Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II trials

<p><b>Background and Purpose:</b> A number of factors have been associated with postthrombolysis intracerebral hemorrhage, but these have varied across studies.</p> <p><b>Methods:</b> We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post–tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of ≥4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days.</p> <p><b>Results:</b> Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P<0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS ≤7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P<0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome.</p> <p><b>Conclusions:</b> Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post–tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.</p&gt

Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-a)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1ß, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1ß and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants

GRB070125: The First Long-Duration Gamma-Ray Burst in a Halo Environment

We present the discovery and high signal-to-noise spectroscopic observations of the optical afterglow of the long-duration gamma-ray burst GRB070125. Unlike all previously observed long-duration afterglows in the redshift range 0.5 < z 1.0 A) absorption features in the wavelength range 4000 - 10000 A. The sole significant feature is a weak doublet we identify as Mg II 2796 (W = 0.18 +/- 0.02 A), 2803 (W = 0.08 +/- 0.01) at z = 1.5477 +/- 0.0001. The low observed Mg II and inferred H I column densities are typically observed in galactic halos, far away from the bulk of massive star formation. Deep ground-based imaging reveals no host directly underneath the afterglow to a limit of R > 25.4 mag. Either of the two nearest blue galaxies could host GRB070125; the large offset (d >= 27 kpc) would naturally explain the low column density. To remain consistent with the large local (i.e. parsec scale) circum-burst density inferred from broadband afterglow observations, we speculate GRB070125 may have occurred far away from the disk of its host in a compact star-forming cluster. Such distant stellar clusters, typically formed by dynamical galaxy interactions, have been observed in the nearby universe, and should be more prevalent at z>1 where galaxy mergers occur more frequently.Comment: 8 pages, accepted in Ap

Discovery of the Very Red Near-Infrared and Optical Afterglow of the Short-Duration GRB 070724A

[Abridged] We report the discovery of the near-infrared and optical afterglow of the short-duration gamma-ray burst GRB070724A. The afterglow is detected in i,J,H,K observations starting 2.3 hr after the burst with K=19.59+/-0.16 mag and i=23.79+/-0.07 mag, but is absent in images obtained 1.3 years later. Fading is also detected in the K-band between 2.8 and 3.7 hr at a 4-sigma significance level. The optical/near-IR spectral index, beta_{O,NIR}=-2, is much redder than expected in the standard afterglow model, pointing to either significant dust extinction, A_{V,host}~2 mag, or a non-afterglow origin for the near-IR emission. The case for extinction is supported by a shallow optical to X-ray spectral index, consistent with the definition for ``dark bursts'', and a normal near-IR to X-ray spectral index. Moreover, a comparison to the optical discovery magnitudes of all short GRBs with optical afterglows indicates that the near-IR counterpart of GRB070724A is one of the brightest to date, while its observed optical emission is one of the faintest. In the context of a non-afterglow origin, the near-IR emission may be dominated by a mini-supernova, leading to an estimated ejected mass of M~10^-4 Msun and a radioactive energy release efficiency of f~0.005 (for v~0.3c). However, the mini-SN model predicts a spectral peak in the UV rather than near-IR, suggesting that this is either not the correct interpretation or that the mini-SN models need to be revised. Finally, the afterglow coincides with a star forming galaxy at z=0.457, previously identified as the host based on its coincidence with the X-ray afterglow position (~2" radius). Our discovery of the optical/near-IR afterglow makes this association secure.Comment: Submitted to ApJ; 10 pages, 5 figures, 1 tabl

Constraining GRB Emission Physics with Extensive Early-Time, Multiband Follow-up

Understanding the origin and diversity of emission processes responsible for Gamma-ray Bursts (GRBs) remains a pressing challenge. While prompt and contemporaneous panchromatic observations have the potential to test predictions of the internal-external shock model, extensive multiband imaging has been conducted for only a few GRBs. We present rich, early-time, multiband datasets for two \swift\ events, GRB 110205A and GRB 110213A. The former shows optical emission since the early stages of the prompt phase, followed by the steep rising in flux up to ~1000s after the burst ($t^{-\alpha}$ with $\alpha=-6.13 \pm 0.75$). We discuss this feature in the context of the reverse-shock scenario and interpret the following single power-law decay as being forward-shock dominated. Polarization measurements, obtained with the RINGO2 instrument mounted on the Liverpool Telescope, also provide hints on the nature of the emitting ejecta. The latter event, instead, displays a very peculiar optical to near-infrared lightcurve, with two achromatic peaks. In this case, while the first peak is probably due to the onset of the afterglow, we interpret the second peak to be produced by newly injected material, signifying a late-time activity of the central engine.Comment: 48 pages,11 figures, 24 tables. Accepted to The Astrophysical Journa

The redshift and afterglow of the extremely energetic gamma-ray burst GRB 080916C

