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The downstream cascade of the inflammatory response to gliadin in celiac intestinal mucosa encompasses the early activation of the innate immunity that triggers the adaptive response. Therefore, the in vitro study of the pathogenic mechanism of celiac disease (CD) on enterocytes alone or mucosal T lymphocytes alone does not fully consider all the aspects of gliadin-dependent inflammation. Although the in vitro culture of specimens of intestinal mucosa obtained from celiac patients is the gold standard for the study of CD, this technique presents several technical challenges and the bioptic specimens are not easily available. So, in this paper, we described the gliadin-dependent cytokine production in a bidimensional cellular system, which is able to mimic both the innate and the adaptive steps of the mucosal immune response of CD. In the upper compartment, the intestinal epithelial cells are grown on a filter, and in the lower compartment, the mononuclear cells isolated from peripheral blood of celiac patients are cultured. Cells were apically exposed to the toxic gliadin peptide p31-43 for 3 h and then with the immunodominant gliadin fragment pα-9 for 21 h. The incubation with gliadin peptides resulted in increased levels of IL-15, INF-γ, IL-6, tumor necrosis factor (TNF)-α, IL-1β, and CCL 2, 3 and 4 in the basal supernatants, with respect to cells exposed to medium alone. The p31-43-driven epithelial priming of mucosal response consists of transglutaminase (TG2)-mediated deamidation of the immunostimulatory gliadin peptides, as demonstrated by the inhibition of pα-9 activity, when the system is exposed to blocking anti-TG2 antibody. [ABSTRACT FROM AUTHOR]

Purpose: Celiac disease (CD) is an autoimmune enteropathy, triggered by dietary gluten. The only treatment is a strict gluten-free diet. Oats are included in the list of gluten-free ingredients by European Regulation, but the safety of oats in CD is still a matter of debate. The present study examined the capability of different oat cultivars of activating the gliadin-induced transglutaminase-2 (TG2)-dependent events in some in vitro models of CD. In addition, we compared this capability with the electrophoresis pattern of peptic-tryptic digests of the proteins of the oat cultivars. Methods: K562(S) cells agglutination, transepithelial electrical resistance of T84-cell monolayers, intracellular levels of TG2 and phosphorylated form of protein 42-44 in T84 cells were the early gliadin-dependent events studied. Results: The results showed that the Nave oat cultivar elicited these events, whereas Irina and Potenza varieties did not. The ability of a cultivar to activate the above-described events was associated with the electrophoretic pattern of oat proteins and their reactivity to anti-gliadin antibodies. Conclusion: We found significant differences among oat cultivars in eliciting the TG2-mediated events of CD inflammation. Therefore, the safety of an oat cultivar in CD might be screened in vitro by means of biochemical and biological assays, before starting a clinical trial to definitely assess its safety. [ABSTRACT FROM AUTHOR]

