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Sample records for pylori usurps cell

  1. Cycle Inhibiting Factors (Cifs: Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

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    Eric Oswald

    2011-03-01

    Full Text Available Cycle inhibiting factors (Cifs are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

  2. Uzurpacija zemljišta : Land usurpation

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    Jusuf Topoljak

    2011-12-01

    Full Text Available Rad na temu „Uzurpacija zemljišta“ izlaže problematiku uzurpacije zemljišta u Bosni i Hercegovini. Velika je uloga geodezije u rješavanju ovakvog, za društvo kompleksnog problema. U radu su date naznake definisanja i rješavanja problema uzurpiranog zemljišta. : Work on the topic of "land usurpation," exposes the issue of land usurpation in Bosnia and Herzegovina. Geodesy has a very important role in solving such a complex problem for the whole society. In this paper are given hints of defining and solving the problem of land usurpation.

  3. Helicobacter pylori impairs murine dendritic cell responses to infection.

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    Ya-Hui Wang

    Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

  4. Uzurpacija zemljišta : Land usurpation

    OpenAIRE

    Jusuf Topoljak; Admir Mulahusić

    2011-01-01

    Rad na temu „Uzurpacija zemljišta“ izlaže problematiku uzurpacije zemljišta u Bosni i Hercegovini. Velika je uloga geodezije u rješavanju ovakvog, za društvo kompleksnog problema. U radu su date naznake definisanja i rješavanja problema uzurpiranog zemljišta. : Work on the topic of "land usurpation," exposes the issue of land usurpation in Bosnia and Herzegovina. Geodesy has a very important role in solving such a complex problem for the whole society. In this paper are given hints of defin...

  5. Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

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    Holck, Susanne; Holm, I.L.; Holck, P.P.

    2007-01-01

    Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytoki...

  6. Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

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    Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

    2014-12-01

    Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

  7. Human lactoferrin increases Helicobacter pylori internalisation into AGS cells.

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    Coray, Dorien S; Heinemann, Jack A; Tyrer, Peter C; Keenan, Jacqueline I

    2012-05-01

    Helicobacter pylori has high global infection rates and can cause other undesirable clinical manifestations such as duodenal ulcer (DU) and gastric cancer (GC). Frequencies of re-infection after therapeutic clearance and rates of DU versus GC vary geographically and differ markedly between developed and developing countries, which suggests additional factors may be involved. The possibility that, in vivo, lactoferrin (Lf) may play a subtle role in modulating micronutrient availability or bacterial internalisation with implications for disease etiology is considered. Lf is an iron binding protein produced in mammals that has antimicrobial and immunomodulatory properties. Some bacteria that regularly colonise mammalian hosts have adapted to living in high Lf environments and we investigated if this included the gastric pathogen H. pylori. We found that H. pylori was able to use iron from fully iron-saturated human Lf (hLf) whereas partially iron-saturated hLf (apo) did not increase H. pylori growth. Instead, apo-hLf increased adherence to and internalisation of bacteria into cultured epithelial cells. By increasing internalisation, we speculate that apo-human lactoferrin may contribute to H. pylori's ability to persistence in the human stomach, an observation that potentially has implications for the risk of H. pylori-associated disease.

  8. The nucleolus and herpesviral usurpation.

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    Ni, Liwen; Wang, Shuai; Zheng, Chunfu

    2012-12-01

    The nucleolus is a distinct subnuclear compartment known as the site for ribosome biogenesis in eukaryotes. Consequently, the nucleolus is also proposed to function in cell-cycle control, stress sensing and senescence, as well as in viral infection. An increasing number of viral proteins have been found to localize to the nucleolus. In this article, we review the current understanding of the functions of the nucleolus, the molecular mechanism of cellular and viral protein targeting to the nucleolus and the functional roles of the nucleolus during viral infection with a specific focus on the herpesvirus family.

  9. Cell-cycle inhibition by Helicobacter pylori L-asparaginase.

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    Claudia Scotti

    Full Text Available Helicobacter pylori (H. pylori is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.

  10. B-Cell and T-Cell Immune Responses to Experimental Helicobacter pylori Infection in Humans

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    Nurgalieva, Zhannat Z.; Conner, Margaret E.; Opekun, Antone R.; Zheng, Carl Q.; Elliott, Susan N.; Ernst, Peter B.; Osato, Michael; Estes, Mary K.; Graham, David Y.

    2005-01-01

    The acute antibody and T-cell immune response to Helicobacter pylori infection in humans has not been studied systematically. Serum from H. pylori-naive volunteers challenged with H. pylori and cured after 4 or 12 weeks was tested by enzyme-linked immunosorbent assays for anti-H. pylori-specific immunoglobulin M (IgM) and IgA established using bacterial lysates from homologous (the infecting strain) and heterologous H. pylori. Proteins recognized by IgM antibody were identified by mass spectrometry of immunoreactive bands separated by two-dimensional gel electrophoresis. Mucosal T-cell subsets (CD4, CD8, CD3, and CD30 cells) were assessed by immunohistochemistry. All 18 infected volunteers developed H. pylori-specific IgM responses to both homologous or heterologous H. pylori antigens. H. pylori antigens reacted with IgM antibody at 4 weeks postinfection. IgM Western blotting showed immunoreactivity of postinfection serum samples to multiple H. pylori proteins with molecular weights ranging between 9,000 (9K) to 150K with homologous strains but only a 70K band using heterologous antigens. Two-dimensional electrophoresis demonstrated that production of H. pylori-specific IgM antibodies was elicited by H. pylori flagellins A and B, urease B, ABC transporter binding protein, heat shock protein 70 (DnaK), and alkyl hydroperoxide reductase. Mucosal CD3, CD4, and CD8 T-cell numbers increased following infection. IgM antibody responses were detected to a range of homologous H. pylori antigens 2 to 4 weeks postchallenge. The majority of H. pylori proteins were those involved in motility and colonization and may represent targets for vaccine development. PMID:15845507

  11. Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Norn, Svend

    2007-01-01

    Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytoki......Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load...... and the proliferative marker Ki-67. H. pylori infection, bacteria load and inflammatory activity were associated with increased cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53 was significantly correlated to IFN-γ, IL-8 and IL-10. The H. pylori-positive state was furthermore accompanied...... of the gastrointestinal tract, such studies in cell turnover may provide insights valuable in the investigations of potential precursors of gastric malignancies....

  12. Destructive effects of butyrate on the cell envelope of Helicobacter pylori.

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    Yonezawa, Hideo; Osaki, Takako; Hanawa, Tomoko; Kurata, Satoshi; Zaman, Cynthia; Woo, Timothy Derk Hoong; Takahashi, Motomichi; Matsubara, Sachie; Kawakami, Hayato; Ochiai, Kuniyasu; Kamiya, Shigeru

    2012-04-01

    Helicobacter pylori can be found in the oral cavity and is mostly detected by the use of PCR techniques. Growth of H. pylori is influenced by various factors in the mouth, such as the oral microflora, saliva and other antimicrobial substances, all of which make colonization of the oral cavity by H. pylori difficult. In the present study, we analysed the effect of the cell supernatant of a representative periodontal bacterium Porphyromonas gingivalis on H. pylori and found that the cell supernatant destroyed the H. pylori cell envelope. As P. gingivalis produces butyric acid, we focused our research on the effects of butyrate and found that it significantly inhibited the growth of H. pylori. H. pylori cytoplasmic proteins and DNA were detected in the extracellular environment after treatment with butyrate, suggesting that the integrity of the cell envelope was compromised and indicating that butyrate has a bactericidal effect on H. pylori. In addition, levels of extracellular H. pylori DNA increased following treatment with the cell supernatant of butyric acid-producing bacteria, indicating that the cell supernatant also has a bactericidal effect and that this may be due to its butyric acid content. In conclusion, butyric acid-producing bacteria may play a role in affecting H. pylori colonization of the oral cavity.

  13. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells

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    Machado, Ana Manuel Dantas; Figueiredo, Ceu; Touati, Eliette

    2009-01-01

    of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori infection, the activity and expression of base excision repair...... and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. CONCLUSIONS: Our results suggest that H. pylori...

  14. Association of mast cells with helicobacter pylori infection in the antral mucosa

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    SR KC

    2011-03-01

    Full Text Available Background: Helicobacter pylori infection is associated with mixed inflammatory cell infiltrate consisting of neutrophils, eosinophils, lymphocytes and plasma cells. Helicobacter pylori lead to mast cell degranulation and release of active chemical compounds in in-vitro conditions. The objective of this study was to find out the association of mast cell density and Helicobacter pylori in the antral mucosa of the stomach. Materials and Methods: A total of 150 endoscopic biopsies were included in the study. In addition to routine Hematoxylin and Eosin stained slides, Giemsa stain was done in each case for the evaluation of Helicobacter pylori and mast cell density in the gastric mucosa. Results: Out of 150 gastric biopsies with histopathological diagnosis of chronic gastritis, 36 cases (24% were positive for Helicobacter pylori. In the antral mucosa, mast cell density was significantly higher in the Helicobacter pylori-positive group than in the Helicobacter pylori-negative group (P<0.01. Conclusion: Mast cells may play a role in the development of Helicobacter pylori gastritis. Keywords: Gastritis; Mast Cell; Helicobacter pylori DOI: 10.3126/jpn.v1i1.4448 Journal of Pathology of Nepal (2011 Vol.1, 34-36

  15. Alterations in Helicobacter pylori triggered by contact with gastric epithelial cells

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    Elizabeth M. Johnson

    2012-02-01

    Full Text Available Helicobacter pylori lives within the mucus layer of the human stomach, in close proximity to gastric epithelial cells. While a great deal is known about the effects of H. pylori on human cells and the specific bacterial products that mediate these effects, relatively little work has been done to investigate alterations in H. pylori that may be triggered by bacterial contact with human cells. In this review, we discuss the spectrum of changes in bacterial physiology and morphology that occur when H. pylori is in contact with gastric epithelial cells. Several studies have reported that cell contact causes alterations in H. pylori gene transcription. In addition, H. pylori contact with gastric epithelial cells promotes the formation of pilus-like structures at the bacteria-host cell interface. The formation of these structures requires multiple genes in the cag pathogenicity island, and these structures are proposed to have an important role in the type IV secretion system-dependent process through which CagA enters host cells. Finally, H. pylori contact with epithelial cells can promote bacterial replication and the formation of microcolonies, phenomena that are facilitated by the acquisition of iron and other nutrients from infected cells. In summary, the gastric epithelial cell surface represents an important niche for H. pylori, and upon entry into this niche, the bacteria alter their behavior in a manner that optimizes bacterial proliferation and persistent colonization of the host.

  16. Human gastric mucins differently regulate Helicobacter pylori proliferation, gene expression and interactions with host cells.

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    Emma C Skoog

    Full Text Available Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.

  17. Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

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    Peter Wimmer

    2015-08-01

    Full Text Available Posttranslational modifications (PTMs of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub and small ubiquitin-like modifier (SUMO moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.

  18. Helicobacter pylori gastritis in a child with sickle cell anemia and recurrent abdominal pain.

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    Kennedy, L; Mahoney, D H; Redel, C A

    1997-01-01

    Recurrent abdominal pain is a common complaint in children with sickle cell disease. Helicobacter pylori gastritis has recently been described in association with recurrent abdominal pain in children. A case report is given of a 16-year-old black male with hemoglobin SS disease presenting with recurrent abdominal pain and hematemesis. Endoscopic exam of the upper gastrointestinal tract revealed gastritis, and biopsy confirmed H. pylori infection. Serology studies demonstrated increased anti-H. pylori antibody titers. The young man responded well to treatment, with resolution of his symptoms. Helicobacter pylori infection is a new diagnostic consideration for children with recurrent abdominal pain and should be included in the differential diagnosis of children with sickle cell disease, especially when abdominal pain is recurrent and accompanied by vomiting. Larger case studies will be necessary to determine the true incidence of H. pylori in children with sickle cell disease and recurrent abdominal pain.

  19. H. pylori attenuates TNBS-induced colitis via increasing mucosal Th2 cells in mice.

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    Wu, Yi-Zhong; Tan, Gao; Wu, Fang; Zhi, Fa-Chao

    2017-09-26

    There is an epidemiological inverse relationship between Helicobacter pylori ( H. pylori ) infection and Crohn's disease (CD). However, whether H. pylori plays a protective role against CD remains unclear. Since 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis is thought to resemble CD, we investigated whether H. pylori can attenuate TNBS-induced colitis in mice. Here we show that H. pylori can attenuate the severity of TNBS-induced colitis. In addition, H. pylori not only down-regulates Th17 and Th1 cytokine expression, but can up-regulate Th2 cytokine expression and increase the Th2:Th17 ratio of CD4 + T in the colonic mucosa of TNBS-induced colitis. Our results indicate that H. pylori attenuates TNBS-induced colitis mainly through increasing Th2 cells in murine colonic mucosa. Our finding offers a novel view on the role of H. pylori in regulating gastrointestinal immunity, and may open a new avenue for development of therapeutic strategies in CD by making use of asymptomatic H. pylori colonization.

  20. Helicobacter pylori infection generates genetic instability in gastric cells

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    Machado, Ana Manuel Dantas; Figueiredo, Céu; Seruca, Raquel

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  1. Crosstalk between Helicobacter pylori and gastric epithelial cells is impaired by docosahexaenoic acid.

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    Marta Correia

    Full Text Available H. pylori colonizes half of the world's population leading to gastritis, ulcers and gastric cancer. H. pylori strains resistant to antibiotics are increasing which raises the need for alternative therapeutic approaches. Docosahexaenoic acid (DHA has been shown to decrease H. pylori growth and its associated-inflammation through mechanisms poorly characterized. We aimed to explore DHA action on H. pylori-mediated inflammation and adhesion to gastric epithelial cells (AGS and also to identify bacterial structures affected by DHA. H. pylori growth and metabolism was assessed in liquid cultures. Bacterial adhesion to AGS cells was visualized by transmission electron microscopy and quantified by an Enzyme Linked Immunosorbent Assay. Inflammatory proteins were assessed by immunoblotting in infected AGS cells, previously treated with DHA. Bacterial total and outer membrane protein composition was analyzed by 2-dimensional gel electrophoresis. Concentrations of 100 µM of DHA decreased H. pylori growth, whereas concentrations higher than 250 µM irreversibly inhibited bacteria survival. DHA reduced ATP production and adhesion to AGS cells. AGS cells infected with DHA pre-treated H. pylori showed a 3-fold reduction in Interleukin-8 (IL-8 production and a decrease of COX2 and iNOS. 2D electrophoresis analysis revealed that DHA changed the expression of H. pylori outer membrane proteins associated with stress response and metabolism and modified bacterial lipopolysaccharide phenotype. As conclusions our results show that DHA anti-H. pylori effects are associated with changes of bacteria morphology and metabolism, and with alteration of outer membrane proteins composition, that ultimately reduce the adhesion of bacteria and the burden of H. pylori-related inflammation.

  2. A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis.

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    Zhuang, Yuan; Cheng, Ping; Liu, Xiao-fei; Peng, Liu-sheng; Li, Bo-sheng; Wang, Ting-ting; Chen, Na; Li, Wen-hua; Shi, Yun; Chen, Weisan; Pang, Ken C; Zeng, Ming; Mao, Xu-hu; Yang, Shi-ming; Guo, Hong; Guo, Gang; Liu, Tao; Zuo, Qian-fei; Yang, Hui-jie; Yang, Liu-yang; Mao, Fang-yuan; Lv, Yi-pin; Zou, Quan-ming

    2015-09-01

    Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Usurpation of a Crowned Lapwing Vanellus coronatus nest by ...

    African Journals Online (AJOL)

    I report an instance of usurpation of a Crowned Lapwing Vanellus coronatus nest by a pair of African Wattled Lapwings Vanellus senegalensis. The nest, which originally contained a single Crowned Lapwing egg, eventually contained an additional three Wattled Lapwing eggs, before it was predated. Although parents of ...

  4. Cape Vulture usurps Bearded Vulture nest | Crowson | Vulture News

    African Journals Online (AJOL)

    Cape Vulture usurps Bearded Vulture nest. John Crowson, Sonja Krüger. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More ...

  5. Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pylori

    International Nuclear Information System (INIS)

    Skvarc, Miha; Stubljar, David; Kopitar, Andreja Natasa; Jeverica, Samo; Tepes, Bojan; Kos, Janko; Ihan, Alojz

    2013-01-01

    The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of inhibition of cathepsin X is delayed

  6. The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance

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    Lou Rose Malamug

    2014-01-01

    Full Text Available Infection, for example, Helicobacter pylori (H. pylori, has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM. Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW, non-Hispanic black (NHB, and Mexican Americans (MA aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on the H. pylori status. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR and beta cell function (HOMA-B in subjects without diabetes based on the H. pylori status. The results were adjusted for age, body mass index (BMI, poverty index, education, alcohol consumption, tobacco use, and physical activity. The H. pylori status was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females. H. pylori infection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction.

  7. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

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    Nina Bertaux-Skeirik

    2015-02-01

    Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

  8. Effect on cell surface hydrophobicity and susceptibility of Helicobacter pylori to medicinal plant extracts.

    Science.gov (United States)

    Annuk, H; Hirmo, S; Türi, E; Mikelsaar, M; Arak, E; Wadström, T

    1999-03-01

    Effects on aqueous extracts of medicinal plants on ten Helicobacter pylori strains were studied by the salt aggregation test to determine the possibility to modulate their cell surface hydrophobicity and by an agar diffusion assay for detection of antimicrobial activity. It was established that aqueous extracts of bearberry and cowberry leaves enhance cell aggregation of all H. pylori strains tested by the salt aggregation test, and the extract of bearberry possessed a remarkable bacteriostatic activity. Pure tannic acid showed a result similar to that of bearberry and cowberry extracts which contained a large amount of tannins. In contrast, extracts of wild camomile and pineapple-weed, which blocked aggregation of H. pylori, contained small amounts of tannins and did not reveal any antimicrobial activity. Tannic acid seems to be the component of bearberry and cowberry aqueous extracts with the highest activity to decrease cell surface hydrophobicity as well as in antibacterial activity against H. pylori.

  9. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repai...

  10. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

    Science.gov (United States)

    Lewinska, Anna; Wnuk, Maciej

    2017-04-01

    Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

  11. Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

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    Hsueh-Fen Juan

    2012-08-01

    Full Text Available Helicobacter pylori (H. pylori, the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+, single mutant (ΔvacA or ΔcagA or double mutant (ΔvacA/ΔcagA strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca2+ influx. Ca2+-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.

  12. Influence of Helical Cell Shape on Motility of Helicobacter Pylori

    Science.gov (United States)

    Hardcastle, Joseph; Martinez, Laura; Salama, Nina; Bansil, Rama; Boston University Collaboration; University of Washington Collaboration

    2014-03-01

    Bacteria's body shape plays an important role in motility by effecting chemotaxis, swimming mechanisms, and swimming speed. A prime example of this is the bacteria Helicobacter Pylori;whose helical shape has long been believed to provide an advantage in penetrating the viscous mucus layer protecting the stomach lining, its niche environment. To explore this we have performed bacteria tracking experiments of both wild-type bacteria along with mutants, which have a straight rod shape. A wide distribution of speeds was found. This distribution reflects both a result of temporal variation in speed and different shape morphologies in the bacterial population. Our results show that body shape plays less role in a simple fluid. However, in a more viscous solution the helical shape results in increased swimming speeds. In addition, we use experimentally obtained cell shape measurements to model the hydrodynamic influence of cell shape on swimming speed using resistive force theory. The results agree with the experiment, especially when we fold in the temporal distribution. Interestingly, our results suggest distinct wild-type subpopulations with varying number of half helices can lead to different swimming speeds. NSF PHY

  13. A Helicobacter pylori Homolog of Eukaryotic Flotillin Is Involved in Cholesterol Accumulation, Epithelial Cell Responses and Host Colonization

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    Melanie L. Hutton

    2017-06-01

    Full Text Available The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as “lipid rafts.” Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248 with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01. HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05, and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05. Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.

  14. Maintenance of the cell morphology by MinC in Helicobacter pylori.

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    Pei-Yu Chiou

    Full Text Available In the model organism Escherichia coli, Min proteins are involved in regulating the division of septa formation. The computational genome analysis of Helicobacter pylori, a gram-negative microaerophilic bacterium causing gastritis and peptic ulceration, also identified MinC, MinD, and MinE. However, MinC (HP1053 shares a low identity with those of other bacteria and its function in H. pylori remains unclear. In this study, we used morphological and genetic approaches to examine the molecular role of MinC. The results were shown that an H. pylori mutant lacking MinC forms filamentous cells, while the wild-type strain retains the shape of short rods. In addition, a minC mutant regains the short rods when complemented with an intact minCHp gene. The overexpression of MinCHp in E. coli did not affect the growth and cell morphology. Immunofluorescence microscopy revealed that MinCHp forms helix-form structures in H. pylori, whereas MinCHp localizes at cell poles and pole of new daughter cell in E. coli. In addition, co-immunoprecipitation showed MinC can interact with MinD but not with FtsZ during mid-exponential stage of H. pylori. Altogether, our results show that MinCHp plays a key role in maintaining proper cell morphology and its function differs from those of MinCEc.

  15. Macrophage migration inhibitory factor stimulated by Helicobacter pylori increases proliferation of gastric epithelial cells

    Science.gov (United States)

    Xia, Harry Hua-Xiang; Lam, Shiu Kum; Chan, Annie O.O.; Lin, Marie Chia Mi; Kung, Hsiang Fu; Ogura, Keiji; Berg, Douglas E.; Wong, Benjamin C. Y.

    2005-01-01

    AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro. METHODS: A cytotoxic wild-type H pylori strain (TN2)and its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter. RESULTS: The wild-type strain and the isogenic mutants, TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared. CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H

  16. Helicobacter pylori-induced IL-33 modulates mast cell responses, benefits bacterial growth, and contributes to gastritis.

    Science.gov (United States)

    Lv, Yi-Pin; Teng, Yong-Sheng; Mao, Fang-Yuan; Peng, Liu-Sheng; Zhang, Jin-Yu; Cheng, Ping; Liu, Yu-Gang; Kong, Hui; Wang, Ting-Ting; Wu, Xiao-Long; Hao, Chuan-Jie; Chen, Weisan; Yang, Shi-Ming; Zhao, Yong-Liang; Han, Bin; Ma, Qiang; Zou, Quan-Ming; Zhuang, Yuan

    2018-04-25

    Interleukin (IL)-induced inflammatory responses are critical for the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. IL-33 represents a recently discovered proinflammatory cytokine involved in inflammatory diseases, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric IL-33 mRNA and protein expression were elevated in gastric mucosa of both patients and mice infected with H. pylori, which is positively correlated with bacterial load and the degree of gastritis. IL-33 production was promoted via extracellular regulated protein kinases (ERK) signaling pathway activation by gastric epithelial cells in a cagA-dependent manner during H. pylori infection, and resulted in increased inflammation and bacteria burden within the gastric mucosa. Gastric epithelial cell-derived IL-33 promoted TNF-α production from mast cells in vitro, and IL-33 increased TNF-α production in vivo. Increased TNF-α inhibited gastric epithelial cell proliferation, conducing to the progress of H. pylori-associated gastritis and bacteria colonization. This study defined a patent regulatory networks involving H. pylori, gastric epithelial cell, IL-33, mast cell, and TNF-α, which jointly play a pathological effect within the gastric circumstances. It may be a valuable strategy to restrain this IL-33-dependent pathway in the treatment of H. pylori-associated gastritis.

  17. Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells

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    Max Koeppel

    2015-06-01

    Full Text Available Infection with the human pathogen Helicobacter pylori (H. pylori is a major risk factor for gastric cancer. Since the bacterium exerts multiple genotoxic effects, we examined the circumstances of DNA damage accumulation and identified regions within the host genome with high susceptibility to H. pylori-induced damage. Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes. We thus demonstrate an impact of a bacterial infection directed toward specific host genomic regions and describe underlying characteristics that make such regions more likely to acquire heritable changes during infection, which could contribute to cellular transformation.

  18. The number of Foxp3-positive regulatory T cells is increased in Helicobacter pylori gastritis and gastric cancer.

    Science.gov (United States)

    Jang, Tae Jung

    2010-01-15

    Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. Recent studies have shown that CD4(+) CD25(+) Foxp3-positive regulatory T cells (Tregs) suppress the immune response to H. pylori. Persistent H. pylori-associated gastritis is closely associated with gastric carcinogenesis. We investigated the number of Tregs in the context of H. pylori colonization in chronic gastritis, examined the relationship between it and histopathological findings and compared it with that of gastric dysplasia and adenocarcinoma. This study was based on the analysis of gastric biopsy specimens from 126 cases of H. pylori-associated gastritis, 16 cases of H. pylori-negative gastritis, 17 cases of gastric dysplasia, and 25 cases of gastric adenocarcinoma. The number of Tregs was elevated in H. pylori-associated gastritis, where it was positively correlated with the grade of chronic inflammation and the number of lymphoid follicles. It was significantly elevated in adenocarcinomas compared to chronic gastritis and gastric dysplasia. In summary, the number of Tregs is increased in H. pylori-associated gastritis and gastric cancer. Copyright 2009 Elsevier GmbH. All rights reserved.

  19. Helicobacter pylori Type IV Secretion System and Its Adhesin Subunit, CagL, Mediate Potent Inflammatory Responses in Primary Human Endothelial Cells

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    Mona Tafreshi

    2018-02-01

    Full Text Available The Gram-negative bacterium, Helicobacter pylori, causes chronic gastritis, peptic ulcers, and gastric cancer in humans. Although the gastric epithelium is the primary site of H. pylori colonization, H. pylori can gain access to deeper tissues. Concurring with this notion, H. pylori has been found in the vicinity of endothelial cells in gastric submucosa. Endothelial cells play crucial roles in innate immune response, wound healing and tumorigenesis. This study examines the molecular mechanisms by which H. pylori interacts with and triggers inflammatory responses in endothelial cells. We observed that H. pylori infection of primary human endothelial cells stimulated secretion of the key inflammatory cytokines, interleukin-6 (IL-6 and interleukin-8 (IL-8. In particular, IL-8, a potent chemokine and angiogenic factor, was secreted by H. pylori-infected endothelial cells to levels ~10- to 20-fold higher than that typically observed in H. pylori-infected gastric epithelial cells. These inflammatory responses were triggered by the H. pylori type IV secretion system (T4SS and the T4SS-associated adhesin CagL, but not the translocation substrate CagA. Moreover, in contrast to integrin α5β1 playing an essential role in IL-8 induction by H. pylori upon infection of gastric epithelial cells, both integrin α5β1 and integrin αvβ3 were dispensable for IL-8 induction in H. pylori-infected endothelial cells. However, epidermal growth factor receptor (EGFR is crucial for mediating the potent H. pylori-induced IL-8 response in endothelial cells. This study reveals a novel mechanism by which the H. pylori T4SS and its adhesin subunit, CagL, may contribute to H. pylori pathogenesis by stimulating the endothelial innate immune responses, while highlighting EGFR as a potential therapeutic target for controlling H. pylori-induced inflammation.

  20. Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice

    Science.gov (United States)

    Gray, Brian M.; Fontaine, Clinton A.; Poe, Sara A.

    2013-01-01

    Disease due to the gastric pathogen Helicobacter pylori varies in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model of H. pylori gastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-γ) is essential for induction of gastritis but showed that IFN-γ-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-γ. Tumor necrosis factor alpha (TNF-α) and IL-17F were also elevated in association with disease. These results indicate that while H. pylori-specific CD4+ T cells and IFN-γ are both essential for induction of gastritis due to H. pylori, IFN-γ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-α, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due to H. pylori is associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway. PMID:23264048

  1. Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells

    Science.gov (United States)

    Bektaş, Mehmet; Saraç, Nurşen; Çetinkaya, Hülya; Törüner, Murat; Erdemli, Esra; Keskin, Onur; Soykan, İrfan; Oktay, Esen Ismet; Korkut, Esin; Üstün, Yusuf; Bahar, Kadir

    2012-01-01

    Background Excessive release of gastrin leads to hypertrophy and hyperplasia of enterochromaffin-like cells (ECL) and prolonged stimulation of these cells causes functional impairment. The purpose of this study was to investigate the effect of Helicobacter pylori (H. pylori) infection and long-term proton pump inhibitors (PPI) use on ECL cells. Methods Fifteen patients who underwent endoscopy because of dyspeptic symptoms were enrolled in the present study. Biopsies were taken from corpus and antrum and existence of H. pylori was investigated with culture, cytology and CLOtest. The patients were divided into 3 groups. Group-A: H. pylori-negative, never treated previously with PPI; Group-B: H. pylori-positive, never treated previously with PPI; and group-C: H. pylori-negative and continuously treated with PPI for more than 6 months before the subject recruitment period. The features of ECL cell in oxyntic glands were examined with electron microscopy on biopsy specimens. Results ECL cells were completely normal in Group A. In group B, moderate hyperplasia and vacuolization was seen in ECL cells. In group C, ECL cell hyperplasia was observed and vacuoles with greater amounts of granules in enlarged vesicles were found more intensely in cytoplasm. Conclusion The use of PPI for a long period of time and presence of H. pylori infection are risk factors for ECL hyperplasia. PMID:24714139

  2. EGFR tyrosine kinase inhibitory peptide attenuates Helicobacter pylori-mediated hyper-proliferation in AGS enteric epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Himaya, S.W.A. [Marine Bio-Process Research Center, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of); Dewapriya, Pradeep [Department of Chemistry, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of); Kim, Se-Kwon, E-mail: sknkim@pknu.ac.kr [Marine Bio-Process Research Center, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of); Department of Chemistry, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of)

    2013-06-15

    Helicobacter pylori infection is one of the most critical causes of stomach cancer. The current study was conducted to explore the protective effects of an isolated active peptide H-P-6 (Pro-Gln-Pro-Lys-Val-Leu-Asp-Ser) from microbial hydrolysates of Chlamydomonas sp. against H. pylori-induced carcinogenesis. The peptide H-P-6 has effectively suppressed H. pylori-induced hyper-proliferation and migration of gastric epithelial cells (AGS). However, the peptide did not inhibit the viability of the bacteria or invasion into AGS cells. Therefore, the effect of the peptide on regulating H. pylori-induced molecular signaling was investigated. The results indicated that H. pylori activates the EGFR tyrosine kinase signaling and nuclear translocation of the β-catenin. The EGFR activation has led to the up-regulation of PI3K/Akt signaling pathway. Moreover, the nuclear translocation levels of β-catenin were significantly increased as a result of Akt mediated down-regulation of GSK3/β protein levels in the cytoplasm. Both of these consequences have resulted in increased expression of cell survival and migration related genes such as c-Myc, cyclin-D, MMP-2 and matrilysin. Interestingly, the isolated peptide potently inhibited H. pylori-mediated EGFR activation and thereby down-regulated the subsequent P13K/Akt signaling leading to β-catenin nuclear translocation. The effect of the peptide was confirmed with the use of EGFR tyrosine kinase inhibitor AG1487 and molecular docking studies. Collectively this study identifies a potent peptide which regulates the H. pylori-induced hyper-proliferation and migration of AGS cells at molecular level. - Highlights: • Chlamydomonas sp. derived peptide H-P-6 inhibits H. pylori-induced pathogenesis. • H-P-6 suppresses H. pylori-induced hyper-proliferation and migration of AGS cells. • The peptide inhibits H. pylori-induced EGFR activation.

  3. Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection.

    Science.gov (United States)

    Bagheri, Nader; Shirzad, Hedayatollah; Elahi, Shokrollah; Azadegan-Dehkordi, Fatemeh; Rahimian, Ghorbanali; Shafigh, Mohammedhadi; Rashidii, Reza; Sarafnejad, Abdulfatah; Rafieian-Kopaei, Mahmoud; Faridani, Rana; Tahmasbi, Kamran; Kheiri, Soleiman; Razavi, Alireza

    2017-09-01

    Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-β1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). The numbers of CD4 + and Foxp3 + T cells as well as the expression of IL-10, TGF-β1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4 + T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3 + T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3 + T cells and the expression of IL-10, TGF-β1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4 + T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4 + and Foxp3 + T cells as well as the expression of IL-10, TGF-β1, FOXP3 and INF-γ were positively

  4. Phylogeographic origin of Helicobacter pylori determines host-adaptive responses upon coculture with gastric epithelial cells.

    Science.gov (United States)

    Sheh, Alexander; Chaturvedi, Rupesh; Merrell, D Scott; Correa, Pelayo; Wilson, Keith T; Fox, James G

    2013-07-01

    While Helicobacter pylori infects over 50% of the world's population, the mechanisms involved in the development of gastric disease are not fully understood. Bacterial, host, and environmental factors play a role in disease outcome. To investigate the role of bacterial factors in H. pylori pathogenesis, global gene expression of six H. pylori isolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factors cagA, vacA, and babB and were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis. Our data suggest that gene expression profiles of clinical isolates can discriminate strains by phylogeographic origin and that these profiles are associated with changes in expression of the proinflammatory and protumorigenic cytokine IL-8 and levels of apoptosis in host epithelial cells. These findings support the hypothesis that bacterial factors determined by the phylogeographic origin of H. pylori strains may promote increased gastric disease.

  5. Production of Autoantibodies by Murine B-1a Cells Stimulated with Helicobacter pylori Urease through Toll-Like Receptor 2 Signaling ▿ †

    Science.gov (United States)

    Kobayashi, Fumiko; Watanabe, Eri; Nakagawa, Yohko; Yamanishi, Shingo; Norose, Yoshihiko; Fukunaga, Yoshitaka; Takahashi, Hidemi

    2011-01-01

    Helicobacter pylori infection is associated with several autoimmune diseases, in which autoantibody-producing B cells must be activated. Among these B cells, CD5-positive B-1a cells from BALB/c mice were confirmed to secrete autoantibodies when cocultured with purified H. pylori urease in the absence of T cells. To determine the mechanisms for autoantibody production, CD5-positive B-1a cells were sorted from murine spleen cells and stimulated with either purified H. pylori urease or H. pylori coated onto plates (referred to hereafter as plate-coated H. pylori), and autoantibody production was measured by enzyme-linked immunosorbent assay (ELISA). Complete urease was not secreted from H. pylori but was visually expressed over the bacterium-like endotoxin. Urease-positive plated-coated H. pylori stimulated B-1a cells to produce autoantibodies, although urease-deficient isotype-matched H. pylori did not. Autoantibody secretion by B-1a cells was inhibited when bacteria were pretreated with anti-H. pylori urease-specific antibody having neutralizing ability against urease enzymatic activity but not with anti-H. pylori urease-specific antibody without neutralizing capacity. The B-1a cells externally express various Toll-like receptors (TLRs): TLR1, TLR2, TLR4, and TLR6. Among the TLRs, blocking of TLR2 on B-1a cells with a specific monoclonal antibody (MAb), T2.5, inhibited autoantibody secretion when B-1a cells were stimulated with plate-coated H. pylori or H. pylori urease. Moreover, B-1a cells from TLR2-knockout mice did not produce those autoantibodies. The present study provides evidence that functional urease expressed on the surface of H. pylori will directly stimulate B-1a cells via innate TLR2 to produce various autoantibodies and may induce autoimmune disorders. PMID:21947775

  6. Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis

    NARCIS (Netherlands)

    Liu, Y.; Vosmaer, G. D. C.; Tytgat, G. N. J.; Xiao, S.-D.; ten Kate, F. J. W.

    2005-01-01

    Background: Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease. Aim: To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D

  7. Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells

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    Rieder Gabriele

    2011-11-01

    Full Text Available Abstract Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS and the effector protein cytotoxin-associated gene A (CagA of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells.

  8. Colony variation of Helicobacter pylori: pathogenic potential is correlated to cell wall lipid composition.

    Science.gov (United States)

    Bukholm, G; Tannaes, T; Nedenskov, P; Esbensen, Y; Grav, H J; Hovig, T; Ariansen, S; Guldvog, I

    1997-05-01

    Differences in expression of disease after infection with Helicobacter pylori have so far been connected with host factors and bacterial interstrain variation. In this study, spontaneous and ecology-mediated intrastrain variation was examined. Four clinical isolates of H. pylori were shown to give rise to two colony forms. Bacterial morphology was examined by electron microscopy. Bacterial fractions were examined for proteins using ion exchange chromatography and SDS-PAGE; for lipids using thin-layer chromatography, lipid anion-exchange chromatography, column chromatography on silica gel, 31P-NMR, gas chromatography and mass spectrometry. Bacterial in vitro invasiveness and adhesiveness were examined in two different systems, and urease and VacA toxin were assayed by Western blot analysis. H. pylori was shown to give rise to two colony forms: at normal pH the population was dominated by L colonies. One strain was chosen for further studies. Bacteria from L colonies retained VacA toxin and urease, did not invade or adhere to epithelial cells, and contained normal quantities of phosphatidylethanolamine. In a small frequency, spontaneous S colonies were formed. Bacteria from these colonies released VacA and urease, adhered to and invaded epithelial cells and contained increased amounts of lysophosphatidyl ethanolamine and phosphatidyl serine. After addition of HCl to the culture medium (pH6), almost only S colonies were formed. The results demonstrate that environmental factors, such as HCl, can change the bacterial cell wall, and thereby enhance expression of virulence factors of H. pylori in vitro. A similar in vivo variation would have implications for our understanding of the interaction between HCl secretion in the gastric mucosa and H. pylori in the development of peptic ulcer disease.

  9. In vitro suppression of dendritic cells by Helicobacter pylori OipA.

    Science.gov (United States)

    Teymournejad, Omid; Mobarez, Ashraf M; Hassan, Zuhair M; Moazzeni, Seyed M; Ahmadabad, Hassan N

    2014-04-01

    Outer inflammatory protein A (OipA) has an important role in Helicobacter pylori pathogenesis. In this study, we purified the outer membrane protein and evaluated the effects of this protein on maturation and cytokine production by dendritic cells (DCs). The oipA gene was inserted into pET28a, and this construct was transformed into Escherichia coli BL21 (DE3). Purification of the recombinant protein was performed by Ni-NTA affinity chromatography. Immature DCs were purified from spleen of C57BL/6 mice with more than 90% purity and were treated with several concentrations of OipA (1-20 μg/mL) overnight. Expression of maturation markers (CD86, CD40, and MHC-II) on the surface of DCs and production of IL-10 and IL-12 were assessed by flow cytometry and ELISA, respectively. The expression of DC maturation markers CD40, CD86, and MHC-II was downregulated on the surface of OipA-treated DCs at concentrations of 10 and 20 μg/mL compared with negative control. Production of IL-10 decreases with increasing OipA concentration at a concentration of 5 μg/mL, but we detected no change in IL-12 production. Inability to eliminate H. pylori from stomach is partly due to the evasion of the bacteria from the immune response. DCs are central mediators between innate and adaptive immunity, and DC cytokines direct the types of adaptive immune response. This study indicated that OipA of H. pylori is a DC maturation suppression factor. Previous studies have shown that H. pylori manage tolerogenic programming in DCs leading to long-time gastric colonization. In conclusion, H. pylori OipA helps the establishment of chronic infection with reduction in IL-10 and suppression of DC maturation. © 2014 John Wiley & Sons Ltd.

  10. Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.

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    Yuki Ito

    Full Text Available Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer, while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT, which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/- or wild-type mice, bacterial recovery significantly increased in Jα18(-/- compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/- compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

  11. Foveolar cells phagocytose apoptotic neutrophils in chronic active Helicobacter pylori gastritis.

    Science.gov (United States)

    Caruso, R A; Fedele, F; Di Bella, C; Mazzon, E; Rigoli, L

    2012-11-01

    The recognition and removal of apoptotic inflammatory cells by tissue macrophages and non-professional phagocytes, in a process called efferocytosis, is required for resolution of inflammation and is actively anti-inflammatory. We have previously demonstrated phagocytosis of apoptotic neutrophils by tumor cells in human gastric carcinoma, but to date, there have been no studies investigating this process in chronic active Helicobacter pylori gastritis. Biopsy specimens from 28 subjects with or without H. pylori infection and active inflammation were examined and graded according to the updated Sydney system. Light microscopy, electron microscopy, and Terminal Deoxynucleotidyltransferase-Mediated UTP End Labeling staining were used to identify apoptosis. H. pylori infection was detected by histology and by molecular assay in 16 out of 28 cases. DNA from paraffin-embedded gastric biopsies was amplified using primers specific for cagA, for the cag "empty site" as well as for the s and m alleles of vacA. The more virulent cagA-positive strains were found in five out of nine patients with chronic active gastritis. The vacA s1/m1 and s2/m1 genotypes were more common in nine patients with chronic active gastritis, while the vacA s2/m2 genotype was more frequent in seven patients with chronic inactive gastritis. Apoptotic neutrophils were also detected within the cytoplasmic vacuoles of the foveolar cells of nine cases with chronic active gastritis. Transmission electron micrographs revealed further apoptotic neutrophils within spacious phagosomes of foveolar cells in a similar manner to those described in late-phase efferocytosis both in vivo and in vitro. These new observations expand the morphological spectrum of gastritis in patients infected with more virulent H. pylori strains, compatible with an anti-inflammatory role for the gastric epithelial cells in their removal of apoptotic neutrophils during active chronic gastritis.

  12. IRAK-M expression limits dendritic cell activation and proinflammatory cytokine production in response to Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Jessica Shiu

    Full Text Available Helicobacter pylori (H. pylori infects the gastric mucosa and persists for the life of the host. Bacterial persistence may be due to the induction of regulatory T cells (Tregs whichmay have protective effects against other diseases such as asthma. It has been shown that H. pylori modulates the T cell response through dendritic cell reprogramming but the molecular pathways involved are relatively unknown. The goal of this study was to identify critical elements of dendritic cell (DC activation and evaluate potential influence on immune activation. Microarray analysis was used to demonstrate limited gene expression changes in H. pylori stimulated bone marrow derived DCs (BMDCs compared to the BMDCs stimulated with E. coli. IRAK-M, a negative regulator of TLR signaling, was upregulated and we selectedit for investigation of its role in modulating the DC and T cell responses. IRAK-M(-/- and wild type BMDC were compared for their response to H. pylori. Cells lacking IRAK-M produced significantly greater amounts of proinflammatory MIP-2 and reduced amounts of immunomodulatory IL-10 than wild type BMDC. IRAK-M(-/- cells also demonstrated increased MHC II expression upon activation. However, IRAK-M(-/- BMDCs were comparable to wild type BMDCs in inducing T-helper 17 (TH17 and Treg responses as demonstrated in vitro using BMDC CD4+ T cells co-culture assays,and in vivo though the adoptive transfer of CD4(+ FoxP3-GFP T cells into H. pylori infected IRAK-M(-/- mice. These results suggest that H. pylori infection leads to the upregulation of anti-inflammatory molecules like IRAK-M and that IRAK-M has a direct impact on innate functions in DCs such as cytokine and costimulation molecule upregulation but may not affect T cell skewing.

