Host Epithelial Interactions with Helicobacter Pylori: A Role for Disrupted Gastric Barrier Function in the Clinical Outcome of Infection?

Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population

Matrix Metalloproteinase-2 and -9 Secreted by Leukemic Cells Increase the Permeability of Blood-Brain Barrier by Disrupting Tight Junction Proteins

Central nervous system (CNS) involvement remains an important cause of morbidity and mortality in acute leukemia, the mechanisms of leukemic cell infiltration into the CNS have not yet been elucidated. The blood-brain barrier (BBB) makes CNS become a refugee to leukemic cells and serves as a resource of cells that seed extraneural sites. How can the leukemic cells disrupt this barrier and invasive the CNS, even if many of the currently available chemotherapies can not cross the BBB? Tight junction in endothelial cells occupies a central role in the function of the BBB. Except the well known role of degrading extracellular matrix in metastasis of cancer cells, here we show matrix metalloproteinase (MMP)-2 and -9, secreted by leukemic cells, mediate the BBB opening by disrupting tight junction proteins in the CNS leukemia. We demonstrated that leukemic cells impaired tight junction proteins ZO-1, claudin-5 and occludin resulting in increased permeability of the BBB. However, these alterations reduced when MMP-2 and -9 activities were inhibited by RNA interference strategy or by MMP inhibitor GM6001 in an in vitro BBB model. We also found that the disruption of the BBB in company with the down-regulation of ZO-1, claudin-5 and occludin and the up-regulation of MMP-2 and -9 in mouse brain tissues with leukemic cell infiltration by confocal imaging and the assay of in situ gelatin zymography. Besides, GM6001 protected all mice against CNS leukemia. Our findings suggest that the degradation of tight junction proteins ZO-1, claudin-5 and occludin by MMP-2 and -9 secreted by leukemic cells constitutes an important mechanism in the BBB breakdown which contributes to the invasion of leukemic cells to the CNS in acute leukemia

Epithelial: Helicobacter pylori interactions

Bibliography: p. 126-141The dynamic and selective barrier formed by the epithelial cells of the human gastric mucosa is crucial in the protection against microbial pathogens. Peptides produced by the human host such as epidermal growth factor (EGF) are important in maintaining mucosal integrity and protecting the host from bacterial colonization. This study investigated the effect of H. pylori, a human gastric pathogen implicated in the development of gastroduodenal ulcers and gastric cancers, on epithelial barrier structure and function in vivo and in vitro. In addition, the effect of EGF on H. pylori colonization and viability was also examined. Bacterial load and gastritis increased over 14, 70 and 100 days in C57Bl/6 mice infected with H. pylori strain SS1. Infected mice also had a transient increase in gastric, but not duodenal, permeability on day 73 of the infection. Confluent, non-transformed intestinal epithelial cells (SCBN) grown on Transwells and exposed to H. pylori strain SS1 (VacA+/CagA+) had an increase in the passage of 3000MW Dextran. In contrast, H. pylori strains LC11 (VacA+/CagA+) and LC20 (VacA-/CagA-) did not change the permeability of SCBN cells to 3000MW Dextran. By immunohistochemistry and western blotting, H. pylori strain SS 1 disrupted tight junction (TJ) occludin, claudin-4 and claudin-5 in SCBN cells. The addition of a specific inhibitor of MLCK prevented the increase in epithelial permeability and disruption of tight junctional claudin-4 and claudin-5. Oral, daily administration of human recombinant EGF (100Jµg/kg) to infected mice 10 days prior to sacrifice significantly lowered the number of H. pylori recovered from gastric tissues. However, co-culture of H. pylori and EGF (100µM) had no effect on bacterial growth or metabolism. Stomach sections from infected-EGF treated animals had a different pattern of surface carbohydrate expression compared to infected animals. Disruptions of the tight junction observed in this study implicate previously unrecognized host cell signaling pathways, including the regulation of tight junctional claudin-4, claudin-5 and the phosphorylation of myosin light chain, in the pathogenesis of H. pylori infection. In addition, oral administration of EGF, independent of a direct microbiocidal action, can decrease the colonization of the stomach by H. pylori

Mario Girardi, Basilio di Cesarea e il culto dei martiri nel IV secolo: Scrittura e tradizione

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Bibliotheca Basiliana universalis : a study of the manuscript tradition of the works of Basil of Caesarea /

Volumes 2-5 have subtitle: A study of the manuscript tradition, translations and editions of the works of Basil of Caesarea.Subsequently designated as volume 1 of the series Corpus Christianorum, Claves - Subsidia (see Corpus Christianorum website).Includes bibliographical references and indexes.1. The letters2,1 The Homiliae Morales, Hexaemeron, De Litteris, with additional coverage of the letters : manuscripts2,2 The Homiliae Morales, Hexaemeron, De Litteris, with additional coverage of the letters : editions, translations3. The Ascetica, Contra Eunomium 1-3, Ad Amphilochium de spiritu sancto, dubia et spuria, with supplements to volumes I-II4,1 Testimonia, liturgical and canonical compositions, florilegia, catenae, iconography : testimonia4,2 Testimonia, liturgical and canonical compositions, florilegia, catenae, iconography : the manuscripts - libraries4,3 Testimonia, liturgical and canonical compositions, florilegia, catenae, iconography : liturgical and canonical compositions, florilegia, catenae, iconography5. Studies of Basil of Caesarea and his world : an annotated bio-bibliograph