The detection of GeV photons from gamma-ray bursts (GRBs) has important consequences for the interpretation and modelling of these most-energetic cosmological explosions. The full exploitation of the high-energy measurements relies, however, on the accurate knowledge of the distance to the events. Here we report on the discovery of the afterglow and subsequent redshift determination of GRB 080916C, the first GRB detected by the Fermi Gamma-Ray Space Telescope with high significance detection of photons at >0.1 GeV. Observations were done with 7-channel imager GROND at the 2.2m MPI/ESO telescope, the SIRIUS instrument at the Nagoya-SAAO 1.4m telescope in South Africa, and the GMOS instrument at Gemini-S. The afterglow photometric redshift of z=4.35+-0.15, based on simultaneous 7-filter observations with the Gamma-Ray Optical and Near-infrared Detector (GROND), places GRB 080916C among the top 5% most distant GRBs, and makes it the most energetic GRB known to date. The detection of GeV photons from such a distant event is rather surprising. The observed gamma-ray variability in the prompt emission together with the redshift suggests a lower limit for the Lorentz factor of the ultra-relativistic ejecta of Gamma > 1090. This value rivals any previous measurements of Gamma in GRBs and strengthens the extreme nature of GRB 080916C.Comment: 6 pages, 5 figures; subm. to A&

The distribution of equivalent widths in long GRB afterglow spectra

The extreme brightness of gamma-ray burst (GRB) afterglows and their simple spectral shape make them ideal beacons to study the interstellar medium of their host galaxies through absorption line spectroscopy. Using 69 low-resolution GRB afterglow spectra, we conduct a study of the rest-frame equivalent width (EW) distribution of features with an average rest-frame EW larger than 0.5 A. To compare an individual GRB with the sample, we develop EW diagrams as a graphical tool, and we give a catalogue with diagrams for the 69 spectra. We introduce a line strength parameter (LSP) that allows us to quantify the strength of the absorption features as compared to the sample by a single number. Using the distributions of EWs of single-species features, we derive the distribution of column densities by a curve of growth (CoG) fit. We find correlations between the LSP and the extinction of the GRB, the UV brightness of the host galaxies and the neutral hydrogen column density. However, we see no significant evolution of the LSP with the redshift. There is a weak correlation between the ionisation of the absorbers and the energy of the GRB, indicating that, either the GRB event is responsible for part of the ionisation, or that galaxies with high-ionisation media produce more energetic GRBs. Spectral features in GRB spectra are, on average, 2.5 times stronger than those seen in QSO intervening damped Lyman-alpha (DLA) systems and slightly more ionised. In particular we find larger excess in the EW of CIV1549 relative to QSO DLAs, which could be related to an excess of Wolf-Rayet stars in the environments of GRBs. From the CoG fitting we obtain an average number of components in the absorption features of GRBs of 6.00(-1.25,+1.00). The most extreme ionisation ratios in our sample are found for GRBs with low neutral hydrogen column density, which could be related to ionisation by the GRB emission.Comment: 37 pages, 31 figures, 15 tables. Accepted for publication in Astonomy and Astrophysic

The Afterglow and Environment of the Short GRB111117A

We present multi-wavelength observations of the afterglow of the short GRB111117A, and follow-up observations of its host galaxy. From rapid optical and radio observations we place limits of r \gtrsim 25.5 mag at \deltat \approx 0.55 d and F_nu(5.8 GHz) < 18 \muJy at \deltat \approx 0.50 d, respectively. However, using a Chandra observation at t~3.0 d we locate the absolute position of the X-ray afterglow to an accuracy of 0.22" (1 sigma), a factor of about 6 times better than the Swift-XRT position. This allows us to robustly identify the host galaxy and to locate the burst at a projected offset of 1.25 +/- 0.20" from the host centroid. Using optical and near-IR observations of the host galaxy we determine a photometric redshift of z=1.3 (+0.3,-0.2), one of the highest for any short GRB, and leading to a projected physical offset for the burst of 10.5 +/- 1.7 kpc, typical of previous short GRBs. At this redshift, the isotropic gamma-ray energy is E_{gamma,iso} \approx 3\times10^51 erg (rest-frame 23-2300 keV) with a peak energy of E_{pk} \approx 850-2300 keV (rest-frame). In conjunction with the isotropic X-ray energy, GRB111117A appears to follow our recently-reported E_x,iso-E_gamma,iso-E_pk universal scaling. Using the X-ray data along with the optical and radio non-detections we find that for a blastwave kinetic energy of E_{K,iso} \approx E_{gamma,iso}, the circumburst density is n_0 \sim 3x10^(-4)-1 cm^-3 (for a range of epsilon_B=0.001-0.1). Similarly, from the non-detection of a break in the X-ray light curve at t<3 d, we infer a minimum opening angle for the outflow of theta_j> 3-10 degrees (depending on the circumburst density). We conclude that Chandra observations of short GRBs are effective at determining precise positions and robust host galaxy associations in the absence of optical and radio detections.Comment: ApJ accepted versio