  13. Up-regulated Th17 cell function is associated with increased peptic ulcer disease in Helicobacter pylori-infection.

    Science.gov (United States)

    Bagheri, Nader; Razavi, Alireza; Pourgheysari, Batoul; Azadegan-Dehkordi, Fatemeh; Rahimian, Ghorbanali; Pirayesh, Ashkan; Shafigh, Mohammedhadi; Rafieian-Kopaei, Mahmoud; Fereidani, Rana; Tahmasbi, Kamran; Shirzad, Hedayatollah

    2018-06-01

    During Helicobacter pylori (H. pylori) infection CD4 + T cells in the gastric lamina propria are hyporesponsive and polarized by Th1/Th17 cell responses controlled by Treg cells. The objective of this study was to determine the number of Th17 cells in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Th17 cells. A total of 89 H. pylori-infected gastritis patients, 63 H. pylori-infected peptic ulcer patients and 48 H. pylori-negative non-ulcer dysplasia patients were enrolled in this study. The number of Th17 was determined by immunohistochemistry. IL-8 and IL-17A expressions were determined by real-time polymerase chain reaction (qPCR). Also, the grade of chronic and active inflammation was investigated for involvement according to the density of neutrophils and mononuclear in gastric mucosal crypts, from one to all crypts. The number of Th17 cells and the expression of IL-8 and IL-17A in infected patients were significantly higher than uninfected subjects. The number of Th17 cells and the expression of IL-8 and IL-17A in infected patients with peptic ulcer were significantly higher than patients with gastritis. Additionally, the numbers of Th17 cells as well as the expression of IL-8 and IL-17A were positively correlated with the degree of H. pylori density in infected patients with peptic ulcer, while this correlation was negative in infected patients with gastritis. The numbers of Th17 cells as well as the expression of IL-8 and IL-17A were positively correlated with the degree of chronic inflammation. The predominant Th17 cell responses may play a role in the pathogenesis of peptic ulcers disease in infected patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. The HP0256 gene product is involved in motility and cell envelope architecture of Helicobacter pylori

    LENUS (Irish Health Repository)

    Douillard, Francois P

    2010-04-08

    Abstract Background Helicobacter pylori is the causative agent for gastritis, and peptic and duodenal ulcers. The bacterium displays 5-6 polar sheathed flagella that are essential for colonisation and persistence in the gastric mucosa. The biochemistry and genetics of flagellar biogenesis in H. pylori has not been fully elucidated. Bioinformatics analysis suggested that the gene HP0256, annotated as hypothetical, was a FliJ homologue. In Salmonella, FliJ is a chaperone escort protein for FlgN and FliT, two proteins that themselves display chaperone activity for components of the hook, the rod and the filament. Results Ablation of the HP0256 gene in H. pylori significantly reduced motility. However, flagellin and hook protein synthesis was not affected in the HP0256 mutant. Transmission electron transmission microscopy revealed that the HP0256 mutant cells displayed a normal flagellum configuration, suggesting that HP0256 was not essential for assembly and polar localisation of the flagella in the cell. Interestingly, whole genome microarrays of an HP0256 mutant revealed transcriptional changes in a number of genes associated with the flagellar regulon and the cell envelope, such as outer membrane proteins and adhesins. Consistent with the array data, lack of the HP0256 gene significantly reduced adhesion and the inflammatory response in host cells. Conclusions We conclude that HP0256 is not a functional counterpart of FliJ in H. pylori. However, it is required for full motility and it is involved, possibly indirectly, in expression of outer membrane proteins and adhesins involved in pathogenesis and adhesion.

  15. Patterns of Adherence of Helicobacter pylori Clinical Isolates to Epithelial Cells, and its Association with Disease and with Virulence Factors.

    Science.gov (United States)

    Vázquez-Jiménez, Flor Elizabeth; Torres, Javier; Flores-Luna, Lourdes; Cerezo, Silvia Giono; Camorlinga-Ponce, Margarita

    2016-02-01

    Adherence to the gastric epithelium is one of the most important steps of Helicobacter pylori to remain and cause disease. The aim of this study was to analyze whether H. pylori isolates from patients with different gastroduodenal diseases present differences in the pattern of adherence to gastric epithelial cells (AGS), in the ability to induce IL-8, and in the presence of virulence genes. We tested 75 H. pylori strains isolated from nonatrophic gastritis, gastric cancer, and duodenal ulcer patients. The adhesion pattern and IL-8 induction were determined in AGS cells, and invasion of AGS cells was studied using a gentamicin protection assay. The IL-8 levels induced were determined by ELISA. Helicobacter pylori strains presented diffuse adherence (DA) and localized (LA) adherence patterns, similar to those described for enteropathogenic E. coli (EPEC), were observed in AGS cells. A DA pattern was observed in 57% and LA in 43% of the strains, and DA was more frequent in isolates from patients with gastric cancer (p = 0.044). Strains with a LA pattern induced higher levels of IL-8 (p = 0.042) in AGS cells. The adherence pattern was not associated with neither invasiveness nor with the presence of virulence genes. Our study shows that H. pylori strains present adherence patterns to AGS cells resembling those observed in EPEC and that these patterns may be associated with disease and with activity on AGS cells. © 2015 John Wiley & Sons Ltd.

  16. Glycosylation-related gene expression in HT29-MTX-E12 cells upon infection by Helicobacter pylori.

    Science.gov (United States)

    Cairns, Michael T; Gupta, Ananya; Naughton, Julie A; Kane, Marian; Clyne, Marguerite; Joshi, Lokesh

    2017-10-07

    To identify glycosylation-related genes in the HT29 derivative cell line, HT29-MTX-E12, showing differential expression on infection with Helicobacter pylori ( H. pylori ). Polarised HT29-MTX-E12 cells were infected for 24 h with H. pylori strain 26695. After infection RNA was isolated from both infected and non-infected host cells. Sufficient infections were carried out to provide triplicate samples for microarray analysis and for qRT-PCR analysis. RNA was isolated and hybridised to Affymetrix arrays. Analysis of microarray data identified genes significantly differentially expressed upon infection. Genes were grouped into gene ontology functional categories. Selected genes associated with host glycan structure (glycosyltransferases, hydrolases, lectins, mucins) were validated by real-time qRT-PCR analysis. Infection of host cells was confirmed by the isolation of live bacteria after 24 h incubation and by PCR amplification of bacteria-specific genes from the host cell RNA. H. pylori do not survive incubation under the adopted culture conditions unless they associate with the adherent mucus layer of the host cell. Microarray analysis identified a total of 276 genes that were significantly differentially expressed ( P < 0.05) upon H. pylori infection and where the fold change in expression was greater than 2. Six of these genes are involved in glycosylation-related processes. Real-time qRT-PCR demonstrated significant downregulation (1.8-fold, P < 0.05) of the mucin MUC20. REG4 was heavily expressed and significantly downregulated (3.1-fold, P < 0.05) upon infection. Gene ontology analysis was consistent with previous studies on H. pylori infection. Gene expression data suggest that infection with H. pylori causes a decrease in glycan synthesis, resulting in shorter and simpler glycan structures.

  17. Teprenone, but not H2-receptor blocker or sucralfate, suppresses corpus Helicobacter pylori colonization and gastritis in humans: teprenone inhibition of H. pylori-induced interleukin-8 in MKN28 gastric epithelial cell lines.

    Science.gov (United States)

    Miyake, Kazumasa; Tsukui, Taku; Shinji, Yoko; Shinoki, Kei; Hiratsuka, Tetsuro; Nishigaki, Hitoshi; Futagami, Seiji; Wada, Ken; Gudis, Katya; Iwakiri, Katsuhiko; Yamada, Nobutaka; Sakamoto, Choitsu

    2004-04-01

    The role of teprenone in Helicobacter pylori-associated gastritis has yet to be determined. To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylori colonization of the gastric mucosa in H. pylori-infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2-RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori-induced interleukin (IL)-8 production in MKN28 gastric epithelial cells. A total of 68 patients were divided into three groups, each group undergoing a 3-month treatment with either teprenone (150 mg/day), H2-RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL-8 production in MKN28 gastric epithelial cells was measured by enzyme-linked immunosorbent assay (ELISA). Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylori density of the corpus (before vs. after: 2.49 +/- 0.22 vs. 2.15 +/- 0.23, p =.009; 2.36 +/- 0.25 vs. 2.00 +/- 0.24, p =.035, respectively), with no significant differences seen in either the sucralfate or H2-RA groups. Teprenone inhibited H. pylori-enhanced IL-8 production in MKN28 gastric epithelial cells in vitro, in a dose-dependent manner. Teprenone may modify corpus H. pylori-associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL-8 production in the gastric mucosa.

  18. The dynamics of heat shock system activation in Monomac-6 cells upon Helicobacter pylori infection.

    Science.gov (United States)

    Pierzchalski, P; Jastrzebska, M; Link-Lenczowski, P; Leja-Szpak, A; Bonior, J; Jaworek, J; Okon, K; Wojcik, P

    2014-12-01

    Immune system cells, particularly phagocytes, are exposed to direct contact with pathogens. Because of its nature - elimination of pathogenes - their cytoprotective systems supposed to be quick and forceful. Physiological consequence of phagocytosis for the phagocyte is the apoptotic death to prevent the eventual survival of bacteria as intracellular parasites. However, in some cases, defense systems used by the bacteria force the immune cells to prolong the contact with the pathogen for its effective elimination. Experiments were performed on Monomac-6 cells exposed to live CagA, VacA expressing Helicobacter pylori (H. pylori) over different period of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polymerase chain reaction, Western-blot and electrophoretic mobility shift assay, respectively. We found that Monomac-6 cells infection with H. pylori resulted in the translocation of the entire cellular content of the heat shock protein 70 (HSP70) into the cytoplasm, where its presence could protect cell against toxic products of engulfed bacteria and premature apoptosis. At the same time the nuclear translocation of heat shock factor 1 (HSF-1) and activation of HSP70 gene transcription was noticed. Action of HSP70 might to postpone monocyte apoptosis through protecting cytoplasmic and nuclear proteins from damaging effect of bacterial products, what could be the defending mechanism against the toxic stress caused by engulfed bacteria and provide the immune cell with the sufficient amount of time required for neutralization of the bacteria from phagosomes, even at the expense of temporary lack of the protection of nuclear proteins.

  19. Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase

    International Nuclear Information System (INIS)

    An, Doo Ri; Kim, Hyoun Sook; Kim, Jieun; Im, Ha Na; Yoon, Hye Jin; Yoon, Ji Young; Jang, Jun Young; Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar; Kim, Soon-Jong; Lee, Byung Il; Suh, Se Won

    2015-01-01

    H. pylori Csd3 (HP0506), together with other peptidoglycan hydrolases, plays an important role in determining cell shape. Its crystal structure in the latent state is reported. Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by the trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its d, d-endopeptidase activity cleaves the d-Ala 4 -mDAP 3 peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a d, d-carboxypeptidase that cleaves off the terminal d-Ala 5 from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different. The C-terminal LytM domain contains the catalytic site with a Zn 2+ ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain

  20. Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    An, Doo Ri [Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Hyoun Sook [Seoul National University, Seoul 151-742 (Korea, Republic of); Seoul National University, Seoul 151 742 (Korea, Republic of); Kim, Jieun; Im, Ha Na; Yoon, Hye Jin; Yoon, Ji Young; Jang, Jun Young [Seoul National University, Seoul 151-742 (Korea, Republic of); Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar [University of Notre Dame, Notre Dame, IN 46556 (United States); Kim, Soon-Jong [Mokpo National University, Chonnam 534-729 (Korea, Republic of); Lee, Byung Il [National Cancer Center, Gyeonggi 410-769 (Korea, Republic of); Suh, Se Won, E-mail: sewonsuh@snu.ac.kr [Seoul National University, Seoul 151-742 (Korea, Republic of); Seoul National University, Seoul 151-742 (Korea, Republic of)

    2015-03-01

    H. pylori Csd3 (HP0506), together with other peptidoglycan hydrolases, plays an important role in determining cell shape. Its crystal structure in the latent state is reported. Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by the trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its d, d-endopeptidase activity cleaves the d-Ala{sup 4}-mDAP{sup 3} peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a d, d-carboxypeptidase that cleaves off the terminal d-Ala{sup 5} from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different. The C-terminal LytM domain contains the catalytic site with a Zn{sup 2+} ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain.

  1. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Backert Steffen

    2011-11-01

    Full Text Available Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ and the cag (cytotoxin-associated genes pathogenicity island encoding a type IV secretion system (T4SS. The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

  2. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

    LENUS (Irish Health Repository)

    Backert, Steffen

    2011-11-01

    Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA\\/B, SabA, AlpA\\/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA\\/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

  3. Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

    Directory of Open Access Journals (Sweden)

    Xiaolin Zhang

    2016-10-01

    Full Text Available Metronidazole (MNZ is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori. The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC, plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.

  4. Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Desler, Claus; Boggild, Sisse

    2013-01-01

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and....... pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection. (C) 2013 Elsevier Ireland Ltd. All rights reserved....

  5. Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

    Science.gov (United States)

    Pachathundikandi, Suneesh Kumar; Tegtmeyer, Nicole; Backert, Steffen

    2013-01-01

    Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α5β1 receptor. Other targeted membrane-based receptors include the integrins αvβ3, αvβ5, and β2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed. PMID:24280762

  6. Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

    Science.gov (United States)

    Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

    2014-12-01

    Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

  7. Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by mononuclear cells.

    Science.gov (United States)

    Hussein, Nawfal R; Argent, Richard H; Marx, Christian K; Patel, Sapna R; Robinson, Karen; Atherton, John C

    2010-07-15

    Infection with Helicobacter pylori possessing a newly described virulence factor--duodenal ulcer-promoting gene A (dupA)--has been associated with duodenal ulceration and increased gastric inflammation. The dupA locus of 34 strains was sequenced. A panel of dupA mutants was generated and cocultured with human gastric epithelial cells and peripheral blood mononuclear cells; proinflammatory cytokine release was measured. IL8 expression was measured in human gastric biopsy specimens and related to the dupA and cagA status of infecting strains. Most H. pylori strains had a dupA allele that was longer (1884 bp; dupA1) than previously described dupA alleles, although some had truncated versions (dupA2). Unlike the best-characterized H. pylori virulence determinant, the cag pathogenicity island (cag PaI), neither dupA type induced release of interleukin (IL)-8 from gastric epithelial cells. However, infections due to dupA-positive strains were associated with higher-level mucosal IL-8 messenger RNA expression in the human stomach than were infections due to dupA-negative strains. To explain this paradox, we found that dupA1 (but not dupA2 or the cag PaI) substantially increased H. pylori-induced IL-12p40 and IL-12p70 production from CD14(+) mononuclear cells. Other T helper 1-associated cytokines were also modestly induced. We suggest that virulent H. pylori strains cause inflammation by stimulating epithelial cells through cag-encoded proteins and mononuclear inflammatory cells through dupA1 products.

  8. The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells

    OpenAIRE

    Djekic, Aleksandra; M?ller, Anne

    2016-01-01

    VacA is a pore-forming toxin that has long been known to induce vacuolization in gastric epithelial cells and to be linked to gastric disorders caused by H. pylori infection. Its role as a major colonization and persistence determinant of H. pylori is less well-understood. The purpose of this review is to discuss the various target cell types of VacA and its mechanism of action; specifically, we focus on the evidence showing that VacA targets myeloid cells and T-cells to directly and indirect...

  9. Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

    Directory of Open Access Journals (Sweden)

    Sinem Oktem-Okullu

    Full Text Available The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1, IL-17 (Th17, and FOXP3 (Treg expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

  10. Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

    Science.gov (United States)

    Oktem-Okullu, Sinem; Tiftikci, Arzu; Saruc, Murat; Cicek, Bahattin; Vardareli, Eser; Tozun, Nurdan; Kocagoz, Tanil; Sezerman, Ugur; Yavuz, Ahmet Sinan; Sayi-Yazgan, Ayca

    2015-01-01

    The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

  11. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-01-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  12. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  13. Genetic battle between Helicobacter pylori and humans. The mechanism underlying homologous recombination in bacteria, which can infect human cells.

    Science.gov (United States)

    Hanada, Katsuhiro; Yamaoka, Yoshio

    2014-10-01

    Helicobacter pylori is a gram-negative pathogenic bacterium that colonises the human stomach. The chronic infection it causes results in peptic ulcers and gastric cancers. H. pylori can easily establish a chronic infection even if the immune system attacks this pathogen with oxidative stress agents and immunoglobulins. This is attributed to bacterial defence mechanisms against these stresses. As a defence mechanism against oxidative stresses, in bacterial genomes, homologous recombination can act as a repair pathway of DNA's double-strand breaks (DSBs). Moreover, homologous recombination is also involved in the antigenic variation in H. pylori. Gene conversion alters genomic structures of babA and babB (encoding outer membrane proteins), resulting in escape from immunoglobulin attacks. Thus, homologous recombination in bacteria plays an important role in the maintenance of a chronic infection. In addition, H. pylori infection causes DSBs in human cells. Homologous recombination is also involved in the repair of DSBs in human cells. In this review, we describe the roles of homologous recombination with an emphasis on the maintenance of a chronic infection. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  14. Chemokines and antimicrobial peptides have a cag-dependent early response to Helicobacter pylori infection in primary human gastric epithelial cells.

    Science.gov (United States)

    Mustapha, Pascale; Paris, Isabelle; Garcia, Magali; Tran, Cong Tri; Cremniter, Julie; Garnier, Martine; Faure, Jean-Pierre; Barthes, Thierry; Boneca, Ivo G; Morel, Franck; Lecron, Jean-Claude; Burucoa, Christophe; Bodet, Charles

    2014-07-01

    Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to gastric adenocarcinoma cells

    OpenAIRE

    Tharmalingam, Nagendran; Kim, Sa-Hyun; Park, Min; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong Bae

    2014-01-01

    Background Piperine is a compound comprising 5-9% of black pepper (Piper nigrum), which has a variety of biological roles related to anticancer activities. Helicobacter pylori has been classified as a gastric carcinogen, because it causes gastritis and gastric cancer by injecting the virulent toxin CagA and translocating VacA. The present study investigated the inhibitory action of piperine on H. pylori growth and adhesion. Methods Inhibition of H. pylori growth was determined by the broth ma...

  16. IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Beverly R E A Dixon

    Full Text Available Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP, lipocalin (LCN and some β-defensins in both human and primary mouse gastric epithelial cells (GEC and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response.

  17. Helicobacter pylori induces IL-1β and IL-18 production in human monocytic cell line through activation of NLRP3 inflammasome via ROS signaling pathway.

    Science.gov (United States)

    Li, Xiang; Liu, Sheng; Luo, Jingjing; Liu, Anyuan; Tang, Shuangyang; Liu, Shuo; Yu, Minjun; Zhang, Yan

    2015-06-01

    This study investigated whether Helicobacter pylori could activate the nucleotide-binding oligomerization domain-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome in human macrophages and the involvement of reactive oxygen species (ROS) in inflammasome activation. Phorbol-12-myristate-13-acetate (PMA)-differentiated human acute monocytic leukemia cell line THP-1 was infected with H. pylori. The levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in supernatant were measured by ELISA. Intracellular ROS level was analyzed by flow cytometry. Quantitative real-time PCR and western blot analysis were employed to determine the mRNA and protein expression levels of NLRP3 and caspase-1 in THP-1 cells, respectively. Our results showed that H. pylori infection could induce IL-1β and IL-18 production in PMA-differentiated THP-1 cells in a dose- and time-dependent manner. Moreover, secretion of IL-1β and IL-18 in THP-1 cells following H. pylori infection was remarkably reduced by NLRP3-specific small interfering RNA treatment. In addition, the intracellular ROS level was elevated by H. pylori infection, which could be eliminated by the ROS scavenger N-acetylcysteine (NAC). Furthermore, NAC treatment could inhibit NLRP3 inflammasome formation and caspase-1 activation and suppress the release of IL-1β and IL-18 from H. pylori-infected THP-1 cells. These findings provide novel insights into the innate immune response against H. pylori infection, which could potentially be used for the prevention and treatment of H. pylori-related diseases. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. The importance of TH22 and TC22 cells in the pathogenesis of Helicobacter pylori-associated gastric diseases.

    Science.gov (United States)

    Shamsdin, Seyedeh Azra; Alborzi, Abdolvahab; Rasouli, Manoochehr; Ghaderi, Abbas; Lankrani, Kamran B; Dehghani, Seyed Mohsen; Pouladfar, Gholam Reza

    2017-06-01

    An association exists between Helicobacter pylori (H. pylori), peptic ulcers, gastritis, and sometimes gastric carcinomas. Th22 cells have protective and inflammatory roles in defense against microbes. We investigated the frequencies of Th22, Tc22, Th22/17, and Tc22/17 cells in addition to the changes in levels of cytokines IL-22, IL-6, IL-23, TNF-α, IL-1β, and TGF-β in sera from patients with H. pylori-associated gastritis, and peptic ulcer, and in uninfected patients. A total of 76 patients with H. pylori-associated disorders formed the studied group. Frequencies of T-cell subsets were determined by flow cytometry. Levels of cytokines IL-22, IL-6, IL-23, TNF-α, IL-1β, and TGF-β in the sera and supernatants of patients were measured by ELISA and flow cytometry. The study participants included 32 males and 44 females with a mean age of 38.5±15.3 years. We divided the infected group into peptic ulcer and gastritis (mild, moderate, active chronic, and chronic). The frequencies of Th22, Tc22, and Tc22/17 increased significantly in the peptic ulcer, moderate, active chronic, and chronic gastritis groups compared to the uninfected group. Th22/17 only increased significantly in the chronic gastritis group. We observed significant increases in IL-22 in the moderate and active chronic gastritis, IL-23 in the active chronic and chronic gastritis, and TNF-α in the peptic ulcer and moderate gastritis groups. Following in vitro antigenic stimulation, we observed significantly higher levels of IL-1β, IL-23, and IL-6 in the active chronic gastritis group, as well as IL-6 and IL-1β in the chronic gastritis group compared to the uninfected group. Increased Th22, Tc22, and Tc22/17 cells and IL-22 levels appear to be influential in progression and severity of H. pylori infection. Th22/17 can be an interesting therapeutic target for chronic H. pylori infections where eradication is more difficult. © 2016 John Wiley & Sons Ltd.

  19. Saccharomyces boulardii expresses neuraminidase activity selective for α2,3-linked sialic acid that decreases Helicobacter pylori adhesion to host cells.

    Science.gov (United States)

    Sakarya, Serhan; Gunay, Necati

    2014-10-01

    Helicobacter pylori is a major causative agent of gastritis and peptic ulcer disease and is an established risk factor for gastric malignancy. Antibiotic combination therapy can eradicate H. pylori. As these same regimens can evoke adverse effects and resistance, new alternative therapies or adjunctive treatments are needed. A probiotic approach may provide a novel strategy for H. pylori treatment. In the current study, two probiotic bacteria, Lactobacillus acidophilus and Lactobacillus reuteri, and a probiotic yeast, Saccharomyces boulardii, were evaluated for their ability to influence H. pylori viability, adherence to gastric and duodenal cells, as well as the effect of S. boulardii on cell surface expression of sialic acid. Our results indicate that S. boulardii contains neuraminidase activity selective for α(2-3)-linked sialic acid. This neuraminidase activity removes surface α(2-3)-linked sialic acid, the ligand for the sialic acid-binding H. pylori adhesin, which in turn, inhibits H. pylori adherence to duodenal epithelial cells. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  20. H. pylori and mitochondrial changes in epithelial cells: The role of oxidative stress H. pylori y alteraciones mitocondriales en células epiteliales: Relación con estrés oxidativo

    Directory of Open Access Journals (Sweden)

    M. Calvino-Fernández

    2010-01-01

    Full Text Available Infection with H. pylori plays a role in the pathogenesis of gastritis, peptic ulcer, gastric carcinoma, and gastric lymphoma, but mechanisms leading to the various clinical manifestations remain obscure and are the primary focus of research in this field. Proliferation and apoptosis are essential in the maintenance of gastric tissue homeostasis, and changes seen in their balance may condition gastric mucosal changes during infection. Thus, excessive apoptosis or proliferation inhibition will result in cell mass loss, which is observed in gastric ulcers. On the other hand, accelerated epithelial cell turnover is characteristic of carcinogenic mucosas. There is also scientific evidence that demonstrates an association between H. pylori infection and exacerbated synthesis of free radicals, the latter being well known as a primary cause of cell death. A thorough review of the literature and the results of our experimental research lead to conclude that H. pylori-induced oxidative stress activates the intrinsic pathway of apoptosis. Structural and functional changes caused by this process on mitochondrial organelles lie at the origin of gastric mucosal toxicity, and lead to the development of the various manifestations associated with this infection. Based on these data we suggest that therapy with antioxidants should prove beneficial for the clinical management of patients with H. pylori infection.

  1. Relationship between VacA Toxin and Host Cell Autophagy in Helicobacter pylori Infection of the Human Stomach: A Few Answers, Many Questions

    Directory of Open Access Journals (Sweden)

    Vittorio Ricci

    2016-07-01

    Full Text Available Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about half the global population and represents the greatest risk factor for gastric malignancy. The relevance of H. pylori for gastric cancer development is equivalent to that of tobacco smoking for lung cancer. VacA toxin seems to play a pivotal role in the overall strategy of H. pylori towards achieving persistent gastric colonization. This strategy appears to involve the modulation of host cell autophagy. After an overview of autophagy and its role in infection and carcinogenesis, I critically review current knowledge about the action of VacA on host cell autophagy during H. pylori infection of the human stomach. Although VacA is a key player in modulation of H. pylori-induced autophagy, a few discrepancies in the data are also evident and many questions remain to be answered. We are thus still far from a definitive understanding of the molecular mechanisms through which VacA affects autophagy and the consequences of this toxin action on the overall pathogenic activity of H. pylori.

  2. Involvement of microRNAs-MMPs-E-cadherin in the migration and invasion of gastric cancer cells infected with Helicobacter pylori.

    Science.gov (United States)

    Yang, Yongmei; Li, Xiaohui; Du, Jie; Yin, Youcong; Li, Yuanjian

    2018-06-15

    It has been found that Helicobacter pylori (H. pylori)is not only the main cause of gastric cancer, but also closely related to its metastasis. E-cadherin cleavage induced by matrix metalloproteinases (MMPs) plays an important role in the tumor metastasis. In the present study, we investigated the role of microRNAs-MMPs-E-cadherin in migration and invasion of gastric cancer cells treated with H. pylori. The results showed that H. pylori induced migration and invasion of SGC-7901 cells with a down-regulation of E-cadherin expression, which were abolished by MMPs knock down, E-cadherin overexpression, mimics of miR128 and miR148a. MiR128/miR148a inhibitors restored MMP-3/MMP-7 expression, down-regulated E-cadherin level, and accelerated cellular migration and invasion. This study suggests that H. pylori induces migration and invasion of gastric cancer cells through reduction of E-cadherin function by activation of MMP-3, - 7. The present results also suggest that the activated MMPs/E-cadherin pathway is related with down-regulation of miR128/miR148a in the human gastric cancer cells infected with H. pylori. Copyright © 2018. Published by Elsevier Inc.

  3. Activation of EGFR and ERBB2 by Helicobacter pylori Results in Survival of Gastric Epithelial Cells with DNA Damage

    Science.gov (United States)

    Chaturvedi, Rupesh; Asim, Mohammad; Piazuelo, M. Blanca; Yan, Fang; Barry, Daniel P.; Sierra, Johanna Carolina; Delgado, Alberto G.; Hill, Salisha; Casero, Robert A.; Bravo, Luis E.; Dominguez, Ricardo L.; Correa, Pelayo; Polk, D. Brent; Washington, M. Kay; Rose, Kristie L.; Schey, Kevin L.; Morgan, Douglas R.; Peek, Richard M.; Wilson, Keith T.

    2014-01-01

    BACKGROUND & AIMS The gastric cancer-causing pathogen Helicobacter pylori upregulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOXhigh cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. METHODS SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H pylori-infected Egfrwa5 mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. Phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsies from Colombian and Honduran cohorts were analyzed by immunohistochemistry. RESULTS SMOX expression and DNA damage were decreased, and apoptosis increased in H pylori-infected Egfrwa5 mice. H pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damagehigh apoptosislow cells. Phosphoproteomic analysis revealed increased EGFR and ERBB2 signaling. Immunoblot analysis demonstrated the presence of a phosphorylated (p)EGFR–ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damagehigh apoptosislow cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR–ERBB2, and pERBB2 were increased predominantly in tissues demonstrating gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR–ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. CONCLUSIONS In an analysis

  4. HELICOBACTER PYLORI

    Science.gov (United States)

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  5. Helicobacter pylori

    Science.gov (United States)

    ... your child aspirin, aspirin-containing medicines, ibuprofen, or anti-inflammatory drugs because these may irritate the stomach or cause stomach bleeding. With prolonged antibiotic therapy, H. pylori gastritis and peptic ulcer disease ( ...

  6. Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

    Directory of Open Access Journals (Sweden)

    Lee Jang-Ming

    2009-05-01

    Full Text Available Abstract Background Overexpression of Cyclooxygenase-2 (COX-2 was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC. One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP, H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9. COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3. The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5. Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9, and the effect was observed to be enhanced for the lower third ESCC

  7. Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study.

    Science.gov (United States)

    Hu, Huang-Ming; Kuo, Chao-Hung; Lee, Chien-Hung; Wu, I-Chen; Lee, Ka-Wo; Lee, Jang-Ming; Goan, Yih-Gang; Chou, Shah-Hwa; Kao, Ein-Long; Wu, Ming-Tsang; Wu, Deng-Chyang

    2009-05-23

    Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 - 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 - 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 - 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 - 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 - 0.47, p for

  8. Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.

    Science.gov (United States)

    Ichikawa, Hitomi; Sugimoto, Mitsushige; Uotani, Takahiro; Sahara, Shu; Yamade, Mihoko; Iwaizumi, Moriya; Yamada, Takanori; Osawa, Satoshi; Sugimoto, Ken; Miyajima, Hiroaki; Yamaoka, Yoshio; Furuta, Takahisa

    2015-04-01

    Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266). Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer. © 2014 John Wiley & Sons Ltd.

  9. Characterization of Lactobacillus salivarius strains B37 and B60 capable of inhibiting IL-8 production in Helicobacter pylori-stimulated gastric epithelial cells.

    Science.gov (United States)

    Panpetch, Wimonrat; Spinler, Jennifer K; Versalovic, James; Tumwasorn, Somying

    2016-10-18

    Interleukin (IL)-8 is the key agent for initiating an inflammatory response to infection with Helicobacter pylori. Some strains of Lactobacillus spp. are known to colonize the stomach and suppress inflammation caused by H. pylori. In this study, we characterized two gastric-derived lactobacilli, Lactobacillus salivarius (LS) strains B37 and B60, capable of inhibiting H. pylori-induced IL-8 production by gastric epithelial cells. Conditioned media from LS-B37 and LS-B60 suppressed H. pylori-induced IL-8 production and mRNA expression from AGS cells without inhibiting H. pylori growth. These conditioned media suppressed the activation of NF-κB but did not suppress c-Jun activation. IL-8 inhibitory substances in conditioned media of LS-B37 and LS-B60 are heat-stable and larger than 100 kDa in size. The inhibitory activity of LS-B37 was abolished when the conditioned medium was treated with α-amylase but still remained when treated with either proteinase K, trypsin, lipase or lysozyme. The activity of LS-B60 was abolished when the conditioned medium was treated with either amylase or proteinase K but still remained when treated with lysozyme. Treatment with lipase and trypsin also significantly affected the inhibitory activity of LS-B60 although the conditioned medium retained IL-8 suppression statistically different from media control. These results suggest that L. salivarius strains B37 and B60 produce different immunomodulatory factors capable of suppressing H. pylori-induced IL-8 production from gastric epithelial cells. Our results suggest that the large, heat-stable immunomodulatory substance(s) present in the LCM of LS-B37 is a polysaccharide, while the one(s) of LS-B60 is either complex consisting of components of polysaccharide, lipid and protein or includes multiple components such as glycoprotein and lipoprotein.

  10. Are Mucosa CD4+/CD8+ T-Cells Expressions Correlated with the Endoscopic Appearance of Chronic Gastritis Related with Helicobacter pylori Infection?

    Science.gov (United States)

    Ratnasari, Neneng; Bayupurnama, Putut; Maduseno, Sutanto; Indrarti, Fahmi; Triwikatmani, Catharina; Harijadi, Achmad; Nurdjanah, Siti

    2016-06-01

    Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4+ and CD8+T-cells Objective. To investigate the correlation between CD4+/CD8+ T-cells in gastric mucosa with endoscopic appearance in chronic gastritis with or without H.pylori infection. Prospective, cross sectional study is performed in a chronic dyspepsia population in July-November 2009 at Dr. Sardjito General Hospital Yogyakarta, Indonesia. The update Sydney system was used to analyze the gastroscopy appearance. Biopsy specimens were stained with HE-stain and IHC-stain. Data were analyzed by t-test, Mann-Whitney and Spearman correlation test. Number of 88 consecutive subjects are enrolled the study (50% male; 50% female), age 46±15 years; 25% H.pylori positive. The expression of CD4+ and CD8+ were higher in H.pylori negative subjects, but only the CD4+ was significant (P=0.011). A significant correlation was found between CD4+ and CD8+ in both subjects (r(Hp+)=0.62 and r(Hp-)=0.68; P<0.05). The expression of CD4+ and CD8+ in H.pylori positive showed a significant correlation with gastric lesions (r(CD4+)=-0.60; r(CD8+)=-0.42 ; P<0.05), only erosion showed a significant difference in both subjects. A positive correlation was found between CD4+ and CD8+ infiltration in both subjects with or without H.pylori infection, and a negative correlation was only found between gastric lesion with CD4+ and CD8+ infiltration in H.pylori subject.

  11. Clustering of Helicobacter pylori VacA in lipid rafts, mediated by its receptor, receptor-like protein tyrosine phosphatase beta, is required for intoxication in AZ-521 Cells

    DEFF Research Database (Denmark)

    Nakayama, Masaaki; Hisatsune, Jyunzo; Yamasaki, Eiki

    2006-01-01

    Helicobacter pylori vacuolating cytotoxin, VacA, induces multiple effects on epithelial cells through different cellular events: one involves pore formation, leading to vacuolation, mitochondrial damage, and apoptosis, and the second involves cell signaling, resulting in stimulation of proinflamm......Helicobacter pylori vacuolating cytotoxin, VacA, induces multiple effects on epithelial cells through different cellular events: one involves pore formation, leading to vacuolation, mitochondrial damage, and apoptosis, and the second involves cell signaling, resulting in stimulation...

  12. Helicobacter pylori infection

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007715.htm Helicobacter pylori infection To use the sharing features on this page, please enable JavaScript. Helicobacter pylori ( H pylori ) is a type of bacteria that ...

  13. Production of IFN-γ and IL-4 Against Intact Catalase and Constructed Catalase Epitopes of Helicobacter pylori From T-Cells.

    Science.gov (United States)

    Ghasemian Safaei, Hajieh; Faghri, Jamshid; Moghim, Sharareh; Nasr Esfahani, Bahram; Fazeli, Hossein; Makvandi, Manoochehr; Adib, Minoo; Rashidi, Niloufar

    2015-12-01

    Helicobacter pylori infection is highly prevalent in the developing countries. It causes gastritis, peptic ulcer disease, and gastrocarcinoma. Treatment with drugs and antibiotics is problematic due to the following reasons: cost, resistance to antibiotics, prolonged treatment and using multiple drugs. Catalase is highly conserved among the Helicobacter species and is important to the survival of the organism. It is expressed in high amounts and is exposed to the surface of this bacterium; therefore it represents a suitable candidate vaccine antigen. A suitable approach in H. pylori vaccinology is the administration of epitope based vaccines. Therefore the responses of T-cells (IFN-γ and IL-4 production) against the catalase of H. pylori were determined. Then the quality of the immune responses against intact catalase and three epitopes of catalase were compared. In this study, a composition of three epitopes of the H. pylori catalase was selected based on Propred software. The effect of catalase epitopes on T-cells were assayed and immune responses identified. The results of IFN-γ, IL-4 production against antigens, epitopes, and recombinant catalase by T-cells were compared for better understanding of epitope efficiency. The current research demonstrated that epitope sequence stimulates cellular immune responses effectively. In addition, increased safety and potency as well as a reduction in time and cost were advantages of this method. Authors are going to use this sequence as a suitable vaccine candidate for further research on animal models and humans in future.

  14. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...

  15. Inflammation, immunity, and vaccines for Helicobacter pylori

    DEFF Research Database (Denmark)

    D'Elios, Mario M; Andersen, Leif P

    2009-01-01

    Helicobacter pylori infects almost half of the population worldwide and represents the major cause of gastroduodenal diseases, such as duodenal and gastric ulcer, gastric adenocarcinoma, autoimmune gastritis, and B-cell lymphoma of mucosa-associated lymphoid tissue. Helicobacter pylori induces...

  16. Homeostatic Mass Control in Gastric Non-Neoplastic Epithelia under Infection of Helicobacter pylori: An Immunohistochemical Analysis of Cell Growth, Stem Cells and Programmed Cell Death

    International Nuclear Information System (INIS)

    Kato, Kenji; Hasui, Kazuhisa; Wang, Jia; Kawano, Yoshifumi; Aikou, Takashi; Murata, Fusayoshi

    2008-01-01

    We evaluated homeostatic mass control in non-neoplastic gastric epithelia under Helicobacter pylori (HP) infection in the macroscopically normal-appearing mucosa resected from the stomach with gastric cancer, immunohistochemically analyzing the proliferation, kinetics of stem cells and programmed cell death occurring in them. Ki67 antigen-positive proliferating cells were found dominantly in the elongated neck portion, sparsely in the fundic areas and sporadically in the stroma with chronic infiltrates. CD117 could monitor the kinetics of gastric stem cells and showed its expression in two stages of gastric epithelial differentiation, namely, in transient cells from the gastric epithelial stem cells to the foveolar and glandular cells in the neck portion and in what are apparently progenitor cells from the gastric stem cells in the stroma among the infiltrates. Most of the nuclei were positive for ssDNA in the almost normal mucosa, suggesting DNA damage. Cleaved caspase-3-positive foveolar cells were noted under the surface, suggesting the suppression of apoptosis in the surface foveolar cells. Besides such apoptosis of the foveolar cells, in the severely inflamed mucosa apoptotic cells were found in the neck portion where most of the cells were Ki67 antigen-positive proliferating cells. Beclin-1 was recognized in the cytoplasm and in a few nuclei of the fundic glandular cells, suggesting their autophagic cell death and mutated beclin-1 in the nuclei. Taken together, the direct and indirect effects of HP infection on the gastric epithelial proliferation, differentiation and programmed cell death suggested the in-situ occurrence of gastric cancer under HP infection

  17. Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion

    OpenAIRE

    Sundrud, Mark S.; Torres, Victor J.; Unutmaz, Derya; Cover, Timothy L.

    2004-01-01

    Recent evidence indicates that the secreted Helicobacter pylori vacuolating toxin (VacA) inhibits the activation of T cells. VacA blocks IL-2 secretion in transformed T cell lines by suppressing the activation of nuclear factor of activated T cells (NFAT). In this study, we investigated the effects of VacA on primary human CD4+ T cells. VacA inhibited the proliferation of primary human T cells activated through the T cell receptor (TCR) and CD28. VacA-treated Jurkat T cells secreted markedly ...

  18. Acetylated Rhamnogalacturonans from Immature Fruits of Abelmoschus esculentus Inhibit the Adhesion of Helicobacter pylori to Human Gastric Cells by Interaction with Outer Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Christian Thöle

    2015-09-01

    Full Text Available Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori to stomach tissue. The present study investigates structural and functional features of polymers responsible for this inhibition of bacterial attachment to host cells. Ammonium sulfate precipitation of an aqueous extract yielded two fractions at 60% and 90% saturation with significant antiadhesive effects against H. pylori, strain J99, (FE60% 68% ± 15%; FE90% 75% ± 11% inhibition rates after preincubation of the bacteria at 1 mg/mL. Sequential extraction of okra fruits yielded hot buffer soluble solids (HBSS with dose dependent antiadhesive effects against strain J99 and three clinical isolates. Preincubation of H. pylori with HBSS (1 mg/mL led to reduced binding to 3ʹ-sialyl lactose, sialylated Lea and Lex. A reduction of bacterial binding to ligands complementary to BabA and SabA was observed when bacteria were pretreated with FE90%. Structural analysis of the antiadhesive polysaccharides (molecular weight, monomer composition, linkage analysis, stereochemistry, and acetylation indicated the presence of acetylated rhamnogalacturonan-I polymers, decorated with short galactose side chains. Deacetylation of HBSS and FE90% resulted in loss of the antiadhesive activity, indicating esterification being a prerequisite for antiadhesive activity.

  19. BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa.

    Science.gov (United States)

    Akazawa, Yuko; Matsuda, Katsuya; Isomoto, Hajime; Matsushima, Kayoko; Kido, Yoko; Urabe, Shigetoshi; Yamaghchi, Naoyuki; Ohnita, Ken; Takeshima, Fuminao; Kondo, Hisayoshi; Tsugawa, Hitoshi; Suzuki, Hidekazu; Moss, Joel; Nakao, Kazuhiko; Nakashima, Masahiro

    2015-09-01

    BH3-only protein, Bim, is a pro-apoptotic protein that mediates mitochondria-dependent cell death. However, the role of Bim in Helicobacter pylori-associated gastritis remains unclear. This study aimed to assess the cellular localization of Bim and its possible role in H. pylori-induced gastritis. The study was conducted on biopsy specimens obtained from 80 patients who underwent upper gastrointestinal endoscopy (H. pylori-negative: n=30, positive: n=50). Association between Bim mRNA expression and severity of gastritis was evaluated and the localization of Bim was examined by immunofluorescence. Bim mRNA expression was positively correlated with the degree of gastritis, as defined by the Sydney system. Immunohistochemical analysis confirmed increased Bim expression in H. pylori-infected gastric mucosa compared with uninfected mucosa in both humans and mice. Bim localized in myeloperoxidase- and CD138-positive cells of H. pylori-infected lamina propria and submucosa of the gastric tract, indicating that this protein is predominantly expressed in neutrophils and plasma cells. In contrast, Bim did not localize in CD20-, CD3-, or CD68-positive cells. Bim was expressed in the mitochondria, where it was partially co-localized with activated Bax and cleaved-PARP. In conclusion, Bim is expressed in neutrophils and plasma cells in H. pylori-associated gastritis, where it may participate in the termination of inflammatory response by causing mitochondria-mediated apoptosis in specific leucocytes. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Helicobacter pylori Diversity and Gastric Cancer Risk

    Directory of Open Access Journals (Sweden)

    Timothy L. Cover

    2016-03-01

    Full Text Available Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI. Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed.

  1. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...... of the stomach. The bacteria are accompanied by characteristic inflammatory changes in the gastric mucosa. The significance for gastritis, chronic ulceration, non-ulcer dyspepsia and carcinoma of the stomach is discussed. HP occurs in a great proportion of the population of the world and the frequency increases...

  2. Effects of prolonged chlorine exposures upon PCR detection of Helicobacter pylori DNA.

    Science.gov (United States)

    The effect of low doses of free chlorine on the detection by qPCR of Helicobacter pylori (H. pylori) cells by qPCR in tap water was monitored. H. pylori target sequences (within suspended, intact cells at densities of 102 to 103 cells /ml) were rendered undetectable by qPCR an...

  3. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions.

    Directory of Open Access Journals (Sweden)

    Xue-Song Zhang

    2015-02-01

    Full Text Available Helicobacter pylori persistently colonizes the human stomach, with mixed roles in human health. The CagA protein, a key host-interaction factor, is translocated by a type IV secretion system into host epithelial cells, where its EPIYA tyrosine phosphorylation motifs (TPMs are recognized by host cell kinases, leading to multiple host cell signaling cascades. The CagA TPMs have been described as type A, B, C or D, each with a specific conserved amino acid sequence surrounding EPIYA. Database searching revealed strong non-random distribution of the B-motifs (including EPIYA and EPIYT in Western H. pylori isolates. In silico analysis of Western H. pylori CagA sequences provided evidence that the EPIYT B-TPMs are significantly less associated with gastric cancer than the EPIYA B-TPMs. By generating and using a phosphorylated CagA B-TPM-specific antibody, we demonstrated the phosphorylated state of the CagA B-TPM EPIYT during H. pylori co-culture with host cells. We also showed that within host cells, CagA interaction with phosphoinositol 3-kinase (PI3-kinase was B-TPM tyrosine-phosphorylation-dependent, and the recombinant CagA with EPIYT B-TPM had higher affinity to PI3-kinase and enhanced induction of AKT than the isogenic CagA with EPIYA B-TPM. Structural modeling of the CagA B-TPM motif bound to PI3-kinase indicated that the threonine residue at the pY+1 position forms a side-chain hydrogen bond to N-417 of PI3-kinase, which cannot be formed by alanine. During co-culture with AGS cells, an H. pylori strain with a CagA EPIYT B-TPM had significantly attenuated induction of interleukin-8 and hummingbird phenotype, compared to the isogenic strain with B-TPM EPIYA. These results suggest that the A/T polymorphisms could regulate CagA activity through interfering with host signaling pathways related to carcinogenesis, thus influencing cancer risk.

