Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood-pressure independent effect

Compound 21 (C21), selective agonist of AT2 receptors, shows antinflammatory effects in hypertension and nephroprotection in diabetes. The aim of this study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague Dawley rats. Cyclosporine-A (15mg/kg/day, i.p.) and cyclosporine-A plus C21 (0.3 mg/kg /day, i.p) were administered for 1 and 4 weeks. Control groups was left without any treatment. Blood pressure (plethysmographic method) and 24 hour albuminuria were measured once a week. At the end of the experiments, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and IV collagen expression.After 1 and 4 weeks, the rats treated with cyclosporine showed a significant increase (p <0.01) in blood pressure, no significant changes in albuminuria, a significant increase (p <0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared to the control rats. Treatment with C21 did not modify the cyclosporine dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (p <0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared to rats treated with cyclosporine.The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases

A broad iron line in the Chandra/HETG spectrum of 4U 1705-44

We present the results of a Chandra 30 ks observation of the low mass X-ray binary and atoll source 4U 1705-44. Here we concentrate on the study of discrete features in the energy spectrum at energies below 3 keV, as well as on the iron Kalpha line, using the HETG spectrometer on board of the Chandra satellite. Below 3 keV, three narrow emission lines are found at 1.47, 2.0, and 2.6 keV. The 1.47 and 2.6 keV are probably identified with Ly-alpha emission from Mg XII and S XVI, respectively. The identification of the feature at 2.0 keV is uncertain due to the presence of an instrumental feature at the same energy. The iron Kalpha line at ~6.5 keV is found to be intrinsically broad (FWHM ~ 1.2 keV); its width can be explained by reflection from a cold accretion disk extending down to 15 km from the neutron star center or by Compton broadening in the external parts of a hot (~2 keV) Comptonizing corona. We finally report here precise X-ray coordinates of the source.Comment: 8 pages including 2 figures. ApJ Letters, in pres

An XMM-Newton study of the 401 Hz accreting pulsar SAX J1808.4-3658 in quiescence

SAX J1808.4-3658 is a unique source being the first Low Mass X-ray Binary showing coherent pulsations at a spin period comparable to that of millisecond radio pulsars. Here we present an XMM-Newton observation of SAX J1808.4-3658 in quiescence, the first which assessed its quiescent luminosity and spectrum with good signal to noise. XMM-Newton did not reveal other sources in the vicinity of SAX J1808.4-3658 likely indicating that the source was also detected by previous BeppoSAX and ASCA observations, even if with large positional and flux uncertainties. We derive a 0.5-10 keV unabsorbed luminosity of L_X=5x10^{31} erg/s, a relatively low value compared with other neutron star soft X-ray transient sources. At variance with other soft X-ray transients, the quiescent spectrum of SAX J1808.4-3658 was dominated by a hard (Gamma~1.5) power law with only a minor contribution (<10%) from a soft black body component. If the power law originates in the shock between the wind of a turned-on radio pulsar and matter outflowing from the companion, then a spin-down to X-ray luminosity conversion efficiency of eta~10^{-3} is derived; this is in line with the value estimated from the eclipsing radio pulsar PSR J1740-5340. Within the deep crustal heating model, the faintness of the blackbody-like component indicates that SAX J1808.4-3658 likely hosts a massive neutronstar (M>1.7 solar masses).Comment: Paper accepted for publication in ApJ

Timing an Accreting Millisecond Pulsar: Measuring the Accretion Torque in IGR J00291+5934

We present here a timing analysis of the fastest accreting millisecond pulsar IGR J00291+5934 using RXTE data taken during the outburst of December 2004. We corrected the arrival times of all the events for the orbital (Doppler) effects and performed a timing analysis of the resulting phase delays. In this way we find a clear parabolic trend of the pulse phase delays showing that the pulsar is spinning up as a consequence of accretion torques during the X-ray outburst. The accretion torque gives us for the first time an independent estimate of the mass accretion rate onto the neutron star, which can be compared with the observed X-ray luminosity. We also report a revised value of the spin period of the pulsar.Comment: Proceedings of the Frascati Workshop 2005: Multifrequency Behaviour of High Energy Cosmic Sources, Vulcano, May 23-28. 7 pages including 1 figur

