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

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

Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study.

AIM: To assess the value of long-chain omega-3 fatty acids (FAs) supplementation in addition to amino-salicylic-acid (5-ASA) in pediatric patients with Crohn's disease (CD). METHODS: Thirty-eight patients (20 males and 18 females, mean age 10.13 years, range 5-16 years) with CD in remission were randomized into two groups and treated for 12 mo. Group I (18 patients) received 5-ASA (50 mg/kg/d)+ omega-3 FAs as triglycerides in gastro-resistant capsules, 3 g/d (eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g). Group II (20 patients) received 5-ASA (50 mg/kg/d)+ olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS: The number of patients who relapsed at 1 year was significantly lower in group I than in group II (P < 0.001). Patients in group I had a significant increase in the incorporation of EPA and DHA (P < 0.001) and a decrease in the presence of arachidonic acids. CONCLUSION: Enteric-coated omega-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD

Multifrequency Observations of the Blazar 3C 279 in January 2006

We report first results of a multifrequency campaign from radio to hard X-ray energies of the prominent gamma-ray blazar 3C 279, which was organised around an INTEGRAL ToO observation in January 2006, and triggered on its optical state. The variable blazar was observed at an intermediate optical state, and a well-covered multifrequency spectrum from radio to hard X-ray energies could be derived. The SED shows the typical two-hump shape, the signature of non-thermal synchrotron and inverse-Compton (IC) emission from a relativistic jet. By the significant exposure times of INTEGRAL and Chandra, the IC spectrum (0.3 - 100 keV) was most accurately measured, showing - for the first time - a possible bending. A comparison of this 2006 SED to the one observed in 2003, also centered on an INTEGRAL observation, during an optical low-state, reveals the surprising fact that - despite a significant change at the high-energy synchrotron emission (near-IR/optical/UV) - the rest of the SED remains unchanged. In particular, the low-energy IC emission (X- and hard X-ray energies) remains the same as in 2003, proving that the two emission components do not vary simultaneously, and provides strong constraints on the modelling of the overall emission of 3C 279.Comment: 4 pages, 6 figures; to be published in the Proc. of the 6th INTEGRAL workshop "The Obscured Universe" (Moscow, July 2-8, 2006), eds. S. Grebenev, R. Sunyaev, C. Winkler, ESA SP 622 (2006

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

The Very Young Type Ia Supernova 2012cg: Discovery and Early-Time Follow-Up Observations

On 2012 May 17.2 UT, only 1.5 +/- 0.2 d after explosion, we discovered SN 2012cg, a Type Ia supernova (SN Ia) in NGC 4424 (d ~ 15 Mpc). As a result of the newly modified strategy employed by the Lick Observatory SN Search, a sequence of filtered images was obtained starting 161 s after discovery. Utilizing recent models describing the interaction of SN ejecta with a companion star, we rule out a ~1 M_Sun companion for half of all viewing angles and a red-giant companion for nearly all orientations. SN 2012cg reached a B-band maximum of 12.09 +/- 0.02 mag on 2012 June 2.0 and took ~17.3 d from explosion to reach this, typical for SNe Ia. Our pre-maximum brightness photometry shows a narrower-than-average B-band light curve for SN 2012cg, though slightly overluminous at maximum brightness and with normal color evolution (including some of the earliest SN Ia filtered photometry ever obtained). Spectral fits to SN 2012cg reveal ions typically found in SNe Ia at early times, with expansion velocities >14,000 km/s at 2.5 d past explosion. Absorption from C II is detected early, as well as high-velocity components of both Si II 6355 Ang. and Ca II. Our last spectrum (13.5 d past explosion) resembles that of the somewhat peculiar SN Ia 1999aa. This suggests that SN 2012cg will have a slower-than-average declining light curve, which may be surprising given the faster-than-average rising light curve.Comment: re-submitted to ApJL, 4 figures, 1 tabl

Paradoxical psoriasis induced by Anti-TNFα treatment: Evaluation of disease-specific clinical and genetic markers

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical– pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p= 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p= 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice

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&