  4. "Targeted disruption of the epithelial-barrier by Helicobacter pylori"

    Directory of Open Access Journals (Sweden)

    Wroblewski Lydia E

    2011-11-01

    Full Text Available Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier.

  5. Helicobacter pylori seropositivity and risk of lung cancer.

    Directory of Open Access Journals (Sweden)

    Jill Koshiol

    Full Text Available Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA antigens, we calculated odds ratios (ORs and 95% confidence intervals (95% CIs for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6 or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7. Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.

  6. The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.

    Science.gov (United States)

    Wang, You-Hua; Lv, Zhi-Fa; Zhong, Yao; Liu, Dong-Sheng; Chen, Shu-Ping; Xie, Yong

    2017-02-01

    Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. The internalization level in the eradication success group was 5.40±5.78 × 10 -3  cfu/cell, and the median was 6.194 × 10 -3  cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10 -3  cfu/cell, and the median was 10.28 × 10 -3  cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (Pinternalization levels were compared (P>.05). The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure. © 2016 John Wiley & Sons Ltd.

  7. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  8. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    International Nuclear Information System (INIS)

    Yang, Man; Li, Fu-gang; Xie, Xi-sheng; Wang, Shao-qing; Fan, Jun-ming

    2014-01-01

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells

  9. Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells.

    Directory of Open Access Journals (Sweden)

    Amanda Oldani

    2009-10-01

    Full Text Available Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA(+/VacA(+H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its

  10. Clinical Manifestations of Helicobacter pylori-Negative Gastritis.

    Science.gov (United States)

    Shiota, Seiji; Thrift, Aaron P; Green, Linda; Shah, Rajesh; Verstovsek, Gordana; Rugge, Massimo; Graham, David Y; El-Serag, Hashem B

    2017-07-01

    There are data to suggest the existence of non-Helicobacter pylori gastritis. However, the risk factors and clinical course for H pylori-negative gastritis remain unclear. We aimed to examine the prevalence and determinants of H pylori-negative gastritis in a large multiethnic clinical population. We conducted a cross-sectional study among patents scheduled for an elective esophagastroduodenoscopy or attending selected primary care clinics and eligible for screening colonoscopy at a single Veterans Affairs medical center. We identified cases of H pylor-negative gastritis, H pylori-positive gastritis, and H pylori-negative nongastritis, where gastritis was defined by the presence of neutrophils and/or mononuclear cells. Risk factors for H pylori-negative gastritis were analyzed in logistic regression models. A total of 1240 patients had information from all biopsy sites, of whom 695 (56.0%) had gastritis. H pylori-negative gastritis was present in 123 patients (9.9% of all study subjects and 17.7% of all patients with gastritis). Among all patients with gastritis, African Americans were statistically significantly less likely than non-Hispanic whites to have H pylori-negative gastritis (odds ratio, 0.25; 95% confidence interval, 0.14-0.43). Conversely, PPI users were more likely to have H pylori-negative gastritis than H pylori-positive gastritis compared with nonusers (odds ratio, 2.02; 95% confidence interval, 1.17-3.49). The cumulative incidence of gastric erosions and ulcers were higher in patients with H pylori-negative gastritis than H pylori-negative nongastritis. We found that H pylori-negative gastritis was present in approximately 18% of patients with gastritis. The potential for H pylori-negative gastritis to progress or the risk of gastric cancer of those with gastric mucosal atrophy/intestinal metaplasia remains unclear. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. A Novel Assay for Easy and Rapid Quantification of Helicobacter pylori Adhesion

    DEFF Research Database (Denmark)

    Skindersoe, Mette E; Rasmussen, Lone; Andersen, Leif P

    2015-01-01

    BACKGROUND: Reducing adhesion of Helicobacter pylori to gastric epithelial cells could be a new way to counteract infections with this organism. We here present a novel method for quantification of Helicobacter pylori adhesion to cells. METHODS: Helicobacter pylori is allowed to adhere to AGS...

  12. Autophagy-related genes in Helicobacter pylori infection.

    Science.gov (United States)

    Tanaka, Shingo; Nagashima, Hiroyuki; Uotani, Takahiro; Graham, David Y; Yamaoka, Yoshio

    2017-06-01

    In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H. pylori infection are not yet fully understood. We analyzed autophagy-related gene expression in H. pylori-infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection. Microarray analysis of 226 autophagy-related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori-positive specimens (n=86) were significantly less than those in H. pylori-negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori-positive and 77 H. pylori-negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes. Autophagy-related gene expression profiling using high-throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells. © 2017 John Wiley & Sons Ltd.

  13. Inhibitory activity of mangiferin on Helicobacter pylori -induced ...

    African Journals Online (AJOL)

    Conclusion: We, concluded that MF treatment with H. pylori-infected AGS cells significantly suppressed the adhesion and invasion process as well as deactivated NF-p65 thereby blocking inflammatory response and thus lower the incidence of gastric carcinoma. Keywords: Gastric cancer, mangiferin, AGS cells, H. pylori, ...

  14. Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway.

    Science.gov (United States)

    Devi, Savita; Ansari, Suhail A; Vadivelu, Jamuna; Mégraud, Francis; Tenguria, Shivendra; Ahmed, Niyaz

    2014-02-01

    The envisaged roles and partly understood functional properties of Helicobacter pylori protein HP0986 are significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study its subcellular localization or homing in AGS cells. Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF

  15. A morphometric study of antral G-cell density in a sample of adult general population: comparison of three different methods and correlation with patient demography, helicobacter pylori infection, histomorphology and circulating gastrin levels

    DEFF Research Database (Denmark)

    Petersson, Fredrik; Borch, Kurt; Rehfeld, Jens F

    2008-01-01

    whether these methods are intercorrelated and the relation of these methods to plasma gastrin concentrations, demography, the occurrence of H. pylori infection and chronic gastritis. Gastric antral mucosal biopsy sections from 273 adults (188 with and 85 without H pylori infection) from a general...... population sample were examined immunohistochemically for G-cells using cell counting, stereology (point counting) and computerized image analysis. Gastritis was scored according to the updated Sydney system. Basal plasma gastrin concentrations were measured by radioimmunoassay. The three methods for G...

  16. Helicobacter pylori VacA, acting through receptor protein tyrosine phosphatase ?, is crucial for CagA phosphorylation in human duodenum carcinoma cell line AZ-521

    OpenAIRE

    Nakano, Masayuki; Yahiro, Kinnosuke; Yamasaki, Eiki; Kurazono, Hisao; Akada, Junko; Yamaoka, Yoshio; Niidome, Takuro; Hatakeyama, Masanori; Suzuki, Hidekazu; Yamamoto, Taro; Moss, Joel; Isomoto, Hajime; Hirayama, Toshiya

    2016-01-01

    ABSTRACT Helicobacter pylori, a major cause of gastroduodenal diseases, produces vacuolating cytotoxin (VacA) and cytotoxin-associated gene A (CagA), which seem to be involved in virulence. VacA exhibits pleiotropic actions in gastroduodenal disorders via its specific receptors. Recently, we found that VacA induced the phosphorylation of cellular Src kinase (Src) at Tyr418 in AZ-521 cells. Silencing of receptor protein tyrosine phosphatase (RPTP)?, a VacA receptor, reduced VacA-induced Src ph...

  17. Effect of curcumin on Helicobacter pylori biofilm formation ...

    African Journals Online (AJOL)

    Three-dimensional structure of biofilm was imaged by scanning electron microscopy. The effect of curcumin on H. pylori adherence to HEp-2 cells was also investigated. Subinhibitory concentrations of curcumin inhibited the biofilm in dose dependent manner. However, H.pylori could restore ability to form biofilm during ...

  18. Helicobacter Pylori –Infected Patients | Eltayeb | Sudan Journal of ...

    African Journals Online (AJOL)

    Background: The role of Helicobacter pylori on gastric carcinogenesis is still unclear but it is considered to predispose carriers to gastric cancer. Objective: The aim of this study is to investigate the relationship between the extent of DNA damage of normal gastric epithelial cells and H. Pylori positive & negative gastritis ...

  19. Controversies in the Helicobacter pylori/duodenal ulcer story.

    Science.gov (United States)

    Hobsley, Michael; Tovey, Frank I; Holton, John

    2008-12-01

    In patients with Helicobacter pylori-positive duodenal ulcer (DU), the organism must be eradicated to achieve rapid, stable healing. However, evidence is against much else that is commonly accepted. (1) Does H. pylori cause the ulcer? Evidence against includes archaeopathology, geographical prevalence, temporal relationships and H. pylori-negative DU patients. DU can recur after eradication of H. pylori infection, and DUs may remain healed after reduction of acid secretion despite persistent infection. The faster healing of ulcers when H. pylori has been eradicated is due to the organism's interference with neoangiogenesis and the healing of wounded epithelial cells. (2) Does H. pylori infection persist until pharmacologically eradicated? Studies based on current infection show that H. pylori infection is a labile state that can change in 3 months. High rates of gastric acid secretion result in spontaneous cure, whereas low rates permit re-infection. Hydrochloric acid, necessary for producing a DU, is strongly associated with the likelihood of an ulcer. At the start, patients owe their ulcer to gastric hypersecretion of hydrochloric acid; approximately 60% may be H. pylori-negative. If acid is suppressed, the less acid milieu encourages invasion by H. pylori, especially if the strain is virulent.

  20. Host pathogen interactions in Helicobacter pylori related gastric cancer

    Science.gov (United States)

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  1. Helicobacter pylori gastritis

    International Nuclear Information System (INIS)

    Urban, B.A.; Fishman, E.K.; Kuhlman, J.E.; Jones, B.

    1990-01-01

    This paper reports on the CT scans of patients with Helicobacter pylori (formerly Campylobacter pylori) infection and histologic gastritis reviewed to determine if the inflammatory changes can mimic the CT appearance of gastric neoplasm. Records were obtained of 288 consecutive cases of biopsy-confirmed. Helicobacter pylori gastritis, spanning a 21-month period from July 1988 to March 1990. Abdominal CT scans had been performed in 70 of these cases and were retrospectively reviewed. RESULTS: Seven of the 70 cases of confirmed Helicobacter pylori gastritis were suggestive of malignancy on CT

  2. Helicobacter pylori and oral pathology: relationship with the gastric infection.

    Science.gov (United States)

    Adler, Isabel; Muiño, Andrea; Aguas, Silvia; Harada, Laura; Diaz, Mariana; Lence, Adriana; Labbrozzi, Mario; Muiño, Juan Manuel; Elsner, Boris; Avagnina, Alejandra; Denninghoff, Valeria

    2014-08-07

    Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.

  3. The Middle Fragment of Helicobacter pylori CagA Induces Actin Rearrangement and Triggers Its Own Uptake into Gastric Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Abolghasem Tohidpour

    2017-07-01

    Full Text Available Cytotoxin-associated gene product A (CagA is a major virulence factor secreted by Helicobacter pylori. CagA activity in the gastric epithelium is associated with higher risk of gastric cancer development. Bacterial type IV secretion system (T4SS-mediated translocation of CagA into the cytosol of human epithelial cells occurs via a poorly understood mechanism that requires CagA interaction with the host membrane lipid phosphatidylserine (PS and host cell receptor integrin α5β1. Here we have characterized the isolated recombinant middle fragment of CagA (CagA-M that contains the positively-charged PS-binding region (aa 613–636 and a putative β1 integrin binding site, but lacks the EPIYA region, secretion signal peptide and the CagA multimerization motif. We show that CagA-M, when immobilized on latex beads, is capable of binding to, and triggering its own uptake into, gastric epithelial cells in the absence of infection with cagA-positive H. pylori. Using site-directed mutagenesis, fluorescent and electron microscopy, and highly-specific inhibitors, we demonstrate that the cell-binding and endocytosis-like internalization of CagA-M are dependent on (1 binding to PS; (2 β1 integrin activity; and (3 actin dynamics. Interaction of CagA-M with the host cells is accompanied by the development of long filopodia-like protrusions (macrospikes. This novel morphology is different from the hummingbird phenotype induced by the translocation of full-length CagA. The determinants within CagA-M and within the host that are important for endocytosis-like internalization into host cells are very similar to those observed for T4SS-mediated internalization of full-length CagA, suggesting that the latter may involve an endocytic pathway.

  4. Immune response to H pylori

    Science.gov (United States)

    Suarez, Giovanni; Reyes, Victor E; Beswick, Ellen J

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer, attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium. PMID:17007009

  5. Frequency of γδ T Cells and Invariant Natural Killer T Cells in Helicobacter Pylori-infected Patients with Peptic Ulcer and Gastric Cancer.

    Science.gov (United States)

    Shadman, Mojtaba; Rajabian, Zeinab; Ajami, Abolghasem; Hussein-Nattaj, Hadi; Rafiei, Alireza; Hosseini, Vahid; Taghvaei, Tarang; Abbasi, Ali; Tehrani, Mohsen

    2015-10-01

    To clarify the effect of γδ T cells and invariant Natural Killer T (iNKT) cells in pathophysiology of dyspeptic disorders, number of these two cells in patients with non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were compared.Patients with dyspepsia were divided into three groups of NUD, PUD, and GC according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD3+TCRγδ(+) T cells and CD3+Va24Ja18+ iNKT cells were determined by flow cytometry. Immunohistochemistry (IHC) was also used for identifying the TCRγδ+ cells.Forty two patients with NUD (31.6%), 44 with PUD (33.1%), and 47 with GC (35.3%) were included in the study. The frequency of CD3+TCRγδ(+) T cells in peripheral blood of patients with GC (2.71±0.25) was significantly lower than that in NUD (3.97±0.32, p<0.05) and PUD groups (3.87±0.32, p<0.05). However, there was no significant difference in CD3+TCRγδ(+) T cell percentage between the NUD and PUD groups. The frequency of TCRγδ(+) lymphocytes was significantly lower in tissue samples from patients with GC (4.81±0.53) than in NUD (11.09±1.09, p<0.0001) and PUD groups (11.11±1.01, p<0.0001). Also, we could not find any significant difference in the percentage of mucosal TCRγδ+ cells between the NUD and PUD groups. The results showed no significant difference in iNKT cells percentage among the three groups of patients.The results suggest that decreasing number of γδ T cells may be related to development and progression of gastric cancer.

  6. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

    Directory of Open Access Journals (Sweden)

    Songhua Zhang

    Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

  7. Helicobacter pylori genomic microevolution during naturally occurring transmission between adults.

    Directory of Open Access Journals (Sweden)

    Bodo Linz

    Full Text Available The human gastric pathogen Helicobacter pylori is usually acquired during childhood and, in the absence of treatment, chronic infection persists through most of the host's life. However, the frequency and importance of H. pylori transmission between adults is underestimated. Here we sequenced the complete genomes of H. pylori strains that were transmitted between spouses and analysed the genomic changes. Similar to H. pylori from chronic infection, a significantly high proportion of the determined 31 SNPs and 10 recombinant DNA fragments affected genes of the hop family of outer membrane proteins, some of which are known to be adhesins. In addition, changes in a fucosyltransferase gene modified the LPS component of the bacterial cell surface, suggesting strong diversifying selection. In contrast, virulence factor genes were not affected by the genomic changes. We propose a model of the genomic changes that are associated with the transmission and adaptation of H. pylori to a new human host.

  8. Differences in the Antigens of Helicobacter pylori Strains Influence on the Innate Immune Response in the In Vitro Experiments

    Directory of Open Access Journals (Sweden)

    Miha Skvarc

    2014-01-01

    Full Text Available The immune response to Helicobacter pylori importantly determines the pathogenesis of infection as well as the success of antibiotic eradication of the bacteria. Strains of H. pylori were gathered from 14 patients who failed to eradicate H. pylori infection with antibiotics—therapy resistant strains (TRS—or from patients who were able to eradicate H. pylori infection—therapy susceptible strains (TSS. The THP-1 cells were stimulated with H. pylori antigens. Cathepsin X expression on THP-1 cells and concentration of cytokines in the supernatant of THP-1 cells were measured with a flow cytometer. TSS H. pylori antigens increased the proportion of cathepsin X positive cells compared to TRS H. pylori antigens. TSS H. pylori antigens induced higher secretion of IL-12 and IL-6 compared to TRS H. pylori antigens (P<0.001; 0.02. Polymyxin B, a lipid A inhibitor, lowered the secretion of IL-12 and IL-6 in TRS and TSS. We demonstrated a H. pylori strain-dependent cathepsin X and cytokine expression that can be associated with H. pylori resistance to eradication due to lack of effective immune response. Differences in lipid A of H. pylori might have an influence on the insufficient immune response, especially on phagocytosis.

  9. Detection of Helicobacter pylori in Oral Lesions

    Directory of Open Access Journals (Sweden)

    Soussan Irani

    2013-12-01

    Full Text Available Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000. In addition, there was a statistically significant difference between the lesions examined (P=0.042. Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000, inside the blood vessels (P=0.003, inside the salivary gland duct (P=0.036, and muscle layer (P=0.122. Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested.

  10. Helicobacter Pylori Infections

    Science.gov (United States)

    ... the stomach. It is the main cause of peptic ulcers, and it can also cause gastritis and stomach ... inflammation. This can lead to gastritis or a peptic ulcer. Researchers aren't sure how H. pylori spreads. ...

  11. Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

    Directory of Open Access Journals (Sweden)

    Yuichi Matsuo

    2017-03-01

    Full Text Available Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system.

  12. Helicobacter pylori and nonmalignant diseases.

    LENUS (Irish Health Repository)

    Alakkari, Alaa

    2012-02-01

    Research published over the past year has documented the continued decline of Helicobacter pylori-related peptic ulcer disease and increased recognition of non-H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer complications and associated mortality remain stubbornly high. The role of H. pylori in functional dyspepsia is unclear, with some authors considering H. pylori-associated nonulcer dyspepsia a distinct organic entity. There is increasing acceptance of an inverse relationship between H. pylori and gastroesophageal reflux disease (GERD), but little understanding of how GERD might be more common\\/severe in H. pylori-negative subjects. Research has focused on factors such as different H. pylori phenotypes, weight gain after H. pylori eradication, and effects on hormones such as ghrelin that control appetite.

  13. Gastric angiogenesis and Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    I. D. Pousa

    Full Text Available The formation of new blood vessels seen in conditions commonly associated with Helicobacter pylori (H. pylori infection, including gastritis, peptic ulcer, and gastric carcinoma, prompts consideration of a potential relationship between mucosal colonization by this organism and the angiogenic process. H. pylori directly or indirectly damages endothelial cells, which induces a number of changes in the microvasculature of the gastric mucosa. In H. pylori-associated conditions, that is, in gastritis, peptic ulcer and gastric carcinoma, there is an increased concentration of angiogenic factors, and subsequently a formation of new blood vessels. However, this early angiogenesis -which is activated to repair the gastric mucosa- is subsequently inhibited in patients with peptic ulcer, and ulcer healing is thus delayed. This may be due to the antiproliferative action of this organism on endothelial cells. While the angiogenic process becomes inhibited in infected patients with peptic ulcer, it remains seemingly active in those with gastritis or gastric cancer. This fact is in support of the notion suggested by various studies that peptic ulcer and gastric cancer are mutually excluding conditions. In the case of gastric cancer, neoangiogenesis would enhance nutrient and oxygen supply to cancer cells, and thus tumor growth and metastatic spread.

  14. Halitosis and Helicobacter pylori infection

    NARCIS (Netherlands)

    Tangerman, A.; Winkel, E. G.; de Laat, L.; van Oijen, A. H.; de Boer, W. A.

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to

  15. Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI expression

    Directory of Open Access Journals (Sweden)

    Treiber Gerhard

    2011-05-01

    Full Text Available Abstract Background Mucosal levels of Secretory Leukocyte Protease Inhibitor (SLPI are specifically reduced in relation to H. pylori-induced gastritis. Progranulin is an epithelial growth factor that is proteolytically degraded into fragments by elastase (the main target of SLPI. Considering the role of SLPI for regulating the activity of elastase, we studied whether the H. pylori-induced reduction of SLPI and the resulting increase of elastase-derived activity would reduce the Progranulin protein levels both ex vivo and in vitro. Methods The expression of Progranulin was studied in biopsies of H. pylori-positive, -negative and -eradicated subjects as well as in the gastric tumor cell line AGS by ELISA, immunohistochemistry and real-time RT-PCR. Results H. pylori-infected subjects had about 2-fold increased antral Progranulin expression compared to H. pylori-negative and -eradicated subjects (P H. pylori infection; both epithelial and infiltrating immune cells contributed to the higher Progranulin expression levels. The H. pylori-induced upregulation of Progranulin was verified in AGS cells infected by H. pylori. The down-regulation of endogenous SLPI expression in AGS cells by siRNA methodology did not affect the Progranulin expression independent of the infection by H. pylori. Conclusions Taken together, Progranulin was identified as novel molecule that is upregulated in context to H. pylori infection. In contrast to other diseases, SLPI seems not to have a regulatory role for Progranulin in H. pylori-mediated gastritis.

  16. Mechanism of H. pylori intracellular entry: an in vitro study

    Directory of Open Access Journals (Sweden)

    Hui eLiu

    2012-03-01

    Full Text Available The majority of H. pylori reside on gastric epithelial cell surfaces and in the overlying mucus, but a small fraction of H. pylori enter host epithelial and immune cells. To explore the role of the nudA invasin in host cell entry, a ΔnudA deletion derivative of strain J99 was constructed and transformants were verified by PCR and by fluorescence in situ hybridization. AGS cells were inoculated with either wild type (WT strain J99 or its ΔnudA mutant to determine the fraction of bacteria that were bound to the cells and inside these cells using the gentamicin protection assay. We observed no significant difference between either the density of H. pylori bound to AGS cell membranes or the density of intracellular H. pylori. To further explore this finding, separate chambers of each culture were fixed in glutaraldehyde for transmission electron microscopy (TEM and immunogold TEM. This addition to the classical gentamicin assay demonstrated that there were significantly more intracellular, and fewer membrane-bound, H. pylori in WT-infected AGS cells than in ΔnudA allele infected cells. Thus, the sum of intracellular and membrane-bound H. pylori was similar in the two groups. Since no other similar TEM study has been performed, it is at present unknown whether our observations can be reproduced by others Taken together however, our observations suggest that the classical gentamicin protection assay is not sufficiently sensitive to analyze H. pylori cell entry and that the addition of TEM to the test demonstrate that nudA plays a role in H. pylori entry into AGS cells in vitro. In addition, deletion of the invasin gene appears to limit H. pylori to the AGS cell surface, where it may be partly protected against gentamicin. In contrast, this specific environment may render H. pylori more vulnerable to host defense and therapeutic intervention, and less prone to trigger normal immune, carcinogenic, and other developmental response pathways.

  17. Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

    LENUS (Irish Health Repository)

    Kell, M R

    2012-02-03

    BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

  18. Do Helicobacter pylori therapeutic vaccines need to be tailored to the age of the recipient?

    Science.gov (United States)

    Sutton, Philip; Robinson, Karen

    2012-04-01

    Helicobacter pylori infections typically commence during childhood and last for life. Freire de Melo and colleagues compared cytokine profiles in the stomachs of H. pylori-infected and H. pylori-uninfected children and adults from Brazil. They suggest that the immune effector response in infected children differs from infected adults, specifically that stomachs of infected children contained elevated regulatory T-cell markers and less IL-17 compared with adults. As vaccine-mediated protection against H. pylori is believed to involve IL-17 and to be inhibited by regulatory T cells, this raises the possibility that individual H. pylorivaccines may have different efficacies in children and adults.

  19. Helicobacter pylori protein HP0986 (TieA) interacts with mouse TNFR1 and triggers proinflammatory and proapoptotic signaling pathways in cultured macrophage cells (RAW 264.7).

    Science.gov (United States)

    Ansari, Suhail A; Devi, Savita; Tenguria, Shivendra; Kumar, Ashutosh; Ahmed, Niyaz

    2014-08-01

    HP0986 protein of Helicobacter pylori has been shown to trigger induction of proinflammatory cytokines (IL-8 and TNF-α) through the activation of NF-κB and also to induce Fas mediated apoptosis of human macrophage cells (THP-1). In this study, we unravel mechanistic details of the biological effects of this protein in a murine macrophage environment. Up regulation of MCP-1 and TNF-α in HP0986-induced RAW 264.7 cells occurred subsequent to the activation and translocation of NF-κB to the cell nucleus. Further, HP0986 induced apoptosis of RAW 264.7 cells through Fas activation and this was in agreement with previous observations made with THP-1 cells. Our studies indicated activation of TNFR1 through interaction with HP0986 and this elicited the aforementioned responses independent of TLR2, TLR4 or TNFR2. We found that mouse TNFR1 activation by HP0986 facilitates formation of a complex comprising of TNFR1, TRADD and TRAF2, and this occurs upstream of NF-κB activation. Furthermore, FADD also forms a second complex, at a later stage, together with TNFR1 and TRADD, resulting in caspase-8 activation and thereby the apoptosis of RAW 264.7 cells. In summary, our observations reveal finer details of the functional activity of HP0986 protein in relation to its behavior in a murine macrophage cell environment. These findings reconfirm the proinflammatory and apoptotic role of HP0986 signifying it to be an important trigger of innate responses. These observations form much needed baseline data entailing future in vivo studies of the functions of HP0986 in a murine model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. An investigation of compositions and effects of local herbal Glycyrrhiza glabra and Mentha pulegium extracts on Helicobacter pylori and cell Line of stomach cancer (AGS by MTT assays

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    Fereshteh Salmani Jamaat1

    2017-07-01

    Full Text Available Background & Aim:According to globally development of stomach cancer especially in Ardabil, Iran, as the second major cause of mortality throughout the world, increased drug-resistant bacteria including Helicobacter pylori as the most important risk factors for stomach cancer, and side effects of antibiotics and chemical drugs normally used to treat. Experimental: The current research was conducted to investigate the anticancer and antimicrobial effects of native herbs of liquorice (Glycyrrhiza glabra and pennyroyal (Mentha pulegium extractions for finding a solution with the lowest complications in control or treatment of stomach cancer.The extractions were firstly obtained using Soxhlet and methanol solvent and then their compounds were determined by GC/MS. Antimicrobial activity, MIC and MBC of the extractions were assessed respectively using agar diffusion and broth dilution test and the anticancer effect on stomach cancer (cell line AGS was assessed by MTT assay. H. pylori ATCC 26695 was respectively revived and purified on Brucella broth containing 7% citrated horse serum and Columbia agar. Results: The analysis showed that liquorice extract contains 15 compositions, mainly consists of 26.48% Nonane, 23.38% Ethylcyclohexan, 8.29% 3-Bromodecane, 10.31% trans-2-Heptenal, 8.93% 9-Octadecenamide and 4.68% β-pregna and pennyroyal extract contains 17 compositions, mainly including 3.36% Camphor, 22.79% Pulegone, 4.92% Paramenth-3-n8-l, 8.06% Menthoforan, 7.54% Cis-Isopulegon and 24.58% α-Selinene. The bacteria were resistant or semi-sensitive to common antibiotics, whereas had considerable sensitivity to herbal extracts and liquorice showed almost three times more antibacterial effect. Pennyroyal extract had no cytotoxic effects, but the anticancer effect was observed in liquorice extract with optimal concentration of 25 μg/ml after 48 hours. Recommended applications/industries: In conclusion, liquorice extract due to the significant health

  1. Variation in the number of EPIYA-C repeats in CagA protein from Colombian Helicobacter pylori strains and its ability to induce hummingbird phenotype in gastric epithelial cells Variación en el número de repeticiones EPIYA-C en la proteína CagA de aislamientos colombianos de Helicobacter pylori y su capacidad para inducir fenotipo colibrí en células epiteliales gástricas

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    María Mercedes Bravo

    2010-08-01

    Full Text Available Introduction. Studies using Western Helicobacter pylori strains have shown that a risk factor for gastric cancer is the number of EPIYA-C motifs in the cytotoxin-associated A protein. CagA is delivered into epithelial cells, where it becomes tyrosine phosphorylated in their EPIYA repeats and induces cytoskeleton rearrangements.
    Objectives. The objective of this study was to evaluate H. pylori cagA positive strains isolated from Colombian patients with gastroduodenal diseases for the number of EPIYA-C repeats in cagA and their ability to induce cytoskeleton rearrangements in epithelial cells.
    Materials and methods. We analyzed the 3' EPIYA repeats region of cagA by PCR in 93 H. pylori cagA positive strains from 49 patients with gastritis, 17 with gastric cancer, and 24 with duodenal ulcer. AGS cells exposed to the various H. pylori isolates were evaluated for rearrangements in their cytoskeleton.
    Results. Strains with one EPIYA-C were the most frequent in gastritis and duodenal ulcer patients. Strains with three EPIYA-C were mainly found in gastric cancer. We found a significantly higher risk of gastric cancer for individuals infected with strains harboring three EPIYA-C motifs (OR=12.4, CI95%: 2.32-66.3. Strains from gastric cancer showed significantly higher percentages of induction of cytoskeleton rearrangements in comparison with those from gastritis (p Mann-Whitney<0.005.
    Conclusions. H. pylori strains with three EPIYA-C repeats can confer an increased risk of cancer to infected individuals.Introducción. En los aislamientos de Helicobacter pylori del hemisferio occidental, se ha observado que el número de repeticiones EPIYA-C en la proteína CagA es un factor de riesgo para cáncer gástrico. La proteína CagA es introducida en la célula epitelial y, posteriormente, es fosforilada en las tirosinas presentes en los motivos EPIYA e induce rearreglos en el citoesqueleto.
    Objetivos. Nuestro propósito fue evaluar el n

  2. Helicobacter pylori as a crucial factor in intestinal metaplasia development of gastric mucosa

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    Sergii Vernygorodskyi

    2016-06-01

    Full Text Available Helicobacter pylori (H. pylori is detected on the surface of gastric epithelium and in goblet cells, predominantly in patients with chronic atrophic gastritis and incomplete intestinal metaplasia (IM. H. pylori infection persistence leads to the formation of gastrointestinal phenotype of IM. H. pylori can be considered as an etiological factor of IM. It inhibits the expression of SOX2 in gastric epithelial cells, hence activating transcription factor CDX2 as a counterpart to MUC5AC gene inhibition and MUC2 gene induction. Thus, in metaplastic cells, programming differentiation after intestinal phenotype will develop. The role of H. pylori in the origin of intestinal metaplasia of gastric mucosa was defined in this study to elucidate the probable mechanism of cell reprogramming. The activation of CDX2, with simultaneous inactivation and decreased number of genes (e.g., SHH, SOX2, and RUNX3 responsible for gastric differentiation, was identified to cause the appearance of IM.

  3. Impact of Helicobacter pylori on the healing process of the gastric barrier

    Science.gov (United States)

    Mnich, Eliza; Kowalewicz-Kulbat, Magdalena; Sicińska, Paulina; Hinc, Krzysztof; Obuchowski, Michał; Gajewski, Adrian; Moran, Anthony P; Chmiela, Magdalena

    2016-01-01

    AIM To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover. METHODS In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. RESULTS We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway. CONCLUSION In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier. PMID:27672275

  4. Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

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    Ivana Hitkova

    Full Text Available Caveolin-1 (Cav1 is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori is a major risk factor for human gastric cancer (GC where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS, infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird" compared to AGS cells stably transfected with Cav1 (AGS/Cav1. Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1 to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87 and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1 to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells.

  5. Growth cycle of Helicobacter pylori in gastric mucous layer.

    Science.gov (United States)

    Nakazawa, Teruko

    2002-12-01

    Helicobacter pylori bacterium is characterized by its strong urease activity. Our studies on the role of H. pylori urease revealed; (i) it is essential for colonization, (ii) exogenous urea is required for acid resistance, (iii) the bacteria have the ability to move toward urea and sodium bicarbonate, (iv) urea hydrolysis accelerates chemotactic locomotion, and (v) decay of urease mRNA to accomplish the active center is pH-regulated; i.e., the mRNA is stabilized and destabilized under acidic and neutral conditions, respectively. Based on the above results, I propose the growth cycle of H. pylori in gastric mucous layer. H. pylori bacteria proliferate on the epithelial cell surface by utilizing nutrients derived from degraded cells. Proliferated bacteria leave the cell surface to pH-variable region where they encounter strong acid. Urease is activated with simultaneous opening of UreI channel so that urea is hydrolyzed to neutralize acid. Chemotaxis of H. pylori toward urea and sodium bicarbonate that are abundant on the cell surface is accelerated by urea hydrolysis so that the bacteria go back to the cell surface for the next round of proliferation. This growth cycle may allow the bacteria to infect persistently in the stomach.

  6. Colonization and infection by Helicobacter pylori in humans.

    Science.gov (United States)

    Andersen, Leif Percival

    2007-11-01

    When Helicobacter pylori arrives in the human stomach, it may penetrate the mucin layer and adhere to the gastric epithelial cells or it may pass through the stomach without colonizing the mucosa. In this paper, the colonization process and the ensuing immunological response will be briefly described. Urease production is necessary for H. pylori to establish a pH-neutral microenvironment around the bacteria. The flagella enable the bacteria to move and the shape of H. pylori makes it possible to penetrate the mucin layer where it comes into contact with the gastric epithelial cells. H. pylori contains several adhesins that enable it to adhere to the epithelial cells. This adherence activates IL-8 which, together with bacterial antigens, attracts polymorphs and monocytes and causes acute gastritis. Antigen-presenting cells activate lymphocytes and other mononuclear cells that are attracted to the inflamed mucosa, causing chronic superficial gastritis and initiating a cytotoxic or an antigen-producing Th response. The infection is established within a few weeks after the primary exposure to H. pylori. After this initial colonization, many chemical, biochemical, and immunologic reactions take place that are of importance in the progress of the infection and the development of disease.

  7. Pathobiology of Helicobacter pylori-induced Gastric Cancer

    Science.gov (United States)

    Amieva, Manuel; Peek, Richard M.

    2015-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

  8. Prevalence of Helicobacter Pylori in Gastric Fluid in the Surgical Patient

    Science.gov (United States)

    1998-05-01

    highest rates of H. pylori infection occur in areas with the highest rates of stomach cancer, such as China, Japan, Peru and Scotland. However, even in the...Mahoney, D.H. (1997). Helicobacter pylori gastritis in a child with sickle cell anemia and recurrent abdominal pain. Journal of Hematology and

  9. Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases

    NARCIS (Netherlands)

    Götz, J. M.; Thio, J. L.; Verspaget, H. W.; Offerhaus, G. J.; Biemond, I.; Lamers, C. B.; Veenendaal, R. A.

    1997-01-01

    Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely,

  10. Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity

    NARCIS (Netherlands)

    Amedei, Amedeo; Bergman, Mathijs P.; Appelmelk, Ben J.; Azzurri, Annalisa; Benagiano, Marisa; Tamburini, Carlo; van der Zee, Ruurd; Telford, John L.; Vandenbroucke-Grauls, Christina M. J. E.; D'Elios, Mario M.; del Prete, Gianfranco

    2003-01-01

    Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+-adenosine triphosphatase as autoantigen. Here, we report that H. pylori-infected patients with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells

  11. Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota

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    Yao-Jong Yang

    2016-02-01

    Full Text Available As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D. Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.

  12. No evidence for Helicobacter pylori in oral lichen planus.

    Science.gov (United States)

    Hulimavu, Shwetha R; Mohanty, Leeky; Tondikulam, Narayan V; Shenoy, Sadhana; Jamadar, Saleha; Bhadranna, Abhishek

    2014-09-01

    Oral lichen planus is a T-cell-mediated mucosal disease of unknown etiology. Numerous predisposing factors have been put forward in the etiology of this disease. This includes stress, drugs, genetic susceptibility, certain viruses, and bacterial infections. Recently, there have been studies published on possible role of Helicobacter pylori infection in pathogenesis of mucocutaneous diseases including oral lichen planus (OLP). The aim of this study was to detect immunohistochemically the presence of Helicobacter pylori in oral lichen planus. Paraffin-embedded tissue blocks of 50 cases of OLP and 10 cases of normal buccal mucosal biopsies and 6 endoscopic biopsies of patients with peptic ulcer (control group) were sectioned and stained by hematoxylin and eosin. Serial sections of same were stained immunohistochemically using Anti-Helicobacter pylori antibody and observed under microscope for presence or absence of Helicobacter pylori. Except for the control group, none of the cases of OLP and normal buccal mucosal biopsies showed positivity for Helicobacter pylori. As we did not detect the presence of Helicobacter pylori in any of the OLP cases, we question the role of these organisms in the pathogenesis of OLP planus if any. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Ma, Ning; Adachi, Yukihiko; Hiraku, Yusuke; Horiki, Noriyuki; Horiike, Shinichirou; Imoto, Ichiro; Pinlaor, Somchai; Murata, Mariko; Semba, Reiji; Kawanishi, Shosuke

    2004-01-01

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2 ' -deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  14. Infection with Helicobacter pylori is associated with protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Sharon Perry

    2010-01-01

    Full Text Available Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis.We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29% meeting criteria for latent tuberculosis (TB infection (LTBI, 45 (46% were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA, and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005, though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44. Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04.H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

  15. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

    Science.gov (United States)

    Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

    2017-04-01

    We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

  16. Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection.

    Science.gov (United States)

    Lee, Sun-Young

    2016-09-01

    Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer.

  17. Diagnosis of gastritis caused by Helicobacter pylori in children by means of an ELISA.

    Science.gov (United States)

    Czinn, S J; Carr, H S; Speck, W T

    1991-01-01

    In this study, the systemic immune response to bacterial cell sonicates of Helicobacter pylori was characterized in children with symptomatic gastroduodenal disease. Isotype-specific antibodies to H. pylori in samples of serum from 16 children with culture-proven disease caused by H. pylori and from 19 controls with negative cultures were measured by ELISA with bacterial cell lysates. The levels in serum of IgA antibody to cell sonicates of H. pylori were significantly higher in the patients with positive cultures than in the controls. Only 45% of patients were infected when the established optical density cutoff was used to discriminate between patients infected and not infected with H. pylori. Levels of IgM antibody in serum were not significantly higher in patients who were infected with H. pylori. On the basis of this survey and of previous work conducted in our laboratory, we conclude that at a serum dilution of 1:800, IgG but not IgA or IgM antibody to H. pylori is useful in the rapid screening of symptomatic children for the presence of H. pylori.

  18. Inactivation of Helicobacter pylori by Chloramination

    Science.gov (United States)

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  19. A study on the effect of Helicobacter pylori infection on p53 expression in gastric cancer and gastritis tissues.

    Science.gov (United States)

    Salih, Barik A; Gucin, Zuhal; Bayyurt, Nizamettin

    2013-09-16

    Helicobacter pylori cause damage to gastric epithelial cells and alterations in the p53 gene that lead to cancer development. This study aimed to determine the correlation of p53 expression with H. pylori using immunohistochemistry, RFLP-PCR, and histopathology. Gastric biopsy samples from gastric cancer (GC) (n = 54) and gastritis (n = 31) patients were examined for histopathological changes and expression of p53 protein by immunohistochemistry. Immunohistochemical analysis of p53 protein expression in H. pylori-positive GC sections showed an average of 44.3% positive cells in tumors and 6.9% in normal tissues, as compared to 16.4% and 4.4% in H. pylori-negative sections. P53 expression showed significant association with H. pylori (P = 0.005), invasion depth (P = 0.029) and inflammation reaction (P = 0.008). In gastritis sections, no difference in the average p53 staining in H. pylori-positive or -negative sections was seen. PCR-RFLP results also showed no difference in genotype frequencies of p53 in H. pylori-positive or -negative gastritis sections. Histopathology study of H. pylori-positive GC sections showed that 97.2% were the intestinal type and 2.8% the diffuse type, while in H. pylori-negative sections 35.2% were the intestinal type and 64.8% the diffuse type. Biopsy sections from H. pylori-positive gastritis patients revealed more severe inflammation than those of H. pylori-negative patients. Our results show that H. pylori infection affects p53 expression in GC. The average p53 expression was significantly higher in tumor than in normal tissues. In gastritis sections p53 expression was significantly associated with H. pylori.

  20. Management of Helicobacter Pylori Infection

    African Journals Online (AJOL)

    Dr Olaleye

    90%, the sequential therapy seems to have a potential of becoming the standard first-line treatment for H pylori infection in the interim, while search is being made for the ideal antimicrobial monotherapy. . Keywords: Helicobacter pylori, Dyspepsia, Gastric cancer, Gastric Ulcer, Duodenal ulcer. INTRODUCTION. 1. Since the ...

  1. Endoscopic transmission of Helicobacter pylori

    NARCIS (Netherlands)

    Tytgat, G. N.

    1995-01-01

    The contamination of endoscopes and biopsy forceps with Helicobacter pylori occurs readily after endoscopic examination of H. pylori-positive patients. Unequivocal proof of iatrogenic transmission of the organism has been provided. Estimates for transmission frequency approximate to 4 per 1000

  2. Helicobacter pylori infection and iron deficiency in teenage females in New Zealand.

    Science.gov (United States)

    Fraser, Alan G; Scragg, Robert; Schaaf, David; Metcalf, Patricia; Grant, Cameron C

    2010-04-30

    Iron deficiency is an important problem in New Zealand children and young adults. Iron deficiency and Helicobacter pylori (H. pylori) infection are each more common in Māori and Pacific Island ethnic groups. This study seeks to determine if H. pylori infection is associated with iron deficiency. 792 female students from 7 Auckland high schools (median age 16 years) had H. pylori serology and tests for iron deficiency assessed by a combination of serum ferritin, iron saturation and mean cell volume. The prevalence of positive H. pylori serology was highest for Pacific Island students (49.0%; CI 38.0-60.0), intermediate for Māori (26.7%; CI 16.9-36.4) and Asian (24.7%; CI 12.6-36.7) and lowest for European (13.7%; 6.0-21.4) piron saturation (p=0.013), but not of ferritin (p=0.068), haemoglobin (p=0.08) or mean cell volume (p=0.16), compared to those with negative serology. Positive H. pylori serology was associated with increased risk of iron deficiency (RR 1.20; CI 1.08-1.34), but not anaemia (RR 1.01; CI 0.87-1.18), after adjusting for age, ethnicity and school SES decile. This study indicates that H. pylori infection is associated with iron deficiency in adolescent females. There are significant differences in H. pylori serology amongst different ethnic groups in New Zealand.

  3. Identification of Viable Helicobacter pylori in Drinking Water Supplies by Cultural and Molecular Techniques.

    Science.gov (United States)

    Santiago, Paula; Moreno, Yolanda; Ferrús, M Antonía

    2015-08-01

    Helicobacter pylori is one of the most common causes of chronic bacterial infection in humans, directly related to peptic ulcer and gastric cancer. It has been suggested that H. pylori can be acquired through different transmission routes, including water. In this study, culture and qPCR were used to detect and identify the presence of H. pylori in drinking water. Furthermore, the combined techniques PMA-qPCR and DVC-FISH were applied for detection of viable cells of H. pylori. Among 24 drinking water samples, 16 samples were positive for the presence of H. pylori, but viable cells were only detected in six samples. Characteristic colonies, covered by a mass of bacterial unspecific growth, were observed on selective agar plates from an only sample, after enrichment. The mixed culture was submitted to DVC-FISH and qPCR analysis, followed by sequencing of the amplicons. Molecular techniques confirmed the growth of H. pylori on the agar plate. Our results demonstrate for the first time that H. pylori can survive and be potentially infective in drinking water, showing that water distribution systems could be a potential route for H. pylori transmission. © 2015 John Wiley & Sons Ltd.

