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

The challenge of treatment in potential celiac disease

Potential celiac disease (PCD) is defined by the presence of positive serum antibodies, HLA-DQ2/DQ8 haplotypes, and a normal small intestinal mucosa (Marsh grade 0-1). This condition occurs in one-fifth of celiac disease (CD) patients and usually represents a clinical challenge. We reviewed genetic, histologic, and clinical features of this specific condition by performing a systematic search on MEDLINE, Embase, and Scholar database. Accordingly, we identified different genetic features in patients with PCD compared to the classical forms. Frequently, signs of inflammation (deposits of immunoglobulin A (IgA) and/or increased number of intraepithelial lymphocytes) can be clearly identify in the mucosa of PCD patients after an accurate histological assessment. Finally, the main challenge is represented by the treatment: the gluten-free diet should be considered only in the presence of gluten-dependent symptoms in both children and adults. What is known: (i) potential celiac disease (PCD) occurs in one-fifth of all celiac diseases (CD), and (ii) despite the absence of classical lesions, clear signs of inflammation are often detectable. What is new: (i) patients with PCD show different genetic features, and (ii) the presence of gluten-dependent symptoms is the main determinant to initiate the gluten-free diet, after a complete diagnostic work-up

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

Discovery of the Very Red Near-Infrared and Optical Afterglow of the Short-Duration Grb 070724a

We report the discovery of the near-infrared and optical afterglow of the short-duration gamma-ray burst GRB 070724A. The afterglow is detected in iJHKs observations starting 2.3 hr after the burst with Ks = 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 Ks-band between 2.8 and 3.7 hr at a 4σ significance level. The optical/near-IR spectral index, βO,NIR −2, is much redder than expected in the standard afterglow model, pointing to either significant dust extinction, A host V ≈ 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 nearIR 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 GRB 070724A 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 M⊙ and a radioactive energy release efficiency of f ∼ 5×10−3 (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, and furthermore localizes the burst to the outskirts of the galaxy, with an offset of 4.8±0.1 kpc relative to the host center. At such a large offset, the possible large extinction points to a dusty environment local to the burst and rules out a halo or intergalactic origin.Astronom