Background: A submucosal tumor (SMT) of the stomach, which is an occasional finding during routine upper gastrointestinal endoscopy, may pose diagnostic and therapeutic challenges. Methods: To assess whether endoscopic submucosal dissection (ESD) is a feasible approach to definitively cure SMTs, the authors performed a retrospective cohort study with two endoscopic italian centers. Results: The study consisted of 20 patients with SMTs who underwent ESD. The patients underwent ESD and were followed up by endoscopy. We analyzed complete resection rate, frequency of complications, and survival. The overall rate of R0 resection was 90 % (18/20), with two endoscopic failures, one for a submucosal tumor and one for a neoplasm deeply infiltrating the proper muscle layer. The median procedure time was 119.1 min (range 40-240 min). The median size of the resected specimens was 29 mm (range 15-60 mm). Perforation occurred in 3 patients; all were treated conservatively. There were no cases of severe bleeding. Based on histopathological findings, 6 cases of ectopic pancreas, 1 of ectopic spleen, 3 of leiomyoma, and 10 of gastrointestinal stromal tumor (GIST) were diagnosed. Complete resection was obtained in all GIST cases. Among the 10 GIST cases treated by ESD, no death occurred: the 5-year disease-specific survival rate was 100 %. Conclusions: The high success rate of 90 % and the low incidence of complications should indicate ESD is the correct diagnostic and definitive treatment in selected patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The association between maternal celiac disease (CD) and both reduced fertility and increased risk of adverse pregnancy-related events has been long documented. However, no evidences are available regarding the pathogenic mechanisms of this link. The aim of this study was to determine whether anti-tissue transglutaminase (anti-tTG) antibodies are involved in the damage of trophoblastic cells in vitro.METHODS:Human primary trophoblastic cells, isolated from term placenta, were exposed to anti-tTG immunoglobulin G (IgG) antibodies, both commercially available and separated from sera of three untreated celiac women. The ability of anti-tTG antibodies to bind to trophoblastic cells, invasiveness of placental cells through a layer of extracellular matrix, and the activity of cellular matrix metalloprotease (MMP) and cellular apoptosis were evaluated, as indicators of trophoblast damage, by TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) and annexin V expression.RESULTS:Anti-tTG IgG showed a specific dose- and time-dependent binding to human trophoblast. In addition, trophoblastic cells, after being exposed to anti-tTG IgG antibodies, both commercially available and separated from sera of celiac women, showed an impaired invasiveness, a decreased activity of cellular MMP, and a greater percentage of TUNEL positivity and annexin V positivity.CONCLUSIONS:We showed that the binding of anti-tTG antibodies to trophoblast might represent a key mechanism by which the embryo implantation and pregnancy outcome are impaired in untreated celiac pregnant women. Because healthy trophoblast development is essential for placental and fetal development, these data provide a novel mechanism for CD-induced infertility, early pregnancy loss, and intrauterine growth retardation. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) has been developed as treatment for early gastric cancer (EGC) by Japanese authors. However, there are no reports about its possible implementation in the Western setting. The aim of the present work is to determine the safety and efficacy of the endoscopic treatments for EGC in an Italian cohort. Forty-five patients for a total of 48 gastric lesions were enrolled in the study. Thirty-six EMR procedures were performed with the strip biopsy technique using a double-channel endoscope. En bloc resection refers to resection in one piece, while piecemeal refers to resections in which the lesion was removed in multiple fragments. A total of 12 ESD were performed and completed with IT knife. We define as curative treatment lateral and vertical margins of the resected specimens free of cancer and repeat endoscopic finding of no recurrent disease. Out of 36 EMR procedures, 10 were piecemeal resections (28%), while 26 were en bloc (72%). ESD led to en bloc resection in 11/12 cases (92%). Histological assessment of curability in the EMR group was achieved in 56% of the cases, and in 92% of the ESD group. Mean follow-up period was 31 months (range: 12–71 months). There was no local recurrence or distant metastasis in the curative group patients. These results seem to confirm the safety and the clinical efficacy of the ESD procedure in the Western world too. [ABSTRACT FROM AUTHOR]

Patients with celiac disease have an increased rate of enteropathy-associated T-cell lymphoma, but conflicting data are available about the protective role of a gluten-free diet with regard to the development of this malignancy. We followed 1,757 celiac patients for a total period of 31,801 person-years, collecting data about the frequency of gluten intake and the incidence of the enteropathy-associated T-cell lymphoma. Out of the nine celiac patients who developed an intestinal lymphoma [standard morbidity ratio of 6.42 (95% CI = 2.9-12.2; P < 0.001)], only two kept a strict gluten-free diet after the diagnosis of celiac disease and developed the malignancy after the peridiagnosis period of 3 years, dropping therefore the standard morbidity ratio to 0.22 (95%CI = 0.02-0.88; P < 0.001). The risk of developing an intestinal lymphoma for the celiac patients that used to have dietary gluten was significant (X(2 )= 4.8 P = 0.01). These results show that a strict gluten-free diet is protective towards the development of enteropathy-associated T-cell lymphoma. [ABSTRACT FROM AUTHOR]