  4. Development of gastric cancer associated with Helicobacter pylori infection.

    Science.gov (United States)

    Sugiyama, Toshiro

    2004-09-01

    Helicobacter pylori infection is associated with histological gastritis, gastric atrophy, gastric cancer and mucosa-associated lymphoid tissue lymphoma in the stomach. However, gastric cancer only develops in a minority of infected individuals. Such clinical diversity is caused by variations in the interactions between H. pylori pathogenicity, host susceptibility, and environmental factors. Based on evidence from three prospective epidemiological studies, the International Agency for Research on Cancer and the World Health Organization (IARC/WHO) concluded in 1994 that H. pylori has a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. Two large-scale, prospective, epidemiological studies have recently been reported in Japan and have confirmed that H. pylori infection constitutes a high risk factor for the development of gastric cancer, at least in males. In order to obtain evidence that eradication of H. pylori leads to a reduction in the occurrence of gastric cancer, reversibility of precancerous lesions, gastric atrophy or intestinal metaplasia should be proven after eradication treatment. A biopsy specimen from the lesser curvature of the corpus is the most sensitive for evaluating the regression of gastric atrophy on histology, and the evaluation needs be conducted at least 13 months after treatment. In a Mongolian gerbil model with or without low-dose chemical carcinogens, it has been demonstrated that H. pylori can lead to the development of gastric cancer. Experimental studies have elucidated that virulence factors of H. pylori interact with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster; it encodes the type IV secretion machinery system forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird phenotype, a growth factor-like effect. The other gene products are

  5. Seroprevalence of Helicobacter pylori in Seventh-Day Adventists and other groups in Maryland. Lack of association with diet.

    Science.gov (United States)

    Hopkins, R J; Russell, R G; O'Donnoghue, J M; Wasserman, S S; Lefkowitz, A; Morris, J G

    1990-11-01

    To evaluate the possible role of diet in the transmission of Helicobacter pylori, we compared H pylori seroprevalence among Seventh-Day Adventists (who are vegetarian and abstain from alcohol, caffeine, and meat; n = 94) and two non-Seventh-Day Adventist control groups (n = 168). With the use of an enzyme-linked immunosorbent assay H pylori antigen prepared in a French pressure cell, we found no difference in seroprevalence among these groups; however, seropositivity strongly correlated with age and black race.

  6. Reduced infectivity of waterborne viable but nonculturable Helicobacter pylori strain SS1 in mice.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Fontaine, Clinton; Brewster, Rebecca; Wu, Jianfeng; Eisenberg, Joseph N S; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2017-08-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of viable but nonculturable (VBNC) H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne VBNCH. pylori could cause gastric infection. We performed five mouse experiments to assess the infectivity of VBNCH. pylori in various exposure scenarios. VBNC viability was examined using Live/Dead staining and Biolog phenotype metabolism arrays. High doses of VBNCH. pylori in water were chosen to test the "worst-case" scenario for different periods of time. One experiment also investigated the infectious capabilities of VBNC SS1 using gavage. Further, immunocompromised mice were exposed to examine infectivity among potentially vulnerable groups. After exposure, mice were euthanized and their stomachs were examined for H. pylori infection using culture and PCR methodology. VBNC cells were membrane intact and retained metabolic activity. Mice exposed to VBNCH. pylori via drinking water and gavage were not infected, despite the various exposure scenarios (immunocompromised, high doses) that might have permitted infection with VBNCH. pylori. The positive controls exposed to viable, culturable H. pylori did become infected. While other studies that have used viable, culturable SS1 via gavage or drinking water exposures to successfully infect mice, in our study, waterborne VBNC SS1 failed to colonize mice under all test conditions. Future studies could examine different H. pylori strains in similar exposure scenarios to compare the relative infectivity of the VBNC vs the viable, culturable state, which would help inform future risk assessments of H. pylori in water. © 2017 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  7. Pleiotropic Actions of Helicobacter pylori Vacuolating Cytotoxin, VacA

    OpenAIRE

    Isomoto, Hajime; Moss, Joel; Hirayama, Toshiya

    2010-01-01

    Helicobacter pylori produces a vacuolating cytotoxin, VacA, and most virulent H. pylori strains secrete VacA. VacA binds to two types of receptor-like protein tyrosine phosphatase (RPTP), RPTPα and RPTPβ, on the surface of host cells. VacA bound to RPTPβ, relocates and concentrates in lipid rafts in the plasma membrane. VacA causes vacuolization, membrane anion-selective channel and pore formation, and disruption of endosomal and lysosomal activity in host cells. Secreted VacA is processed in...

  8. Helicobacter pylori in gastroduodenal perforation

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    Bharat B Dogra

    2014-01-01

    Full Text Available Background:peptic ulcers were earlier believed to be caused by dietary factors, gastric acid, and stress. However, in 1983, Warren and Marshall identified the correlation between Helicobacter pylori (H. pylori and peptic ulcers. It is now well established that most of the peptic ulcers occur as a result of H. pylori infection. But the co-relation between perforated peptic ulcer and H. pylori infection is not yet fully established. Aims and objectives : to study the prevalence of H. pylori infection in patients with perforated peptic ulcer. Materials and methods: this was a prospective study carried out in all cases of perforated peptic ulcer reporting in surgical wards of a medical college during 2008-2010. A total of 50 cases, presenting as acute perforation of duodenum and stomach during this period, formed the study group. After resuscitation, all the cases were subjected to emergency exploratory laparotomy. The exact site of perforation was identified, biopsy was taken from the ulcer margin from 2-3 sites and the tissue was sent for H. pylori culture and histopathological examination. Simple closure of perforation, omentoplasty, thorough peritoneal lavage and drainage was carried out. Results: out of the 50 cases of perforated peptic ulcer, 38 happened to be males, and only 12 were females. The age of the patients ranged from 20 to 70 years. All the patients underwent only emergency laparotomy. As many as 46 cases (92% turned out to be positive for H. pylori and only four cases (8% were negative for this infection. Postoperatively, patients who were found to be positive for H. pylori were put on anti-H. pylori treatment. Conclusion: there was a high prevalence of H. pylori infection in patients with perforated gastroduodenal ulcers.

  9. Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis.

    Science.gov (United States)

    Yu, Hong-Jing; Liu, Wei; Chang, Zhen; Shen, Hui; He, Li-Juan; Wang, Sha-Sha; Liu, Lu; Jiang, Yuan-Ying; Xu, Guo-Tong; An, Mao-Mao; Zhang, Jun-Dong

    2015-06-07

    To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1β, IL-10, IL-6, G-CSF and MIP-2 (P gastritis by inhibiting the inflammatory response in gastric epithelial cells.

  10. Phenotypic and genotypic characterization of Helicobacter pylori from patients with and without peptic ulcer disease

    DEFF Research Database (Denmark)

    Petersen, A M; Fussing, V; Colding, H

    2000-01-01

    ) profile of H. pylori strains were recorded; randomly amplified polymorphic DNA (RAPD) and urease gene typing were performed and correlated with diagnostic groups. RESULTS: Electron micrographs showed that H. pylori strains from patients with gastric ulcers adhered more frequently through filamentous...... ulcers were more prone to autoagglutinate than were strains from the other diagnostic groups (P = 0.03). H. pylori strains from gastric ulcer patients were found to be more homogeneous, as determined by RAPD and urease gene typing, than strains from the other diagnostic groups (P ..., a positive correlation was found between a patient's age and the adhesion to AGS cells of the patient's H. pylori strain (P = 0.006). CONCLUSION: A combination of an H. pylori autoagglutination test, RAPD, and urease gene typing may be useful in separating gastric ulcer-related strains from duodenal ulcer...

  11. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

    Science.gov (United States)

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro. PMID:27158376

  12. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

    Directory of Open Access Journals (Sweden)

    Philip A. Robinson

    2013-10-01

    Full Text Available Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.

  13. Fragmentation of CagA Reduces Hummingbird Phenotype Induction by Helicobactor pylori.

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    Chih-Chi Chang

    Full Text Available Infection with Helicobacter pylori (H. pylori has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.

  14. Low prevalence of H. pylori Infection in HIV-Positive Patients in the Northeast of Brazil

    Directory of Open Access Journals (Sweden)

    Silva Cícero IS

    2011-02-01

    Full Text Available Abstract Background This study conducted in Northeastern Brazil, evaluated the prevalence of H. pylori infection and the presence of gastritis in HIV-infected patients. Methods There were included 113 HIV-positive and 141 age-matched HIV-negative patients, who underwent upper gastrointestinal endoscopy for dyspeptic symptoms. H. pylori status was evaluated by urease test and histology. Results The prevalence of H. pylori infection was significantly lower (p H. pylori status and gender, age, HIV viral load, antiretroviral therapy and the use of antibiotics. A lower prevalence of H. pylori was observed among patients with T CD4 cell count below 200/mm3; however, it was not significant. Chronic active antral gastritis was observed in 87.6% of the HIV-infected patients and in 780.4% of the control group (p = 0.11. H. pylori infection was significantly associated with chronic active gastritis in the antrum in both groups, but it was not associated with corpus chronic active gastritis in the HIV-infected patients. Conclusion We demonstrated that the prevalence of H. pylori was significantly lower in HIV-positive patients compared with HIV-negative ones. However, corpus gastritis was frequently observed in the HIV-positive patients, pointing to different mechanisms than H. pylori infection in the genesis of the lesion.

  15. Pristup uzurpacijama zemljišta na teritoriji općine Maglaj : Approach of land usurpation of municipality of Maglaj theritory

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    Faris Habibović

    2012-12-01

    Full Text Available Rad na temu „Pristup uzurpacijama zemljišta na teritoriji općine Maglaj“obrađuje postupak raspravljanja uzurpacija na teritoriji općine Maglaj uz korištenje odgovarajućih softverskih aplikacija. U okviru rada je opisan postupak povlačenja granične linije između šuma i šumskog zemljišta sa jedne strane i poljoprivrednog zemljišta sa druge strane, a potom su date karakteristike uzurpiranog zemljišta-parcela. Granična linija je na planovima povučena u AutoCAD programskom paketu, a baza podataka kao i pregledna skica za sve šumske komplekse izrađena koristeći softversku aplikaciju ArcGIS. U radu su obrađene tri katastarske općine (k.o. Ošve, k.o. Moševac i k.o. Ravna. : This paper deals with the process of discussing land usurpation in the territory of Maglaj municipality using appropriate software applications. Drawing procedure of the boundary line between the forest (forest land and farmland is described. Later are given characteristics of usurped land - lots. Boundary line is drawn on the plans in AutoCAD software, and the database and review drafts of all forest complexes have been made using ArcGIS software application. In this paper three cadastral municipalities are processed (cadastral municipality Ošve, cadastral municipality Moševac and cadastral municipality Ravna.

  16. Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis.

    Science.gov (United States)

    Matak, Pavle; Heinis, Mylène; Mathieu, Jacques R R; Corriden, Ross; Cuvellier, Sylvain; Delga, Stéphanie; Mounier, Rémi; Rouquette, Alexandre; Raymond, Josette; Lamarque, Dominique; Emile, Jean-François; Nizet, Victor; Touati, Eliette; Peyssonnaux, Carole

    2015-04-01

    Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer. The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but, surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H. pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes in driving this pathology. Copyright © 2015 by The American Association of Immunologists, Inc.

  17. Helicobacter pylori infection in children.

    Science.gov (United States)

    Kalach, Nicolas; Bontems, Patrick; Raymond, Josette

    2017-09-01

    Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies. The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial. The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests. The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy. Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children. © 2017 John Wiley & Sons Ltd.

  18. Virus-cell fusion inhibitory activity of novel analogue peptides based on the HP (2-20) derived from N-terminus of Helicobacter pylori Ribosomal Protein L1.

    Science.gov (United States)

    Woo, Eun-Rhan; Lee, Dong Gun; Chang, Young-Su; Park, Yoonkyung; Hahm, Kyung-Soo

    2002-12-01

    HP (2-20) (AKKVFKRLEKLFSKIQNDK) is the antibacterial sequence derived from N-terminus of Helicobacter pylori Ribosomal Protein L1 (RPL1). It has a broad-spectrum microbicidal activity in vitro that is thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that HP (2-20) might be possessed virus-cell fusion inhibitory activity. To develop the novel virus-cell fusion inhibitory peptides, several analogues with amino acid substitution were designed to increase or decrease only net hydrophobic region. In particular, substitution of Gln and Asp for hydrophobic amino acid, Trp at position 17 and 19 of HP (2-20) (Anal 3) caused a dramatic increase in virus-cell fusion inhibitory activity without hemolytic effect.

  19. Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Naoki Mori; Chie Ishikawa; Masachika Senba

    2011-01-01

    AIM: To investigate and elucidate the molecular mech-anism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori ) infection.METHODS: The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononu-clear cells (PBMCs), and CD4+T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori -induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island ( cagPAI) and virD4 were used to elucidate the role of cagPAI-encoding type Ⅳ secretion system and CagA in CD69 expression.RESULTS: CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of pa-tients with H. pylori -positive gastritis. Although cagPAI-positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cag-PAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4+T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori -induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori -induced CD69 mRNA expression.CONCLUSION: The results suggest that H. pylori in-duces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori -induced gastritis.

  20. Virulence Factors of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Paul Sinclair

    1991-01-01

    environment with respect to pH. The spiral shape of the cells and their flagellar motility allow them to wind themselves into the mucous layer of the stomach. Some evidence exists for the production of strong proteolytic activity, hence degrading the mucous barrier and increasing permeability for the organism. Cyroroxin excreted by the bacteria may have some effect on the surrounding cells, with the possible lysis and release of bacterial growth factors. There is evidence that a chemotactic response is present due to these growth factors and their higher concentration in the intracellular spaces. The presence of specific and nonspecific adhesion has also been demonstrated, thus allowing the bacterium, once at the epithelial cell surface, to attach and avoid being washed off by movement within the stomach. Although treatment with antimicrobials eradicates the organism and improves symptoms of peptic ulcer patients, there is no indication that the same occurs in nonulcer dyspepsia patients. Further work is essential to describe the virulence mechanisms of H pylori and the possible pathogenic role of the organism.

  1. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Dominguez-Bello, Maria Gloria; Kronsteiner, Barbara; Carbo, Adria; Lu, Pinyi; Viladomiu, Monica; Pedragosa, Mireia; Zhang, Xiaoying; Sobral, Bruno W; Mane, Shrinivasrao P; Mohapatra, Saroj K; Horne, William T; Guri, Amir J; Groeschl, Michael; Lopez-Velasco, Gabriela; Hontecillas, Raquel

    2012-01-01

    There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI) interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(-) strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM) and increased adipose tissue regulatory T cells (Treg) cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4) in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.

  2. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Josep Bassaganya-Riera

    Full Text Available BACKGROUND: There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(- strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM and increased adipose tissue regulatory T cells (Treg cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4 in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. CONCLUSIONS/SIGNIFICANCE: Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.

  3. Does Helicobacter pylori exhibit corkscrew motion while swimming?

    Science.gov (United States)

    Constantino, Maira; Hardcastle, Joseph; Bansil, Rama

    2015-03-01

    Helicobacter pylori is a spiral shaped bacterium associated with ulcers, gastric cancer, gastritis among other diseases. In order to colonize the harsh acidic environment of the stomach H. pylori has to go across the viscoelastic mucus layer of the stomach. Many studies have been conducted on the swimming of H. pylori in viscous media however none have taken into account the influence of cell-body shape on the trajectory. We present an experimental study of the effects of body shape in the swimming trajectory of H. pylori in viscous media by a quantitative analysis of the bacterium rotation and translation in gels using phase contrast microscopy and particle tracking techniques. Preliminary microscopic tracking measurements show very well defined helical trajectories in the spiral-shaped wild type H. pylori. These helical trajectories are not seen in rod-shaped mutants which sometimes display whirling motion about one end acting as a hinge. We will present an analysis of the different trajectories for bacteria swimming in media with different viscoelastic parameters. Supported by the National Science Foundation PHY PoLS.

  4. A novel system of cytoskeletal elements in the human pathogen Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Barbara Waidner

    2009-11-01

    Full Text Available Pathogenicity of the human pathogen Helicobacter pylori relies upon its capacity to adapt to a hostile environment and to escape from the host response. Therefore, cell shape, motility, and pH homeostasis of these bacteria are specifically adapted to the gastric mucus. We have found that the helical shape of H. pylori depends on coiled coil rich proteins (Ccrp, which form extended filamentous structures in vitro and in vivo, and are differentially required for the maintenance of cell morphology. We have developed an in vivo localization system for this pathogen. Consistent with a cytoskeleton-like structure, Ccrp proteins localized in a regular punctuate and static pattern within H. pylori cells. Ccrp genes show a high degree of sequence variation, which could be the reason for the morphological diversity between H. pylori strains. In contrast to other bacteria, the actin-like MreB protein is dispensable for viability in H. pylori, and does not affect cell shape, but cell length and chromosome segregation. In addition, mreB mutant cells displayed significantly reduced urease activity, and thus compromise a major pathogenicity factor of H. pylori. Our findings reveal that Ccrp proteins, but not MreB, affect cell morphology, while both cytoskeletal components affect the development of pathogenicity factors and/or cell cycle progression.

  5. Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection

    DEFF Research Database (Denmark)

    Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

    2015-01-01

    studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major...... studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last...... year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection....

  6. Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression.

    Science.gov (United States)

    Wex, Thomas; Kuester, Doerthe; Schönberg, Cornelius; Schindele, Daniel; Treiber, Gerhard; Malfertheiner, Peter

    2011-05-26

    Mucosal levels of Secretory Leukocyte Protease Inhibitor (SLPI) are specifically reduced in relation to H. pylori-induced gastritis. Progranulin is an epithelial growth factor that is proteolytically degraded into fragments by elastase (the main target of SLPI). Considering the role of SLPI for regulating the activity of elastase, we studied whether the H. pylori-induced reduction of SLPI and the resulting increase of elastase-derived activity would reduce the Progranulin protein levels both ex vivo and in vitro. The expression of Progranulin was studied in biopsies of H. pylori-positive, -negative and -eradicated subjects as well as in the gastric tumor cell line AGS by ELISA, immunohistochemistry and real-time RT-PCR. H. pylori-infected subjects had about 2-fold increased antral Progranulin expression compared to H. pylori-negative and -eradicated subjects (P Progranulin and SLPI levels were identified. Immunohistochemical analysis confirmed the upregulation of Progranulin in relation to H. pylori infection; both epithelial and infiltrating immune cells contributed to the higher Progranulin expression levels. The H. pylori-induced upregulation of Progranulin was verified in AGS cells infected by H. pylori. The down-regulation of endogenous SLPI expression in AGS cells by siRNA methodology did not affect the Progranulin expression independent of the infection by H. pylori. Taken together, Progranulin was identified as novel molecule that is upregulated in context to H. pylori infection. In contrast to other diseases, SLPI seems not to have a regulatory role for Progranulin in H. pylori-mediated gastritis.

  7. Oxyntic gastric atrophy in Helicobacter pylori gastritis is distinct from autoimmune gastritis.

    Science.gov (United States)

    Venerito, Marino; Varbanova, Mariya; Röhl, Friedrich-Wilhelm; Reinhold, Dirk; Frauenschläger, Katrin; Jechorek, Doerthe; Weigt, Jochen; Link, Alexander; Malfertheiner, Peter

    2016-08-01

    To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection. Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology. Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively). H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Helicobacter pylori and Peptic Ulcers

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC's Dr. David Swerdlow discusses the relationship between Helicobacter pylori and peptic ulcer disease and trends in hospitalization rates for peptic ulcer disease in the United States between 1998 and 2005.

  9. Treatment of Helicobacter pylori infections: Mitigating factors and ...

    African Journals Online (AJOL)

    Helicobacter pylori is a Gram-negative, microaerophilic spiral or motile rod that infects about half the world's population with a very high prevalence in the developing world. It is an important aetiological factor in the development of gastritis, peptic ulcer disease, gastric atrophy and B cell mucosa associated lymphoid tissue ...

  10. Intercellular communication in Helicobacter pylori: luxS is essential for the production of an extracellular signaling molecule.

    Science.gov (United States)

    Forsyth, M H; Cover, T L

    2000-06-01

    Individual bacteria of numerous species can communicate and coordinate their actions via the production, release, and detection of extracellular signaling molecules. In this study, we used the Vibrio harveyi luminescence bioassay to determine whether Helicobacter pylori produces such a factor. Cell-free conditioned media from H. pylori strains 60190 and 26695 each induced >100-fold-greater luminescence in V. harveyi than did sterile culture medium. The H. pylori signaling molecule had a molecular mass of 100-fold-greater luminescence in the V. harveyi bioassay than did conditioned medium from either mutant strain. Production of the signaling molecule was restored in an H. pylori luxS null mutant strain by complementation with a single intact copy of luxS placed in a heterologous site on the chromosome. In addition, Escherichia coli DH5alpha produced autoinducer activity following the introduction of an intact copy of luxS from H. pylori. Production of the signaling molecule by H. pylori was growth phase dependent, with maximal production occurring in the mid-exponential phase of growth. Transcription of H. pylori vacA also was growth phase dependent, but this phenomenon was not dependent on luxS activity. These data indicate that H. pylori produces an extracellular signaling molecule related to AI-2 from V. harveyi. We speculate that this signaling molecule may play a role in regulating H. pylori gene expression.

  11. Elevated interleukin-32 expression is associated with Helicobacter pylori-related gastritis.

    Directory of Open Access Journals (Sweden)

    Liu-Sheng Peng

    Full Text Available BACKGROUND: Interleukin-32 (IL-32 is a recently discovered proinflammatory cytokine involved in inflammatory diseases. We investigated the expression of IL-32 and its regulation mechanism in the inflammatory response of patients with Helicobacter pylori (H. pylori infection. DESIGN AND METHODS: IL-32 mRNA and protein expression in gastric tissues was detected by quantitative real-time PCR and immunohistochemistry. The regulation of IL-32 in human gastric epithelia cell line AGS was investigated by different cytokine stimulation and different H. pylori strain infection. RESULTS: Gastric IL-32 mRNA and protein expression were elevated in patients with H. pylori infection and positively correlated with gastritis. In H. pylori-infected patients, the mRNA level of IL-32 was also correlated with that of proinflammatory cytokines IL-1β and TNF-α. In vitro IL-1β and TNF-α could upregulate IL-32 mRNA and protein level in AGS cells, which was dependent on NF-κB signal pathway. The regulation of IL-32 expression in response to H. pylori-infection could be weakened by using neutralizing antibodies to block IL-1β and TNF-α. Moreover, H. pylori-infected AGS cells also induced IL-32 mRNA and protein expression, which was dependent on CagA. CONCLUSIONS: IL-32 level is elevated in patients with H. pylori infection and its expression is regulated by proinflammatory stimuli, suggesting that IL-32 may play a role in the pathogenesis of H. pylori-related gastritis.

  12. Prevalence of Helicobacter Pylori Infection Among Patients ...

    African Journals Online (AJOL)

    Conclusion: The prevalence of H. pylori infection is significantly high in rural and suburban population of Ernakulam district, Kerala. Early detection and prompt treatment are essential for prevention of serious complications. Keywords: Gastrointestinal complications, Helicobacter pylori infection, Histopathological ...

  13. HELICOBACTER PYLORI: THE CAUSATIVE AGENT OF PEPTIC ...

    African Journals Online (AJOL)

    DR. AMINU

    Helicobacter pylori by treatment with antibiotics in peptic ulcer patients resulted in the healing of the ulcer. ... and gastric cancers. .... H. pyloris cause chronic active gastritis in humans and ... of the night when the stomach is empty and is.

  14. Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer

    International Nuclear Information System (INIS)

    Liu, Ningning; Zhou, Ning; Chai, Ni; Liu, Xuan; Jiang, Haili; Wu, Qiong; Li, Qi

    2016-01-01

    Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development. To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells. H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor–node–metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway. The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers

  15. Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population.

    Science.gov (United States)

    Nguyen, L T; Uchida, T; Tsukamoto, Y; Kuroda, A; Okimoto, T; Kodama, M; Murakami, K; Fujioka, T; Moriyama, M

    2010-08-01

    The dupA gene of Helicobacter pylori was suggested to be a risk factor for duodenal ulcer but protective against gastric cancer. The present study aimed to re-examine the role of dupA in H. pylori-infected Japanese patients. We found that dupA status was not associated with any gastroduodenal disease, histological score of chronic gastritis or with the extent of interleukin-8 production from gastric cell lines. These results indicate that dupA is unlikely to be a virulence factor of H. pylori in the Japanese population.

  16. What Do We Do about Helicobacter pylori?

    Directory of Open Access Journals (Sweden)

    CJ Hawkey

    1999-01-01

    Full Text Available Heliobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs cause ulcers by different mechanisms. Under some circumstances, patients infected with H pylori may be less prone to NSAID-associated ulcers than those who are H pylori-negative. Eradication trials have yielded differing results. However, those who have studied patients who have a past history of ulcer disease and are already established on NSAIDs have shown no benefit from H pylori eradication.

  17. A Novel Assay for Easy and Rapid Quantification of Helicobacter pylori Adhesion.

    Science.gov (United States)

    Skindersoe, Mette E; Rasmussen, Lone; Andersen, Leif P; Krogfelt, Karen A

    2015-06-01

    Reducing adhesion of Helicobacter pylori to gastric epithelial cells could be a new way to counteract infections with this organism. We here present a novel method for quantification of Helicobacter pylori adhesion to cells. Helicobacter pylori is allowed to adhere to AGS or MKN45g cells in a 96-well microtiter plate. Then wells are added saponin, which lyses the cells without affecting the bacteria. After addition of alamarBlue(®) (resazurin) and 1- to 2-hour incubation, fluorescence measurements can be used to quantify the number of adherent bacteria. By use of the method, we demonstrate that adhesion of both a sabA and babA deletion mutant of H. pylori is significantly reduced compared to the wild type. The method offers a number of applications and may be used to compare the adherence potential of different strains of H. pylori to either cells or different materials or to screen for potential anti-adhesive compounds. The results presented here suggest that this easy and reproducible assay is well suited for quantitative investigation of H. pylori adhesion. © 2015 John Wiley & Sons Ltd.

  18. ( Asteraceae ) methanol extracts against Helicobacter pylori

    African Journals Online (AJOL)

    Methanol vehicle did not affect H. pylori growth. Conclusion: The observed antibacterial effect of G. glutinosum extracts may be of benefit as an adjuvant treatment of diseases caused by H. pylori. Key words: Gymnosperma glutinosum, Helicobacter pylori, methanol extract, minimal inhibitory concentration (MIC).

  19. Helicobacter Pylori : Serological Testing and Treatment in ...

    African Journals Online (AJOL)

    Purpose: Helicobacter pylori has been strongly associated with dyspepsia and eradication of H. pylori after a non-invasive testing is an integral part of most management guidelines. This study evaluated the benefit of serological testing and treatment of H. pylori in Nigerian patients presenting with uninvestigated dyspepsia.

  20. [Helicobacter pylori -- 2010].

    Science.gov (United States)

    Buzás, György Miklós

    2010-12-05

    Helicobacter pylori, discovered 27 years ago, has remained the most prevalent infectious agent in the world. In the author's hypothesis, the increase of peptic ulcer prevalence in the 19-20th century could be attributable to the extended worldwide use of gastric tubes for secretory testing which led to the iatrogenic transmission of pathogenic strains. Helicobacter pylori outer membrane proteins (OMP), and duodenal ulcer promoting (dupA) proteins were identified as novel virulence factors, leading to the production of pro-inflammatory cytokines, which could be future targets of therapy. There is no ideal first-line eradication of the infection and according to expert's opinion, the efficiency of these regimens has fallen gradually in recent years to unacceptably low levels; however, in the author's opinion this is a multifactorial phenomenon which can not be generalized. As alternative drugs, the efficiency of levofloxacin, furazolidone and rifabutin has been proven by meta-analyses. Sequential and bismuth-free quadruple therapies, although highly efficient, are not yet used on a large scale. The recurrence of the infection is 2.27%/year in developed and of 13.0%/year in developing countries. Spontaneous eradication occurred in 8-20% of the children and 5-11% of adults. The prevalence of clarithromycin resistance is increasing worldwide. In Hungary, it has reached 10.9% in county cities, according to a national survey. In a district of Budapest called Ferencváros, the prevalence between 2005 and 2009 was 16-22%, with no increasing trend. The development of enzymatic inhibitors (urease, carbonic anhydrase and gamma-glutamyl transpeptidase), modified antibiotics and efflux pump inhibitors seem promising ways because these compounds do not lead to resistance; however, none have yet been used in humans.

  1. EGFR and Bcl-2 in gastric mucosa of children infected with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Ewa Ryszczuk

    2016-03-01

    Full Text Available Aim: The aim of the study was to evaluate the expression of EGFR and Bcl-2 proteins as inhibitory markers of apoptosis in surface epithelial cells and gland cells of antral gastric mucosa in children infected with Helicobacter pylori according to the severity and activity of antral gastritis and to assess the correlation between the number of cells expressing EGFR and the number of cells expressing Bcl-2 in H. pylori infected children.Materials and methods: The study included 44 children: 68.2% with chronic gastritis and positive IgG against H. pylori, and 31.8% with functional disorders of the gastrointestinal tract and with normal IgG against H. pylori. The evaluation of EGFR expression in gastric mucosa was performed immunohistochemically using monoclonal mouse anti-EGFR antibody. The polyclonal antibody was used to determine the expression of anti-Bcl-2.Results: A significant increase in the number of cells expressing EGFR and Bcl-2 protein was found in the epithelial cells in severe as well as mild and moderate gastritis in the group of children infected with H. pylori. An increase in the number of cells expressing EGFR and Bcl-2 protein was also found in the epithelial cells in group I according to the activity of gastritis. There was a statistically significant positive correlation between the numbers of cells expressing EGFR and Bcl-2 in H. pylori infected children.Conclusion: Increased expression of EGFR and Bcl-2 proteins in the epithelial cells and a statistically significant positive correlation between the numbers of cells expressing EGFR and Bcl-2 in H. pylori infected children could suggest increased regeneration abilities of gastric mucosa.

  2. Agreement Between Serology and Histology for Detection of Helicobacter pylori Infection

    International Nuclear Information System (INIS)

    Iqbal, S.; Fatima, S.; Raheem, A.; Khan, A. H.

    2013-01-01

    Objective: To determine the percentage agreement between serology and histology for detection of Helicobacter (H.) pylori infection. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Pathology and Microbiology, The Aga Khan University and Hospital, Karachi, from January to December 2009. Methodology: Fifty subjects were selected by non-probability purposive sampling from laboratory data who had serological testing of H. pylori IgG antibody, prior to histological evaluation of endoscopic gastric or/and duodenal biopsies. Serological Quantification of H. pylori IgG was carried out with HpG screen ELISA kit (Genesis Diagnostics, UK), using an enzyme linked immunosorbent assay for detection of IgG antibodies against H. pylori. Manufacturer's recommended cutoff value was used and results were considered positive when greater than 7 U/ml. For histological diagnosis, an expert histopathologist characterized the presence of spiral bacteria in the mucosal layer or the surface of epithelial cells on microscopic examination, as a positive test. Results: An agreement of 0.72 was found by Kappa statistics between serology and histopathology results and a good diagnostic accuracy (86%) of serological testing was observed for the diagnosis of H. pylori infection. Conclusion: A substantial agreement was found between serology and histopathology results to detect the H. pylori infection. Laboratory-based serologic testing using ELISA technology to detect IgG antibodies is inexpensive, noninvasive and convenient method to detect the H. pylori infection in primary care setting. (author)

  3. Nutrition and Helicobacter pylori: Host Diet and Nutritional Immunity Influence Bacterial Virulence and Disease Outcome

    Directory of Open Access Journals (Sweden)

    Kathryn P. Haley

    2016-01-01

    Full Text Available Helicobacter pylori colonizes the stomachs of greater than 50% of the world’s human population making it arguably one of the most successful bacterial pathogens. Chronic H. pylori colonization results in gastritis in nearly all patients; however in a subset of people, persistent infection with H. pylori is associated with an increased risk for more severe disease outcomes including B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma and invasive adenocarcinoma. Research aimed at elucidating determinants that mediate disease progression has revealed genetic differences in both humans and H. pylori which increase the risk for developing gastric cancer. Furthermore, host diet and nutrition status have been shown to influence H. pylori-associated disease outcomes. In this review we will discuss how H. pylori is able to create a replicative niche within the hostile host environment by subverting and modifying the host-generated immune response as well as successfully competing for limited nutrients such as transition metals by deploying an arsenal of metal acquisition proteins and virulence factors. Lastly, we will discuss how micronutrient availability or alterations in the gastric microbiome may exacerbate negative disease outcomes associated with H. pylori colonization.

  4. Loop-Mediated Isothermal Amplification as a Fast Noninvasive Method of Helicobacter pylori Diagnosis.

    Science.gov (United States)

    Yari, Farideh; Abiri, Ramin; Aryan, Ehsan; Ahmadi Jouybari, Touraj; Navabi, Jafar; Alvandi, Amirhooshang

    2016-09-01

    Helicobacter pylori infection is etiologically associated with some important health problems such as gastric cancer. Because of the high clinical importance of H. pylori infection, development of a noninvasive test for the detection of H. pylori is desirable. In this study, a loop-mediated isothermal amplification (LAMP) targeted ureC of H. pylori was evaluated on 100 stool specimens and compared with a stool antigen test. Culture and rapid urease test were considered as gold standards. The overall detection rate of the fecal antigen test and LAMP was 58% and 82%, respectively. The analytical sensitivity of the fecal antigen test and LAMP was 500 and 10 H. pylori cells/g and 10 fg DNA/reaction, which is equal to six H. pylori genome. LAMP technique has been characterized by high sensitivity and low detection limit for the detection of H. pylori in stool specimen. Clinical diagnostic performance of LAMP was better than the stool antigen test. © 2015 Wiley Periodicals, Inc.

  5. Detection of viable Helicobacter pylori inside free-living amoebae in wastewater and drinking water samples from Eastern Spain.

    Science.gov (United States)

    Moreno-Mesonero, Laura; Moreno, Yolanda; Alonso, José Luis; Ferrús, M Antonia

    2017-10-01

    Helicobacter pylori is one of the most concerning emerging waterborne pathogens. It has been suggested that it could survive in water inside free-living amoebae (FLA), but nobody has studied this relationship in the environment yet. Thus, we aimed to detect viable H. pylori cells from inside FLA in water samples. Sixty-nine wastewater and 31 drinking water samples were collected. FLA were purified and identified by PCR and sequencing. For exclusively detecting H. pylori inside FLA, samples were exposed to sodium hypochlorite and assayed by specific PMA-qPCR, DVC-FISH and culture. FLA were detected in 38.7% of drinking water and 79.7% of wastewater samples, even after disinfection. In wastewater, Acanthamoeba spp. and members of the family Vahlkampfiidae were identified. In drinking water, Acanthamoeba spp. and Echinamoeba and/or Vermamoeba were present. In 39 (58.2%) FLA-positive samples, H. pylori was detected by PMA-qPCR. After DVC-FISH, 21 (31.3%) samples harboured viable H. pylori internalized cells. H. pylori was cultured from 10 wastewater samples. To our knowledge, this is the first report that demonstrates that H. pylori can survive inside FLA in drinking water and wastewater, strongly supporting the hypothesis that FLA could play an important role in the transmission of H. pylori to humans. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

    Directory of Open Access Journals (Sweden)

    Yang Yao-Jong

    2012-03-01

    Full Text Available Abstract Background H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways. Results Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100 of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting. Conclusions H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

  7. Evaluation of the anti-adhesive effect of milk fat globule membrane glycoproteins on Helicobacter pylori in the human NCI-N87 cell line and C57BL/6 mouse model.

    Science.gov (United States)

    Horemans, Tessa; Kerstens, Monique; Clais, Sofie; Struijs, Karin; van den Abbeele, Pieter; Van Assche, Tim; Maes, Louis; Cos, Paul

    2012-08-01

     The interest in non-antibiotic therapies for Helicobacter pylori infections in man has considerably grown because increasing numbers of antibiotic-resistant strains are being reported. Intervention at the stage of bacterial attachment to the gastric mucosa could be an approach to improve the control/eradication rate of this infection.  Fractions of purified milk fat globule membrane glycoproteins were tested in vitro for their cytotoxic and direct antibacterial effect. The anti-adhesive effect on H. pylori was determined first in a cell model using the mucus-producing gastric epithelial cell line NCI-N87 and next in the C57BL/6 mouse model after dosing at 400 mg/kg protein once or twice daily from day -2 to day 4 post-infection. Bacterial loads were determined by using quantitative real-time PCR and the standard plate count method.  The milk fat globule membrane fractions did not show in vitro cytotoxicity, and a marginal antibacterial effect was demonstrated for defatted milk fat globule membrane at 256 μg/mL. In the anti-adhesion assay, the results varied from 56.0 ± 5.3% inhibition for 0.3% crude milk fat globule membrane to 79.3 ± 3.5% for defatted milk fat globule membrane. Quite surprisingly, in vivo administration of the same milk fat globule membrane fractions did not confirm the anti-adhesive effects and even caused an increase in bacterial load in the stomach.  The promising anti-adhesion in vitro results could not be confirmed in the mouse model, even after the highest attainable exposure. It is concluded that raw or defatted milk fat globule membrane fractions do not have any prophylactic or therapeutic potential against Helicobacter infection. © 2012 Blackwell Publishing Ltd.

  8. Rolle verschiedener sekretierter oder translokalisierter Effektormoleküle des gastrischen Pahogens Helicobacter pylori

    OpenAIRE

    Lind, Judith

    2015-01-01

    H. pylori is estimated to colonize the human stomach in almost 50% of the world population and has established itself as survival specialist by avoiding host cell recognition and elimination. Pathologic effects due to its persistence are depending on a multitude of host-pathogen interactions and infection may develop from simple symptoms to chronic gastritis, peptic ulcer or even cancer formation. More virulent strains of H. pylori encode a type IV secretion system (T4SS) able to translocate ...

  9. Vacuolating Cytotoxin of Helicobacter pylori Plays a Role during Colonization in a Mouse Model of Infection

    OpenAIRE

    Salama, Nina R.; Otto, Glen; Tompkins, Lucy; Falkow, Stanley

    2001-01-01

    Helicobacter pylori, the causative agent of gastritis and ulcer disease in humans, secretes a toxin called VacA (vacuolating cytotoxin) into culture supernatants. VacA was initially characterized and purified on the basis of its ability to induce the formation of intracellular vacuoles in tissue culture cells. H. pylori strains possessing different alleles of vacA differ in their ability to express active toxin. Those strains expressing higher toxin levels are correlated with more severe gast...

  10. Duodenal ulcer promoting gene of Helicobacter pylori.

    Science.gov (United States)

    Lu, Hong; Hsu, Ping-I; Graham, David Y; Yamaoka, Yoshio

    2005-04-01

    Identification of a disease-specific H pylori virulence factors predictive of the outcome of infection remains unachieved. We used the polymerase chain reaction and Southern blot to compare the presence of 14 vir homologue genes with clinical presentation of H pylori infection, mucosal histology, and mucosal interleukin (IL)-8 levels. We examined 500 H pylori strains from East Asia and South America, including 120 with gastritis, 140 with duodenal ulcer (DU), 110 with gastric ulcer (GU), and 130 with gastric cancer. Only 1 gene that encompassed both jhp0917 and jhp0918 called dupA (duodenal ulcer promoting gene) was associated with a specific clinical outcome. dupA was present in 42% of DU vs. 21% of gastritis (adjusted odds ratio [OR] = 3.1, 95% confidence interval [CI]: 1.7-5.7). Its presence was also associated with more intense antral neutrophil infiltration and IL-8 levels and was a marker for protection against gastric atrophy, intestinal metaplasia, and gastric cancer (OR for gastric cancer = 0.42, 95% CI: 0.2-0.9 compared with gastritis). In vitro studies in gastric epithelial cells using dupA -deleted and -complemented mutants showed that the dupA plays roles in IL-8 production, in activation of transcription factors responsible for IL-8 promoter activity, and in increased survivability at low pH. dupA is a novel marker associated with an increased risk for DU and reduced risk for gastric atrophy and cancer. Its association with DU-promoting and -protective effects against atrophy/cancer was evident in both Asian and Western countries.

  11. When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children.

    Science.gov (United States)

    Kienesberger, Sabine; Perez-Perez, Guillermo I; Olivares, Asalia Z; Bardhan, Pradip; Sarker, Shafiqul A; Hasan, Kh Zahid; Sack, R Bradley; Blaser, Martin J

    2018-03-01

    Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.

  12. No evidence of a role for mitochondrial complex I in Helicobacter pylori pathogenesis.

    Science.gov (United States)

    Ng, Garrett Z; Ke, Bi-Xia; Laskowski, Adrienne; Thorburn, David R; Sutton, Philip

    2017-06-01

    Complex I is the first enzyme complex in the mitochondrial respiratory chain, responsible for generating a large fraction of energy during oxidative phosphorylation. Recently, it has been identified that complex I deficiency can result in increased inflammation due to the generation of reactive oxygen species by innate immune cells. As a reduction in complex I activity has been demonstrated in human stomachs with atrophic gastritis, we investigated whether complex I deficiency could influence Helicobacter pylori pathogenesis. Ndufs6 gt/gt mice have a partial complex I deficiency. Complex I activity was quantified in the stomachs and immune cells of Ndufs6 gt/gt mice by spectrophotometric assays. Ndufs6 gt/gt mice were infected with H. pylori and bacterial colonization assessed by colony-forming assay, gastritis assessed histologically, and H. pylori -specific humoral response quantified by ELISA. The immune cells and stomachs of Ndufs6 gt/gt mice were found to have significantly decreased complex I activity, validating the model for assessing the effects of complex I deficiency in H. pylori infection. However, there was no observable effect of complex I deficiency on either H. pylori colonization, the resulting gastritis, or the humoral response. Although complex I activity is described to suppress innate immune responses and is decreased during atrophic gastritis in humans, our data suggest it does not affect H. pylori pathogenesis. © 2017 John Wiley & Sons Ltd.

  13. Helicobacter heilmannii-associated Gastritis: Clinicopathologic Findings and Comparison with Helicobacter pylori-associated Gastritis

    Science.gov (United States)

    Kwak, Ji Eun; Chang, Sun Hee; Kim, Hanseong; Chi, Je G.; Kim, Kyung-Ah; Yang, Jeon Ho; Lee, June Sung; Moon, Young-Soo; Kim, Kyoung-Mee

    2007-01-01

    The aims of this study were to evaluate the clinicopathologic features of Helicobacter heilmannii-associated gastritis and to compare H. heilmannii-associated gastritis with H. pylori-associated gastritis. We reviewed 5,985 consecutive gastric biopsy specimens. All cases of chronic gastritis with Helicobacter infection were evaluated with the Updated Sydney System, and the grades of all gastritis variables were compared between H. heilmannii-associated gastritis and H. pylori-associated gastritis groups. There were 10 cases of H. heilmannii-associated gastritis (0.17%) and 3,285 cases of H. pylori-associated gastritis (54.9%). The organisms were superficially located within the mucous layer without adhesion to epithelial cells. Interestingly, in one case many intracytoplasmic H. heilmannii organisms were observed in parietal cells with cell damage. A case of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma concomitant with H. heilmannii infection was detected. Compared to H. pylori-associated gastritis, H. heilmannii-associated gastritis showed less severe neutrophilic activity (pgastritis devoid of erosion or ulcer (p=0.0309). In conclusion, we present the detailed clinicopathologic findings of H. heilmannii-associated gastritis compared to H. pylori-associated gastritis. H. heilmannii-associated gastritis is uncommon and milder than H. pylori-associated gastritis, however it may be noteworthy with respect to the development of MALT lymphoma. PMID:17297253

  14. Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

    Science.gov (United States)

    Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

    2017-01-01

    Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

  15. DRUG RESISTANCE IN HELICOBACTER PYLORI

    Directory of Open Access Journals (Sweden)

    Júlia Silveira VIANNA

    Full Text Available ABSTRACT Background Helicobacter pylori has a worldwide distribution and is associated with the pathogenesis of various diseases of the digestive system. Treatment to eradicate this microorganism involves the use of a combination of antimicrobials, such as amoxicillin, metronidazole, clarithromycin, and levofloxacin, combined with proton pump inhibitors. Although the current therapy is effective, a high rate of treatment failure has been observed, mainly because of the acquisition of point mutations, one of the major resistance mechanisms developed by H. pylori. This phenomenon is related to frequent and/or inappropriate use of antibiotics. Conclusion This review reported an overview of the resistance to the main drugs used in the treatment of H. pylori, confirming the hypothesis that antibacterial resistance is a highly local phenomenon and genetic characteristics of a given population can influence which therapy is the most appropriate.

