells this particular glucocorticoid action is not mediated through lipocortin I or II induction

The Different Structures of the Two Classes of Starless Cores

We describe a model for the thermal and dynamical equilibrium of starless cores that includes the radiative transfer of the gas and dust and simple CO chemistry. The model shows that the structure and behavior of the cores is significantly different depending on whether the central density is either above or below about 10^5 cm-3. This density is significant as the critical density for gas cooling by gas-dust collisions and also as the critical density for dynamical stability, given the typical properties of the starless cores. The starless cores thus divide into two classes that we refer to as thermally super-critical and thermally sub-critical.This two-class distinction allows an improved interpretation of the different observational data of starless cores within a single model.Comment: ApJ in pres

Methanol in W3(H2O) and Surrounding Regions

We present the results of an interferometric study of 38 millimeter-wave lines of CH3OH in the region around the water maser source W3(H2O) and a region extending about 30" to the south and west of the hydroxyl maser source W3(OH). The methanol emitting region around W3(H2O) has an extent of 2.0" x 1.2" (4400 x 2600 AU). The density is of order 1.e7 cm-3, sufficient to thermalize most of the methanol lines. The kinetic temperature is approximately 140 K and the methanol fractional abundance greater than 1.e-6, indicative of a high degree of grain mantle evaporation. The W3(H2O) source contains sub-structure, with peaks corresponding to the TW source and Wyrowski's B/C, separated by 2500 AU in projection. The kinematics are consistent with these being distinct protostellar cores in a wide binary orbit and a dynamical mass for the region of a few tens of Mo. The extended methanol emission to the southwest of W3(OH) is seen strongly only from the lowest excitation lines and from lines known elsewhere to be class I methanol masers, namely the 84.5 GHz 5(-1)-4(0)E and 95.2 GHz 8(0)-7(1)A+ lines. Within this region there are two compact clumps, which we denote as swA and swB, each about 15" (0.16 pc projected distance) away from W3(OH). Excitation analysis of these clumps indicates the presence of lines with inverted populations but only weak amplification. The sources swA and swB appear to have kinetic temperatures of order 50-100 K and densities of order 1.e5 - 1.e6 cm-3. The methanol fractional abundance for the warmer clump is of order 1.e-7, suggestive of partial grain mantle evaporation. The clumping occurs on mass scales of order 1 Mo.Comment: 28 pages including 6 figures and 4 tables, accepted by Ap

Water abundances in high-mass protostellar envelopes: Herschel observations with HIFI

We derive the dense core structure and the water abundance in four massive star-forming regions which may help understand the earliest stages of massive star formation. We present Herschel-HIFI observations of the para-H2O 1_11-0_00 and 2_02-1_11 and the para-H2-18O 1_11-0_00 transitions. The envelope contribution to the line profiles is separated from contributions by outflows and foreground clouds. The envelope contribution is modelled using Monte-Carlo radiative transfer codes for dust and molecular lines (MC3D and RATRAN), with the water abundance and the turbulent velocity width as free parameters. While the outflows are mostly seen in emission in high-J lines, envelopes are seen in absorption in ground-state lines, which are almost saturated. The derived water abundances range from 5E-10 to 4E-8 in the outer envelopes. We detect cold clouds surrounding the protostar envelope, thanks to the very high quality of the Herschel-HIFI data and the unique ability of water to probe them. Several foreground clouds are also detected along the line of sight. The low H2O abundances in massive dense cores are in accordance with the expectation that high densities and low temperatures lead to freeze-out of water on dust grains. The spread in abundance values is not clearly linked to physical properties of the sources.Comment: 8 pages, 5 figures, accepted for publication the 15/07/2010 by Astronomy&Astrophysics as a letter in the Herschel-HIFI special issu

Unbiased large spectroscopic surveys of galaxies selected by SPICA using dust bands

The mid-infrared (IR) range contains many spectral features associated with large molecules and dust grains such as polycyclic aromatic hydrocarbons (PAHs) and silicates. These are usually very strong compared to fine-structure gas lines, and thus valuable in studying the spectral properties of faint distant galaxies. In this paper, we evaluate the capability of low-resolution mid-IR spectroscopic surveys of galaxies that could be performed by SPICA. The surveys are designed to address the question how star formation and black hole accretion activities evolved over cosmic time through spectral diagnostics of the physical conditions of the interstellar/circumnuclear media in galaxies. On the basis of results obtained with Herschel far-IR photometric surveys of distant galaxies and Spitzer and AKARI near- to mid-IR spectroscopic observations of nearby galaxies, we estimate the numbers of the galaxies at redshift z > 0.5, which are expected to be detected in the PAH features or dust continuum by a wide (10 deg^2) or deep (1 deg^2) blind survey, both for a given observation time of 600 hours. As by-products of the wide blind survey, we also expect to detect debris disks, through the mid-IR excess above the photospheric emission of nearby main-sequence stars, and we estimate their number. We demonstrate that the SPICA mid-IR surveys will efficiently provide us with unprecedentedly large spectral samples, which can be studied further in the far-IR with SPICA.Comment: Paper accepted for publication on PASA on 18th October 2017, as part of the SPICA Special Issu

Phase-field modeling of microstructural pattern formation during directional solidification of peritectic alloys without morphological instability

During the directional solidification of peritectic alloys, two stable solid phases (parent and peritectic) grow competitively into a metastable liquid phase of larger impurity content than either solid phase. When the parent or both solid phases are morphologically unstable, i.e., for a small temperature gradient/growth rate ratio ($G/v_p$), one solid phase usually outgrows and covers the other phase, leading to a cellular-dendritic array structure closely analogous to the one formed during monophase solidification of a dilute binary alloy. In contrast, when $G/v_p$ is large enough for both phases to be morphologically stable, the formation of the microstructurebecomes controlled by a subtle interplay between the nucleation and growth of the two solid phases. The structures that have been observed in this regime (in small samples where convection effect are suppressed) include alternate layers (bands) of the parent and peritectic phases perpendicular to the growth direction, which are formed by alternate nucleation and lateral spreading of one phase onto the other as proposed in a recent model [R. Trivedi, Metall. Mater. Trans. A 26, 1 (1995)], as well as partially filled bands (islands), where the peritectic phase does not fully cover the parent phase which grows continuously. We develop a phase-field model of peritectic solidification that incorporates nucleation processes in order to explore the formation of these structures. Simulations of this model shed light on the morphology transition from islands to bands, the dynamics of spreading of the peritectic phase on the parent phase following nucleation, which turns out to be characterized by a remarkably constant acceleration, and the types of growth morphology that one might expect to observe in large samples under purely diffusive growth conditions.Comment: Final version, minor revisions, 16 pages, 14 EPS figures, RevTe