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The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John WileySons, Ltd.

Objective. Most of the recent studies suggest that oats are well tolerated by celiac disease (CD) patients. However, it is still possible that different oat cultivars may display different biological properties relevant for CD pathogenesis. We aimed to investigate biological and immunological properties of two oat varieties, Avena genziana and Avena potenza, in relation to their safety for CD patients. Material and Methods. Phosphorylation of extracellular signal-regulated kinase (ERK) and transepithelial electrical resistance (TEER) were evaluated in CaCo-2 cells treated with peptic–tryptic (PT) digests from the two oats and from gliadin (PTG). With the same PT-digests, duodenal biopsies from 22 CD patients were treated in vitro for 24 h and density of CD25 + cells in lamina propria and of intraepithelial CD3 + T cells was measured, as well as crypt cell proliferation and epithelial expression of interleukin 15. Finally, interferon g (IFN-g) production was measured as evidence of gliadin-specific T-cell activation by PT-digests. Results. In contrast to PTG, oats PT-digests were not able to induce significant increase in ERK phosphorylation and decrease in TEER in CaCo-2 cells. In the organ culture system, oats PTdigests, unlike PTG, did not induce significant increase in crypt enterocyte proliferation, increase in interleukin 15 expression or in lamina propria CD25 + cells. Nevertheless Avena potenza increased intraepithelial T-cell density, while Avena genzianainduced IFN-g production in 3/8 CD intestinal T cell lines. Conclusions. Our data show that Avena genziana and Avena potenza do not display in vitro activities related to CD pathogenesis. Some T-cell reactivity could be below the threshold for clinical relevance.

In children younger than 2 years of age, a diagnosis of celiac disease (CD) is difficult to make because anti-endomysium (anti-EMA)/anti-tissue transglutaminase 2 (anti-TG2) antibodies are less sensitive than in older children. The aim of our study was to evaluate how many children younger than 2 years of age and diagnosed with CD, were negative for serum anti-TG2 antibodies and to test the hypothesis that in these patients, TG2-specific IgA deposits could instead be present at mucosal level.A total of 104 children younger than 2 years of age and 179 children older than 2 years, all of whom had been diagnosed with CD, were investigated for serum CD-associated antibodies (anti-gliadin [AGA] IgA and IgG, EMA-IgA, anti-TG2-IgA). The presence of intestinal anti-TG2 extracellular IgA deposits was searched by using double immunofluorescence in 56 of the patients younger than 2 years of age and in 40 of those who were older than 2 years.In children with CD who were younger than 2 years of age, high levels of AGA-IgA were found in 93/104 (89%) and 98/104 (94%) were found of have high levels of AGA-IgG. In children older than the age of 2 years with CD, 120/179 (67%) had high levels of AGA-IgA and 151/179 (84%) had high levels of AGA-IgG. Serum EMA were present in 92/104 (88%) in the younger group and in 176/179 (98%) of the older group. Ninety-one of 104 children (87%) younger and 172/179 (96%) older than 2 years showed high serum levels of anti-TG2. Finally, 41/56 (73%) children younger than 2 years and all of the 40 children (100%) older than 2 years of age showed mucosal anti-TG2-IgA deposits.EMA and anti-TG2-antibody measurements show higher sensitivity for the diagnosis of CD in children older than 2 years compared with younger children. The search for mucosal deposits of anti-TG2-IgA does not improve the diagnostic performance.

SummaryThe diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)γδ+ intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRγδ+ IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRγδ+ IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRγδ+ IELs than controls (P

The aim of this study was to assess the impact of two differnt therapeutic interventions on own perception of HRQOL n IBD patient. Methods and materials. Children and adolescents ffected by IBD were divided in two groups: first group in tandard therapy (5ASA and azathioprine); second group in tandard therapy plus monthly infusions of autologous red lood cell loaded with dexametasone -21P, because of their ependence. Quality of life was assessed by a self-administered quesionnaire, Short Form 36 Health Survey (SF-36), that all ubjects completed. The SF-36 is divided in two major roups physical and mental, which include 7 domains. ann–Whitney U-test was performed to compare the RQOL between the 2 groups of IBD patients. Results. A total of 76 IBD patients followed at our Gasroenterology Unit aged 8-18 years were included. Among hem 35 were affected by CD and 41 by UC (42 boys, 34 irls). 56 patients were treated with the standard therapy and 0 with standard therapy plus the infusions of autologous BC loaded with DEX 21-P (11 CD and 9 CU). No sigificant differences were found between the two groups for hysical and mental indexes (median 77, IQR 63–81 versus 5, IQR 70–94 p= 0.07, and 71, IQR 52–82 versus 74, IQR 0–89 p= 0.5 respectively). Regarding the different domains, perception of general ealth was significantly lower in the group of patients treated ith the infusions of autologous RBC loaded with DEX-21P n comparison to the group treated with standard therapy. o other significant differences were found in other domains Physical Functioning, Body Pain, Vitality, Social Function, motional and Mental Health). Conclusion. Perception of general health seems to be ower in the group of patients treated with the infusions of utologous RBC loaded with DEX-21P. We can hypothesize hat these group of patients had more severe or active disase, and the monthly hospitalization impacts on their general ealth. Future research should investigate to correlate their isease activity with HRQOL.

Objective. Anti-tissue transglutaminase (anti-TG2) IgA utoantibodies are detectable in serum of the great majorty of patients with untreated coeliac disease (CD). Many vidence suggest that they are primarily produced in the ntestinal mucosa. The detection of IgA anti-TG2 intestinal eposits is proposed to be a specific and sensitive tool for the iagnosis of CD. The aim of this work is to investigate the resence of anti-TG2 IgA autoantibodies in the small intesine of patients with potential CD (subjects with presence n the serum of anti-endomysium antibodies (EMA) and/or igh levels of anti-TG2, and a normal intestinal mucosa). The resence of intestinal anti-TG2 IgA has been related to the volution to severe enteropathy. Methods. The study involved 27 children with potential D (18 F and 9 M, median age 8 years and 3 months). All atients were asymptomatic and showed HLA consistent with D; they continued a gluten free diet and underwent clinical nd laboratory controls every 6 months, and a second biopsy fter 2 years. Anti-TG2 IgA intestinal deposits were detected y double immunofluorescence and confocal microscopy. Results. 20/27 (74%) patients showed anti-TG2 IgA ntestinal deposits at the beginning of the study. After two ears 12/20 still presented a normal intestinal mucosa with gA anti-TG2 intestinal deposits, while in 4 cases such eposits were not observed even if the patients continued o present a positive serology for CD and a normal mucosa. inally, 4/20 (20%) children with IgA deposits presented, t the time of the second biopsy, villous atrophy. Of the even patients who were negative for anti-TG2 IgA intestinal eposits at the time of the first biopsy, 4/7 were confirmed gain negative for those deposits after 2 years; 3/7 become ositive and one of them developed villous atrophy. Conclusions. Most patients with potential CD presented nti-TG2 IgA intestinal deposits, but not always there was orrespondence with the presence in the serum. Only 4/20 atients with potential CD, who showed intestinal deposits f anti-TG2 IgA at the time of the diagnosis, developed vilous atrophy. In patients with potential CD, after two years f follow-up, the presence of IgA anti-TG2 deposits is not redictive of the development of the mucosal atrophy.