The discovery of hard X-ray emission in the persistent flux of the Rapid Burster

We report the first detection with INTEGRAL of persistent hard X-ray emission (20 to 100 keV) from the Rapid Burster (MXB 1730-335), and describe its full spectrum from 3 to 100 keV. The source was detected on February/March 2003 during one of its recurrent outbursts. The source was clearly detected with a high signal to noise ratio during the single pointings and is well distinguished from the neighboring source GX 354-0. The 3 - 100 keV X-ray spectrum of the persistent emission is well described by a two-component model consisting of a blackbody plus a power-law with photon index ~ 2.4. The estimated luminosity was ~ 8.5x10^{36} erg/s in the 3 - 20 keV energy band and \~ 1.3x10^{36} erg/s in the 20 - 100 keV energy range, for a distance of 8 kpc.Comment: 5 pages, 6 figures, 1 table. Accepted for publication in A&

Capacitance-conductance investigation on the phase transitions in Ga nanoparticles

We have reported on coupled capacitance-conductance measurements on Ga nanoparticles embedded in vitreous matrices. The melting of nanoparticles was clearly detected as an abrupt increase in the capacitance vs. temperature scans. The influence of the embedding matrix and of the frequency of the applied field on the dielectric response was checked. The presence of a hysteresis cycle between melting and solidification has been detected. The technique allows the identification of the various solid phases of confined Ga

An XMM-Newton and INTEGRAL view on the hard state of EXO 1745-248 during its 2015 outburst

CONTEXT - Transient low-mass X-ray binaries (LMXBs) often show outbursts lasting typically a few-weeks and characterized by a high X-ray luminosity ($L_{x} \approx 10^{36}-10^{38}$ erg/sec), while for most of the time they are found in X-ray quiescence ($L_X\approx10^{31} -10^{33}$ erg/sec). EXO 1745-248 is one of them. AIMS - The broad-band coverage, and the sensitivity of instrument on board of {\xmm} and {\igr}, offers the opportunity to characterize the hard X-ray spectrum during {\exo} outburst. METHODS - In this paper we report on quasi-simultaneous {\xmm} and {\igr} observations of the X-ray transient {\exo} located in the globular cluster Terzan 5, performed ten days after the beginning of the outburst (on 2015 March 16th) shown by the source between March and June 2015. The source was caught in a hard state, emitting a 0.8-100 keV luminosity of $\simeq10^{37}$~{\lumcgs}. RESULTS - The spectral continuum was dominated by thermal Comptonization of seed photons with temperature $kT_{in}\simeq1.3$ keV, by a cloud with moderate optical depth $\tau\simeq2$ and electron temperature $kT_e\simeq 40$ keV. A weaker soft thermal component at temperature $kT_{th}\simeq0.6$--0.7 keV and compatible with a fraction of the neutron star radius was also detected. A rich emission line spectrum was observed by the EPIC-pn on-board {\xmm}; features at energies compatible with K-$\alpha$ transitions of ionized sulfur, argon, calcium and iron were detected, with a broadness compatible with either thermal Compton broadening or Doppler broadening in the inner parts of an accretion disk truncated at $20\pm6$ gravitational radii from the neutron star. Strikingly, at least one narrow emission line ascribed to neutral or mildly ionized iron is needed to model the prominent emission complex detected between 5.5 and 7.5 keV. (Abridged)Comment: 14 pages, 6 figure, 2 tables. Accepted for publication on A&A (21/03/2017

BCR-ABL1 doubling-times and halving-times may predict CML response to tyrosine kinase inhibitors

