Analysis of viral nucleic acids in duodenal biopsies from adult patients with active celiac disease: in search for an etiological relationship

BACKGROUND AND AIM: Celiac Disease (CD) is a multisystemic chronic inflammatory autoimmune disease which develops in genetically predisposed subjects and it is triggered by the ingestion of gluten. After the interaction between HLA-DQ2/DQ8 and gluten-derived peptides, lymphocytes T CD4+ start a specific immune response which ends in a chronic inflammation and mucosal damage. CD pathogenesis is complex and not entirely understood, probably due to an alteration in the gastrointestinal immune system or to its aberrant regulation. Furthermore, many environmental and immune factors could be involved, particularly viral infections. The aim of the study was to observe possible relationships between CD and infections from HHV-6 A/B, EBV, CMV, adenovirus and rotavirus. MATERIAL AND METHODS: Thirty-nine adult patients (aged 18-65 yrs) have been enrolled: specifically, 24 duodenal biopsies from active CD patients and 15 biopsies from non-CD patients were analyzed. CD diagnosis has been performed by means of serological antibodies, histology of duodenal biopsies and duodenal biopsy organ culture. Viral nucleic acids were extracted from duodenal biopsies and then amplified using Real-Time PCR technique. RESULTS: HHV-6B was found in 62.5% of CD patients and in 73.3% of non-CD patients (p=0.13). EBV was found in 4.5% of CD patients and 6.7% of non-CD patients (p=0.35). Nucleic acids from HHV-6A, CMV, adenovirus and rotavirus were not detected in any group. HHV-6B viral load in CD patients was higher than in non-CD patients, but data were not statistically significant (p=0.54). CD patients with HHV-6B viral load >50000 copies/ml resulted to be younger and had lower anti-tTG antibody titers found at organ culture than patients with lower HHV-6B viral load (p>0.05). CONCLUSIONS: There seems to be no difference in viral load and/or in the detection of viruses between CD and non-CD patients. Thus, our data do not support the possible relationship between CD and viral infections, although a larger population is needed to confirm our study results

Type 1 diabetes, thyroid, gastric and adrenal humoral autoantibodies are present altogether in almost one third of adult celiac patients at diagnosis, with a higher frequency than children and adolescent celiac patients

Background: No data are available on the frequency of organ-specific humoral autoimmunity at diagnosis of adult celiac disease (CD). Aim: To evaluate the humoral immunoreactivities specific of type 1 diabetes (T1D), thyroid (THD), atrophic-gastritis (AG) and Addison’s (AD) diseases in 92 adult CD patients at diagnosis and 237 adult healthy subjects (CTRL). Methods: T1D, THD and AD specific autoantibodies were analyzed by radioimmunoprecipitation assays. AG autoantibodies were detected by enzyme-linked immunosorbent assay. Results: Of 92 CD patients, 31.5% were positive for at least one of the organ-specific autoantibodies investigated (p <.0001 vs CTRL). Thyroid, diabetes, gastric and adrenal-autoantibodies, that increase with age at diagnosis, were detected in 12.0%, 10.9%, 10.9%, 2.2% of CD patients, respectively. Gastric- and diabetes- rather than thyroid- and adrenal-autoimmunity seem to be specifically related to presence of CD. Conclusions: One third of adult CD patients at diagnosis is target of at least one organ-specific autoantibody. A systematic organ-specific autoantibody screening in these patients might be of value to promptly identify, prevent or treat the relative diseases

Definição do padrão de ramificação da plantas jovens da erva-mate, no nível de unidade de crescimento.