  16. Outer membrane vesicles enhance the carcinogenic potential of Helicobacter pylori.

    Science.gov (United States)

    Chitcholtan, Kenny; Hampton, Mark B; Keenan, Jacqueline I

    2008-12-01

    Chronic Helicobacter pylori infection is associated with an increased risk of gastric carcinogenesis. These non-invasive bacteria colonize the gastric mucosa and constitutively shed small outer membrane vesicles (OMV). In this study, we investigated the direct effect of H.pylori OMV on cellular events associated with carcinogenesis. We observed increased micronuclei formation in AGS human gastric epithelial cells treated with OMV isolated from a toxigenic H.pylori strain (60190). This effect was absent in OMV from strain 60190v:1 that has a mutant vacA, indicating VacA-dependent micronuclei formation. VacA induces intracellular vacuolation, and reduced acridine orange staining indicated disruption in the integrity of these vacuoles. This was accompanied by an alteration in iron metabolism and glutathione (GSH) loss, suggesting a role for oxidative stress in genomic damage. Increasing intracellular GSH levels with a GSH ester abrogated the VacA-mediated increase in micronuclei formation. In conclusion, OMV-mediated delivery of VacA to the gastric epithelium may constitute a new mechanism for H.pylori-induced gastric carcinogenesis.

  17. FLOW MEDIATED DILATION AND CAROTID INTIMA MEDIA THICKNESS IN PATIENTS WITH CHRONIC GASTRITIS ASSOCIATED WITH HELICOBACTER PYLORI INFECTION.

    Science.gov (United States)

    Judaki, Arezo; Norozi, Siros; Ahmadi, Mohammad Reza Hafezi; Ghavam, Samira Mis; Asadollahi, Khairollah; Rahmani, Asghar

    2017-12-01

    Endothelial dysfunction is one of the early stages of vascular diseases. The aim of this study was to investigate the endothelial dysfunction markers in patients with chronic gastritis associated with Helicobacter pylori (H. pylori) infection. By a cross sectional study, basic and clinical information of 120 participants (40 patients with positive H. pylori infection, 40 patients with negative H. pylori infection and 40 healthy people) were analyzed. Carotid intima media thickness and flow-mediated dilation levels were measured in all patients and controls. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured with Elisa for all subjects. IgG level was assessed in chronic gastritis patients. The flow-mediated dilation level in patients with positive H. pylori infection (0.17%±0.09) was significantly lower than those with negative H. pylori infection (0.21% ±0.10, Pgastritis. The levels of flow-mediated dilation, carotid intima media thickness and sICAM-1 were higher among patients with positive H. pylori infection. Patients with chronic gastritis associated with H. pylori infection are at risk of endothelial dysfunction due to flow-mediated dilation and carotid intima media thickness abnormalities and increased level of sICAM-1 and sVCAM-1.

  18. Food constituents enhance urease activity in Healicobacter pylori.

    OpenAIRE

    Mizote, Tomoko; Inatsu, Sakiko; Ehara, Keiko

    2005-01-01

    Urease activity of Helicobacter pylori recovered from the stomach of H. pylori-infected Mongolian gerbils was affected by the diet used after infection. The effect of dietary components on urease activity was investigated by growth of H. pylori in…

  19. Prevalence of Helicobacter pylori among Nigerian patients with ...

    African Journals Online (AJOL)

    pylori positive. Conclusion: The prevalence of H. pylori among dyspeptics using biopsy based methods is high in the South-Western part of Nigeria. It is therefore important to test and treat H. pylori among Nigerians with dyspepsia.

  20. Epstein Barr virus and Helicobacter pylori co-infection are positively associated with severe gastritis in pediatric patients.

    Directory of Open Access Journals (Sweden)

    María G Cárdenas-Mondragón

    Full Text Available H. pylori infection is acquired during childhood and causes a chronic inflammatory response in the gastric mucosa, which is considered the main risk factor to acquire gastric cancer (GC later in life. More recently, infection by Epstein-Barr virus (EBV have also been associated with GC. The role of EBV in early inflammatory responses and its relationship with H. pylori infection remains poorly studied. Here, we assessed whether EBV infection in children correlated with the stage of gastritis and whether co-infection with H. pylori affected the severity of inflammation.333 pediatric patients with chronic abdominal pain were studied. From them, gastric biopsies were taken and inflammation graded according to the Sydney system; peripheral blood was drawn and antibodies against EBV (IgG and IgM anti-VCA and H. pylori (IgG anti-whole bacteria and anti-CagA were measured in sera. We found that children infected only by EBV presented mild mononuclear (MN and none polymorphonuclear (PMN cell infiltration, while those infected by H. pylori presented moderate MN and mild PMN. In contrast, patients co-infected with both pathogens were significantly associated with severe gastritis. Importantly, co-infection of H. pylori CagA+/EBV+ had a stronger association with severe MN (PR 3.0 and PMN (PR 7.2 cells than cases with single H. pylori CagA+ infection.Co-infection with EBV and H. pylori in pediatric patients is associated with severe gastritis. Even single infections with H. pylori CagA+ strains are associated with mild to moderate infiltration arguing for a cooperative effect of H. pylori and EBV in the gastric mucosa and revealing a critical role for EBV previously un-appreciated. This study points out the need to study both pathogens to understand the mechanism behind severe damage of the gastric mucosa, which could identified children with increased risk to present more serious lesions later in life.

  1. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis

    Directory of Open Access Journals (Sweden)

    Cheng-Yen Kao

    2016-02-01

    Full Text Available Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1 Survival in the acidic stomach; (2 movement toward epithelium cells by flagella-mediated motility; (3 attachment to host cells by adhesins/receptors interaction; (4 causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.

  2. Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases β-amyloid by enhancing expression of presenilin-2

    Directory of Open Access Journals (Sweden)

    Xiu-Lian eWang

    2014-04-01

    Full Text Available Helicobacter pylori (H.pylori infection is related with a high risk of Alzheimer’s Disease (AD, but the intrinsic link between H.pylori infection and AD development is still missing. In the present study, we explored the effect of H.pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H.pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H.pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2, one key component of γ-secretase involved in Aβ production. Incubation of H.pylori filtrate with N2a cells which over-express APP also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H.pylori on cognition and Aβ production. We conclude that soluble surface fractions of H.pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.

  3. Helicobacter pylori infection and nonmalignant diseases.

    Science.gov (United States)

    Sjomina, Olga; Heluwaert, Frederic; Moussata, Driffa; Leja, Marcis

    2017-09-01

    A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial. © 2017 John Wiley & Sons Ltd.

  4. Mechanisms of disease: Helicobacter pylori virulence factors.

    Science.gov (United States)

    Yamaoka, Yoshio

    2010-11-01

    Helicobacter pylori plays an essential role in the development of various gastroduodenal diseases; however, only a small proportion of people infected with H. pylori develop these diseases. Some populations that have a high prevalence of H. pylori infection also have a high incidence of gastric cancer (for example, in East Asia), whereas others do not (for example, in Africa and South Asia). Even within East Asia, the incidence of gastric cancer varies (decreasing in the south). H. pylori is a highly heterogeneous bacterium and its virulence varies geographically. Geographic differences in the incidence of gastric cancer can be explained, at least in part, by the presence of different types of H. pylori virulence factor, especially CagA, VacA and OipA. However, it is still unclear why the pathogenicity of H. pylori increased as it migrated from Africa to East Asia during the course of evolution. H. pylori infection is also thought to be involved in the development of duodenal ulcer, which is at the opposite end of the disease spectrum to gastric cancer. This discrepancy can be explained in part by the presence of H. pylori virulence factor DupA. Despite advances in our understanding of the development of H. pylori-related diseases, further work is required to clarify the roles of H. pylori virulence factors.

  5. Significant Reduction in Helicobacter pylori Load in Humans with Non-viable Lactobacillus reuteri DSM17648: A Pilot Study.

    Science.gov (United States)

    Holz, Caterina; Busjahn, Andreas; Mehling, Heidrun; Arya, Stefanie; Boettner, Mewes; Habibi, Hajar; Lang, Christine

    2015-06-01

    Reducing the amount of Helicobacter pylori in the stomach by selective bacterial-bacterial cell interaction was sought as an effective and novel method for combating the stomach pathogen. Lactobacillus reuteri DSM17648 was identified as a highly specific binding antagonist to H. pylori among more than 700 wild-type strains of Lactobacillus species. Applying a stringent screening procedure, the strain DSM17648 was identified as selective binder to H. pylori cells under in vivo gastric conditions. The strain DSM17648 co-aggregates the pathogen in vivo and in vitro. The specific co-aggregation occurs between Lact. reuteri DSM17648 and different H. pylori strains and serotypes, as well as H. heilmannii, but not with Campylobacter jejuni or other commensal oral and intestinal bacteria. Lact. reuteri DSM17648 was shown in a proof-of-concept single-blinded, randomized, placebo-controlled pilot study to significantly reduce the load of H. pylori in healthy yet infected adults. Reducing the amount of H. pylori in the stomach by selective bacterial-bacterial cell interaction might be an effective and novel method for combating the stomach pathogen. Lact. reuteri DSM17648 might prove useful as an adhesion blocker in antibiotic-free H. pylori therapies.

  6. Plasticity of gene-regulatory networks controlling sex determination: of masters, slaves, usual suspects, newcomers, and usurpators.

    Science.gov (United States)

    Herpin, Amaury; Schartl, Manfred

    2015-10-01

    Sexual dimorphism is one of the most pervasive and diverse features of animal morphology, physiology, and behavior. Despite the generality of the phenomenon itself, the mechanisms controlling how sex is determined differ considerably among various organismic groups, have evolved repeatedly and independently, and the underlying molecular pathways can change quickly during evolution. Even within closely related groups of organisms for which the development of gonads on the morphological, histological, and cell biological level is undistinguishable, the molecular control and the regulation of the factors involved in sex determination and gonad differentiation can be substantially different. The biological meaning of the high molecular plasticity of an otherwise common developmental program is unknown. While comparative studies suggest that the downstream effectors of sex-determining pathways tend to be more stable than the triggering mechanisms at the top, it is still unclear how conserved the downstream networks are and how all components work together. After many years of stasis, when the molecular basis of sex determination was amenable only in the few classical model organisms (fly, worm, mouse), recently, sex-determining genes from several animal species have been identified and new studies have elucidated some novel regulatory interactions and biological functions of the downstream network, particularly in vertebrates. These data have considerably changed our classical perception of a simple linear developmental cascade that makes the decision for the embryo to develop as male or female, and how it evolves. © 2015 The Authors.

  7. Epidemiology of Helicobacter pylori infection.

    Science.gov (United States)

    Burucoa, Christophe; Axon, Anthony

    2017-09-01

    The study of Helicobacter pylori genetic variability brought us interesting data on the history of mankind. Based on multilocus sequence typing and more recently on whole-genome sequencing, paleomicrobiology still attracts the attention of global researchers in relation to its ancestor roots and coexistence with humans. Three studies determining the prevalence of virulence factors illustrates the controversial results obtained since 30 years by studies trying to associate prevalence of different virulence markers and clinical outcomes of H. pylori infection. Three articles analyzed the prevalence and risk of multiple (genetically distinct isolates) and mixed (susceptible and resistant isolates) infections. A number of studies confirm that H. pylori prevalence is falling worldwide especially in the developed world and in children but that the level of infection is higher in certain ethnic minorities and in Migrants. There is little new in identifying the mode of H. pylori transmission though intrafamilial spread appears to be important. There have, however, been some interesting papers on the presence of the organism in food, water, and the oral cavity. © 2017 John Wiley & Sons Ltd.

  8. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection. A...

  9. Helicobacter pylori and Peptic Ulcers

    Centers for Disease Control (CDC) Podcasts

    2010-08-17

    In this podcast, CDC's Dr. David Swerdlow discusses the relationship between Helicobacter pylori and peptic ulcer disease and trends in hospitalization rates for peptic ulcer disease in the United States between 1998 and 2005.  Created: 8/17/2010 by National Center for Emerging and Zoonotic Infectious Diseases.   Date Released: 8/17/2010.

  10. Helicobacter pylori infection and serum ferritin

    DEFF Research Database (Denmark)

    Berg, Gabriele; Bode, G; Blettner, M

    2001-01-01

    OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin...... in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot. RESULTS: In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study...... were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 microg/dl among H. pylori-infected compared with 63.8 microg/dl among uninfected persons. A multiple linear regression model with log...

  11. Alcohol consumption and Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Lappus, N

    1999-01-01

    Alcohol has strong antimicrobial activity and stimulates gastric acid secretion. Alcohol consumption may therefore compromise the living conditions of Helicobacter pylori in the stomach. We assessed the relation of alcohol consumption with H. pylori infection among 1,785 participants ages 18...... prevalence of H. pylori infection was 39.2%. There was a clear inverse dose-response-relation between reported alcohol consumption and H. pylori infection. The relation persisted after control for potential confounding factors. The adjusted prevalence ratios (95% confidence intervals) for H. pylori infection...... among persons who consumed up to 10, 10 to 20, and more than 20 gm of alcohol per day compared with non-drinkers were 0.93 (0.77-1.13), 0.82 (0.65-1.04), and 0.71 (0.55-0.92). The inverse relation between alcohol consumption and H. pylori infection was even stronger when individuals with an indication...

  12. A thin-layer liquid culture technique for the growth of Helicobacter pylori.

    Science.gov (United States)

    Joo, Jung-Soo; Park, Kyung-Chul; Song, Jae-Young; Kim, Dong-Hyun; Lee, Kyung-Ja; Kwon, Young-Cheol; Kim, Jung-Min; Kim, Kyung-Mi; Youn, Hee-Shang; Kang, Hyung-Lyun; Baik, Seung-Chul; Lee, Woo-Kon; Cho, Myung-Je; Rhee, Kwang-Ho

    2010-08-01

    Several attempts have been successful in liquid cultivation of Helicobaccter pylori. However, there is a need to improve the growth of H. pylori in liquid media in order to get affluent growth and a simple approach for examining bacterial properties. We introduce here a thin-layer liquid culture technique for the growth of H. pylori. A thin-layer liquid culture system was established by adding liquid media to a 90-mm diameter Petri dish. Optimal conditions for bacterial growth were investigated and then viability, growth curve, and released proteins were examined. Maximal growth of H. pylori was obtained by adding 3 mL of brucella broth supplemented with 10% horse to a Petri dish. H. pylori grew in both DMEM and RPMI-1640 supplemented with 10% fetal bovine serum and 0.5% yeast extract. Serum-free RPMI-1640 supported the growth of H. pylori when supplemented with dimethyl-beta-cyclodextrin (200 microg/mL) and 1% yeast extract. Under optimal growth, H. pylori grew exponentially for 28 hours, reaching a density of 3.4 OD(600) with a generation time of 3.3 hours. After 24 hours, cultures at a cell density of 1.0 OD(600) contained 1.3 +/- 0.1 x 10(9 )CFU/mL. gamma-Glutamyl transpeptidase, nuclease, superoxide dismutase, and urease were not detected in culture supernatants at 24 hours in thin-layer liquid culture, but were present at 48 hours, whereas alcohol dehydrogenase, alkylhydroperoxide reductase, catalase, and vacuolating cytotoxin were detected at 24 hours. Thin-layer liquid culture technique is feasible, and can serve as a versatile liquid culture technique for investigating bacterial properties of H. pylori.

  13. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Directory of Open Access Journals (Sweden)

    Michael D. Burkitt

    2017-02-01

    Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

  14. Comparison of PCR and common clinical tests for the diagnosis of H. pylori in dyspeptic patients.

    Science.gov (United States)

    Pacheco, N; Mago, V; Gómez, I; Gueneau, P; Guelrud, M; Reyes, N; Pericchi, L R; Domínguez-Bello, M G

    2001-04-01

    Helicobacter pylori has been recognized as a major gastric pathogen. The objective of this study was to assess the diagnostic value of common clinical tests to detect H. pylori infection, by comparison with PCR. Serum and gastric biopsy specimens from 106 dyspeptic patients were examined. Serology was performed with Pyloriset Dry test, and biopsies were examined histologically, for rapid urease activity and PCR amplification of an ureA gene segment of H. pylori. PCR primers were specific for H. pylori and required at least 1.47 pg of H. pylori DNA, corresponding to about 800 bacterial cells. According to serology, histology, rapid urease, and PCR, positive results were respectively found in 56%, 86%, 64%, and 85% of dyspeptic patients, primarily with gastritis. Relative to PCR, the sensitivity (and specificity) was 55% (38%) for serology, 86% (13%) for histology, 70% (69%) for urease. When combining histology and urease, Bayesian analysis of data indicated no advantage of using combined methods over rapid urease test alone. Histology should not any longer be considered a gold standard test for Helicobacter pylori. Urea breath test still seems the first option for non invasive diagnostic. If an invasive diagnostic is justified, highly specific and sensitive molecular methods should be used to examine specimens.

  15. Repeat-Associated Plasticity in the Helicobacter pylori RD Gene Family▿ †

    Science.gov (United States)

    Shak, Joshua R.; Dick, Jonathan J.; Meinersmann, Richard J.; Perez-Perez, Guillermo I.; Blaser, Martin J.

    2009-01-01

    The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3′ region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5′ region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host. PMID:19749042

  16. Repeat-associated plasticity in the Helicobacter pylori RD gene family.

    Science.gov (United States)

    Shak, Joshua R; Dick, Jonathan J; Meinersmann, Richard J; Perez-Perez, Guillermo I; Blaser, Martin J

    2009-11-01

    The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host.

  17. Helicobacter pylori: a sexually transmitted bacterium?

    OpenAIRE

    Dimitriadi, Dimitra

    2014-01-01

    Introduction Oral sex (fellatio) is a very common sexual activity. H. pylori is mainly a gastric organism, but studies have reported that infected individuals may permanently or transiently carry H. pylori in their mouth and saliva. Material and methods A Pubmed search was conducted using the words infection, oral sex and urethritis. Results The existing studies support the hypothesis that H. pylori could be a causative agent of non?gonococcal urethritis. Conclusions It is possible that H. py...

  18. Alteration in Methylation Pattern of Retinoblastoma 1 Gene Promotor Region in Intestinal Metaplasia with or without Helicobacter pylori and Gastric Cancer Patients.

    Science.gov (United States)

    Boyacioglu, Seda Orenay; Kasap, Elmas; Yuceyar, Hakan; Korkmaz, Mehmet

    2016-01-01

    Helicobacter pylori, intestinal metaplasia (IM), and gene methylation play important roles in gastric carcinogenesis. However, the association among H. pylori infection, IM, gastric cancer (GC), and gene methylation is not fully understood. Cell cycle control involving retinoblastoma 1 (RB1) gene is one of the main regulatory pathways reported to be altered in gastric carcinogenesis. The purpose of this research is to assess the methylation status of RB1 gene in GC and IM with or without H. pylori infection, and to discuss the possible role of H. pylori-induced RB1 gene methylation in the mechanism of gastric carcinogenesis. The methylation profile of RB1 gene was analyzed by sodium bisulfite modification and methylation-specific PCR in GC (n = 24), IM patients with H. pylori positive (n = 20) and negative (n = 20), and control subjects (n = 20). According to methylation levels in RB1 gene; the high correlation values were detected between H. pylori positive-IM group and GC group, and between H. pylori positive-IM and H. pylori negative-IM groups (p gene. High methylation levels in RB1 gene in H. pylori positive individuals may suggest an elevated risk of gastric cancer occurrence.

  19. 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    2013-04-01

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  20. Helicobacter pylori and non-malignant diseases.

    Science.gov (United States)

    Matysiak-Budnik, Tamara; Laszewicz, Wiktor; Lamarque, Dominique; Chaussade, Stanislas

    2006-10-01

    The prevalence of Helicobacter pylori-associated peptic ulcers, in particular duodenal ulcers, is decreasing following decreasing prevalence of H. pylori infection, while the frequency of non-steroidal anti-inflammatory drugs (NSAIDs)-induced and H. pylori-negative idiopathic ulcers is increasing. The incidence of bleeding ulcers has been stable during the last decades. Several putative H. pylori virulence genes, i.e., cag, vacA, babA, or dupA, as well as host-related genetic factors like IL-1beta and TNFalpha-gene polymorphism, have been proposed as risk factors for duodenal ulcer. H. pylori eradication may prevent NSAID complications, in particular, when it is performed before introduction of NSAIDs. There is a complex association between H. pylori and gastroesophageal reflux disease (GERD), and the impact of H. pylori eradication on the appearance of GERD symptoms depends on various host- and bacteria-related factors. Eradication of H. pylori in GERD is recommended in patients before instauration of a long-term PPI treatment to prevent the development of gastric atrophy. A small proportion (10%) of non-ulcer dyspepsia cases may be attributed to H. pylori and may benefit from eradication treatment. A test-and-treat strategy is more cost-effective than prompt endoscopy in the initial management of dyspepsia.

  1. Helicobacter Pylori Seropostivity of Colon Cancer

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    F. Tugba Kos

    2014-03-01

    Full Text Available Aim: Until now many researches have showed that Helicobacter pylori infection may be etiological factor of colorectal cancer. The aim of current study was to investigate the frequency of H.pylori infection seropositivity of colorectal cancer patients and compare the clinicopathological features of H.pylori positive patients with negative ones. Material and Method: Seventy four colorectal patients were included in study. Retrospectively, patients clinical features, surgery history and pathological characteristics were screened. Patients group serum samples were collected. H.pylori Ig G level were quantitatively measured with ELISA method and levels above 5 arbU/ml were accepted as seropositive. Results: Patients median age was 60.5 ( range 26-83 and 56.8% (n=42 were male. H.pylori Ig G was positive in 37.8% (n=28 and negative in 62.2% (n=46 of patient group. H.pylori serpositive and negative patients median age of diagnosis were 56 and 64 respectively (p=0.01. There were no significant difference between H.pylori seropositive group when compared with negative group according to age, level of CEA and Ca 19-9, stage, lymph node involvement, perineural and vascular invasion, presence of polyps, differantion, localisation of tumours. Discussion: H.pylori seropositive patients were diagnosed at younger age. Association of this finding with etiology was confusing. Further studies with healthy controls may provide detailed information about whether H.pylori seropositivity is associated with colorectal cancer etiology.

  2. Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

    Science.gov (United States)

    Lee, Inchul

    2014-06-07

    Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

  3. Antiadhesive Properties of Abelmoschus esculentus (Okra) Immature Fruit Extract against Helicobacter pylori Adhesion

    Science.gov (United States)

    Shevtsova, Anna; Glocker, Erik; Borén, Thomas; Hensel, Andreas

    2014-01-01

    Background Traditional Asian and African medicine use immature okra fruits (Abelmoschus esculentus) as mucilaginous food to combat gastritis. Its effectiveness is due to polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach tissue. The present study investigates the antiadhesive effect in mechanistic detail. Methodology A standardized aqueous fresh extract (Okra FE) from immature okra fruits was used for a quantitative in vitro adhesion assay with FITC-labled H. pylori J99, 2 clinical isolates, AGS cells, and fluorescence-activated cell sorting. Bacterial adhesins affected by FE were pinpointed using a dot-blot overlay assay with immobilized Lewisb, sialyl-Lewisa, H-1, laminin, and fibronectin. 125I-radiolabeled Okra FE polymer served for binding studies to different H. pylori strains and interaction experiments with BabA and SabA. Iron nanoparticles with different coatings were used to investigate the influence of the charge-dependence of an interaction on the H. pylori surface. Principal findings Okra FE dose-dependently (0.2 to 2 mg/mL) inhibited H. pylori binding to AGS cells. FE inhibited the adhesive binding of membrane proteins BabA, SabA, and HpA to its specific ligands. Radiolabeled compounds from FE bound non-specifically to different strains of H. pylori, as well as to BabA/SabA deficient mutants, indicating an interaction with a still-unknown membrane structure in the vicinity of the adhesins. The binding depended on the charge of the inhibitors. Okra FE did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. Conclusion Non-specific interactions between high molecular compounds from okra fruits and the H. pylori surface lead to strong antiadhesive effects. PMID:24416297

  4. Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection.

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    Adria Carbo

    Full Text Available T helper (Th cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE-based and agent-based modeling (ABM to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches

  5. Detection of H. Pylori infection on dyspepsia patients with IgA H. Pylori antibody

    Science.gov (United States)

    Loesnihari, R.

    2018-03-01

    Helicobacter pylori (H. pylori) has a big role in the relapse and pathogenesis of the upper gastrointestinal disease. Dyspepsia is characterized by uncomfortable feeling at the upper gastrointestinal area. IgA H. pylori antibody was in two-thirds of H. pylori infected patients, but about 7.2% of IgA H. Pylori antibody became the only positive result of the test between the two serology test (IgG and IgA). A cross-sectional study was conducted in 38 patients with dyspepsia. The IgA antibody test for H. pylori in the serum of dyspepsia patient conducted through the ELISA test. The hemoglobin levels, leukocytes, platelets number, and H. pylori infection via IgA antibody test on ulcer and non-ulcer dyspepsia patient had no significant difference. There was a relation between the number of platelets in the infected H. pylori patients compared to the non-infected patients. H. pylori infection in the ulcer and non-ulcer dyspepsia patient with serology method was 18%. H. pylori infection number on ulcer dyspepsia was not higher than the non-ulcer dyspepsia, all ulcer dyspepsia patients who were with H. pylori found with a lesion on the antrum.

  6. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

    Science.gov (United States)

    Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

    2007-02-01

    Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

  7. Factors that mediate colonization of the human stomach by Helicobacter pylori.

    Science.gov (United States)

    Dunne, Ciara; Dolan, Brendan; Clyne, Marguerite

    2014-05-21

    Helicobacter pylori (H. pylori) colonizes the stomach of humans and causes chronic infection. The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells. The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease. Colonization of gastric mucus is likely to be key to the establishment of chronic infection. How H. pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review. We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals. H. pylori infection of the gastric mucosa has become a paradigm for chronic infection. Understanding of why H. pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease.

  8. Multipronged regulatory functions of a novel endonuclease (TieA) from Helicobacter pylori.

    Science.gov (United States)

    Devi, Savita; Ansari, Suhail A; Tenguria, Shivendra; Kumar, Naveen; Ahmed, Niyaz

    2016-11-02

    Helicobacter pylori portrays a classical paradigm of persistent bacterial infections. A well balanced homeostasis of bacterial effector functions and host responses is purported to be the key in achieving long term colonization in specific hosts. H. pylori nucleases have been shown to assist in natural transformation, but their role in virulence and colonization remains elusive. Therefore, it is imperative to understand the involvement of these nucleases in the pathogenesis of H. pylori Here, we report the multifaceted role of a TNFR-1 interacting endonuclease A (TieA) from H. pylori. tieA expression is differentially regulated in response to environmental stress and post adherence to gastric epithelial cells. Studies with isogenic knockouts of tieA revealed it to be a secretory protein which translocates into the host gastric epithelial cells independent of a type IV secretion system, gets phosphorylated by DNA-PK kinase and auto-phosphorylates as serine kinase. Furthermore, TieA binds to and cleaves DNA in a non-specific manner and promotes Fas mediated apoptosis in AGS cells. Additionally, TieA induced pro-inflammatory cytokine secretion via activation of transcription factor AP-1 and signaled through MAP kinase pathway. Collectively, TieA with its multipronged and moonlighting functions could facilitate H. pylori in maintaining a balance of bacterial adaptation, and elimination by the host responses. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Immune Evasion Strategies and Persistence of Helicobacter pylori.

    Science.gov (United States)

    Mejías-Luque, Raquel; Gerhard, Markus

    Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

  10. Helicobacter pylori colonization of the oral cavity: A milestone discovery

    Science.gov (United States)

    Yee, John KC

    2016-01-01

    Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization. PMID:26811613

  11. Emerging antimicrobial resistance pattern of Helicobacter pylori in central Gujarat

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    H B Pandya

    2014-01-01

    Full Text Available Background: Antimicrobial resistance is a growing problem in H. pylori treatment. The study was intended to evaluate the prevalence of resistance amongst 80 H.pylori isolates cultured from biopsy taken during routine endoscopies in 2008-2011. Materials and Methods: 855 gastro duodenal biopsies were collected and cultured on H.pylori selective medium (containing Brucella agar and Columbia agar (Hi media, with Skirrow′s supplement (antibiotic supplement and 7% human blood cells. H.pylori was isolated from 80 specimens. The antimicrobial susceptibility of H.pylori isolates was carried out by the Kirby Bauer technique against metronidazole (5 µg, clarithromycin (15 µg, ciprofloxacin (5 µg, amoxicillin (10 µg, tetracycline (30 µg, erythromycin (15 µg, levofloxacin (5 µg, and furazolidone (50 µg (Sigma- Aldrich, MO. Results: 83.8% isolates were resistant to metronidazole, 58.8% were resistant to Clarithromycin 72.5% were resistant to Amoxicillin, 50% to Ciprofloxacin and 53.8% to tetracycline. furazolidone, erythromycin and Levofloxacin showed only 13.8% resistance to H.pylori. Multi drug resistance with metronidazole+ clarithromycin+ tetracycline was 85%. For all the drugs Antimicrobial resistance rate was found higher in males compare to females. Metronidazole and amoxicillin resistance was found noteworthy in patients with duodenal ulcer (p = 0.018, gastritis (P = 0.00, and in reflux esophagitis (P = 0.00. clarithromycin and tetracycline resistance was suggestively linked with duodenitis (P = 0.018, while furazolidone, erythromycin and levofloxacin showed excellent sensitivity in patients with duodenitis (P value- 0.018, gastritis (P= 0.00 and reflux esophagitis (P = 0.00. Resistance with metronidazole (P = 0.481, clarithromycin (P= 0.261, amoxicillin (P = 0.276, tetracycline (P = 0.356, ciprofloxacin (P = 0.164 was not correlated well with Age-group and Gender of the patients. Conclusion: A very high percentage of patients were infected

  12. Magnitude of Helicobacter pylori among Dyspeptic patients ...

    African Journals Online (AJOL)

    Background: Helicobacter pylori (H.pylori) infection is predominantly acquired in childhood from family members. The infection can cause dypepepsia, chronic and acute gastritis and gastric cancer. Dyspepsia is the most common illness in the Ethiopian population visiting outpatient department of health facilities, and it has ...

  13. Helicobacter pylori: From Infection to Cure

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    ABR Thomson

    1996-01-01

    Full Text Available Over 380 abstracts, presentations and posters of recent advances were highlighted at the European and International Helicobacter pylori meeting held July 7 to 9, 1995 in Edinburgh, Scotland. New advances abound, with major interest focusing on the simple, safe, inexpensive new `gold standard’ for H pylori eradication therapy: a single week of tid omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg, or omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. To avoid false negative results, two biopsies must be taken from the antrum and two from the gastric body at least four weeks after completion of eradication therapy, and ideally should be supplemented with at least one further H pylori test such as a biopsy for urease activity or culture, or a urea breath test. While most patients with a gastric or duodenal ulcer (DU who do not consume nonsteroidal anti-inflammatory drugs are infected with H pylori, the association is much less apparent in those with a DU who present with an upper gastrointestinal hemorrhage. H pylori eradication for nonulcer dyspepsia is not widely recommended, and the patient with a DU given effective H pylori eradication who presents with dyspepsia likely has erosive esophagitis rather than recurrent DU or H pylori. Gastroenterologists are at increased risk of H pylori infection, particularly older gastroenterologists who are very busy endoscopists.

  14. Prevalence of Helicobacter Pylori Infection Among Patients ...

    African Journals Online (AJOL)

    was seen. Conclusion: The prevalence of H. pylori infection is significantly high in rural and suburban population of Ernakulam district, Kerala. Early detection and prompt treatment are essential for prevention of serious complications. Keywords: Gastrointestinal complications, Helicobacter pylori infection, Histopathological ...

  15. Management of Helicobacter Pylori Infection | Jemilohun | African ...

    African Journals Online (AJOL)

    This review aims at outlining the various diagnostic and therapeutic options available to the clinician in the management of H. pylori infection with an appraisal of their strength and weaknesses. Relevant literatures on diagnosis and treatment of H. pylori infection in texts and journals were reviewed. Extensive internet ...

  16. Seroprevalence of Helicobacter pylori in human immunodeficiency ...

    African Journals Online (AJOL)

    Background: This study assessed the seroprevalence of Helicobacter pylori antibodies among Iranian patients with human immunodeficiency virus (HIV) infection. It also examines whether anti H. pylori seroprevalence was associated with the severity of the HIV infection or the antiretroviral treatment. Material and Methods: ...

  17. Helicobacter pylori and upper digestive diseases - diagnosis ...

    African Journals Online (AJOL)

    Results: The prevalence of Helicobacter pylori in patients with various upper gastrointestinal problems was 84.7%. The use of medication that can reduce the H. pylori density was common among the infected patients, as history of antibiotics use, acid suppressant use and medications for eradication treatment were ...

  18. Helicobacter pylori and non-malignant diseases.

    Science.gov (United States)

    Furuta, Takahisa; Delchier, Jean-Charles

    2009-09-01

    It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.

  19. Geographic pathology of Helicobacter pylori gastritis

    NARCIS (Netherlands)

    Liu, Yi; Ponsioen, Cyriel I. J.; Xiao, Shu-Dong; Tytgat, Guido N. J.; ten Kate, Fiebo J. W.

    2005-01-01

    Background and aim. Helicobacter pylori is etiologically associated with gastritis and gastric cancer. There are significant geographical differences between the clinical manifestation of H. pylori infections. The aim of this study was to compare gastric mucosal histology in relation to age among H.

  20. Current knowledge on alleviating Helicobacter pylori infections through the use of some commonly known natural products: bench to bedside

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    Malliga Raman Murali

    2014-09-01

    Full Text Available Helicobacter pylori, a spiral-shaped Gram-negative bacterium, has been classified as a class I carcinogen by the World Health Organization and recognized as the causative agent for peptic ulcers, duodenal ulcer, gastritis, mucosa-associated lymphoid tissue lymphomas, and gastric cancer. Owing to their alarming rate of drug resistance, eradication of H. pylori remains a global challenge. Triple therapy consisting of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole, is generally the recommended standard for the treatment of H. pylori infection. Complementary and alternative medicines have a long history in the treatment of gastrointestinal ailments and various compounds has been tested for anti-H. pylori activity both in vitro and in vivo; however, their successful use in human clinical trials is sporadic. Hence, the aim of this review is to analyze the role of some well-known natural products that have been tested in clinical trials in preventing, altering, or treating H. pylori infections. Whereas some in vitro and in vivo studies in the literature have demonstrated the successful use of a few potential natural products for the treatment of H. pylori-related infections, others indicate a need to consider natural products, with or without triple therapy, as a useful alternative in treating H. pylori-related infections. Thus, the reported mechanisms include killing of H. pylori urease inhibition, induction of bacterial cell damage, and immunomodulatory effect on the host immune system. Furthermore, both in vitro and in vivo studies have demonstrated the successful use of some potential natural products for the treatment of H. pylori-related infections. Nevertheless, the routine prescription of potential complementary and alternative medicines continues to be restrained, and evidence on the safety and efficacy of the active compounds remains a subject of ongoing debate.

  1. Isocitrate dehydrogenase of Helicobacter pylori potentially induces humoral immune response in subjects with peptic ulcer disease and gastritis.

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    M Abid Hussain

    Full Text Available BACKGROUND: H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD, an important house keeping protein of H. pylori. METHODOLOGY/PRINCIPAL FINDINGS: Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD. CONCLUSIONS/SIGNIFICANCE: ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1 and therefore, may not be a notable proinflammatory agent.

  2. Assessment of Risk and Sero-Prevalence of Helicobacter pylori Colonization among Remote Orang Asli Tribes in Peninsula Malaysia

    Science.gov (United States)

    Thevakumar, Kavitha; Chandren, Josephine Rebecca; Perez-Perez, Guillermo Ignacio; Chua, Eng Guan; Teh, Lay Kek; Salleh, Mohd Zaki; Tan, Jin Ai Mary Anne; Leow, Alex Hwong Ruey; Goh, Khean Lee; Tay, Alfred Chin Yen; Marshall, Barry J.; Vadivelu, Jamuna; Loke, Mun Fai; Wong, Li Ping

    2016-01-01

    The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes. PMID:27441568

  3. Komplet remission af højmalignt lymfom i ventriklen efter eradikation af Helicobacter pylori

    DEFF Research Database (Denmark)

    Høeg, Rasmus Tetens; Skau, Anne-Marie; Nørgaard, Peter

    2011-01-01

    . The recommended treatment of DLBCL is chemotherapy followed by involved-field irradiation. However, small prospective trials have shown high rates of complete remission after eradication of H. pylori alone and this treatment is an option in patients of advanced age or with severe co-morbidities.......A 91 year-old man was found to have diffuse large cell B-cell lymphoma (DLBCL), localized to the stomach. Because of his age, his only treatment was anti-Helicobacter pylori therapy. He achieved a complete remission, and six months after the initial presentation, there were no signs of recurrence...

  4. Systems-wide analyses of mucosal immune responses to Helicobacter pylori at the interface between pathogenicity and symbiosis

    Science.gov (United States)

    Kronsteiner, Barbara; Bassaganya-Riera, Josep; Philipson, Casandra; Viladomiu, Monica; Carbo, Adria; Abedi, Vida; Hontecillas, Raquel

    2016-01-01

    Abstract Helicobacter pylori is the dominant member of the gastric microbiota in over half of the human population of which 5–15% develop gastritis or gastric malignancies. Immune responses to H. pylori are characterized by mixed T helper cell, cytotoxic T cell and NK cell responses. The presence of Tregs is essential for the control of gastritis and together with regulatory CX3CR1+ mononuclear phagocytes and immune-evasion strategies they enable life-long persistence of H. pylori. This H. pylori-induced regulatory environment might contribute to its cross-protective effect in inflammatory bowel disease and obesity. Here we review host-microbe interactions, the development of pro- and anti-inflammatory immune responses and how the latter contribute to H. pylori's role as beneficial member of the gut microbiota. Furthermore, we present the integration of existing and new data into a computational/mathematical model and its use for the investigation of immunological mechanisms underlying initiation, progression and outcomes of H. pylori infection. PMID:26939848

  5. Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection

    Science.gov (United States)

    Fulgione, Andrea; Nocerino, Nunzia; Iannaccone, Marco; Roperto, Sante; Capuano, Federico; Roveri, Norberto; Lelli, Marco; Crasto, Antonio; Calogero, Armando; Pilloni, Argenia Paola; Capparelli, Rosanna

    2016-01-01

    Background The resistance of Helicobacter pylori to the antibiotic therapy poses the problem to discover new therapeutic approaches. Recently it has been stated that antibacterial, immunomodulatory, and antioxidant properties of lactoferrin are increased when this protein is surface-linked to biomimetic hydroxyapatite nanocrystals. Objective Based on these knowledge, the aim of the study was to investigate the efficacy of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles with cell free supernatant from probiotic Lactobacillus paracasei as an alternative therapy against Helicobacter pylori infection. Methods Antibacterial and antinflammatory properties, humoral antibody induction, histopathological analysis and absence of side effects were evaluated in both in vitro and in vivo studies. Results The tests carried out have been demonstrated better performance of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles combined with cell free supernatant from probiotic Lactobacillus paracasei compared to both lactoferrin and probiotic alone or pooled. Conclusion These findings indicate the effectiveness and safety of our proposed therapy as alternative treatment for Helicobacter pylori infection. PMID:27384186

  6. Morphological and Cellular Features of Innate Immune Reaction in Helicobacter pylori Gastritis: A Brief Review

    Directory of Open Access Journals (Sweden)

    Antonio Ieni

    2016-01-01

    Full Text Available Innate and adaptive immunity are both involved in acute and chronic inflammatory processes. The main cellular players in the innate immune system are macrophages, mast cells, dendritic cells, neutrophils, eosinophils, and natural killer (NK, which offer antigen-independent defense against infection. Helicobacter pylori (H. pylori infection presents peculiar characteristics in gastric mucosa infrequently occurring in other organs; its gastric colonization determines a causal role in both gastric carcinomas and mucosa-associated lymphoid tissue lymphoma. In contrast, an active role for Epstein-Barr virus (EBV has been identified only in 9% of gastric carcinomas. The aim of the present review is to discuss the role of cellular morphological effectors in innate immunity during H. pylori infection and gastric carcinogenesis.

  7. Oxidative Stress Resulting From Helicobacter pylori Infection Contributes to Gastric CarcinogenesisSummary

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    Lindsay D. Butcher

    2017-05-01

    Full Text Available Helicobacter pylori is a gram-negative, microaerophilic bacterium that infects the stomach and can lead to, among other disorders, the development of gastric cancer. The inability of the host to clear the infection results in a chronic inflammatory state with continued oxidative stress within the tissue. Reactive oxygen species and reactive nitrogen species produced by the immune and epithelial cells damage the host cells and can result in DNA damage. H pylori has evolved to evoke this damaging response while blunting the host’s efforts to kill the bacteria. This long-lasting state with inflammation and oxidative stress can result in gastric carcinogenesis. Continued efforts to better understand the bacterium and the host response will serve to prevent or provide improved early diagnosis and treatment of gastric cancer. Keywords: AP Endonuclease, DNA Damage, H pylori, Gastric Cancer, Oxidative Stress

  8. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

    Science.gov (United States)

    Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2016-01-01

    Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

  9. Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications.

    Science.gov (United States)

    Yang, Tao-Tao; Cao, Na; Zhang, Hai-Hui; Wei, Jian-Bo; Song, Xiao-Xia; Yi, Dong-Min; Chao, Shuai-Heng; Zhang, Li-Da; Kong, Ling-Fei; Han, Shuang-Yin; Yang, Yu-Xiu; Ding, Song-Ze

    2018-04-15

    Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased

  10. Polymorphisms at Locus 4p14 of Toll-Like Receptors TLR-1 and TLR-10 Confer Susceptibility to Gastric Carcinoma in Helicobacter pylori Infection.

    Directory of Open Access Journals (Sweden)

    M Ravishankar Ram

    Full Text Available Helicobacter pylori (H. pylori -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD, 40 with peptic ulcer disease (PUD and 15 with gastric cancer (GC subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.

  11. Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model

    DEFF Research Database (Denmark)

    Fontenete, Sílvia; Leite, Marina; Cappoen, Davie

    2016-01-01

    ). Finally, the efficiency of FIVH to detect H. pylori SS1 strain in C57BL/6 infected mice was evaluated ex vivo in mucus samples, in cryosections and paraffin-embedded sections by epifluorescence and confocal microscopy. RESULTS: H. pylori SS1 strain infecting C57BL/6 mice was successfully detected...... by the Cy3_HP_LNA/2OMe_PS probe in the mucus, attached to gastric epithelial cells and colonizing the gastric pits. The specificity of the probe for H. pylori was confirmed by microscopy. CONCLUSIONS: In the future this methodology can be used in combination with a confocal laser endomicroscope for in vivo......INTRODUCTION: In this study, we applied fluorescence in vivo hybridization (FIVH) using locked nucleic acid (LNA) probes targeting the bacterial rRNA gene for in vivo detection of H. pylori infecting the C57BL/6 mouse model. A previously designed Cy3_HP_LNA/2OMe_PS probe, complementary...

  12. Gastric angiogenesis and Helicobacter pylori infection Angiogénesis gástrica e infección por Helicobacter pylori

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    I. D. Pousa

    2006-06-01

    Full Text Available The formation of new blood vessels seen in conditions commonly associated with Helicobacter pylori (H. pylori infection, including gastritis, peptic ulcer, and gastric carcinoma, prompts consideration of a potential relationship between mucosal colonization by this organism and the angiogenic process. H. pylori directly or indirectly damages endothelial cells, which induces a number of changes in the microvasculature of the gastric mucosa. In H. pylori-associated conditions, that is, in gastritis, peptic ulcer and gastric carcinoma, there is an increased concentration of angiogenic factors, and subsequently a formation of new blood vessels. However, this early angiogenesis -which is activated to repair the gastric mucosa- is subsequently inhibited in patients with peptic ulcer, and ulcer healing is thus delayed. This may be due to the antiproliferative action of this organism on endothelial cells. While the angiogenic process becomes inhibited in infected patients with peptic ulcer, it remains seemingly active in those with gastritis or gastric cancer. This fact is in support of the notion suggested by various studies that peptic ulcer and gastric cancer are mutually excluding conditions. In the case of gastric cancer, neoangiogenesis would enhance nutrient and oxygen supply to cancer cells, and thus tumor growth and metastatic spread.