In Chronic Myeloid Leukemia (CML), successful treatment requires accurate molecular monitoring to evaluate disease response and provide timely interventions for patients failing to achieve the desired outcomes. We wanted to determine whether measuring BCR-ABL1 mRNA doubling-times (DTs) could distinguish inconsequential rises in the oncogene’s expression from resistance to tyrosine kinase inhibitors (TKIs). Thus, we retrospectively examined BCR-ABL1 evolution in 305 chronic-phase CML patients receiving imatinib mesylate (IM) as a first line treatment. Patients were subdivided in two groups: those with a confirmed rise in BCR-ABL1 transcripts without MR3.0 loss and those failing IM. We found that the DTs of the former patients were significantly longer than those of patients developing IM resistance (57.80 vs. 41.45 days, p = 0.0114). Interestingly, the DT values of individuals failing second-generation (2G) TKIs after developing IM resistance were considerably shorter than those observed at the time of IM failure (27.20 vs. 41.45 days; p = 0.0035). We next wanted to establish if decreases in BCR-ABL1 transcripts would identify subjects likely to obtain deep molecular responses. We therefore analyzed the BCR-ABL1 halving-times (HTs) of a different cohort comprising 174 individuals receiving IM in first line and observed that, regardless of the time point selected for our analyses (6, 12, or 18 months), HTs were significantly shorter in subjects achieving superior molecular responses (p = 0.002 at 6 months; p &lt; 0.001 at 12 months; p = 0.0099 at 18 months). Moreover, 50 patients receiving 2G TKIs as first line therapy and obtaining an MR3.0 (after 6 months; p = 0.003) or an MR4.0 (after 12 months; p = 0.019) displayed significantly shorter HTs than individuals lacking these molecular responses. Our findings suggest that BCR-ABL1 DTs and HTs are reliable tools to, respectively, identify subjects in MR3.0 that are failing their assigned TKI or to recognize patients likely to achieve deep molecular responses that should be considered for treatment discontinuation

Detection of a Hard Tail in the X-ray Spectrum of the Z Source GX 349+2

We present the results of a BeppoSAX observation of the Z source GX 349+2 covering the energy range 0.1-200 keV. The presence of flares in the light curve indicates that the source was in the flaring branch during the BeppoSAX observation. We accumulated energy spectra separately for the non-flaring intervals and the flares. In both cases the continuum is well described by a soft blackbody ($k T_{BB} \sim 0.5$ keV) and a Comptonized spectrum corresponding to an electron temperature of $k T_e \sim 2.7$ keV, optical depth $\tau \sim 10$ (for a spherical geometry), and seed photon temperature of $k T_W \sim 1$ keV. All temperatures tend to increase during the flares. In the non-flaring emission a hard tail dominates the spectrum above 30 keV. This can be fit by a power law with photon index $\sim 2$, contributing $\sim 2$ of the total source luminosity over the BeppoSAX energy range. A comparison with hard tails detected in some soft states of black hole binaries suggests that a similar mechanism could originate these components in black hole and neutron star systems.Comment: 15 pages, including 8 figures, to appear in Ap

A Hard X-ray View on Scorpius X-1 with INTEGRAL: non-Thermal Emission ?

We present here simultaneous INTEGRAL/RXTE observations of Sco X-1, and in particular a study of the hard X-ray emission of the source and its correlation with the position in the Z-track of the X-ray color-color diagram. We find that the hard X-ray (above about 30 keV) emission of Sco X-1 is dominated by a power-law component with a photon index of ~3. The flux in the power-law component slightly decreases when the source moves in the color-color diagram in the sense of increasing inferred mass accretion rate from the horizontal branch to the normal branch/flaring branch vertex. It becomes not significantly detectable in the flaring branch, where its flux has decreased by about an order of magnitude. These results present close analogies to the behavior of GX 17+2, one of so-called Sco-like Z sources. Finally, the hard power law in the spectrum of Sco X-1 does not show any evidence of a high energy cutoff up to 100 - 200 keV, strongly suggesting a non-thermal origin of this component.Comment: 5 pages including 3 figures. Accepted for publication by ApJ Letter