Persistent intraepithelial lymphocytosis in celiac patients adhering to gluten-free diet is not abolished despite a gluten contamination elimination diet

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCR + (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696

Addicts with chronic hepatitis C: Difficult to reach, manage or treat?

AIM: To assess the acceptance, safety and efficacy of care and treatment for chronic hepatitis C (CHC) in drug addicts. METHODS: We designed a multidisciplinary, phase IV prospective cohort study. All illicit drug users (IDUs) visited a Territorial Addiction Service (SerT) in the District of Brescia, and hepatitis C antibody (HCVAb) testing positive were offered as part of a standardised hepatologic visit in our Gastroenterology Unit. Patients with confirmed CHC and without medical contraindications were administered peginterferon alfa-2b 1.5 μg/kg per week plus ribavirin (800-1400 mg/d) for 16-48 wk. All IDUs were unselected because of ongoing addiction and read and signed an informed consent form. Virologic responses at weeks 4 and 12 of therapy, at the end of treatment and 24 wk after the end of treatment were the main measures of efficacy. Adherence was estimated according to the 80/80/80 criteria. RESULTS: From November 2007 to December 2009, 162 HCVAb+ IDUs were identified. Sixty-seven patients (41% of the initial cohort) completed the diagnostic procedure, and CHC was diagnosed in 54 (33% of the total). Forty-nine patients were offered therapy, and 39 agreed (80% of acceptance rate). The prevalent HCV genotype was type 1, and the HCV RNA baseline level was over 5.6 log/mL in 61% of cases. Five patients dropped out, two because of severe adverse events (SAEs) and three without medical need. Twenty-three and 14 patients achieved end of treatment responses (ETRs; 59%) and sustained virologic responses (SVRs; 36%), respectively. Thirty-one patients were fully compliant with the study protocol (80% adherence). The prevalence of host and viral characteristics negatively affecting the treatment response was high: age over 40 years (54%), male gender (85%), overweight body type (36%), previous unsuccessful antiviral therapy (21%), HCV genotype and viral load (60% and 62%, respectively), earlier contact with HBV (40%) and steatosis and fibrosis (44% and 17%, respectively). In a univariate analysis, alcohol intake was associated with a non-response (P = 0.0018, 95%CI: 0.0058-0.4565). CONCLUSION: Drug addicts with CHC can be successfully treated in a multidisciplinary setting using standard antiviral combination therapy, despite several "difficult to reach, manage and treat" characteristics

Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources

Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome whose triggering mechanisms remain unsettled. This study aimed to clarify how cultured peripheral blood mononucleated cells (PBMC) obtained from NCGS patients responded to contact with wheat proteins. Results demonstrated that wheat protein induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS patients, and that the overactivation level depends on the cereal source from which proteins are obtained. CXCL10 is able to decrease the transepithelial resistance of monolayers of normal colonocytes (NCM 460) by diminishing the mRNA expression of cadherin-1 (CDH1) and tight junction protein 2 (TJP2), two primary components of the tight junction strands. Thus, CXCL10 overactivation is one of the mechanisms triggered by wheat proteins in PBMC obtained from NCGS patients. This mechanism is activated to a greater extent by proteins from modern with respect to those extracted from ancient wheat genotypes

Ancient pathogen-driven adaptation triggers increased susceptibility to non-celiac wheat sensitivity in present-day European populations

Details of sequence profiles for each NCWS subject. (XLSX 47 kb

Bio-physical characteristics of gastrointestinal mucosa of celiac patients: comparison with control subjects and effect of gluten free diet-

<p>Abstract</p> <p>Background</p> <p>Intestinal mucosa is leaky in celiac disease (CD), and this alteration may involve changes in hydrophobicity of the mucus surface barrier in addition to alteration of the epithelial barrier. The aims of our study were i) to compare duodenal hydrophobicity as an index of mucus barrier integrity in CD patients studied before (n = 38) and during gluten- free diet (GFD, n = 68), and in control subjects (n = 90), and ii) to check for regional differences of hydrophobicity in the gastro-intestinal tract.</p> <p>Methods</p> <p>Hydrophobicity was assessed by measurement of contact angle (CA) (Rame Hart 100/10 goniometer) generated by a drop of water placed on intestinal mucosal biopsies.</p> <p>Results</p> <p>CA (mean ± SD) of distal duodenum was significantly lower in CD patients (56° ± 10°)) than in control subjects (69° ± 9°, p < 0.0001), and persisted abnormal in patients studied during gluten free diet (56° ± 9°; p < 0.005). CA was significantly higher (62° ± 9°) in histologically normal duodenal biopsies than in biopsies with Marsh 1-2 (58° ± 10°; p < 0.02) and Marsh 3 lesions (57° ± 10°; p < 0.02) in pooled results of all patients and controls studied. The order of hydrofobicity along the gastrointestinal tract in control subjects follows the pattern: gastric antrum > corpus > rectum > duodenum > oesophagus > ileum.</p> <p>Conclusions</p> <p>We conclude that the hydrophobicity of duodenal mucous layer is reduced in CD patients, and that the resulting decreased capacity to repel luminal contents may contribute to the increased intestinal permeability of CD. This alteration mirrors the severity of the mucosal lesions and is not completely reverted by gluten-free diet. Intestinal hydrophobicity exhibits regional differences in the human intestinal tract.</p

Terceirização : a administração pública e a responsabilidade com os débitos trabalhistas

A Administração Pública, ao se deparar com a necessidade de mão-de-obra para realizar as atividades alheias aos seus objetivos institucionais, vem transferindo a terceiros tarefas cuja interrupção comprometeria o andamento da estrutura administrativa. A contratação de empresas para a realização destes serviços tem agregado algumas responsabilidades ao ente público, em especial aos servidores encarregados da fiscalização dos contratos, os quais, além de fiscalizar a execução do objeto contratado, são responsáveis pela fiscalização do cumprimento das obrigações trabalhistas e previdenciárias por parte da empresa contratada. Neste trabalho serão abordadas as conseqüências e responsabilidades de uma fiscalização não realizada a contento, bem como as precauções que o fiscal/gestor do contrato deve ter para se resguardar. Será discutido também como a Administração Pública poderá minimizar os efeitos de uma possível responsabilidade subsidiária quando do inadimplemento das obrigações trabalhistas por parte da empresa contratada. Teceremos, também, algumas considerações acerca da competência da Administração e do Ministério do Trabalho e Emprego para fiscalizar os encargos trabalhistas

Terceirização : a administração pública e a responsabilidade com os débitos trabalhistas

A Administração Pública, ao se deparar com a necessidade de mão-de-obra para realizar as atividades alheias aos seus objetivos institucionais, vem transferindo a terceiros tarefas cuja interrupção comprometeria o andamento da estrutura administrativa. A contratação de empresas para a realização destes serviços tem agregado algumas responsabilidades ao ente público, em especial aos servidores encarregados da fiscalização dos contratos, os quais, além de fiscalizar a execução do objeto contratado, são responsáveis pela fiscalização do cumprimento das obrigações trabalhistas e previdenciárias por parte da empresa contratada. Neste trabalho serão abordadas as conseqüências e responsabilidades de uma fiscalização não realizada a contento, bem como as precauções que o fiscal/gestor do contrato deve ter para se resguardar. Será discutido também como a Administração Pública poderá minimizar os efeitos de uma possível responsabilidade subsidiária quando do inadimplemento das obrigações trabalhistas por parte da empresa contratada. Teceremos, também, algumas considerações acerca da competência da Administração e do Ministério do Trabalho e Emprego para fiscalizar os encargos trabalhistas