  13. An Overview of Helicobacter pylori VacA Toxin Biology

    Science.gov (United States)

    Foegeding, Nora J.; Caston, Rhonda R.; McClain, Mark S.; Ohi, Melanie D.; Cover, Timothy L.

    2016-01-01

    The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA activity is its capacity to stimulate vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to VacA, including gastric epithelial cells, parietal cells, T cells, and other types of immune cells. This review focuses on the wide range of VacA actions that are detectable in vitro, as well as actions of VacA in vivo that are relevant for H. pylori colonization of the stomach and development of gastric disease. PMID:27271669

  14. Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer.

    Science.gov (United States)

    Martínez-Carrillo, D N; Atrisco-Morales, J; Hernández-Pando, R; Reyes-Navarrete, S; Betancourt-Linares, R; Cruz-del Carmen, I; Illades Aguiar, B; Román-Román, A; Fernández-Tilapa, G

    2014-01-01

    Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.

  15. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

    OpenAIRE

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host ...

  16. Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains.

    Science.gov (United States)

    Boyanova, L; Gergova, G; Markovska, R; Yordanov, D; Mitov, I

    2017-12-01

    The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free supernatant (CFS) types. Activity of non-neutralized and non-heat-treated (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase-treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of test strains and those of four GLB strains were active against >71% of antibiotic resistant strains. Two H. pylori strains were BLIS resistant. The heating did not reduce the CFS activity. Briefly, all GLB strains evaluated produced heat-stable BLISs, although GLB and H. pylori strain susceptibility patterns exhibited differences. Bacteriocin-like inhibitory substance activity can be an advantage for the probiotic choice for H. pylori infection control. In this study, anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. © 2017 The Society for Applied Microbiology.

  17. In vitro inhibition of Helicobacter pylori urease with non and semi fermented Camellia sinensis

    Directory of Open Access Journals (Sweden)

    Shoae Hassani A

    2009-01-01

    Full Text Available Purpose: Helicobacter pylori is the etiological agent in duodenal and peptic ulcers. The growing problem of antibiotic resistance by the organism demands the search for novel compounds, especially from natural sources. This study was conducted to evaluate the effect of Camellia sinensis extracts on the urease enzyme that is a major colonization factor for H. pylori. Methods: Minimum inhibitory concentrations of nonfermented and semifermented C. sinensis methanol: water extracts were assessed by broth dilution method. Examination of the urease function was performed by Mc Laren method, and urease production was detected on 12% SDS polyacrylamide gel electrophoresis from whole cell and membrane bound proteins. Results: Both extracts had inhibitory effects against H. pylori and urease production. At a concentration of 2.5 mg/ml of nonfermented extract and 3.5 mg/ml of semifermented extract the production of Ure A and Ure B subunits of the urease enzyme were inhibited completely. A concentration of 4 mg/ml of nonfermented and 5.5 mg/ml of semifermented extract were bactericidal for H. pylori. Conclusions: C. sinensis extracts, especially the nonfermented, could reduce H. pylori population and inhibit urease production at lower concentrations. The superior effect of nonfermented extract is due to its rich polyphenolic compounds and catechin contents.

  18. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

    2011-07-25

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  19. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    International Nuclear Information System (INIS)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua; Hahm, Ki Baik

    2011-01-01

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis

  20. Helicobacter pylori neutrophil-activating protein: A potential Treg modulator suppressing allergic asthma?

    Directory of Open Access Journals (Sweden)

    Anjna eSehrawat

    2015-06-01

    Full Text Available The ultimate aim of immunology is to kill the pathogen without being harmful to the host. But what if eliminating the pathogen in itself is discomforting for the host? One such emerging case is of Helicobacter pylori. Modern medicine, infantile vaccination and ultra-hygienic conditions have led to progressive disappearance of H. pylori in different parts of the world. However, the adversities caused by H. pylori’s absence are much larger than those caused by its presence. Asthma is rising as an epidemic in last few decades and several reports suggest an inverse-relationship between H. pylori’s persistence and early-life onset asthma. Regulatory T cells play an important role in both the cases. This is further supported by experiments on mouse-models. Hence, need of the hour is to discern the relationship between H. pylori and its host and eliminating its negative impacts without disturbing our indigenous microbiota. To resolve whether H. pylori is a pathogen or an amphibiont is another important side. This review explores the biological basis of H. pylori-induced priming of immune system offering resistance to childhood-onset asthma. HP-NAP-Tregs interaction has been predicted using molecular docking and dynamic simulation.

  1. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ki Baik Hahm

    2011-07-01

    Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  2. Treatment of low-grade gastric malt lymphoma using Helicobacter pylori eradication

    Directory of Open Access Journals (Sweden)

    Grgov Saša

    2015-01-01

    Full Text Available Background/Aim. Lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma of the stomach usually occurs as a consequence of Helicobacter pylori (H. pylori infection. The aim of this study was to investigate the long-term effect of treatment of low-grade gastric MALT lymphoma with the H. pylori eradication method. Methods. In the period 2002-2012 in 20 patients with dyspepsia, mean age 55.1 years, the endoscopic and histologic diagnosis of gastric MALT lymphoma in the early stages were made. Histological preparations of endoscopic biopsy specimens were stained with hematoxyllineosin (HE, histochemical and immunohistochemical methods. Results. Endoscopic findings of gastritis were documented in 25% of the patients, and 75% of the patients had hypertrophic folds, severe mucosal hyperemia, fragility, nodularity, exulcerations and rigidity. Histopathologically, pathognomonic diagnostic criterion were infiltration and destruction of glandular epithelium with neoplastic lymphoid cells, the so-called lymphoepithelial lesions. In all 20 patients H. pylori was verified by rapid urease test and Giemsa stain. After the triple eradication therapy complete remission of MALT lymphoma was achieved in 85% of the patients, with no recurrence of lymphoma and H. pylori infection in the average follow-up period of 48 months. In 3 (15% of the patients, there was no remission of MALT lymphoma 12 months after the eradication therapy. Of these 3 patients 2 had progression of MALT lymphoma to diffuse large-cell lymphoma. Conclusion. Durable complete re-mission of low-grade gastric MALT lymphoma is achieved in a high percentage after eradication of H. pylori infection, thus preventing the formation of diffuse large-cell lymphoma and gastric adenocarcinoma.

  3. [The relationship of halitosis and Helicobacter pylori].

    Science.gov (United States)

    Chen, Xi; Tao, Dan-ying; Li, Qing; Feng, Xi-ping

    2007-06-01

    The aim of the study was to investigate the relationship between halitosis and Helicobacter pylori infection in stomach. Fifty subjects without periodontal diseases and systematic disease (exclude gastrointestinal diseases) were included. Infection of H.pylori was diagnosed by biopsy and (14)C-urea breath test. SPSS11.5 software package was used to analyze the data. All the subjects were periodontal healthy according to the periodontal index. The prevalence of H.pylori infection in halitosis subjects was significantly higher than that in the normal subjects (57.1% VS 18.2%, Pperiodontal healthy subjects.

  4. Adherence of Helicobacter pylori to the Gastric Mucosa

    Directory of Open Access Journals (Sweden)

    Marguerite Clyne

    1997-01-01

    Full Text Available Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.

  5. Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

    DEFF Research Database (Denmark)

    Santos, Rita S; Dakwar, George R; Xiong, Ranhua

    2015-01-01

    Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid...... barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without...

  6. Persistent colonization of Helicobacter pylori in human gut induces gastroduodenal diseases

    Directory of Open Access Journals (Sweden)

    Animesh Sarker

    2014-12-01

    Full Text Available Helicobacter pylori are gut bacteria colonize in the epithelial cell lining of the stomach and persist there for long du­ration. Around two-thirds of the world’s populations are infected with H. pylori and cause more than 90 percent of ulcers. The development of persistent inflammation is the main cause of chronic gastritis that finally results in a severe consequence known as stomach cancer. Two major virulence factors cytotoxin-associated gene product (cagA and the vacuolating toxin (vacA are mostly investigated as their close association with gastric carcinoma. In this review, host im­munity against H. pylori infection and their evasion mechanism are intensely explored. It is the fact, that understanding pin point molecular mechanisms of any infection is critical to develop novel strategies to prevent pertinent diseases. .J Microbiol Infect Dis 2014; 4(4: 170-176

  7. Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

    2010-01-01

    Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

  8. Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

    2010-03-01

    Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

  9. Treatment of Helicobacter pylori infection.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    This article aims to examine current best practice in the field reference to first-line, second-line, rescue and emerging treatment regimens for Helicobacter pylori eradication. The recommended first-line treatment in published guidelines in Europe and North American is proton pump inhibitor combined with amoxicillin and clarithromycin being the favoured regimen. Rates of eradication with this regimen however are falling alarmingly due to a combination of antibiotic resistance and poor compliance with therapy. Bismuth based quadruple therapies and levofloxacin based regimes have been shown to be effective second line regimens. Third-line options include regimes based on rifabutin or furazolidone, but susceptibility testing is the most rational option here, but is currently not used widely enough. Sequential therapy is promising but needs further study and validation outside of Italy. Although the success of first line treatments is falling, if compliance is good and a clear treatment paradigm adhered to, almost universal eradication rates can still be achieved. If compliance is not achievable, the problem of antibiotic resistance will continue to beset any combination of drugs used for H. pylori eradication.

  10. Transmission of Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Giuseppina Oderda

    1999-01-01

    Full Text Available Helicobacter pylori infection is one of the most common bacterial infections worldwide. It is accepted as the major cause of chronic gastritis, peptic ulcer, carcinoma of the distal part of the stomach and gastric lymphoma. However, how and when the infection is acquired remain largely unknown. Identification of mode of transmission is vital for developing preventive measures to interrupt its spread, but studies focused on this issue are difficult to implement. From epidemiological studies, it is known that there are great differences in the prevalence of infection in different populations and in ethnic groups originating from high prevalence regions. This is likely related to inferior hygienic conditions and sanitation. In developing countries, infection occurs at a much earlier age. In developed countries, the prevalence of infection is related to poor socioeconomic conditions, particularly density of living. Humans seem to be the only reservoir of H pylori, which spread from person to person by oral-oral, fecal-oral or gastro-oral routes. Most infections are acquired in childhood, possibly from parents or other children living as close contacts. Infection from the environment or from animals cannot be entirely excluded.

  11. Special licorice extracts containing lowered glycyrrhizin and enhanced licochalcone A prevented Helicobacter pylori-initiated, salt diet-promoted gastric tumorigenesis.

    Science.gov (United States)

    Park, Jong-Min; Park, Sang-Ho; Hong, Kyung-Sook; Han, Young-Min; Jang, Sang-Ho; Kim, Eun-Hee; Hahm, Ki-Baik

    2014-06-01

    In spite of cytoprotective and anti-inflammatory actions, conventional licorice extracts (c-lico) were limitedly used due to serious side effects of glycyrrhizin. As our group had successfully isolated special licorice extracts (s-lico) lowering troublesome glycyrrhizin, but increasing licochalcone A, we have compared anti-inflammatory, antioxidative, and cytoprotective actions of s-lico and c-lico against either in vitro or in vivo Helicobacter pylori infection. RT-PCR and Western blot were performed to check anti-inflammatory action and electron spin resonance (ESR) and DCFDA spectroscopy to check antioxidative action. s-lico or c-lico was pretreated 1 hours before H. pylori infection on AGS cells. Interleukin-10 deficient mice inoculated H. pylori and followed with high salt containing pallet diets to produce H. pylori-associated chronic atrophic gastritis and gastric tumors, during which s-lico or c-lico-containing pellet diets were administered up to 24 weeks. s-lico had fabulous efficacy on scavenging ROS which was further confirmed by DCFDA study and ESR measurement. The expressions of COX-2, iNOS, VEGF, and IL-8 were increased after H. pylori infection, of which levels were significantly decreased with s-lico in a dose-dependent manner. s-lico significantly ameliorated hypoxia-induced or H. pylori-induced angiogenic activities. s-lico significantly ameliorated H. pylori-induced gastric damages as well as gastritis. Our animal model showed significant development of gastric tumors including adenoma and dysplasia relevant to H. pylori infection, and s-lico administration significantly attenuated incidence of H. pylori-induced gastric tumorigenesis. Special licorice extracts can be anticipating substance afforded significant attenuation of either H. pylori-induced gastritis or tumorigenesis based on potent antioxidative, anti-inflammatory, and antimutagenic actions. © 2014 John Wiley & Sons Ltd.

  12. Assessment of p21, p53 expression, and Ki-67 proliferative activities in the gastric mucosa of children with Helicobacter pylori gastritis.

    Science.gov (United States)

    Saf, Coskun; Gulcan, Enver Mahir; Ozkan, Ferda; Cobanoglu Saf, Seyhan Perihan; Vitrinel, Ayca

    2015-02-01

    Helicobacter pylori that is generally acquired in childhood and infects the gastric mucosa is considered to be responsible for many pathobiological changes that are linked to the pathogenesis of gastric cancer. Although the majority of studies on the subject have been carried out in adults, there are a limited number of studies on children that reflect the early period of infection and may be of greater significance. We aimed to determine the role of H. pylori infection and/or gastritis in several histopathological changes, p53, p21, and cell proliferation-associated Ki-67 antigen expression in the gastric mucosa. We studied 60 patients with a mean age of 7.5 ± 4.5 years at referral. On the basis of endoscopic appearance and the evaluation of the gastric antral specimens, the patients were divided into three groups: patients without gastritis, patients with H. pylori-positive gastritis, and patients with H. pylori-negative gastritis. To determine the expression of p53, Ki-67, and p21 in gastric biopsy specimens, immunohistochemical stains were performed. The incidence of neutrophil activity, which was one of our histopathologic parameters, was significantly higher in the H. pylori-positive gastritis group than the other two groups. The presence of lymphoid aggregate was more frequent in H. pylori ± gastritis groups than the nongastritis group. p53 expression was found to be significantly higher in the H. pylori-positive gastritis group than the nongastritis group. Ki-67 and p21 expressions were significantly more frequent in the H. pylori-positive gastritis group than the other two groups. When we evaluated the density of H. pylori, as the density of bacteria increases, we found that the expressions of p53, p21, and Ki-67 increased significantly. Expression of the studied precancerous markers in significant amounts indicates the importance of childhood H. pylori infection in the constitution of gastric cancer in adulthood.

  13. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

    Science.gov (United States)

    Burns, Monika; Amaya, Aldo; Bodi, Caroline; Ge, Zhongming; Bakthavatchalu, Vasudevan; Ennis, Kathleen; Wang, Timothy C.; Georgieff, Michael

    2017-01-01

    Helicobacter pylori (H.pylori), a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA), enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40) were used; half were placed on a moderately iron deficient (ID) diet immediately post-weaning, and the other half were maintained on an iron replete (IR) diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet) as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet). All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (pmice on an ID diet (both pmice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA. PMID:28355210

  14. A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication.

    Directory of Open Access Journals (Sweden)

    Tomomitsu Tahara

    Full Text Available The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features.A total of 55 consecutive patients with 64 early gastric cancers (EGCs diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored.The majority of EGCs (63/64 were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001. The degree of endoscopic atrophy improved in the patients with longer post-H. pylori eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all P<0.05. The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers.Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis.

  15. Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA

    Science.gov (United States)

    Schmidt, Thomas P.; Perna, Anna M.; Fugmann, Tim; Böhm, Manja; Jan Hiss; Haller, Sarah; Götz, Camilla; Tegtmeyer, Nicole; Hoy, Benjamin; Rau, Tilman T.; Neri, Dario; Backert, Steffen; Schneider, Gisbert; Wessler, Silja

    2016-03-01

    The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

  16. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

    Directory of Open Access Journals (Sweden)

    Frithjof eGlowinski

    2014-07-01

    Full Text Available Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS, which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12ΔCagA deletion mutant, and a P12ΔT4SS deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr phosphopeptides and analysed by nano-LC-Orbitrap MS. In total, 58 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK familiy. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin linked factors, whereas the T4SS primarily modulates JNK and p38 activation.

  17. [Unpleasant Journey from Helicobacter pylori-associated Gastritis to Gastric Cancer: Cancer Prevention by Taking a Detour].

    Science.gov (United States)

    Lee, Sang Hwan; Park, Jong Min; Han, Young Min; Ko, Weon Jin; Hahm, Ki Baik

    2015-12-01

    As a commensal or a pathogen, Helicobacter pylori can change the balance of a complex interaction that exists among gastric epithelial cells, microbes, and their environment. Therefore, unraveling this complex relationship of these mixtures can be expected to help prevent cancer as well as troublesome unmet medical needs of H. pylori infection. Though gastric carcinogenesis is a multi-step process, precancerous lesion can be reversible in the early phase of mucosal damage before reaching the stage of no return. However, biomarkers to predict rejuvenation of precancerous atrophic gastritis have not been identified yet and gastric cancer prevention is still regarded as an impregnable fortress. However, when we take the journey from H. pylori-associated gastritis to gastric cancer, it provides us with the clue for prevention since there are two main preventive strategies: eradication and anti-inflammation. The evidence supporting the former strategy is now ongoing in Japan through a nation-wide effort to eradicate H. pylori in patients with chronic gastritis, but suboptimal apprehension to increasing H. pylori resistance to antibiotics and patient non-compliance still exists. The latter strategy has been continued in the author'sresearch center under siTRP (short-term intervention to revert premalignant lesion) strategy. By focusing on the role of inflammation in the development of H. pylori-associated gastric carcinogenesis, this review is intended to explain the connection between inflammation and gastric cancer. Strategies on H. pylori eradication, removal of inflammation, and reverting preneoplastic lesion will also be introduced. In the end, we expect to be able to prevent gastric cancer by take a detour from the unpleasant journey, i.e. from H. pylori-associated gastritis to gastric cancer.

  18. Histological and endoscopic features of the stomachs of patients with Chagas disease in the era of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Fernanda Machado Fonseca

    2014-12-01

    Full Text Available Introduction Most studies that have evaluated the stomachs of patients with Chagas disease were performed before the discovery of Helicobacter pylori and used no control groups. This study compared the gastric features of chagasic and non-chagasic patients and assessed whether gastritis could be associated with Chagas disease. Methods Gastric biopsy samples were taken from patients who underwent endoscopy for histological analysis according to the Updated Sydney System. H. pylori infection was assessed by histology, 16S ribosomal ribonucleic acid (rRNA polymerase chain reaction (PCR, serology and the 13C-urea breath test. Patients were considered H. pylori-negative when all of these diagnostic tests were negative. Clinical and socio-demographic data were obtained by reviewing medical records and using a questionnaire. Results The prevalence of H. pylori infection (70.3% versus 71.7% and chronic gastritis (92.2% versus 85% was similar in the chagasic and non-chagasic groups, respectively; such as peptic ulcer, atrophy and intestinal metaplasia. Gastritis was associated with H. pylori infection independent of Chagas disease in a log-binomial regression model. However, the chagasic H. pylori-negative patients showed a significantly higher grade of mononuclear (in the corpus and polymorphonuclear (PMN (in the antrum cell infiltration. Additionally, the patients with the digestive form of Chagas disease showed a significantly lower prevalence of corpus atrophy than those with other clinical forms. Conclusions The prevalence of H. pylori infection and of gastric histological and endoscopic features was similar among the chagasic and non-chagasic patients. Additionally, this is the first controlled study to demonstrate that H. pylori is the major cause of gastritis in patients with Chagas disease.

  19. Effect of depression on Helicobacter pylori infection in patients with gastric cancer and its correlation with oncogene expression

    Institute of Scientific and Technical Information of China (English)

    Chun-Rong Xiao

    2017-01-01

    Objective: To study the effect of depression on Helicobacter pylori (H. pylori) infection in patients with gastric cancer and its correlation with oncogene expression. Methods: A total of 82 patients who accepted radical operation for gastric cancer in Zigong Third People's Hospital between March 2015 and February 2017 were selected as the research subjects and divided into depression group and non-depression group according to the preoperative HAMD scores, and helicobacter pylori infection as well as the mRNA expression of proliferation genes and invasion genes in gastric cancer lesions was detected. Results: The positive rate of H. pylori in gastric cancer lesions of depression group was significantly higher than that of non-depression group; LOXL2, RAB1A, UHRF1, Slug and ADAM8 mRNA expression in gastric cancer lesions of depression group were significantly higher than those of non-depression group while MTS1, NOX, E-cadherin and TIMP1 mRNA expression were significantly lower than those of non-depression group; LOXL2, RAB1A, UHRF1, Slug and ADAM8 mRNA expression in H. pylori-positive gastric cancer lesions of depression group were significantly higher than those in H. pylori-negative gastric cancer lesions of depression group while MTS1, NOX, E-cadherin and TIMP1 mRNA expression were significantly lower than those in H. pylori-negative gastric cancer lesions of depression group. Conclusion: Depression can increase the H. pylori infection rate and promote the proliferation and invasion of cancer cells in gastric cancer lesions.

  20. The histone-like protein HU has a role in gene expression during the acid adaptation response in Helicobacter pylori.

    Science.gov (United States)

    Álvarez, Alhejandra; Toledo, Héctor

    2017-08-01

    Gastritis, ulcers, and gastric malignancy have been linked to human gastric epithelial colonization by Helicobacter pylori. Characterization of the mechanisms by which H. pylori adapts to the human stomach environment is of crucial importance to understand H. pylori pathogenesis. In an effort to extend our knowledge of these mechanisms, we used proteomic analysis and qRT-PCR to characterize the role of the histone-like protein HU in the response of H. pylori to low pH. Proteomic analysis revealed that genes involved in chemotaxis, oxidative stress, or metabolism are under control of the HU protein. Also, expression of the virulence factors Ggt and NapA is affected by the null mutation of hup gene both at neutral and acid pH, as evidenced by qRT-PCR analysis. Those results showed that H. pylori gene expression is altered by shift to low pH, thus confirming that acid exposure leads to profound changes in genomic expression, and suggest that the HU protein is a regulator that may help the bacterium adapt to the acid stress. In accordance with previous reports, we found that the HU protein participates in gene expression regulation when the microorganism is exposed to acid stress. Such transcriptional regulation underlies protein accumulation in the H. pylori cell. © 2017 John Wiley & Sons Ltd.

  1. Prevalence of Helicobacter pylori prevalence and upper gastrointestinal endoscopy in HIV/AIDS patients with gastrointestinal symptoms in the University Teaching Hospitals in Cameroon.

    Science.gov (United States)

    Andoulo, F A; Kowo, M; Ngatcha, G; Ndam, A N; Awouoyiegnigni, B; Sida, M B; Tzeuton, C; Ndjitoyap Ndam, E C

    2016-08-01

    To determine the prevalence of Helicobacter pylori (H. pylori) infection and of various upper gastrointestinal (GI) lesions in HIV + patients with GI symptoms and the relation of H. pylori infection to CD4 cell counts. In all, 56 HIV + patients and 56 age- and sex-matched HIV - controls, all with upper GI symptoms, were evaluated by an upper endoscopy examination and gastric biopsy. H. pylori status was assessed with a urease test and histology. HIV was diagnosed with the rapid test and enzyme-linked immunosorbent assay (ELISA). The prevalence of H. pylori was 50% (28/56 [95%CI 36.3-63.7]) in HIV + subjects and 55% (31/56 [95%CI 41.5-68.7]) in HIV - controls (p = 0.57). H. pylori infection rates did not differ significantly in HIV + patients between those with a CD4 count ≥200/mm 3 (52%) and those with a CD4 count HIV + patients and controls were compared: esophageal candidiasis (61%, 34/56 vs. 7%; pHIV + and HIV - subjects. Prevalence of H. pylori was also lower, although not significantly, among HIV + patients with CD4 T-cell counts below 200/mm 3 . On endoscopy, esophageal candidiasis was the most common finding in HIV + patients, discovered by dysphagia.

  2. Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    Le Guo

    2017-08-01

    Full Text Available Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP, heat shock protein 60 (HSP60 and H. pylori adhesin A (HpaA was constructed based on mucosal adjuvant cholera toxin B subunit (CTB, Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203, and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385 predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203. In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell response, IgG, and secretory IgA (sIgA antibodies to H. pylori. These results indic

  3. Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.

    Science.gov (United States)

    Guo, Le; Yang, Hua; Tang, Feng; Yin, Runting; Liu, Hongpeng; Gong, Xiaojuan; Wei, Jun; Zhang, Ying; Xu, Guangxian; Liu, Kunmei

    2017-01-01

    Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori ( H. pylori ) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori , remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA 27-53 , UreA 183-203 , HpaA 132-141 , and HSP60 189-203 ), and also the epitope-rich regions of urease B subunit (UreB 158-251 and UreB 321-385 ) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori -infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB 158-172 , UreB 181-195 , UreB 211-225 , UreB 349-363 , HpaA 132-141 , and HSP60 189-203 ). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4 + T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori . These results indic ate

  4. Helicobacter pylori infection in patients undergoing appendectomy.

    Science.gov (United States)

    Pavlidis, T E; Atmatzidis, K S; Papaziogas, B T; Souparis, A; Koutelidakis, I M; Papaziogas, T B

    2002-01-01

    Helicobacter pylori has been found in the upper gastrointestinal tract; it is incriminated as aetiological factor in various pathological conditions. This prospective study assesses the presence of this microorganism in the appendix flora and the possible role of its infection in the pathogenesis of acute appendicitis. H. pylori was investigated in 46 consecutive patients undergoing emergent appendectomy for presumed acute appendicitis. Blood sample for serological test of H. pylori infection was drawn before operation. The removed appendix specimen was stained for H. pylori; confirmation was made by PCR (Polymerase Chain Reaction) analysis. The intensity of inflammation was determined pathologically grading from no inflammation to gangrenous appendicitis. Statistical analysis was made using the chi-square test. Seropositivity for H. pylori infection was found in 18 patients (39%), but the microbe was detected in just two appendix specimens (4%). In all seropositive patients acute appendicitis was confirmed by the pathology study; serous (33%) and purulent or gangrenous (67%). The latter incidence in the seronegative patients was 50%. There were found eight specimens (17%) negative for inflammation dealing all with seronegative patients. It seems that H. pylori colonizes the appendix in small proportion and is unlikely to be associated in direct correlation with acute appendicitis. However, seropositive patients with acute inflammation are likely to suffer from purulent or gangrenous form.

  5. Changing epidemiology of Helicobacter pylori in Japan.

    Science.gov (United States)

    Inoue, Manami

    2017-03-01

    Helicobacter pylori (H. Pylori) is known as the most important cause of gastric cancer. The prevalence of H. pylori infection varies widely by geographic area, age, and socioeconomic status. In Japan, H. pylori infection has been highly correlated with the incidence rate of gastric cancer, and a reduction in H. pylori infection is therefore crucial for decreasing the incidence of gastric cancer, especially at the population level. Infection occurs during childhood, commonly before 5 years of age. In Japan, where gastric cancer has ranked as the most common cancer by incidence and mortality for the last several decades, the prevalence of H. pylori infection has dramatically declined by birth cohort effect, mainly due to improvements in the general hygiene environment in childhood. Older generations born before around 1950 show a high prevalence of around 80-90 %, decreasing with age to reach around 10 % or less in those born around the 1990s, and less than 2 % for children born after the year 2000. This change will have generational effects on gastric cancer prevention strategies, both primary and secondary. The risk-stratified approach to gastric cancer prevention should be considered in Japan and other countries which have similarly experienced rapid economic development.

  6. No Helicobacter pylori, no Helicobacter pylori-associated peptic ulcer disease

    NARCIS (Netherlands)

    Tytgat, G. N.

    1995-01-01

    Virtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUs) are the consequence of Helicobacter pylori-associated inflammation. In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb. Gastrin homeostasis is disturbed by H. pylori

  7. II Consenso Brasileiro sobre Helicobacter pylori Second Brazilian Consensus Conference on Helicobacter pylori infection

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    Luiz Gonzaga Vaz Coelho

    2005-06-01

    Full Text Available Avanços significativos ocorridos desde o Primeiro Consenso Brasileiro sobre H. pylori realizado em 1995, em Belo Horizonte, MG, justificam este segundo consenso. O evento foi organizado pela Federação Brasileira de Gastroenterologia e pelo Núcleo Brasileiro para Estudo do Helicobacter, sendo realizado em São Paulo nos dias 19 e 20 de junho de 2004. Contou com a participação das principais autoridades nacionais na área, a partir de lista elaborada pelas duas sociedades organizadoras do evento. Assim, participaram 36 delegados provenientes de 15 estados brasileiros, incluindo gastroenterologistas, patologistas, pediatras e microbiologistas. Os participantes foram alocados em um dos cinco sub-temas a serem contemplados no encontro, a saber: Helicobacter pylori e dispepsia funcional; Helicobacter pylori e AINEs; Helicobacter pylori e doença do refluxo gastroesofágico; tratamento Helicobacter pylori e retratamento Helicobacter pylori. Foi adotado como consensual as decisões que atingissem 70% ou mais de concordância entre os participantes. Os resultados foram apresentados em outubro de 2004 durante sessão especial da VI Semana Brasileira do Aparelho Digestivo, realizada em Recife, PE, e esta publicação apresenta o sumário das principais recomendações e conclusões do evento.Significant progress has been obtained since the First Brazilian Consensus Conference on H. pylori Infection held in 1995, in Belo Horizonte, MG, and justify a second meeting to establish updated guidelines on the current management of H. pylori infection. The Second Brazilian Consensus Conference on H. pylori Infection was organized by the Brazilian Federation of Gastroenterology and Brazilian Nucleus for the Study of Helicobacter and took place on June, 19-20, 2004 in São Paulo, SP. Thirty six delegates coming from 15 different Brazilian states including gastroenterologists, pathologists, microbiologists and pediatricians undertook the meeting. The

  8. Helicobacter pylori virulence factors in development of gastric carcinoma.

    Science.gov (United States)

    Wang, Ming-Yi; Liu, Xiao-Fei; Gao, Xiao-Zhong

    2015-01-01

    Helicobacter pylori plays a vital role in the pathogenesis of gastric carcinoma. However, only a relatively small proportion of individuals infected with H. pylori develop gastric carcinoma. Differences in the incidence of gastric carcinoma among infected individuals can be explained, at least partly, by the different genotypes of H. pylori virulence factors. Thus far, many virulence factors of H. pylori, such as Cag PAI, VacA, OMPs and DupA, have been reported to be involved in the development of gastric cancer. The risk of developing gastric cancer during H. pylori infection is affected by specific host-microbe interactions that are independent of H. pylori virulence factors. In this review, we discuss virulence factors of H. pylori and their role in the development of gastric carcinoma that will provide further understanding of the biological interactions of H. pylori with the host.

  9. Association of specific haplotype of TNFα with Helicobacter pylori ...

    Indian Academy of Sciences (India)

    pylori-mediated duodenal ulcer in eastern Indian population. MEENAKSHI ... IL6 and IL8 revealed no association with H. pylori-mediated duodenal ulcer at the .... cation, belonging to the same caste/ethnic (Bengali–Hindu) background.

  10. Helicobacter Pylori – A Moving Target | Lambiotte | South African ...

    African Journals Online (AJOL)

    Pylori) continues to grow. Testing is also now advised for patients with immune thrombocytopenia purpura, unexplained vitamin B12 or iron deficiency anemia. Despite the indications for treatment of Helicobacter pylori infection widening, definitive ...

  11. Helicobacter pylori infection in Africa: Pathology and microbiological ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Environmental factors are not unique in determining the clinical impact of H. pylori ..... There are various techniques of detecting H. pylori from specimens. ..... urease enzyme that splits urea into ammonia and carbon dioxide.

  12. Prevalence of Helicobacter pylori and risk factors among dyspepsia ...

    African Journals Online (AJOL)

    Helicobacter pylori antibody conjugated with colloid gold nitrocellulose membrane strip and a structured face-to-face interview was also administered to assess risk factors for H. pylori infection. Data were analyzed using SPSS version 20. Logistic ...

  13. Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.

    Directory of Open Access Journals (Sweden)

    Daniel P Barry

    Full Text Available Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2 is essential for transport of L-arginine (L-Arg into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO produced from inducible NO synthase (iNOS, or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2(-/- mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2(-/- mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2(-/- mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection.

  14. Evaluation of gastric histology in children and adolescents with Helicobacter pylori gastritis using the Update Sydney System.

    Science.gov (United States)

    Langner, Marini; Machado, Rodrigo Strehl; Patrício, Francy R S; Kawakami, Elisabete

    2009-01-01

    Although Helicobacter pylori infection is prevalent in our country, there are few studies evaluating the associated histological abnormalities in children. To evaluate the histological features of the gastric mucosa in children and adolescents with Helicobacter pylori gastritis. One hundred and thirty two gastric biopsies from 22 symptomatic patients infected with H. pylori (14F/8M, median age 10 y 5 mo, age range 2 y 11 mo to 16 y 9 mo) were evaluated. Evaluated gastric regions included: antrum (lesser and greater curvature), corpus (lesser and greater curvature), incisura angularis and fundus. Histological examination was performed according to the Updated Sydney System, and regional scores for polymorphonuclear and mononuclear cell infiltrate as well as bacterial density were generated. Fifteen (68.2%) patients presented H. pylori-chronic active gastritis, six (27.3%) presented antrum-predominant H. pylori-chronic active gastritis, and one (4.5%) presented corpus-predominant H. pylori-chronic active gastritis. Polymorphonuclear cell infiltrate and mononuclear cell infiltrate were observed in 93.9% and 98.5% of the biopsy specimens, respectively. Higher histological scores for polymorphonuclear infiltrate, mononuclear infiltrate, and bacterial density were observed in the gastric antrum. Intestinal metaplasia and gastric atrophy were not identified in any patient. Lymphoid aggregates and lymphoid follicles were observed in the gastric antrum of three (13.6%) and seven (31.8%) patients, respectively, but they were not related to antral nodularity. Chronic active gastritis was observed in all patients with H. pylori infection. However, antral or corporeal predominance was not observed in most patients.

  15. Helicobacter pylori-coccoid forms and biofilm formation

    DEFF Research Database (Denmark)

    Andersen, Leif Percival; Rasmussen, Lone

    2009-01-01

    be detected by PCR in water supplies. There is no substantial evidence for viable H. pylori persisting in water supplies. Epidemiological studies suggest that environmental water is a risk factor for H. pylori infection when compared with tap water, and formation of H. pylori biofilm cannot be excluded....... Helicobacter pylori does not seem to take part in biofilm formation in the oral cavity even though the bacterium may be detected....

  16. Association Between Helycobacter Pylori Infection and Pathological Oral Manifestations

    Directory of Open Access Journals (Sweden)

    Carini Francesco

    2016-03-01

    Full Text Available Data from the literature are controversial regarding the presence of Helicobacter pylori (H. pylori in dental plaque and its association with gastric infection. One of the possible mechanisms suggested for re-infection is the recolonization with H. pylori from dental plaque. The purpose of this review was to determine whether dental plaque, poor oral hygiene, and periodontal disease were risk factors for H. pylori infection.

  17. [Helicobacter pylori and gastroduodenal lesions in 547 symptomatic young adults].

    Science.gov (United States)

    Rudelli, A; Vialette, G; Brazier, F; Seurat, P L; Capron, D; Dupas, J L

    1996-01-01

    Helicobacter pylori (H. pylori) is involved in the pathogenesis of gastric inflammatory disorders. Both antral chronic gastritis and H. pylori infection prevalence increase with age. The aim of the study was to assess the prevalence of H. pylori infection in young adults and to study the relationship between endoscopical and histological features and H. pylori infection. The study concerned 547 young patients (age: 18-25 years), undergoing endoscopy for upper gastrointestinal symptoms. The severity and the activity of chronic gastritis was graded by histological examination of antral biopsies. The diagnosis of H. pylori infection was based on histology and culture or urease test. Fifty-three percent of the patients had a normal endoscopy; 44 ulcers were found: 34 duodenal ulcers and 10 gastric ulcers. H. pylori infection was detected in 34% of cases. The prevalence of H. pylori infection was 29.8% in non-ulcer patients, 50% in gastric ulcers and 91% in duodenal ulcers (P < 0.01). Duodenal ulcer, aspect of antral mosaic mucosa and nodular gastritis, were closely related to the presence of H. pylori. There was a significant relationship between H. pylori infection and both the severity (P < 0.01) and the activity (P < 0.01) of the antral chronic gastritis. The prevalence of follicular gastritis was 22% : it was present in 60% of H. pylori positive patients and 2.4% of H. pylori negative patients. H. pylori infection was more frequent in patients from Africa than in Europeans (P < 0.01). There was no significant association between H. pylori infection and different types of diets, settlements (rural vs urban) or symptoms. These results show that in the young population studied, duodenal ulcer, nodular gastritis, antral mosaic mucosa, active chronic gastric and follicular gastritis are closely related to H. pylori infection. They suggest that in the subgroup of non ulcer symptomatic patients, H. pylori prevalence is higher than in the general population.

  18. Detection of Helicobacter pylori urease antigen in saliva in patients with different gastric H. pylori status.

    Science.gov (United States)

    El Khadir, Mounia; Alaoui Boukhris, Samia; Benajah, Dafr-Allah; El Rhazi, Karima; Ibrahimi, Sidi Adil; El Abkari, Mohamed; Harmouch, Taoufiq; Nejjari, Chakib; Mahmoud, Mustapha; Benlemlih, Mohamed; Bennani, Bahia

    2016-07-01

    Finding a simple, accurate, and noninvasive diagnosis method is a substantial challenge for the detection of Helicobacter pylori. The aim of the present study was to compare the presence of H. pylori urease antigen in saliva with the presence of this bacterium in gastric mucosa. Saliva samples and gastric biopsies were taken from 153 consenting Moroccan patients. Saliva samples were analyzed using an immunochromatographic test for urease antigen H. pylori detection. Thereafter, the gastric biopsies were analyzed by histology and polymerase chain reaction (PCR) to detect this bacterium. From a total of 153 recruited Moroccan patients, H. pylori was detected in 28 (18.30%), 87 (57.24%), and 69 (45.10%) cases by saliva test, histology, and PCR, respectively. A significant association was observed between the presence of H. pylori antigen in saliva and age. However, no association was found with sex, H. pylori virulence factors, gastric disease outcome, and density of the bacterium on the gastric mucosa. Considering that only 90 patients presented concordant results on H. pylori diagnosis (positive or negative) by both histology and PCR, the immunochromatographic test showed very low sensitivity (29.79%) and high specificity (90.70%). Of these two tests, the positive and negative predictive values were 77.78% and 54.17%, respectively. The accuracy of the test for salivary detection of urease antigen H. pylori was 58.89%. This study demonstrated a low detection rate of H. pylori antigens in saliva compared with the presence of this bacterium in gastric mucosa, suggesting that saliva cannot be used as a suitable sample for the diagnosis of H. pylori in our study population. Copyright © 2016. Published by Elsevier Taiwan LLC.

  19. A changing gastric environment leads to adaptation of lipopolysaccharide variants in Helicobacter pylori populations during colonization.

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    Anna Skoglund

    2009-06-01

    Full Text Available The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarcinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression.

  20. Diagnosis of Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Nysaeter, G.; Berstad, K.; Weberg, R.; Berstad, A.; Hardardottir, H.

    1992-01-01

    By employing the 14 C-urea breath test as the reference methods the authors determined the specificity and sensitivity of three bioptic methods for diagnosis of Helicobacter pylori infection in 103 subjects. All biopsy specimens were obtained from the gastric antrum. For culture the specificity was 100%. Its applicability was reduced, however, by a low sensitivity (73.8%) and a delay of several days before the final result was available. Microscopy of Loeffler-stained biopsy smears yielded a specificity of 100% and a sensitivity of 92.9%, but the method was regarded time-consuming. The rapid urease test yielded a specificity of 98.4% and a sensitivity of 85.7%. Being quick, simple and inexpensive, the rapid urease test is well suited for routine use in gastroscopy. 17 refs., 4 tabs

  1. Helicobacter pylori infection: past, present and future | Jemilohun ...

    African Journals Online (AJOL)

    Helicobacter pylori infection: past, present and future. ... The discovery of Helicobacter pylori (H. pylori) by Warren and Marshall in 1982 was preceded by nearly a hundred year of inconspicuous publications in ... A major challenge is the absence of a specific antibiotic monotherapy for effective treatment of the infection.

  2. Helicobacter pylori : the causative agent of peptic ulcer ...

    African Journals Online (AJOL)

    This review examines Helicobacter pylori as an organism and as the causative agent of peptic ulcers. The review also examined the classification of ulcers, ... Elimination of Helicobacter pylori by treatment with antibiotics in peptic ulcer patients resulted in the healing of the ulcer. Prevention of Helicobacter pylori infections is ...

  3. Relation between Helicobacter pylori infection and chronic urticaria

    Directory of Open Access Journals (Sweden)

    Adianez Sugrañes-Montalván

    2017-12-01

    Conclusions: In the present study, the relationship between chronic urticaria and Helicobacter pylori infection was demonstrated. Apparently, the eradicating treatment for Helicobacter pylori was effective as the patients had no symptoms after treatment. Specific immunoglobulin G and Urease Test together constitute a suitable diagnostic module for the diagnosis of Helicobacter pylori conditions.

  4. Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion

    Science.gov (United States)

    Bodger, K; Bromelow, K; Wyatt, J; Heatley, R

    2001-01-01

    the surface epithelium in all H pylori positive cases and in 13 of 16 negative cases, especially in areas of surface epithelial degeneration. Lamina propria mononuclear cells (LPMNCs) were positively stained in all H pylori positive cases and in 12 of 16 negative cases, with a significantly greater proportion of positive LPMNCs in the positive group. Conclusions—This study localised IL-10 protein to the gastric epithelium and LPMNCs. In vitro proinflammatory cytokine secretion was increased in H pylori infection (especially CagA positive infection), but blocking endogenous IL-10 secretion did not significantly increase cytokine secretion. IL-10 is implicated in H pylori infection and might "damp down" local inflammation. The role of gastric IL-10 secretion in determining the clinicopathological outcome of infection merits further study. Key Words: Helicobacter pylori infection • interleukin 10 • gastritis • immunohistochemistry PMID:11304845

  5. Gastric mucosa-associated lymphoid tissue lymphomas and Helicobacter pylori infection: A Colombian perspective

    Institute of Scientific and Technical Information of China (English)

    Sally Yepes; Maria Mercedes Torres; Carlos Saavedra; Rafael Andrade

    2012-01-01

    AIM:To assess the significance of chromosome translocation t(11;18)(q21;q21),B-cell lymphoma 10 (BCL-10)protein and Helicobacter pylori (H.pylori) infection in gastric mucosa-associated lymphoid tissue (MALT) lymphoma in Colombia.METHODS:Fifty cases of gastric MALT lymphoma and their respective post-treatment follow-up biopsies were examined to assess the presence of the translocation t(11;18)(q21;q21) as identified by fluorescence in situ hybridization; to detect protein expression patterns of BCL10 using immunohistochemistry; and for evaluation of tumor histology to determine the correlation of these factors and resistance to H.pylori eradication.RESULTS:Infection with H.pylori was confirmed in all cases of gastric MALT lymphoma in association with chronic gastritis.Bacterial eradication led to tumor regression in 66% of cases.The translocation t(11;18)(q21;q21) was not present in any of these cases,nor was there evidence of tumor transformation to diffuse large B-cell lymphoma.Thirty-four percent of the patients showed resistance to tumor regression,and within this group,7 cases,representing 14% of all those analyzed,were considered to be t(11;18)(q21;q21)-positive gastric MALT lymphomas.Protein expression of BCL10 in the nucleus was associated with the presence of translocation and treatment resistance.Cases that were considered unresponsive to therapy were histologically characterized by the presence of homogeneous tumor cells and a lack of plasmacytic differentiation.Responder cases exhibited higher cellular heterogeneity and a greater frequency of plasma cells.CONCLUSION:Both t(11;18)(q21;q21)-positive MALT lymphoma cases and those with nuclear BCL10 expression are considered resistant to H,pylori eradication.It is suggested that chronic antigenic stimulation is not a dominant event in resistant cases.