O objetivo deste trabalho foi determinar os padrões de ramificações de duas GU anuais

Recurrence of gastrointestinal and extra-intestinal symptoms in celiac patients affected by nickel allergic contact mucositis: when proper gluten-free diet is not enough

BACKGROUND AND AIM: Nickel (Ni) is a metal widely present in nature and the prevalence of Ni allergy is increasing. Allergic contact mucositis (MAC) induced by Ni-rich foods is often responsible for IBS-like disorders and it can be diagnosed by means of a Ni oral mucosa patch test (omPT). It has been observed that, after several months of correct gluten-free diet (GFD), many celiac disease (CD) patients show a recrudescence of gastrointestinal and extra-intestinal symptoms, although serological and histological remission has been achieved. This can be due to a Ni load induced by GFD: a greater consumption of Ni-rich foods (e.g. corn) would lead to a consequent intestinal sensitization to Ni in predisposed subjects. Our study aimed to assess the role played by Ni in the recurrence of symptoms in CD subjects after strict GFD. MATERIAL AND METHODS: Twenty celiac patients (all female, age 23-65 yrs) in serological and histological remission after at least 12 months of GFD have been consecutively included: they all were complaining recurrence gastrointestinal and extra-intestinal symptoms. Subjects with organic gastrointestinal pathologies were excluded. A symptom questionnaire (GSRS modified according to the Salerno Experts' Criteria) has been administered to all patients in 4 stages: T0 (during free diet - active CD); T1 (after 12 months of GFD - CD remission); T2 (during GFD - recurrence of symptoms); T3 (during GFD and after 3 months of low-Ni diet). Ni omPT was performed at T2. Statistical analysis was performed using Wilcoxon signed rank test. RESULTS: All 20 patients showed positive Ni omPT, with local and/or systemic alterations confirming Ni ACM diagnosis. The analysis obtained by comparing T2-T3 showed p-value <0.01 for: abdominal pain, bloating, swelling, increased number of evacuations, dermatitis, asthenia; p-value values <0.05 for: heartburn, acid regurgitation, borborygmus, flatulence, loose stools, urgent need for defecation, headache. The other variables were statistically not significant. CONCLUSIONS: Our data suggest that gastrointestinal and extra-intestinal symptoms observed in CD subjects after prolonged and correct GFD may be due to the necessary dietary change and an increased Ni intake. Specifically, these patients developed Ni MAC, diagnosed by specific Ni omPT. We also observed that regression of symptoms may occur after a proper low-Ni diet. We can conclude that GFD may lead to an increased consumption of Ni-rich foods and this could explain the recurrence of apparently gluten-dependent symptoms

Interrupted versus uninterrupted NOAC peri-implantation of cardiac device: A single-centre randomised prospective pilot trial

BACKGROUND: Many patients requiring cardiac implantable electronic device (CIED) implantation are on long-term oral anticoagulant therapy. While continuation of warfarin has been shown to be safe and reduce bleeding complications compared to interruption of warfarin therapy and heparin bridging, it is not known which novel oral anticoagulants (NOAC) regimen (interrupted vs. uninterrupted) is better in this setting. METHODS: One-hundred and one patients were randomized to receive CIED implantation with either interrupted or uninterrupted/continuous NOAC therapy before surgery. No heparin was used in either treatment arm. The primary end-point was the presence of a clinically significant pocket haematoma after CIED implantation. The secondary end-point was a composite of other major bleeding events, device-related infection, thrombotic events and device-related admission length post device implantation. RESULTS: Both treatment groups were equally balanced for baseline variables and concomitant medications. One clinically significant pocket haematoma occurred in the uninterrupted NOAC group and none in the interrupted group (p = 0.320). There was no difference in other bleeding complications. No thrombotic events were observed in either of the two groups. CONCLUSIONS: Despite the paucity of bleeding events, data from this pilot study suggest that uninterrupted NOAC therapy for CIED implantation appears to be as safe as NOAC interruption and does not increase bleeding complications

Role of extracellular microvesicles in celiac disease as potential pathogenetic agents and biomarkers of intestinal inflammation

