A new formulation of oral viscous budesonide in treating of paediatric eosinophilic oesophagitis: a pilot study

OBJECTIVES: Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single-centre, open-label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE. METHODS: We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post-treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks. RESULTS: At the end of PVB trial, endoscopy showed macroscopic remission in 32 patients (88.9%), whereas at histology median pre- and post-treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15-100) to 2.9 (range: 0-30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance-pH were treated also with proton pump inhibitors. No significant difference between pre-/post-treatment morning cortisol levels occurred. CONCLUSIONS: The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo-controlled clinical trials would provide more information about dosing, efficacy, and long-term safety of this formulation, specifically designed for the oesophagus

Distortion of the Stoner-Wohlfarth astroid by a spin-polarized current

The Stoner-Wohlfarth astroid is a fundamental object in magnetism. It separates regions of the magnetic field space with two stable magnetization equilibria from those with only one stable equilibrium and it characterizes the magnetization reversal of nano-magnets induced by applied magnetic fields. On the other hand, it was recently demonstrated that transfer of spin angular momentum from a spin-polarized current provides an alternative way of switching the magnetization. Here, we examine the astroid of a nano-magnet with uniaxial magnetic anisotropy under the combined influence of applied fields and spin-transfer torques. We find that spin-transfer is most efficient at modifying the astroid when the external field is applied along the easy-axis of magnetization. On departing from this situation, a threshold current appears below which spin-transfer becomes ineffective yielding a current-induced dip in the astroid along the easy-axis direction. An extension of the Stoner-Wohlfarth model is outlined which accounts for this phenomenon.Comment: 8 pages, 6 figure

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

Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics

Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children.

Probiotics are viable, nonpathogenic microorganisms (bacteria or yeast) which when administered in adequate amounts, confer a health benefit on the host. At this time, Saccharomyces boulardii is the only yeast commonly used in clinical practice. Literature on this probiotic is wide and even more data become available each year. Thus, it could be problematic for a physician summarize all the best information deriving from basic research and clinical studies. With the aim to help physicians in the use of Saccharomyces boulardii, this paper focuses on the available evidences for its efficacy and safety in different diseases in adult and pediatric patients in order to provide a practical guidance for gastroenterology clinical practice. Indications and dosage for several gastrointestinal diseases for a correct use of this probiotic are provided, and recent insights on its mechanisms of action and possible future clinical application are also discussed

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

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

Non variability of intervening absorbers observed in the UVES spectra of the "naked-eye" GRB080319

The aim of this paper is to investigate the properties of the intervening absorbers lying along the line of sight of Gamma-Ray Burst (GRB) 080319B through the analysis of its optical absorption features. To this purpose, we analyze a multi-epoch, high resolution spectroscopic observations (R=40000, corresponding to 7.5 km/s) of the optical afterglow of GRB080319B (z=0.937), taken with UVES at the VLT. Thanks to the rapid response mode (RRM), we observed the afterglow just 8m:30s after the GRB onset when the magnitude was R ~ 12. This allowed us to obtain the best signal-to-noise, high resolution spectrum of a GRB afterglow ever (S/N per resolution element ~ 50). Two further RRM and target of opportunity observations were obtained starting 1.0 and 2.4 hours after the event, respectively. Four MgII absorption systems lying along the line of sight to the afterglow have been detected in the redshift range 0.5 < z < 0.8, most of them showing a complex structure featuring several components. Absorptions due to FeII, MgI and MnII are also present; they appear in four, two and one intervening absorbers, respectively. One out of four systems show a MgII2796 rest frame equivalent width larger than 1A. This confirms the excess of strong MgII absorbers compared to quasars, with dn/dz = 0.9, ~ 4 times larger than the one observed along quasar lines of sight. In addition, the analysis of multi-epoch, high-resolution spectra allowed us to exclude a significant variability in the column density of the single components of each absorber. Combining this result with estimates of the size of the emitting region, we can reject the hypothesis that the difference between GRB and QSO MgII absorbers is due to a different size of the emitting regions.Comment: 10 pages, 15 ps figures, submitted to MNRA