  6. Comparison of IL-6, IL-8 Concentrations in H. pylori- and non-H. pylori-associated Gastritis

    Directory of Open Access Journals (Sweden)

    Gontar Alamsyah Siregar

    2014-12-01

    Full Text Available BACKGROUND: Helicobacter pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. The gastric mucosal levels of the proinflammatory cytokines Interleukin 6 (IL-6 and IL-8 have been reported to be increased in H. pylori infection, but the serum levels in H. pylori infection is still controversial. The purpose of this study was to investigate the serum levels of IL-6 and IL-8 in H. pylori infection. METHODS: A cross sectional study was done on eighty consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from May-October 2014. Histopathology was performed for the diagnosis of gastritis. Rapid urease test for diagnosis of H. pylori infection. Serum samples were obtained to determine circulating IL-6 and IL-8. Univariate and bivariate analysis (independent t test were done. RESULTS: There were 41.25% patients infected with H. pylori. Circulatory IL-6 levels were significantly higher in H. pylori-infected patients compared to H. pylori negative, but there were no differences between serum levels of IL-8 in H. pylori positive and negative patients. CONCLUSIONS: The immune response to H. pylori promotes systemic inflammation, which was reflected in an increased level of serum IL-6. Serum levels of IL-8 were not significantly different between H. pylori positive and negative. KEYWORDS: Helicobacter pylori, gastritis, IL-6, IL-8, cytokine.

  7. Anti-Helicobacter pylori activity of bioactive components isolated from Hericium erinaceus.

    Science.gov (United States)

    Liu, Jian-Hui; Li, Liang; Shang, Xiao-Dong; Zhang, Jun-Ling; Tan, Qi

    2016-05-13

    The fungus Hericium erinaceus (Bull.) Pers is used in Chinese traditional medicine to treat symptoms related to gastric ulcers. Different extracts from the fungus were assessed for anti-Helicobacter pylori activity to investigate the antibacterial activity of the ethanol extracts from H. erinaceus and verify the traditional indication of use. The fruiting bodies of H. erinaceus were concentrated with ethanol by HPD-100 macroporous resin and the whole extract was partitioned by petroleum ether and chloroform to afford fractions with using a silica gel column. Several pure compounds of petroleum ether extracts were obtained and analyzed using nuclear magnetic resonance (NMR). The activity of the extracts and fractions towards H. pylori was assessed by the microdilution assay and by the disk diffusion assay in vitro. From the most active fraction, two pure compounds were isolated and identified as the main components with anti-H. pylori activity from the fungus H. erinaceus. The cytotoxicity of these two compounds against the human erythroleu-kemia cell line K562 was also evaluated. The crude ethanol extracts from the fungus H. erinaceus were inhibitory to H. pylori. The petroleum ether extracts (PE1s, PE2s) and the chloroform extracts (TEs) demonstrated strong inhibition to H. pylori. The inhibition of H. pylori was observed through an agar dilution test with minimal inhibition concentration (MIC) values from 400μg/mL to 12.5µg/mL. Two pure compounds, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid were isolated from the petroleum ether fractions and identified using (1)H NMR and (13)C NMR spectra analysis. The MIC value for 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone was 12.5-50µg/mL and the MIC value for 2,5-bis(methoxycarbonyl)terephthalic acid was 6.25-25µg/mL. Both two compounds showed weak cytotoxicity against K562 with IC50<200mM. This study revealed that the extracts from petroleum ether contribute to

  8. Helicobacter pylori displays spiral trajectories while swimming like a cork-screw in solutions

    Science.gov (United States)

    Constantino, Maira A.; Hardcastle, Joseph M.; Bansil, Rama; Jabbarzadeh, Mehdi; Fu, Henry C.

    Helicobacter pylori is a helical shaped bacterium that causes gastritis, ulcers and gastric cancer in humans and other animals. In order to colonize the harsh acidic environment of the stomach H. pylori has evolved a unique biochemical mechanism to go across the viscoelastic gel-like gastric mucus layer. Many studies have been conducted on the swimming of H. pylori in viscous media. However a yet unanswered question is if the helical cell shape influences bacterial swimming dynamics or confers any advantage when swimming in viscous solution. We will present measurements of H. pylori trajectories displaying corkscrew motion while swimming in solution obtained by tracking single cells using 2-dimensional phase contrast imaging at high magnification and fast frame rates and simultaneously imaging their shape. We observe a linear relationship between swimming speed and rotation rate. The experimental trajectories show good agreement with trajectories calculated using a regularized Stokeslet method to model the low Reynolds number swimming behavior. Supported by NSF PHY 1410798 (PI: RB).

  9. Evaluation of SD BIOLINE H. pylori Ag rapid test against double ELISA with SD H. pylori Ag ELISA and EZ-STEP H. pylori Ag ELISA tests.

    Science.gov (United States)

    Negash, Markos; Kassu, Afework; Amare, Bemnet; Yismaw, Gizachew; Moges, Beyene

    2018-01-01

    Helicobacter pylori antibody titters fall very slowly even after successful treatment. Therefore, tests detecting H. pylori antibody lack specificity and sensitivity. On the other hand, H. pylori stool antigen tests are reported as an alternative assay because of their reliability and simplicity. However, the comparative performance of H. pylori stool antigen tests for detecting the presence of the bacterium in clinical specimens in the study area is not assessed. Therefore, in this study we evaluated the performance of SD BIOLINE H. pylori Ag rapid test with reference to the commercially available EZ- STEP ELISA and SD BIOLINE H. pylori Ag ELISA tests. Stool samples were collected to analyse the diagnostic performance of SD BIOLINE H. pylori Ag rapid test kit using SD H. pylori Ag ELISA kit and EZ- STEP ELISA tests as a gold standard. Serum samples were also collected from each patient to test for the presence of H. pylori antibodies using dBest H. pylori Test Disk. Sensitivity, specificity, predictive values and kappa value are assessed. P values H. pylori Ag rapid test were: 95.6% (95% CI, 88.8-98.8), 92.5% (95%CI, 89-94.1%), 86.7% (95% CI, 80.5-89.6), and 97.6% (95% CI, 993.9-99.3) respectively. The performance of SD BIOLINE H. pylori Ag rapid test was better than the currently available antibody test in study area. Therefore, the SD BIOLINE Ag rapid stool test could replace and be used to diagnose active H. pylori infection before the commencement of therapy among dyspeptic patients.

  10. Horizontal versus familial transmission of Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Sandra Schwarz

    2008-10-01

    Full Text Available Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorly understood. We studied the genetic relationships of H. pylori isolated from 52 individuals of two large families living in a rural community in South Africa and from 43 individuals of 11 families living in urban settings in the United Kingdom, the United States, Korea, and Colombia. A 3,406 bp multilocus sequence haplotype was determined for a total of 142 H. pylori isolates. Isolates were assigned to biogeographic populations, and recent transmission was measured as the occurrence of non-unique isolates, i.e., isolates whose sequences were identical to those of other isolates. Members of urban families were almost always infected with isolates from the biogeographic population that is common in their location. Non-unique isolates were frequent in urban families, consistent with familial transmission between parents and children or between siblings. In contrast, the diversity of H. pylori in the South African families was much more extensive, and four distinct biogeographic populations circulated in this area. Non-unique isolates were less frequent in South African families, and there was no significant correlation between kinship and similarity of H. pylori sequences. However, individuals who lived in the same household did have an increased probability of carrying the same non-unique isolates of H. pylori, independent of kinship. We conclude that patterns of spread of H. pylori under conditions of high prevalence, such as the rural South African families, differ from those in developed countries. Horizontal transmission occurs frequently between persons who do not belong to a core family, blurring the pattern of familial

  11. Treatment of Helicobacter Pylori in Children

    Directory of Open Access Journals (Sweden)

    F Famouri

    2014-04-01

    Full Text Available Childrenwith Helicobacter infection need treatment. The aim of treatment is elimination of H.Pylori. Most patients with this infection are asymptomatic and without peptic disease. Treatment and management of these patients are controversy. Conventional Treatment: The best treatment for H. pylori eradication regimens should have cure rates of at least 80%, be without major side effects, and induce minimal bacterial resistance. Antibiotics alone have not achieved this. Luminal acidity influences both the effectiveness of some antimicrobial agents and the survival of the bacteri; thus antibiotics have been combined with acid suppression such as proton pump inhibitors (PPIs, bismuth, or H2 antagonists. The “classic” regimen is treatment twice daily for 7 days with a PPI and clarithromycin plus either amoxicillin or metronidazole Bismuth has been used in the treatment of peptic ulcer disease and 1 part o quadruple therapy for H.Pylori but compliance of children for it is low.   Sequential Therapy  Sequential therapyinvolves dual therapy with a PPI and amoxicillin for 5 days followed sequentially by clarithromycin, Tinidazole and omeperazole for 5 days or other triple therapy for 7 days. This treatment has had 97% efficacy.   Adjunctive Therapies A number of studies have showed the potential benefits of probiotic therapy in H. pylori treatment regimens.Consumption of these drugs accompanied with other medications increase H.Pylori eradication.    

  12. Helicobacter Pylori Infection in the Elderly

    Directory of Open Access Journals (Sweden)

    Jyh-Ming Liou

    2008-12-01

    Full Text Available The elderly often seek medical attention because of gastroduodenal diseases. Helicobacter pylori (H. pylori infection is associated with several gastroduodenal diseases and its prevalence increases with age worldwide. It is estimated that 10–15% of infected patients will have peptic ulcer disease and 1% of patients will have gastric cancer or mucosa-associated lymphoid tissue lymphoma. Notably, the most severe clinical outcomes, i.e., gastric cancer and complicated peptic ulcer diseases, usually occur in elderly patients. Thus the test-and-treatment strategy is not recommended for elderly patients with uninvestigated dyspepsia. However, biopsy specimens for the rapid urease test and histology should be taken from both the antrum and corpus to increase the detection rate in elderly patients, especially in those with atrophic gastritis. The urea breath test may increase the detection rate if the rapid urease test or histology are negative in elderly patients with atrophic gastritis. Standard triple therapy and sequential therapy can achieve satisfactory eradication rates for H. pylori in elderly patients. Elderly patients with peptic ulcers may have a similar benefit from treatment of H. pylori infection as non-elderly patients. Eradication of H. pylori infection may also lead to improvement in histologic grading of gastritis, but the risk of gastric cancer cannot be completely reduced, especially in patients with existing premalignant lesions.

  13. Phylogenomics of Colombian Helicobacter pylori isolates.

    Science.gov (United States)

    Gutiérrez-Escobar, Andrés Julián; Trujillo, Esperanza; Acevedo, Orlando; Bravo, María Mercedes

    2017-01-01

    During the Spanish colonisation of South America, African slaves and Europeans arrived in the continent with their corresponding load of pathogens, including Helicobacter pylori . Colombian strains have been clustered with the hpEurope population and with the hspWestAfrica subpopulation in multilocus sequence typing (MLST) studies. However, ancestry studies have revealed the presence of population components specific to H. pylori in Colombia. The aim of this study was to perform a thorough phylogenomic analysis to describe the evolution of the Colombian urban H. pylori isolates. A total of 115 genomes of H. pylori were sequenced with Illumina technology from H. pylori isolates obtained in Colombia in a region of high risk for gastric cancer. The genomes were assembled, annotated and underwent phylogenomic analysis with 36 reference strains. Additionally, population differentiation analyses were performed for two bacterial genes. The phylogenetic tree revealed clustering of the Colombian strains with hspWestAfrica and hpEurope, along with three clades formed exclusively by Colombian strains, suggesting the presence of independent evolutionary lines for Colombia. Additionally, the nucleotide diversity of horB and vacA genes from Colombian isolates was lower than in the reference strains and showed a significant genetic differentiation supporting the hypothesis of independent clades with recent evolution. The presence of specific lineages suggest the existence of an hspColombia subtype that emerged from a small and relatively isolated ancestral population that accompanied crossbreeding of human population in Colombia.

  14. H. Pylori Positivity and Various Pathological, Endoscopic and Clinical Features Correlated with Each Other

    International Nuclear Information System (INIS)

    Coskun, A.; Yukselen, V.; Yasa, M. H.; Karaoglu, A. O.; Meteoglu, I.; Ergin, F.; Kadikoylu, G.

    2015-01-01

    Objective: To investigate the relationship between dyspepsia symptom scores and endoscopic appearances, and histopathological findings and helicobacter pylori positivity in patients having dyspepsia symptom. Methods: The study was conducted at the gastroenterology outpatient clinic of Adnan Menderes University, School of Medicine, Aydin, Turkey from April 2012 to July 2012 and comprised patients between 18-65 years of age who were admitted with dyspepsia. Glasgow dyspepsia severity scoring was done with questions posed orally to the patients. In histopathological evaluation of biopsy specimens according to Sydney criteria, chronic inflammation, activity, atrophy, intestinal metaplasia and helicobacter pylori parameters were used. Total number of eosinophils and number of mast cells were recorded. Results: Of the 60 patients with dyspepsia, 38(63.3 percent) were female and 22(36.7 percent) were male. The degree of activation and severity of inflammation increased significantly with increasing helicobacter pylori positivity(r=0.459'p<0.0001; r=0.475'p<0.0001). A significant relationship was found between inflammation, activation and the number of mast cells (p<0.05).There was no relationship between helicobacter pylori intensity and the eosinophil count (r=0.171; p=0.093). There was also a statistically significant correlation between severity of inflammation and activation and the number of eosinophils (r=0.313;p=0.002;r=0.245;p=0.016). Conclusion: Mast cell density was seen to have a role in the inflammatory processes of helicobacter pylori infection. (author)

  15. The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis

    Science.gov (United States)

    Oleastro, Mónica; Ménard, Armelle

    2013-01-01

    Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1) colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2) evasion from the human immune system and (3) efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence. PMID:24833057

  16. The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Armelle Ménard

    2013-08-01

    Full Text Available Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1 colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2 evasion from the human immune system and (3 efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence.

  17. A Global Overview of the Genetic and Functional Diversity in the Helicobacter pylori cag Pathogenicity Island

    Science.gov (United States)

    Moodley, Yoshan; Uhr, Markus; Stamer, Christiana; Vauterin, Marc; Suerbaum, Sebastian; Achtman, Mark

    2010-01-01

    The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI–carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown. PMID:20808891

  18. Association between Helicobacter pylori seropositivity and Hepatic Encephalopathy

    International Nuclear Information System (INIS)

    Behroozian, R.; Faramarzpur, M.; Rahimi, E.

    2010-01-01

    Objective: The knowledge on Helicobacter pylori (H. pylori) contribution in the pathology of the liver and biliary tract diseases in human is very limited. The aim of this study was to assess the probable association between H. pylori seropositivity and hepatic encephalopathy. Methodology: This is a case control study conducted through three groups, cirrhotics with hepatic encephalopathy (HE), cirrhotics without HE and healthy controls. All subjects were examined serologically for determination of IgG class antibodies to H. pylori based on ELISA technique. Results: H. pylori seropositivity was present in 88% cirrhotic patients with hepatic encephalopathy, 86% cirrhotics without hepatic encephalopathy and 66% healthy controls. Conclusion: According to our results, H. pylori seropositivity rate in cirrhotic patients with or without hepatic encephalopathy was higher than healthy controls. But H. pylori seropositivity rate was not significantly different among cirrhotics with hepatic encephalopathy and those without it.

  19. Neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) is upregulated in gastric mucosa infected with Helicobacter pylori

    DEFF Research Database (Denmark)

    Alpízar-Alpízar, Warner; Laerum, Ole Didrik; Illemann, Martin

    2009-01-01

    characterized here the pattern of expression of NGAL/Lcn2 in gastric mucosa (45 non-neoplastic and 38 neoplastic tissue samples) and explored the connection between NGAL/Lcn2 expression and H. pylori infection. Immunohistochemical analysis showed high NGAL/Lcn2 expression in normal and gastritis-affected mucosa...... compared to low expression in intestinal metaplasia, dysplasia, and gastric cancer. In normal and gastritis-affected mucosa (n=36 tissue samples), NGAL/Lcn2 was more frequently seen in epithelial cells located at the neck and base of the glands in H. pylori-positive cases than in similar epithelial cells...... of noninfected cases (Fisher's exact test, p=0.04). In conclusion, the high expression of NGAL/Lcn2 in normal and gastritis-affected mucosa infected with H. pylori suggests that NGAL/Lcn2 is upregulated locally in response to this bacterial infection. It is discussed whether this may have a causal relation...

  20. Rosacea is associated with Helicobacter pylori

    DEFF Research Database (Denmark)

    Jørgensen, A-H R; Egeberg, A; Gideonsson, R

    2017-01-01

    BACKGROUND: Rosacea is a common skin disease characterized by facial erythema, telangiectasia, papules and pustules. Helicobacter pylori infection has been suggested to play a role in the etiopathogenesis of rosacea. OBJECTIVE: To systematically review and meta-analyse the relationship between...... rosacea and infection with Helicobacter pylori. METHODS: A literature search was performed using PubMed, EMBASE and Web of Science. Data extraction and analyses were performed on descriptive data. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models with Der...... in the quantitative meta-analysis, comprising a total of 928 rosacea patients and 1527 controls. The overall association between Helicobacter pylori infection and rosacea was non-significant (OR 1.68, 95% CI 1.00-2.84, P = 0.052), but analysis restricted to C-urea breath test showed a significant association (OR 3...

  1. Helicobacter pylori vaccine: from past to future.

    Science.gov (United States)

    Agarwal, Kanishtha; Agarwal, Shvetank

    2008-02-01

    Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.

  2. Treatment of Helicobacter pylori infection 2011.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    This article reviews the literature published pertaining to Helicobacter pylori eradication over the last year. The general perception among clinicians and academics engaged in research on H. pylori has been that eradication rates for first-line therapies are falling, although some data published this year have cast doubt on this. The studies published this year have therefore focussed on developing alternative strategies for the first-line eradication of H. pylori. In this regard, clear evidence now exists that both levofloxacin and bismuth are viable options for first-line therapy. The sequential and "concomitant" regimes have also been studied in new settings and may have a role in future algorithms also. In addition, data have emerged that the probiotic Saccharomyces boulardii may be a useful adjunct to antibiotic therapy. Other studies promote individualized therapies based on host polymorphisms, age, and other such demographic factors.

  3. Invasive Tests for Helicobacter Pylori in Children

    Directory of Open Access Journals (Sweden)

    Hien Q Huynh

    2005-01-01

    Full Text Available One of the primary indications for upper gastrointestinal (GI endoscopy in children is the presence of persistent and severe upper abdominal symptoms. Upper GI endoscopies are performed to allow the physician to confirm or rule out upper GI pathology. Additionally, upper GI endoscopies with mucosal biopsies are the gold standard for the diagnosis of Helicobacter pylori infection and its complications in children. The gastric biopsies can be used for the rapid urease test, histological examination and bacterial culture to determine antibiotic sensitivity. DNA extracted in these biopsies can also be subjected to genotyping using molecular methods to determine the presence of H pylori infection, antibiotic resistance mutations and H pylori virulence factors.

  4. In Vitro Anti-Helicobacter pylori Activity of the Probiotic Strain Bacillus subtilis 3 Is Due to Secretion of Antibiotics

    Science.gov (United States)

    Pinchuk, Irina V.; Bressollier, Philippe; Verneuil, Bernard; Fenet, Bernard; Sorokulova, Irina B.; Mégraud, Francis; Urdaci, Maria C.

    2001-01-01

    A limited number of antibiotics can be used against Helicobacter pylori infection, and resistance jeopardizes the success of treatment. Therefore, a search for new agents is warranted. The use of probiotics to enhance gastrointestinal health has been proposed for many years, but the scientific basis of the prophylactic and therapeutic actions of probiotics has not yet been clearly delineated. Probiotic strain Bacillus subtilis 3, whose safety has previously been demonstrated, is known to have antagonistic properties against species of the family Enterobacteriaceae. In the present study, it was also found to inhibit H. pylori. The anti-H. pylori activity present in the cell-free supernatant was not related to pH or organic acid concentration. It was heat stable and protease insensitive. At least two antibiotics, detected by thin-layer chromatography (Rf values, 0.47 and 0.85, respectively) and confirmed by high-performance liquid chromatographic analysis, were found to be responsible for this anti-H. pylori activity. All H. pylori strains tested were sensitive to both compounds. One of these compounds was identified as amicoumacin A, an antibiotic with anti-inflammatory properties. MICs for H. pylori determined in solid and liquid media ranged between 1.7 and 6.8 μg/ml and 0.75 and 2.5 μg/ml, respectively. The underestimation of MICs determined in solid medium may be due to physicochemical instability of the antibiotic under these test conditions. An additive effect between amicoumacin A and the nonamicoumacin antibiotic against H. pylori was demonstrated. PMID:11600371

  5. Gene expression profiling in gastric mucosa from Helicobacter pylori-infected and uninfected patients undergoing chronic superficial gastritis.

    Directory of Open Access Journals (Sweden)

    Ze-Min Yang

    Full Text Available Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray using in vitro culture cells and in vivo gastric biopsies from patients of the Chronic Abdominal Complaint. To further explore the effects of H. pylori infection on host gene expression, we have collected the gastric antral mucosa samples from 6 untreated patients with gastroscopic and pathologic confirmation of chronic superficial gastritis. Among them three patients were infected by H. pylori and the other three patients were not. These samples were analyzed by a microarray chip which contains 14,112 cloned cDNAs, and microarray data were analyzed via BRB ArrayTools software and Ingenuity Pathways Analysis (IPA website. The results showed 34 genes of 38 differentially expressed genes regulated by H. pylori infection had been annotated. The annotated genes were involved in protein metabolism, inflammatory and immunological reaction, signal transduction, gene transcription, trace element metabolism, and so on. The 82% of these genes (28/34 were categorized in three molecular interaction networks involved in gene expression, cancer progress, antigen presentation and inflammatory response. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Taken together, these data indicated that H. pylori infection could alter cellular gene expression processes, escape host defense mechanism, increase inflammatory and immune responses, activate NF-κB and Wnt/β-catenin signaling pathway, disturb metal ion homeostasis, and induce carcinogenesis. All of these might help to explain H. pylori pathogenic mechanism and the gastroduodenal pathogenesis induced by H. pylori infection.

  6. Helicobacter pylori: From Bench to Bedside

    Directory of Open Access Journals (Sweden)

    N Chiba

    1997-01-01

    Full Text Available With the exponential increase in research in the field of Helicobacter pylori a paradigm shift has occurred. It is now recognized that H pylori is a chronic infection of the stomach causing inflammation. Some patients remain asymptomatic, while others may develop dyspepsia, duodenal or gastric ulcer, gastric cancer or a mucosa-associated lymphoid tissue lymphoma. However, the role of H pylori in contributing to nonulcer dyspepsia or nonsteroidal anti-inflammatory drug gastropathy remains controversial. An effective vaccine against H pylori is years away. Major interest has focused on the questions "who should be investigated and therefore treated" and "what is the latest gold standard for eradication of H pylori"? In Europe, guidelines have been developed to help the practitioner answer these important questions. Canadian guidelines will soon be available. For persons with known peptic ulcer disease there should be unequivocal acceptance that the good clinical practice of eradicating H pylori will result in substantial savings in health care expenses. The original 'classical triple therapy' (bismuth, metronidazole and tetracycline [BMT] has now been surpassed by the combination of a proton pump inhibitor (PPI plus two antibiotics (metronidazole plus clarithromycin; amoxicillin plus clarithromycin; or amoxicillin plus metronidazole, each given twice a day for one week. In Canada, the regimen of omeprazole plus one antibiotic (amoxicillin or clarithromycin was approved recently but gives an eradication rate that is lower than the current target of 90%. According to the European (Mäastricht recommendations, if a single treatment attempt with PPI plus two antibiotics fails, PPI plus BMT is recommended.

  7. Brief report: Lactobacillus bulgaricus GLB44 (Proviotic™ ) plus esomeprazole for Helicobacter pylori eradication: A pilot study.

    Science.gov (United States)

    Opekun, Antone R; Gonzales, Savannah A; Al-Saadi, Mahmoud A; Graham, David Y

    2018-04-01

    Recent studies of Lactobacillus delbrueckii subsp. bulgaricus GLB44 plus a proton-pump inhibitor (PPI) reported cures of more than 90% of patients with active Helicobacter pylori infections. To confirm the high H. pylori cure rates reported previously. A pilot study was done in healthy H. pylori-infected volunteers using 3-gram sachet (3 billion cells) of L. delbrueckii GLB44 plus 22.3 mg of esomeprazole b.i.d., for 14 days. The result was determined by urea breath testing 4 weeks after therapy. Stopping rules required for ending enrollment if less than 3 of the first 10 subjects were cured. Nine subjects were entered and because all failed to achieve negative urea breath test, the stopping rule required the study to end. We were unable to confirm reports of achieving a high H. pylori cure rate with L. delbrueckii GLB44 plus a PPI. © 2018 John Wiley & Sons Ltd.

  8. Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis

    Science.gov (United States)

    Toyoshima, Osamu; Tanikawa, Chizu; Yamamoto, Ryuta; Watanabe, Hidenobu; Yamashita, Hiroharu; Sakitani, Kosuke; Yoshida, Shuntaro; Kubo, Michiaki; Matsuo, Keitaro; Ito, Hidemi; Koike, Kazuhiko; Seto, Yasuyuki; Matsuda, Koichi

    2018-01-01

    SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10–5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer. We also assessed the association of rs2294008 with PSCA mRNA expression in the gastric mucosa at various disease stages and found that rs2294008 was associated with PSCA expression (P = 1.3 × 10–12). H. pylori infection (P = 5.1 × 10–8) and eradication therapy (P gastritis compared with mild gastritis only among T allele carriers. Our findings revealed the regulation of PSCA expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection. PMID:29423095

  9. Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori.

    Science.gov (United States)

    Lehours, Philippe; Dupouy, Sandrine; Chaineux, Julien; Ruskoné-Fourmestraux, Agnès; Delchier, Jean-Charles; Morgner, Andrea; Mégraud, Francis; Ménard, Armelle

    2007-04-01

    Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.

  10. Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori

    International Nuclear Information System (INIS)

    Han Cong; Wang Qi; Dong Lei; Sun Haifang; Peng Shuying; Chen Jing; Yang Yiming; Yue Jianmin; Shen Xu; Jiang Hualiang

    2004-01-01

    Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K cat of 3.4 s -1 , K m of 1.7 mM, and K cat /K m of 2000 M -1 s -1 . HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 deg. C. The enzyme activity of Co 2+ -containing HpPDF is apparently higher than that of Zn 2+ -containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori

  11. Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori.

    Science.gov (United States)

    Han, Cong; Wang, Qi; Dong, Lei; Sun, Haifang; Peng, Shuying; Chen, Jing; Yang, Yiming; Yue, Jianmin; Shen, Xu; Jiang, Hualiang

    2004-07-09

    Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K(cat) of 3.4s(-1), K(m) of 1.7 mM, and K(cat) / K(m) of 2000M(-1)s(-1). HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 degrees C. The enzyme activity of Co(2+)-containing HpPDF is apparently higher than that of Zn(2+)-containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori.

  12. Nongenetically modified Lactococcus lactis-adjuvanted vaccination enhanced innate immunity against Helicobacter pylori.

    Science.gov (United States)

    Liu, Wei; Tan, Zhoulin; Liu, Hai; Zeng, Zhiqin; Luo, Shuanghui; Yang, Huimin; Zheng, Lufeng; Xi, Tao; Xing, Yingying

    2017-10-01

    Gram-positive enhancer matrix particles (GEM) produced by Lactococcus lactis can enhance vaccine-induced immune response. However, the mechanism under which this adjuvant mounts the efficacy of orally administered vaccines remains unexplored. We used a prophylactic mice model to investigate the mechanism of GEM-adjuvanted vaccination. Helicobacter pylori urease-specific antibody response was monitored and detected in murine serum by ELISA. Urease-specific splenic cytokine profile was examined. Gastric inflammatory responses were measured on day 43 or 71 by quantitative real-time PCR, flow cytometry and histology. We found that GEM enhanced the efficiency of oral H. pylori vaccine by promoting innate immunity. The vaccine CUE-GEM composed of GEM particles and recombinant antigen CTB-UE provided protection of immunized mice against H. pylori insult. The protective response was associated with induction of postimmunization gastritis and local Th1/Th17 cell-medicated immune response. We showed that innate inflammatory responses including neutrophil chemokines CXCL1-2, neutrophils, and antimicrobial proteins S100A8 and MUC1 were significantly elevated. Within all infected mice, S100A8 and MUC1 levels were negatively correlated with H. pylori burden. Strikingly, mice receiving GEM also show reduction of colonization, possibly through natural host response pathways to recruit CD4 + T cells and promote S100A8 expression. These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection. © 2017 John Wiley & Sons Ltd.

  13. Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

    Directory of Open Access Journals (Sweden)

    Pooladi A

    2011-01-01

    polymorphonuclear and mononuclear cells appeared in the antrum, with an increase in epithelial cell proliferation, and the infiltration of focal oesophageal. Control animals showed no abnormal findings throughout the entire observation period. COX-2 protein was expressed in experimental groups but there were no evidence of cox-2 protein expression in control group.Conclusion: Data showed that the H. pylori caused significant decrease of body weight in experimental group. In addition, histological studies showed evidence of metaplasia in rat stomach. Immunohistochemichas studies showed cox-2 protein expression occurred during early stage of metaplasia induction.

  14. Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

    Directory of Open Access Journals (Sweden)

    F Aeini

    2012-05-01

    . Histopathological studies showed severe infiltration of the lamina propria and submucusaal layer by polymorphonuclear and mononuclear cells appeared in the antrum, with an increase in epithelial cell proliferation, and the infiltration of focal oesophageal. Control animals showed no abnormal findings throughout the entire observation period. COX-2 protein was expressed in experimental groups but there were no evidence of cox-2 protein expression in control group. Conclusion: Data showed that the H. pylori caused significant decrease of body weight in experimental group. In addition, histological studies showed evidence of metaplasia in rat stomach. Immunohistochemichas studies showed cox-2 protein expression occurred during early stage of metaplasia induction.

  15. Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

    Science.gov (United States)

    Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

    2017-12-01

    Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 + T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

  16. 3rd Brazilian consensus on Helicobacter pylori 3º Consenso Brasileiro para Estudo do Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.Os avanços significativos ocorridos desde o Segundo Consenso Brasileiro sobre H. pylori realizado em 2004, em São Paulo, justificam este terceiro consenso. O evento foi organizado pelo Núcleo Brasileiro para Estudo do Helicobacter, departamento da Federação Brasileira de Gastroenterologia, tendo sido realizado em Bento Gonçalves, RS, nos dias 12 a 15 de abril de 2011. Contou com a participação de 30 delegados provenientes das cinco regiões brasileiras e um convidado internacional, incluindo gastroenterologistas

  17. Role of Helicobacter pylori methionine sulfoxide reductase in urease maturation

    Science.gov (United States)

    Kuhns, Lisa G.; Mahawar, Manish; Sharp, Joshua S.; Benoit, Stéphane; Maier, Robert J.

    2014-01-01

    The persistence of the gastric pathogen Helicobacter pylori is due in part to urease and Msr (methionine sulfoxide reductase). Upon exposure to relatively mild (21% partial pressure of O2) oxidative stress, a Δmsr mutant showed both decreased urease specific activity in cell-free extracts and decreased nickel associated with the partially purified urease fraction as compared with the parent strain, yet urease apoprotein levels were the same for the Δmsr and wild-type extracts. Urease activity of the Δmsr mutant was not significantly different from the wild-type upon non-stress microaerobic incubation of strains. Urease maturation occurs through nickel mobilization via a suite of known accessory proteins, one being the GTPase UreG. Treatment of UreG with H2O2 resulted in oxidation of MS-identified methionine residues and loss of up to 70% of its GTPase activity. Incubation of pure H2O2-treated UreG with Msr led to reductive repair of nine methionine residues and recovery of up to full enzyme activity. Binding of Msr to both oxidized and non-oxidized UreG was observed by cross-linking. Therefore we conclude Msr aids the survival of H. pylori in part by ensuring continual UreG-mediated urease maturation under stress conditions. PMID:23181726

  18. Characterization and inactivation of an agmatine deiminase from Helicobacter pylori

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Justin E.; Causey, Corey P.; Lovelace, Leslie; Knuckley, Bryan; Flick, Heather; Lebioda, Lukasz; Thompson, Paul R. (SC)

    2010-11-12

    Helicobacter pylori encodes a potential virulence factor, agmatine deiminase (HpAgD), which catalyzes the conversion of agmatine to N-carbamoyl putrescine (NCP) and ammonia - agmatine is decarboxylated arginine. Agmatine is an endogenous human cell signaling molecule that triggers the innate immune response in humans. Unlike H. pylori, humans do not encode an AgD; it is hypothesized that inhibition of this enzyme would increase the levels of agmatine, and thereby enhance the innate immune response. Taken together, these facts suggest that HpAgD is a potential drug target. Herein we describe the optimized expression, isolation, and purification of HpAgD (10-30 mg/L media). The initial kinetic characterization of this enzyme has also been performed. Additionally, the crystal structure of wild-type HpAgD has been determined at 2.1 {angstrom} resolution. This structure provides a molecular basis for the preferential deimination of agmatine, and identifies Asp198 as a key residue responsible for agmatine recognition, which has been confirmed experimentally. Information gathered from these studies led to the development and characterization of a novel class of haloacetamidine-based HpAgD inactivators. These compounds are the most potent AgD inhibitors ever described.

  19. Antimicrobial Nanotherapeutics Against Helicobacter pylori Infection

    Science.gov (United States)

    Thamphiwatana, Soracha

    Helicobacter pylori (H. pylori) infection with its vast prevalence is responsible for various gastric diseases including gastritis, peptic ulcers, and gastric malignancy. While effective, current treatment regimens are challenged by a fast-declining eradication rate due to the increasing emergence of H. pylori strains resistant to existing antibiotics. Therefore, there is an urgent need to develop novel antibacterial strategies against H. pylori. The first area of this research, we developed a liposomal nanoformulation of linolenic acid (LipoLLA) and evaluated its bactericidal activity against resistant strains of H. pylori. We found that LipoLLA was effective in killing both spiral and dormant forms of the bacteria via disrupting bacterial membranes. LipoLLA eradicated all strains of the bacteria regardless of their antibiotic resistance status. Furthermore, the bacteria did not develop drug resistance toward LipoLLA. Our findings suggest that LipoLLA is a promising antibacterial nanotherapeutic to treat antibiotic-resistant H. pylori infection. The next step, we investigated the in vivo therapeutic potential of LipoLLA for the treatment of H. pylori infection. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha, which were otherwise elevated due to the H. pylori infection. Finally, toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this work indicate that LipoLLA is a promising, new, effective, and safe therapeutic agent for the treatment of H. pylori infection. The second area is stimuli-responsive liposomes development. By adsorbing small chitosan-modified gold nanoparticles (AuChi) onto the outer surface of liposomes, we show that at gastric pH the liposomes have

  20. Association of Helicobacter pylori infection with gastric cancer.

    Science.gov (United States)

    Alexander, G A; Brawley, O W

    2000-01-01

    Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed.

  1. Role of dupA in virulence of Helicobacter pylori.

    Science.gov (United States)

    Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo

    2016-12-14

    Helicobacter pylori ( H. pylori ) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori -associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a ( cagA ) and vacA , there are conflicting data about their actual participation as specific risk factor for H. pylori -related diseases. Duodenal ulcer promoting gene a ( dupA ) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.

  2. Relationship between childhood asthma and Helicobacter pylori infection

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    Ying Wu

    2016-07-01

    Full Text Available Objective: To investigate the correlation between childhood asthma and Helicobacter pylori infection. Methods: A total of 80 children with asthma who were treated in our hospital from May 2012 to May 2015 were selected as the research subjects, and 40 cases of healthy children were selected as control group, the Helicobacter pylori infection of the two groups of patients were compared, the double antibody sandwich enzyme-linked immunosorbent assay was used to detect the serum Helicobacter pylori-IgG, Helicobacter pylori-CagAIgG, IL-4, Helicobacter pylori, IFN-γ and IL-1β, etc., and the correlation between Helicobacter pylori infection and asthma was analyzed. Results: The positive rates of Helicobacter pylori infection in asthma group and children in attack stage were significantly higher than those in control group and children in remission stage (P<0.05. The positive rates of serum Helicobacter pylori-IgG and Helicobacter pylori-CagAIgG in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage (P<0.05. The serum levels of IFN-γ in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage, IL-4 and IL-1β levels in the former were significantly higher than those in the latter (P<0.05. Helicobacter pylori infection positive had significant positive correlation with IL-1β concentration (r=0.75, P<0.05. Conclusions: Helicobacter pylori infection in children has significant positive correlation with the incidence of asthma, suggesting that Helicobacter pylori infection has a certain protective effect on childhood asthma, but persistent Helicobacter pylori infection in children with asthma can aggravate the immune disorder, which is the main reason for the difficulty of treatment of asthma.

  3. Medicinal plant activity on Helicobacter pylori related diseases.

    Science.gov (United States)

    Wang, Yuan-Chuen

    2014-08-14

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori

  4. H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

    Science.gov (United States)

    Bland, David A; Suarez, Giovanni; Beswick, Ellen J; Sierra, Johanna C; Reyes, Victor E

    2006-01-01

    AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells. PMID:16981259

  5. Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer from Helicobacter pylori Infection

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    Kiyoshi Ayada

    2009-01-01

    Full Text Available Helicobacter pylori (H. pylori infection is a definite causative factor for gastric ulcers (GUs. In the present study we detected a specific antigen of gastric epithelial cells (HGC-27 using cell ELISA, which was recognized by the sera of GU patients (n=20 but not in patients with chronic gastritis (CG; n=20 or in healthy volunteers (HC; n=10. This antigen was over-expressed by a stressful (heat-stressed environment, and was identified as elongation factor 2 kinase (EF-2K by western blotting. The GU patients' lymphocytes stimulated by H. pylori specifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1 and cytotoxic T lymphocyte (CTL as opposed to those from CG patients. The target cells (HGC-27 expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU.

  6. Impact of Anti-Helicobacter Therapy of H.pylori-Infected Parents on H.pylori Reinfection Rate in Children after Successful Eradication

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    O.P. Volosovets

    2012-02-01

    Full Text Available The article presents the data about the rate of H.pylori reinfection during 12 months after anti-helicobacter therapy among the children after successful eradication. It was shown that H.pylori reinfection rate was lower in children after successful eradication who were living after the treatment with parents non-infectead with H.pylori than among children who were living with H.pylori-infected parents. It was demonstrated that simultaneous anti-helicobacter therapy in H.pylori-infected parents of children with with chronic gastroduodenal diseases associated with H.pylori decreased H.pylori reinfection rate in children with successful eradication.

  7. Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylori.

    Science.gov (United States)

    Seabra, Catarina Leal; Nunes, Cláudia; Gomez-Lazaro, Maria; Correia, Marta; Machado, José Carlos; Gonçalves, Inês C; Reis, Celso A; Reis, Salette; Martins, M Cristina L

    2017-03-15

    Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5 ® , Miglyol-812 ® ) and a surfactant (Tween 60 ® ). Homogeneous NLC with 302±14nm diameter, -28±3mV surface charge (dynamic and electrophoretic light scattering) and containing 66±7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25μM) than free DHA (>100μM). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur.

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    Xinsheng Teh

    Full Text Available BACKGROUND: Helicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment. METHODS AND FINDINGS: H. pylori was isolated from 102 patients diagnosed with gastrointestinal diseases, who underwent endoscopy at University Malaya Medical Centre (UMMC. The isolates were tested for their susceptibility on eleven antibiotics using Etest. Based on susceptibility test, 32.3% of the isolates were found to have primary metronidazole resistance; followed by clarithromycin (6.8% and fluoroquinolones (6.8%. To further investigate the resistant strains, mutational patterns of gene rdxA, frxA, gyrA, gyrB, and 23S rRNA were studied. Consistent with the previous reports, metronidazole resistance was prevalent in the local population. However, clarithromycin, fluoroquinolone and multi-drug resistance were shown to be emerging. Molecular patterns correlated well with phenotypic data. Interestingly, multi-drug resistant (MDR strains were found to be associated with higher minimum inhibitory concentration (MIC than their single-drug resistant (SDR counterparts. Most importantly, clarithromycin-resistant strains were suggested to have a higher incidence for developing multi-drug resistance. CONCLUSION: Data from this study highlighted the urgency to monitor closely the prevalence of antibiotic resistance in the Malaysian population; especially that of clarithromycin and multi-drug resistance. Further study is needed to understand the molecular association between clarithromycin resistance and multi

  9. Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection.

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    Yoshikazu Furuta

    Full Text Available Helicobacter pylori, a bacterial pathogen that can infect human stomach causing gastritis, ulcers and cancer, is known to have a high degree of genome/epigenome diversity as the result of mutation and recombination. The bacteria often infect in childhood and persist for the life of the host. One of the reasons of the rapid evolution of H. pylori is that it changes its genome drastically for adaptation to a new host. To investigate microevolution and adaptation of the H. pylori genome, we undertook whole genome sequencing of the same or very similar sequence type in multi-locus sequence typing (MLST with seven genes in members of the same family consisting of parents and children in Japan. Detection of nucleotide substitutions revealed likely transmission pathways involving children. Nonsynonymous (amino acid changing mutations were found in virulence-related genes (cag genes, vacA, hcpDX, tnfα, ggt, htrA and the collagenase gene, outer membrane protein (OMP genes and other cell surface-related protein genes, signal transduction genes and restriction-modification genes. We reconstructed various pathways by which H. pylori can adapt to a new human host, and our results raised the possibility that the mutational changes in virulence-related genes have a role in adaptation to a child host. Changes in restriction-modification genes might remodel the methylome and transcriptome to help adaptation. This study has provided insights into H. pylori transmission and virulence and has implications for basic research as well as clinical practice.

  10. Helicobacter pylori infection and duodenal ulcer disease

    NARCIS (Netherlands)

    Tytgat, G. N.; Noach, L. A.; Rauws, E. A.

    1993-01-01

    H. pylori is undoubtedly the dominant factor in the multifactorial peptic ulcer diathesis. We should not ignore the other contributing factors but rather try to identify how they interact with the organism and initiate the ulcerative process. The interplay of acid attack and mucosal defence is

  11. Helicobacter pylori: Beginning the Second Decade

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    Ann Matisko

    1995-01-01

    Full Text Available ‘Beginning the Second Decade’ - a recent international meeting on Helicobacter pylori - was held in conjunction with the VIIth International Workshop on Gastroduodenal Pathology and H pylori and with the meeting of the European Helicobacter pylori Study Group in Houston, Texas from September 30 to October 1, 1994. A menu of 476 abstracts, published in the American Journal of Gastroenterology (1994;89:8, highlighted the explosion of advances in this area. The Houston meeting was followed by the Tenth World Congresses of Gastroenterology from October 2 to 7, 1994 in Los Angeles, California, again with scores of presentations and posters on topics ranging from the epidemiology of H pylori infection to steps towards the development of a human vaccine. All this was in addition to important new work presented earlier in 1994 in New Orleans during Digestive Diseases Week. In this digest of these important meetings, the authors will not regurgitate what the informed reader already knows, but will instead focus on the recent developments in important areas, providing selected key published references for background, and referring to this new work in abstract form which is at the cutting edge of “yesterday’s tomorrow today”.

  12. Helicobacter pylori and early gastric cancer

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Dekker, W.; Tytgat, G. N.

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal

  13. Helicobacter pylori : Prevalence and antibiotic susceptibility among ...

    African Journals Online (AJOL)

    patients, its relationship with gastric pathologies, and associated antibiotic susceptibility profiles, and compared two media to find the appropriate medium that enhances growth and expedites culture and isolation. Methods. Rapid urease and histological tests were used to screen for H. pylori. Culture was performed to test ...