BACKGROUND AND AIM: Celiac Disease (CD) is a chronic intestinal disease caused by the ingestion of gluten. Microvesicles (MVs) belong to a heterogeneous population, released by cells both in homeostasis and pathological conditions. MVs can be considered mediators of inflammation and potential biomarkers. The aim of this study is: 1) to evaluate the possible role of MVs in the propagation of inflammation in CD, using MVs purified by supernatant of duodenal biopsies from CD patients; 2) to identify potential biomarkers by proteomic analysis of pasma-derived MVs from CD patients. MATERIAL AND METHODS: MVs were isolated by molecular exclusion chromatography and ultracentrifugation respectively from plasma and culture supernatant of duodenal biopsies of 10 active CD, 5 remission CD and 6 controls. Proteomic analysis of plasma-derived MVs was performed by mass spectrometry. The possible effects of duodenal-derived MVs on confluent Caco-2 cells were evaluated by measuring Transepithelial Electrical Resistance (TEER) and analyzing the expression of actin, tissue transglutaminase (TG2) and Zonula Occludens-1 (ZO-1). The dosage of IL-8 in the Caco-2 culture supernatant was carried out by ELISA test. The statistical analysis of the data obtained was performed using the Student's t-test. RESULTS: The proteomic analysis of circulating MVs showed 8 proteins from desmosome and cytoskeleton (desmoglein-1 and gamma-enteric actin) associated with the active phase of the disease. Caco-2 cells, treated with the MVs purified from the duodenal biopsies of active CD patients showed: 1) rearrangement of actin filaments; 2) increased expression of TG2; 3) decreased expression of the ZO-1 protein, although an alteration of intestinal permeability was not observed. The analysis of Caco-2 cell supernatants showed a statistically significant increase in IL-8 (p <0.05), in the presence of MVs isolated from biopsies of active CD patients, compared to remission CD patients and controls. CONCLUSIONS: MVs isolated from plasma of active CD patients could represent potential diagnostic and prognostic biomarkers. Although they don’t induce changes in intestinal permeability, MVs could contribute to inflammatory cascade increasing IL-8 production

Modelagem da arquitetura de erva-mate usando software AMAPmod.

O objetivo deste trabalho foi determinar os padrões de crescimento caulinar e padrões de ramificações da erva-mate, com o uso do sistema computacional francês denominado V-Plants, sucessor de AMAPmod

Modelagem da estrutura e da arquitetura de erva-mate.

RESUMO: A arquitetura vegetal permite representar mais realisticamente as interações da planta com seu ambiente, minimizando a ocorrência de fracassos nos estudos que assumem um comportamento biológico baseado em estimativas médias. A modelagem de arquitetura vegetal é uma área de pesquisa nova e promissora na América do Sul. Este trabalho tem como objetivos apresentar os conceitos básicos envolvidos na modelagem da estrutura e da arquitetura de plantas, e relatar as pesquisas em desenvolvimento sobre a análise da estrutura de crescimento da erva-mate (Ilex paraguariensis St. Hil.). No ciclo anual da erva-mate apresentam-se regularmente duas pausas no crescimento que separam as brotações anuais em duas unidades de crescimento (GU) sucessivas. No experimento em campo com 30 plantas adultas foram medidos os parâmetros morfológicos durante dois anos (período entre duas podas). O desenvolvimento arquitetural das plantas está sendo analisado em várias escalas, com o uso do sistema computacional francês denominado AMAPmod. Características não medidas nas plantas adultas, como o padrão de ramificações, foram obtidas em um experimento realizado com plantas jovens. Atualmente estão sendo construídos histogramas e seqüências dos metâmeros das GU?s presentes nos eixos principais das plantas adultas, visando determinar o padrão de crescimento caulinar da erva-mate. Espera-se que a codificação dos ramos das plantas jovens contribua para a obtenção do modelo de desenvolvimento topológico. Esse modelo permitirá observar as caracterizações locais (posição de entrenós) e globais (comprimento de ramos) da espécie. A reconstrução de plantas em 3D considera as inclinações e o azimute de ramos e de componentes foliares recuperados a partir de fotografias, incluindo a diferenciação sexual das plantas.SBIAgro 2007. Na publicação: Silvio Roberto de Medeiros Evangelista

SAT0305 Histology of minor salivary glands in patients with sjÖgren's syndrome, association with clinical and laboratory aspects

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Delayed diagnosis of coeliac disease increases cancer risk

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