  14. Interaction of legionella pneumophila and helicobacter pylori with bacterial species isolated from drinking water biofilms

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    Azevedo Nuno F

    2011-03-01

    Full Text Available Abstract Background It is well established that Legionella pneumophila is a waterborne pathogen; by contrast, the mode of Helicobacter pylori transmission remains unknown but water seems to play an important role. This work aims to study the influence of five microorganisms isolated from drinking water biofilms on the survival and integration of both of these pathogens into biofilms. Results Firstly, both pathogens were studied for auto- and co-aggregation with the species isolated from drinking water; subsequently the formation of mono and dual-species biofilms by L. pneumophila or H. pylori with the same microorganisms was investigated. Neither auto- nor co-aggregation was observed between the microorganisms tested. For biofilm studies, sessile cells were quantified in terms of total cells by SYTO 9 staining, viable L. pneumophila or H. pylori cells were quantified using 16 S rRNA-specific peptide nucleic acid (PNA probes and cultivable cells by standard culture techniques. Acidovorax sp. and Sphingomonas sp. appeared to have an antagonistic effect on L. pneumophila cultivability but not on the viability (as assessed by rRNA content using the PNA probe, possibly leading to the formation of viable but noncultivable (VBNC cells, whereas Mycobacterium chelonae increased the cultivability of this pathogen. The results obtained for H. pylori showed that M. chelonae and Sphingomonas sp. help this pathogen to maintain cultivability for at least 24 hours. Conclusions It appears that M. chelonae may have an important role in the survival of both pathogens in drinking water. This work also suggests that the presence of some microorganisms can decrease the cultivability of L. pneumophila but not the viability which indicates that the presence of autochthonous microorganisms can lead to misleading results when the safety of water is assessed by cultivable methods alone.

  15. Biological evaluation and molecular docking of baicalin and scutellarin as Helicobacter pylori urease inhibitors.

    Science.gov (United States)

    Yu, Xiao-Dan; Zheng, Rong-Bo; Xie, Jian-Hui; Su, Ji-Yan; Huang, Xiao-Qi; Wang, Yong-Hong; Zheng, Yi-Feng; Mo, Zhi-Zhun; Wu, Xiao-Li; Wu, Dian-Wei; Liang, Ye-er; Zeng, Hui-Fang; Su, Zi-Ren; Huang, Ping

    2015-03-13

    Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. To explore the inhibitory effect, kinetics and mechanism of Helicobacter pylori urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor. Lineweaver-Burk and Dixon plots for the Helicobacter pylori urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni(2+) binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. Baicalin and scutellarin effectively suppressed Helicobacter pylori urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4'-hydroxyl gave flavones an advantage to binding with Helicobacter pylori urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of urease inhibition was considered to be blockage of the SH groups of

  16. [The effect of Helicobacter pylori eradication on chronic gastritis].

    Science.gov (United States)

    Kodama, Masaaki; Murakami, Kazunari; Okimoto, Tadayoshi; Fujioka, Toshio

    2013-08-01

    Helicobacter pylori (H. pylori) is a major pathogen of chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Atrophic gastritis and intestinal metaplasia are recognized as precancerous lesion of gastric cancer. Many studies reported that H. pylori eradication had the preventive effect of gastric cancer. Moreover many studies mentioned the improvement of gastric atrophy and/or intestinal metaplasia. Two meta-analysis indicated the improvement of atrophic gastritis but not of intestinal metaplasia. In our study, intestinal metaplasia improved at lesser curvature of the corpus six years after eradication. H. pylori eradication has benefit for gastric cancer prevention provably due to improvement of the precancerous lesion such as atrophic gastritis and intestinal metaplasia. Especially, H. pylori eradication before the appearance of atrophy and intestinal metaplasia has been considered to be effective in inhibiting the development of gastric cancer. Therefore, improvement or elimination of chronic gastritis with H. pylori eradication might have possibility of gastric cancer inhibition.

  17. Dynamic Expansion and Contraction of cagA Copy Number in Helicobacter pylori Impact Development of Gastric Disease

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    Sungil Jang

    2017-02-01

    Full Text Available Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori. Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8 induction. Sequence analysis of the repeat region revealed three cagA homologous areas (CHAs within the cagA repeats. Of these, CHA-ud flanked each of the cagA copies and is likely important for the dynamic variation of cagA copy numbers. Analysis of a large panel of clinical isolates showed that 7.5% of H. pylori strains isolated in the United States harbored multiple cagA repeats, while none of the tested Korean isolates carried more than one copy of cagA. Finally, H. pylori strains carrying multiple cagA copies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction of cagA copy numbers may serve as a novel mechanism by which H. pylori modulates gastric disease development.

  18. Auranofin and N-heterocyclic carbene gold-analogs are potent inhibitors of the bacteria Helicobacter pylori.

    Science.gov (United States)

    Owings, Joshua P; McNair, Nina N; Mui, Yiu Fung; Gustafsson, Tomas N; Holmgren, Arne; Contel, Maria; Goldberg, Joanna B; Mead, Jan R

    2016-07-01

    Auranofin is an FDA-approved gold-containing compound used for the treatment of rheumatoid arthritis. Recent reports of antimicrobial activity against protozoa and bacteria indicate that auranofin targets the reductive enzyme thioredoxin reductase (TrxR). We evaluated auranofin as well as five auranofin analogs containing N-heterocyclic carbenes (instead of the triethylphosphane present in auranofin) and five gold-carbene controls for their ability to inhibit or kill Helicobacter pylori in vitro Auranofin completely inhibited bacterial growth at 1.2 μM. Purified H. pylori TrxR was inhibited by auranofin in a cell-free assay (IC50 ∼88 nM). The most active gold(I)-N-heterocyclic carbene compounds exhibited MICs comparable to auranofin against H. pylori (2 μM), while also exhibiting lower toxicities for human embryonic kidney cells (HEK-293T cells). Median toxic concentrations (TC50) were 13-20-fold higher compared to auranofin indicating that they were less cytotoxic. The N-heterocyclic carbene analogs maybe well tolerated, but further evaluation is needed in vivo Finally, auranofin was synergistic with the antibiotic amoxicillin, suggesting that targeting both the reductive enzyme TrxR and cell wall synthesis may be effective against H. pylori infections. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. [Iron status with particular consideration of soluble transferrin receptors in children and youth with gastritis, with or without Helicobacter pylori infection].

    Science.gov (United States)

    Mierzwa, Grazyna; Augustyńska, Beata; Czerwionka-Szaflarska, Mieczysława; Tyrakowski, Tomasz

    2006-09-01

    Role of Helicobacter pylori infection in chronic gastritis and gastric and/or duodenal ulcers is well known. Simultaneously there are some articles in literature considering H. pylori as a cause of extra-gastrointestinal illnesses such as atopic dermatitis, chronic urticaria or acne rosacea, hypotrophy, Schoenlein-Henoch disease, atherosclerosis or hypochromic anaemia. The aim of the study. was to asses iron status in aspect of plasmatic transferrin receptors concentration among children and youth with chronic gastritis with or without Helicobacter pylori infection. Forty one patients were included as a study group. Range of age was 9-18 years. All patients were diagnosed due to chronic abdominal pains. There were 13 males and 28 females. Blood was collected from every patient for blood cell count, iron, transferrin and transferrin receptors concentration (sTfR) assessment before endoscopy of upper gastrointestinal tract. Concentration of sTfR was higher than age norm among 29 (71%) of patients. Among patients with higher level of sTfR 20 (69%) had normal haemoglobin concentration and in this group 10 patients had H. pylori infection. During analysis of 12 patients with nornal level of sTfR normal haemoglobin concentration was found and among five of them H. pylori infection was stated. Among 21 patients without H. pylori infection 14 had normal level of sTfR and 7 had higher level of sTfR which means that 33% had hidden iron deficiency (involuntary of normal Hb concentrations). Among 15 of 20 patients with H. pylori infection level of sTfR was higher which means that 75% patients with infection had hidden iron deficiency (involuntary of normal Hb concentrations). Level of plasmatic transferrin receptors can be good and sensitive indicator of iron deficiency and can be helpful in differential diagnosis of hypochromic anaemia and anaemia caused by chronic illness including chronic gastritis with Helicobacter pylori infection.

  20. A study of RUNX3, E-cadherin and β-catenin in CagA-positive Helicobacter pylori associated chronic gastritis in Saudi patients.

    Science.gov (United States)

    Wagih, H M; El-Ageery, S M; Alghaithy, A A

    2015-04-01

    H. pylori is the most important risk factor for gastric carcinoma. CagA-positive H. pylori is associated with an increased risk for gastric cancer compared with negative strains. RUNX3 is a tumor suppressor gene, which is related to the genesis of gastric cancer. β-catenin is integrated with E-cadherin in the cell membrane, and aberrant expression of the complex was reported in gastric carcinoma. Aim of this paper is to determine of the relation between RUNX3, E-cadherin and β-catenin in chronic gastritis associated with cagA-positive H. pylori infection. Retrospective study was done on formalin fixed paraffin embedded gastric biopsies blocks of 90 patients diagnosed as H. pylori associated chronic gastritis. H. pylori was detected using modified Giemsa stain. Nested PCR was used for detection of cagA, reverse transcription-PCR for detection of RUNX3 and immunohistochemistry for detection of E-cadherin and β-catenin. Fifty percent of cases were found to be cagA positive. CagA was significantly associated with the intensity of mononuclear inflammation, the intensity of neutrophilic inflammation, the degree of mucosal atrophy and loss of RUNX3 but not with the density of H. pylori, intestinal metaplasia, E-cadherin or β-catenin. There was significant relation between loss of RUNX3 and increasing density of H. pylori, intensity of neutrophilic inflammation, mucosal atrophy and intestinal metaplasia. RUNX3 was found to be significantly correlated with E-cadherin but not with β-catenin. E-cadherin showed decreased expression in 36.7% of biopsies while, β-catenin was decreased in 33% of biopsies. Loss of RUNX3, E-cadherin and β-catenin was considered early events in the cascade of gastric carcinoma development. Loss of RUNX3 but neither E-cadherin nor β-catenin was related to cagA positive H. pylori strains.

  1. Helicobacter pylori moves through mucus by reducing mucin viscoelasticity

    OpenAIRE

    Celli, Jonathan P.; Turner, Bradley S.; Afdhal, Nezam H.; Keates, Sarah; Ghiran, Ionita; Kelly, Ciaran P.; Ewoldt, Randy H.; McKinley, Gareth H.; So, Peter; Erramilli, Shyamsunder; Bansil, Rama

    2009-01-01

    The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner in which H. pylori is able to swim through the viscoelastic mucus gel that coats the stomach wall remains poorly understood. Previous rheology studies on gastric mucin, the key...

  2. Oral and gastric helicobacter pylori : Effects and associations

    OpenAIRE

    Veiga, Nélio; Pereira, Carlos; Resende, Carlos; Amaral, Odete; Ferreira, Manuela; Nelas, Paula; Chaves, Claudia; Duarte, João; Cirnes, Luis; Machado, José Carlos; Ferreira, Paula; Correia, Ilídio J.

    2015-01-01

    Introduction This study consisted in the comparison of the prevalence of Helicobacter pylori (H. pylori) present in the stomach and in saliva of a sample of Portuguese adolescents and the assessment of the association between H. pylori infection with socio-demographic variables and prevalence of dental caries. Materials and Methods A cross-sectional study was designed including a sample of 447 adolescents aged 12 to 19 years old, attending a public school in S?t?o, Portugal. A questionnaire a...

  3. Lymphoid follicles in children with Helicobacter pylori-negative gastritis

    Science.gov (United States)

    Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim

    2017-01-01

    Purpose The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Patients and methods Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. Results A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, pgastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Conclusion Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status. PMID:28860835

  4. [On the rating of Helicobacter pylori in drinking water].

    Science.gov (United States)

    Fedichkina, T P; Solenova, L G; Zykova, I E

    2014-01-01

    There are considered the issues related to the possibility to rate of Helicobacter pylori (H. pylori) content in drinking water. There is described the mechanism of of biofilm formation. The description refers to the biofilm formation mechanism in water supply systems and the existence of H. pylori in those systems. The objective premises of the definition of H. pylori as a potential limiting factor for assessing the quality of drinking water have been validated as follows: H. pylori is an etiologic factor associated to the development of chronic antral gastritis, gastric ulcer and duodenal ulcer, and gastric cancer either, in the Russian population the rate of infection with H. pylori falls within range of 56 - 90%, water supply pathway now can be considered as a source of infection of the population with H. pylori, the existence of WHO regulatory documents considering H. pylori as a candidate for standardization of the quality of the drinking water quite common occurrence of biocorrosion, the reduction of sanitary water network reliability, that creates the possibility of concentrating H. pylori in some areas of the water system and its delivery to the consumer of drinking water, and causes the necessity of the prevention of H. pylori-associated gastric pathology of the population. A comprehensive and harmonized approach to H. pylori is required to consider it as a candidate to its rating in drinking water. Bearing in mind the large economic losses due to, on the one hand, the prevalence of disease caused by H. pylori, and, on the other hand, the biocorrosion of water supply system, the problem is both relevant in terms of communal hygiene and economy.

  5. Evidence of mother-child transmission of Helicobacter pylori infection

    OpenAIRE

    Escobar,Mario Luis; Kawakami,Elisabete

    2004-01-01

    BACKGROUND: Low socioeconomical status is a major risk factor for natural acquisition of Helicobacter pylori (H. pylori) infection in developing countries. Its transmission route is unknown but studies suggest person-to-person transmission. AIM: To evaluate seropositivity of anti-H. pylori antibodies in family members of infected symptomatic index patients as compared to family members of symptomatic uninfected index patients. PATIENTS AND METHODS: One hundred and twelve family members of 38 ...

  6. Nobeli auhinna tõi Helicobacter pylori / Juhan Kaldre

    Index Scriptorium Estoniae

    Kaldre, Juhan

    2005-01-01

    Nobeli meditsiiniauhind määrati sel aastal Austraalia teadlastele Robin Warrenile ja Barry Marshallile, kes avastasid, et gastriit ning peptiline haavand tekib Helicobacter pylori infektsiooni tulemusena

  7. Serum prolidase activity and oxidative status in Helicobacter pylori infection.

    Science.gov (United States)

    Aslan, Mehmet; Nazligul, Yasar; Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Aksoy, Nurten; Celik, Hakim; Erel, Ozcan

    2007-01-01

    During the course of Helicobacter pylori infection, increased oxidative stress plays an important role in the pathogenesis of gastroduodenal mucosal inflammation, which can cause gastric mucosal atrophy that characterized by the replacement of the gastric mucosal glands by collagen fibers. In the present study, we aimed to determine serum prolidase activity and oxidative status, and to find out if there is any association between serum prolidase activity and oxidative status in H. pylori infection. Forty H. pylori-positive and 32 H. pylori-negative subjects were enrolled. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity and total oxidant status measurement and calculation of oxidative stress index. Total antioxidant capacity level was lower in H. pylori-positive group than H. pylori-negative group (ptotal oxidant status, oxidative stress index and prolidase activity were higher (all ptotal antioxidant capacity, total oxidant status and oxidative stress index (p<0.01, r=-0.367; p<0.05, r=0.283; p<0.01, r=0.379; respectively) in H. pylori-positive subjects. H. pylori infection may be associated with increased oxidative stress and increased serum prolidase activity. Increased oxidative stress seems to be associated with increased serum prolidase activity and this association may help to provide a better understanding about the pathogenesis of H. pylori infection.

  8. Chronic Gastritis and its Association with H. Pylori Infection.

    Science.gov (United States)

    Fatema, J; Khan, A H; Uddin, M J; Rahman, M H; Saha, M; Safwath, S A; Alam, M J; Mamun, M A

    2015-10-01

    This cross sectional study was designed to see association of chronic gastritis including its type with H. pylori infection. Consecutive patients undergoing endoscopic examination having histopathological evidence of chronic gastritis were enrolled in the study and was done in Sylhet MAG Osmani Medical College from July 2011 to June 2012. Biopsies were taken from antrum, body and fundus in all patients. Histopathological examinations were done using H-E stain and for detection of H. pylori, rapid urease test, anti-H.pylori antibody test and histopathological test with modified Giemsa stain were done. Patients having results positive in at least two methods were considered infected by H. pylori. Total 80 dyspeptic patients having chronic gastritis were evaluated. Out of them 67(83.8%) had H. pylori infection and 13(16.2%) were H. pylori negative. Among all patients 57(71.2%) had pangastritis and 23(28.8%) had antral gastritis with female and male predominance respectively. H. pylori infection was present in 49(86.0%) cases of pangastritis and 18(78.3%) cases of antral gastritis. H. pylori infection was a little higher among males (34, 50.7%) females (33, 49.3%). H. pylori infection is the predominant cause of chronic gastritis and pangastritis is the major type.

  9. Medicinal plant activity on Helicobacter pylori related diseases

    OpenAIRE

    Wang, Yuan-Chuen

    2014-01-01

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori ...

  10. Let-7b is involved in the inflammation and immune responses associated with Helicobacter pylori infection by targeting Toll-like receptor 4.

    Directory of Open Access Journals (Sweden)

    Gui-gen Teng

    Full Text Available OBJECTIVES: Toll-like receptors (TLRs are important initiators in native immune responses to microbial infections. TLR4 is up-regulated in response to H.pylori infection in gastric epithelial cells. However, the regulatory mechanisms for the expression of TLR4 in H.pylori infection have not been clearly defined. The aims of this study are to present the evidence that microRNA let-7b directly regulates TLR4 expression in human gastric epithelial cells, and subsequently influences the activation of NF-κB and the expression of the downstream genes in H.pylori infection. METHODS: The expression of let-7b was determined in gastric mucosa specimens and in two gastric epithelial cell lines using quantitative RT-PCR. The expression of TLR4 was determined by immunohistochemistry staining and RT-PCR. The potential target of let-7b was identified by luciferase reporter assay and Western blot. Let-7b mimics and inhibitors were used to examine the effects of let-7b on NF-κB activity. The expression of the downstream genes of NF-κB was also determined in cells infected with H.pylori 26695. RESULTS: Let-7b was significantly decreased in gastric mucosa specimens and in gastric epithelial cell lines (AGS, GES-1 infected with H.pylori 26695 (cagA+. Let-7b was complementary to the 3'-UTR of TLR4 mRNA and regulated TLR4 expression via post-transcriptional suppression in gastric epithelium. Infection of H.pylori induced the expression of TLR4 and activated NF-κB in AGS and GES-1 cells. Overexpression of let-7b by mimics downregulated TLR4, and subsequently attenuated NF-κB, MyD88, NF-κB1/p50, RelA/p65. The expression of IL-8, COX-2 and CyclinD1 was inhibited in H.pylori infected cells with let-7b overexpression. Both TAK-242 (TLR4 inhibitor and SN50 (NF-κB inhibitor significantly inhibited the H.pylori induced downregulation of let-7b. CONCLUSIONS: Let-7b targets at TLR4 mRNA, and regulates the activation of NF-κB and the expression of the downstream genes

  11. Slow release of tetracycline from a mucoadhesive complex with sucralfate for eradication of Helicobacter pylori.

    Science.gov (United States)

    Higo, Shoichi; Takeuchi, Hirofumi; Yamamoto, Hiromitsu; Hino, Tomoaki; Kawashima, Yoshiaki

    2008-10-01

    Treatment composed of a gastric mucoadhesive antibiotic with slow release drug delivery is expected to be effective for the eradication of Helicobacter pylori (H. pylori). In this study, we evaluated the slow release property of the tetracycline-sucralfate acidic complex. Tetracycline was the antibiotic selected because of its complexation capacity with sucralfate. Sustained release was tested using two different dissolution test methods: paddle and flow-through cell. The adhesive paste formed from the acidic complex displayed a longer sustained release profile of tetracycline using flow-through cell method. The milder conditions of the flow-through cell method better mimicked the fasted state of the stomach, suggesting that the oral administration with fasting is appropriate for the acidic complex. Furthermore, the paste formation protected the tetracycline from decomposition under an acidic condition, which apparently contributes to long-term release. Change in the zeta potential of the acidic complex particles was helpful in clarifying the release mechanisms of the tetracycline. The data indicated that the immediate release of tetracycline in the early stage of the test was indispensable to the subsequent paste formation that enables slow release. If administrated orally with fasting, the acidic complex rapidly adheres to the gastric mucosa and sustains long-term release of the tetracycline to the gastric lumen or mucus layer. This antibiotic delivery mechanism, which requires only a minimum dosage, may be effective for efficient eradication of H. pylori.

  12. Comparative analysis of the full genome of Helicobacter pylori isolate Sahul64 identifies genes of high divergence.

    Science.gov (United States)

    Lu, Wei; Wise, Michael J; Tay, Chin Yen; Windsor, Helen M; Marshall, Barry J; Peacock, Christopher; Perkins, Tim

    2014-03-01

    Isolates of Helicobacter pylori can be classified phylogeographically. High genetic diversity and rapid microevolution are a hallmark of H. pylori genomes, a phenomenon that is proposed to play a functional role in persistence and colonization of diverse human populations. To provide further genomic evidence in the lineage of H. pylori and to further characterize diverse strains of this pathogen in different human populations, we report the finished genome sequence of Sahul64, an H. pylori strain isolated from an indigenous Australian. Our analysis identified genes that were highly divergent compared to the 38 publically available genomes, which include genes involved in the biosynthesis and modification of lipopolysaccharide, putative prophage genes, restriction modification components, and hypothetical genes. Furthermore, the virulence-associated vacA locus is a pseudogene and the cag pathogenicity island (cagPAI) is not present. However, the genome does contain a gene cluster associated with pathogenicity, including dupA. Our analysis found that with the addition of Sahul64 to the 38 genomes, the core genome content of H. pylori is reduced by approximately 14% (∼170 genes) and the pan-genome has expanded from 2,070 to 2,238 genes. We have identified three putative horizontally acquired regions, including one that is likely to have been acquired from the closely related Helicobacter cetorum prior to speciation. Our results suggest that Sahul64, with the absence of cagPAI, highly divergent cell envelope proteins, and a predicted nontransportable VacA protein, could be more highly adapted to ancient indigenous Australian people but with lower virulence potential compared to other sequenced and cagPAI-positive H. pylori strains.

  13. CagA-positive Helicobacter pylori infection is not associated with decreased risk of Barrett's esophagus in a population with high H. pylori infection rate

    Directory of Open Access Journals (Sweden)

    Ortego Javier

    2006-02-01

    Full Text Available Abstract Background & aim The role that H. pylori infection plays in the development of and Barrett's esophagus (BE is uncertain. We tested the hypothesis that infection with cagA+ Helicobacter pylori strains protects against the development of BE. Methods We studied 104 consecutive patients, residents in an area with a high prevalence of H. pylori infection, with BE and 213 sex- and age-matched controls. H. pylori infection and CagA antibody status were determined by western blot serology. Results H. pylori prevalence was higher in patients with BE than in controls (87.5% vs. 74.6%; OR. 2.3; 95% CI: 1.23–4.59. Increasing age was associated with a higher prevalence of H. pylori (p Conclusion Neither H. pylori infection nor H. pylori infection by CagA+ strains reduce the risk of BE in a population with high prevalence of H. pylori infection.

  14. Oral and gastric Helicobacter pylori: effects and associations.

    Science.gov (United States)

    Veiga, Nélio; Pereira, Carlos; Resende, Carlos; Amaral, Odete; Ferreira, Manuela; Nelas, Paula; Chaves, Claudia; Duarte, João; Cirnes, Luis; Machado, José Carlos; Ferreira, Paula; Correia, Ilídio J

    2015-01-01

    This study consisted in the comparison of the prevalence of Helicobacter pylori (H. pylori) present in the stomach and in saliva of a sample of Portuguese adolescents and the assessment of the association between H. pylori infection with socio-demographic variables and prevalence of dental caries. A cross-sectional study was designed including a sample of 447 adolescents aged 12 to 19 years old, attending a public school in Sátão, Portugal. A questionnaire about socio-demographic variables and oral health behaviors was applied. Gastric H. pylori infection was determined using the urease breath test (UBT). Saliva collection was obtained and DNA was extracted by Polymerase Chain Reaction (PCR) in order to detect the presence of oral H. pylori. The prevalence of gastric H. pylori detected by UBT was 35.9%. Within the adolescents with a gastric UBT positive, only 1.9% were positive for oral H. pylori. The presence of gastric H. pylori was found to be associated with age (>15years, Odds ratio (OR)=1.64, 95%CI=1.08-2.52), residence area (urban, OR=1.48, 95%CI=1.03-2.29) and parents´ professional situation (unemployed, OR=1.22, 95%CI=1.02-1.23). Among those with detected dental caries during the intra-oral observation, 37.4% were positive for gastric H. pylori and 40.2% negative for the same bacterial strain (p=0.3). The oral cavity cannot be considered a reservoir for infection of H. pylori. Gastric H. pylori infection was found to be associated with socio-demographic variables such as age, residence area and socioeconomic status.

  15. Oral and gastric Helicobacter pylori: effects and associations.

    Directory of Open Access Journals (Sweden)

    Nélio Veiga

    Full Text Available This study consisted in the comparison of the prevalence of Helicobacter pylori (H. pylori present in the stomach and in saliva of a sample of Portuguese adolescents and the assessment of the association between H. pylori infection with socio-demographic variables and prevalence of dental caries.A cross-sectional study was designed including a sample of 447 adolescents aged 12 to 19 years old, attending a public school in Sátão, Portugal. A questionnaire about socio-demographic variables and oral health behaviors was applied. Gastric H. pylori infection was determined using the urease breath test (UBT. Saliva collection was obtained and DNA was extracted by Polymerase Chain Reaction (PCR in order to detect the presence of oral H. pylori.The prevalence of gastric H. pylori detected by UBT was 35.9%. Within the adolescents with a gastric UBT positive, only 1.9% were positive for oral H. pylori. The presence of gastric H. pylori was found to be associated with age (>15years, Odds ratio (OR=1.64, 95%CI=1.08-2.52, residence area (urban, OR=1.48, 95%CI=1.03-2.29 and parents´ professional situation (unemployed, OR=1.22, 95%CI=1.02-1.23. Among those with detected dental caries during the intra-oral observation, 37.4% were positive for gastric H. pylori and 40.2% negative for the same bacterial strain (p=0.3.The oral cavity cannot be considered a reservoir for infection of H. pylori. Gastric H. pylori infection was found to be associated with socio-demographic variables such as age, residence area and socioeconomic status.

  16. Helicobacter pylori-Negative Gastritis: Prevalence and Risk Factors

    Science.gov (United States)

    Nordenstedt, Helena; Graham, David Y.; Kramer, Jennifer R.; Rugge, Massimo; Verstovsek, Gordana; Fitzgerald, Stephanie; Alsarraj, Abeer; Shaib, Yasser; Velez, Maria E.; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B.

    2014-01-01

    OBJECTIVES Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. METHODS Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. RESULTS Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P = 0.06). CONCLUSIONS We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known. PMID:23147524

  17. Helicobacter pylori-negative gastritis: prevalence and risk factors.

    Science.gov (United States)

    Nordenstedt, Helena; Graham, David Y; Kramer, Jennifer R; Rugge, Massimo; Verstovsek, Gordana; Fitzgerald, Stephanie; Alsarraj, Abeer; Shaib, Yasser; Velez, Maria E; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B

    2013-01-01

    Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P=0.06). We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known.

  18. Association between Helicobacter pylori concentration and the combining frequency of histopathological findings in gastric biopsies specimens Associação entre a concentração de Helicobacter pylori e a freqüência de combinação de alterações histopatológicas em biopsias gástricas

    Directory of Open Access Journals (Sweden)

    Gisele Alborghetti Nai

    2007-09-01

    Full Text Available BACKGROUND: Helicobacter pylori is the most prevalent infectious agent worldwide. About 90% of patients with chronic gastritis are infected with this bacterium. Some studies have shown a association between the H. pylori concentration and the scores of gastritis activity and severity. AIM: To evaluate the association between H. pylori concentration and the combining frequency of findings on histopathological examination. METHODS: Two hundred consecutive gastric endoscopic biopsies diagnosed as chronic gastritis were retrospectively investigated. The Warthin-Starry silver stain was used to study H. pylori and the following parameters were assessed (according to the Sydney system: 1. infiltration by polymorphonuclear cells in chorio and epithelium (activity graded as mild, moderate and marked; 2. presence of lymphoid follicles; 3. presence of intestinal metaplasia; 4. presence of regenerative cell atypias, graded as mild, moderate and marked; and 5. H. pylori concentration on the mucous covering the foveolar epithelium. RESULTS: The most frequent association was chronic gastritis and activity, regardless of H. pylori concentration. The association of five histopathological findings in the same biopsy has not occurred in the cases of higher concentration of H. pylori. CONCLUSION: Our study has not revealed any association between H. pylori concentration and an increasing in the number of histopathological findings found in the gastric mucosa. Since referring to its presence is much more important than to its concentration.RACIONAL: O Helicobacter pylori é o agente infeccioso com maior prevalência em todo o mundo. Cerca de 90% dos pacientes com gastrite crônica têm infecção por esta bactéria. Alguns estudos demonstram correlação entre a concentração de H. pylori e o grau de severidade e atividade da gastrite. OBJETIVOS: Avaliar a associação entre a concentração de H. pylori e a freqüência de combinações de alterações no exame

  19. Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

    NARCIS (Netherlands)

    Blok, P.; Craanen, M. E.; Offerhaus, G. J.; Dekker, W.; Kuipers, E. J.; Meuwissen, S. G.; Tytgat, G. N.

    1999-01-01

    Data on the differences in molecular profile between H pylori-positive and H pylori-negative early gastric carcinomas, if any, are almost nonexistent. We therefore investigated whether molecular differences can be observed between H pylori-positive and H pylori-negative early gastric carcinomas.

  20. The Effect of Helicobacter pylori Eradication on the Levels of Essential Trace Elements

    Directory of Open Access Journals (Sweden)

    Meng-Chieh Wu

    2014-01-01

    Full Text Available Objective. This study was designed to compare the effect of Helicobacter pylori (H. pylori infection treatment on serum zinc, copper, and selenium levels. Patients and Methods. We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. Results. Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P=0.06. There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P<0.05. The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. Conclusion. H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327.

  1. A fluid model for Helicobacter pylori

    Science.gov (United States)

    Reigh, Shang-Yik; Lauga, Eric

    2015-11-01

    Swimming microorganisms and self-propelled nanomotors are often found in confined environments. The bacterium Helicobacter pylori survives in the acidic environment of the human stomach and is able to penetrate gel-like mucus layers and cause infections by locally changing the rheological properties of the mucus from gel-like to solution-like. In this talk we propose an analytical model for the locomotion of Helicobacter pylori as a confined spherical squirmer which generates its own confinement. We solve analytically the flow field around the swimmer, and derive the swimming speed and energetics. The role of the boundary condition in the outer wall is discussed. An extension of our model is also proposed for other biological and chemical swimmers. Newton Trust.

  2. Helicobacter pylori virulence and cancer pathogenesis.

    Science.gov (United States)

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  3. Helicobacter pylori promotes the expression of Krüppel-like factor 5, a mediator of carcinogenesis, in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jennifer M Noto

    Full Text Available Helicobacter pylori is the strongest known risk factor for the development of gastric adenocarcinoma. H. pylori expresses a repertoire of virulence factors that increase gastric cancer risk, including the cag pathogenicity island and the vacuolating cytotoxin (VacA. One host element that promotes carcinogenesis within the gastrointestinal tract is Krüppel-like factor 5 (KLF5, a transcription factor that mediates key cellular functions. To define the role of KLF5 within the context of H. pylori-induced inflammation and injury, human gastric epithelial cells were co-cultured with the wild-type cag(+ H. pylori strain 60190. KLF5 expression was significantly upregulated following co-culture with H. pylori, but increased expression was independent of the cag island or VacA. To translate these findings into an in vivo model, C57BL/6 mice were challenged with the wild-type rodent-adapted cag(+ H. pylori strain PMSS1 or a PMSS1 cagE(- isogenic mutant. Similar to findings in vitro, KLF5 staining was significantly enhanced in gastric epithelium of H. pylori-infected compared to uninfected mice and this was independent of the cag island. Flow cytometry revealed that the majority of KLF5(+ cells also stained positively for the stem cell marker, Lrig1, and KLF5(+/Lrig1(+ cells were significantly increased in H. pylori-infected versus uninfected tissue. To extend these results into the natural niche of this pathogen, levels of KLF5 expression were assessed in human gastric biopsies isolated from patients with or without premalignant lesions. Levels of KLF5 expression increased in parallel with advancing stages of neoplastic progression, being significantly elevated in gastritis, intestinal metaplasia, and dysplasia compared to normal gastric tissue. These results indicate that H. pylori induces expression of KLF5 in gastric epithelial cells in vitro and in vivo, and that the degree of KLF5 expression parallels the severity of premalignant lesions in human

  4. Expression, crystallization and preliminary crystallographic study of octaprenyl pyrophosphate synthase from Helicobacter pylori

    International Nuclear Information System (INIS)

    Zhang, Jinyong; Zhang, Xiaoli; Mao, Xuhu; Zou, Quanming; Li, Defeng

    2011-01-01

    Octaprenyl pyrophosphate synthase from H. pylori has been expressed, purified and crystallized, and a diffraction data set was collected to 2.00 Å resolution. Octaprenyl pyrophosphate synthase (OPPs) is involved in the synthesis of the side chains of ubiquinone and menaquinone and catalyzes consecutive condensation reactions of farnesyl pyrophosphate with isopentenyl pyrophosphate to generate polyprenyl pyrophosphate and pyrophosphate. In order to investigate the roles played by OPPs in the metabolism of ubiquinone and menaquinone and the enzymatic mechanisms of these enzymes, analysis of the structure–function relationship of OPPs from Helicobacter pylori was initiated. The gene for OPPs was cloned, the protein was expressed, purified and crystallized and a diffraction data set was collected to 2.00 Å resolution. The crystals belonged to space group P4 1 2 1 2 or P4 3 2 1 2, with unit-cell parameters a = b = 109.33, c = 103.41 Å

  5. Characterization of Helicobacter pylori adhesin thiol peroxidase ...

    Indian Academy of Sciences (India)

    Prakash

    H. pylori induces a strong inflammatory response ... 2003). Prx inactivation has also been observed in plants (Kitajima 2008) and yeast .... 2.1 Expression and purification of wild-type and mutant. HpTpx ... density (OD)600 of 0.6–0.8 and induced by 0.5 mM isopropyl ... Far-UV circular dichroism (CD) spectroscopy was used.

  6. DNA-binding activity of TNF-α inducing protein from Helicobacter pylori

    International Nuclear Information System (INIS)

    Kuzuhara, T.; Suganuma, M.; Oka, K.; Fujiki, H.

    2007-01-01

    Tumor necrosis factor-α (TNF-α) inducing protein (Tipα) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-α and chemokine genes and activation of nuclear factor-κB. Since Tipα enters gastric cancer cells, the Tipα binding molecules in the cells should be investigated. The direct DNA-binding activity of Tipα was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tipα and DNA, revealed that the affinity of Tipα for (dGdC)10 is 2400 times stronger than that of del-Tipα, an inactive Tipα. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tipα. And the DNA-binding activity of Tipα was first demonstrated with a molecule secreted from H. pylori

  7. Phenotypic and genotypic characterization of Helicobacter pylori from patients with and without peptic ulcer disease

    DEFF Research Database (Denmark)

    Petersen, A M; Fussing, V; Colding, H

    2000-01-01

    BACKGROUND: Helicobacter pylori plays an important role in peptic ulcer disease, although not all H. pylori-infected persons will develop a peptic ulcer. Currently, H. pylori strains cannot be divided into commensals and pathogens. METHODS: Fifty H. pylori strains were cultured from patients......) profile of H. pylori strains were recorded; randomly amplified polymorphic DNA (RAPD) and urease gene typing were performed and correlated with diagnostic groups. RESULTS: Electron micrographs showed that H. pylori strains from patients with gastric ulcers adhered more frequently through filamentous...... strands and were less frequently found free in mucus than any other diagnostic group (P pylori strains from patients with gastric...

  8. Rosacea and Helicobacter pylori: links and risks

    Directory of Open Access Journals (Sweden)

    Lazaridou E

    2017-08-01

    Full Text Available Elizabeth Lazaridou,1 Chrysovalantis Korfitis,2 Christina Kemanetzi,1 Elena Sotiriou,1 Zoe Apalla,1 Efstratios Vakirlis,1 Christina Fotiadou,1 Aimilios Lallas,1 Demetrios Ioannides1 1First Department of Dermatology and Venereology, Aristotle University Medical School, Thessaloniki, Greece; 2Department of Dermatology, 401 General Army Hospital, Athens, Greece Abstract: Rosacea is a chronic skin disease characterized by facial erythema and telangiectasia. Despite the fact that many hypotheses have been proposed, its etiology remains unknown. In the present review, the possible link and clinical significance of Helicobacter pylori in the pathogenesis of rosacea are being sought. A PubMed and Google Scholar search was performed using the terms “rosacea”, “H.pylori”, “gastrointestinal disorders and H.pylori”, “microorganisms and rosacea”, “pathogenesis and treatment of rosacea”, and “risk factors of rosacea”, and selected publications were studied and referenced in text. Although a possible pathogenetic link between H. pylori and rosacea is advocated by many authors, evidence is still interpreted differently by others. We conclude that further studies are needed in order to fully elucidate the pathogenesis of rosacea. Keywords: eradication, Helicobacter pylori, pathogenesis, rosacea

  9. Helicobacter pylori eradication: gastric cancer prevention.

    Science.gov (United States)

    Leontiadis, Grigorios I; Ford, Alexander Charles

    2015-12-01

    The principal effect of Helicobacter pylori infection is lifelong chronic gastritis, affecting up to 20% of younger adults but 50% to 80% of adults born in resource-rich countries before 1950. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of H pylori eradication treatment on the risk of developing gastric cancer? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). At this update, searching of electronic databases retrieved 208 studies. After deduplication and removal of conference abstracts, 166 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 124 studies and the further review of 42 full publications. Of the 42 full articles evaluated, one systematic review was added at this update. We performed a GRADE evaluation for two PICO combinations. In this systematic overview, we categorised the efficacy for one intervention based on information about the effectiveness and safety of H pylori eradication treatment for the prevention of gastric cancer.

  10. Rescue Therapy for Helicobacter pylori Infection 2012

    Directory of Open Access Journals (Sweden)

    Javier P. Gisbert

    2012-01-01

    Full Text Available Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final—overall—eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy may be used afterwards, and then a levofloxacin-based combination would be a third-line “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based “rescue” therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line “rescue” option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given.

  11. Polymorphisms of the DNA methyltransferase 1 associated with reduced risks of Helicobacter pylori infection and increased risks of gastric atrophy.

    Directory of Open Access Journals (Sweden)

    Jing Jiang

    Full Text Available INTRODUCTION: DNA methyltransferase-1(DNMT1 is an important enzyme in determining genomic methylation patterns in mammalian cells. We investigated the associations between SNPs in the DNMT1 gene and risks of developing H. pylori seropositivity, gastric atrophy and gastric cancer in the Chinese population. METHODS: The study consisted of 447 patients with gastric cancer; 111 patients with gastric atrophy; and 961 healthy controls. Five SNPs, rs10420321, rs16999593, rs8101866, rs8111085 and rs2288349 of the DNMT1 gene were genotyped. Anti-H.pylori IgG was detected by ELISA. Gastric atrophy was screened by the level of serum pepsinogen Ι and II and then confirmed by endoscopy and histopatholgical examinations. RESULTS: The age- and sex-adjusted OR of H. pylori seropositivity was 0.67 (95%CI: 0.51-0.87 for rs8111085 TC/CC genotypes, significantly lower than the TT genotype in healthy controls. The adjusted OR of H.pylori seropositivity was 0.68 (95%CI: 0.52-0.89 for rs10420321 AG/GG genotypes. In addition, patients carrying rs2228349 AA genotype have a significantly increased risk for H.pylori seropositivity (OR=1.67; 95%CI: 1.02-2.75. Further haplotype analyses also showed that the ATTTG and ATCTA are significantly associated with increased risks in H.pylori infection compared to the GTCCG haplotype (OR=1.38, 95%CI: 1.08-1.77; OR=1.40, 95% CI: 1.09-1.80. The adjusted ORs of gastric atrophy were 1.66 (95%CI: 1.06-2.61 for rs10420321 GG genotype, and 1.67 (95%CI 1.06-2.63, P=0.03 for rs8111085 CC genotype, but no association was found between SNPs in the DNMT1 gene and risk of developing gastric cancer. CONCLUSIONS: Individuals with rs10420321 GG and rs8111085 CC genotype of the DNMT1 gene were associated with reduced risks for H.pylori infection. On the other hand, higher risks of gastric atrophy were found in the carriers with these two genotypes compared to other genotypes. Our results suggested that SNPs of DNMT1 could be used as genotypic

  12. Novel protein interactions with an actin homolog (MreB) of Helicobacter pylori determined by bacterial two-hybrid system.

    Science.gov (United States)

    Zepeda Gurrola, Reyna Cristina; Fu, Yajuan; Rodríguez Luna, Isabel Cristina; Benítez Cardoza, Claudia Guadalupe; López López, María de Jesús; López Vidal, Yolanda; Gutíerrez, Germán Rubén Aguilar; Rodríguez Pérez, Mario A; Guo, Xianwu

    2017-08-01

    The bacterium Helicobacter pylori infects more than 50% of the world population and causes several gastroduodenal diseases, including gastric cancer. Nevertheless, we still need to explore some protein interactions that may be involved in pathogenesis. MreB, an actin homolog, showed some special characteristics in previous studies, indicating that it could have different functions. Protein functions could be realized via protein-protein interactions. In the present study, the MreB protein from H. pylori 26695 fused with two tags 10×His and GST in tandem was overexpressed and purified from Escherchia coli. The purified recombinant protein was used to perform a pull-down assay with H. pylori 26695 cell lysate. The pulled-down proteins were identified by mass spectrometry (MALDI-TOF), in which the known important proteins related to morphogenesis were absent but several proteins related to pathogenesis process were observed. The bacterial two-hybrid system was further used to evaluate the protein interactions and showed that new interactions of MreB respectively with VacA, UreB, HydB, HylB and AddA were confirmed but the interaction MreB-MreC was not validated. These results indicated that the protein MreB in H. pylori has a distinct interactome, does not participate in cell morphogenesis via MreB-MreC but could be related to pathogenesis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

    Science.gov (United States)

    Polakovicova, Iva; Jerez, Sofia; Wichmann, Ignacio A.; Sandoval-Bórquez, Alejandra; Carrasco-Véliz, Nicolás; Corvalán, Alejandro H.

    2018-01-01

    Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs), influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1) which are delivered into

  14. Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

    Directory of Open Access Journals (Sweden)

    Iva Polakovicova

    2018-04-01

    Full Text Available Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori, a bacterium present in half of the world population; or by Epstein-Barr virus (EBV, a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs, influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA, a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1 which are

  15. Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

    NARCIS (Netherlands)

    Vollaard, A.M.; Verspaget, H.W.; Ali, S.; Visser, L.G.; Veenendaal, R.A.; Asten, H.A.G.H. van; Widjaja, S.; Surjadi, C.; Dissel, J.T. van

    2006-01-01

    We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration

  16. Association of Helicobacter pylori infection with the Lewis and ABO ...

    African Journals Online (AJOL)

    Because of this controversy and the fact that H. pylori infection and gastric adenocarcinoma are common diseases in Iran, the assessment of the association of H. pylori infection with these blood groups could be valuable. Materials and Methods: In a cross sectional study on 135 adult dyspeptic patients in Mashhad, Iran, ...

  17. Association of Helicobacter pylori infection with peptic ulcer disease ...

    African Journals Online (AJOL)

    Background: Helicobacter pylori infection has been identified as an important risk factor for the development of peptic ulcer disease and is probably the most important cause of relapse in those previously treated for peptic ulcer disease. The aim of this study was to determine the association of Helicobacter pylori infection as ...

  18. Helicobacter pylori prevalence in dyspeptic patients in the Eastern ...

    African Journals Online (AJOL)

    Helicobacter pylori prevalence in dyspeptic patients in the Eastern Cape province – race and disease status. ... Fisher's exact test was used to assess the univariate association between H. pylori infection and the possible risk factors. ... Gender, antibiotic treatment and alcohol consumption may be risk factors for infection.

  19. Helicobacter pylori eradication therapy: A review of current trends ...

    African Journals Online (AJOL)

    Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa‑associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the ...

  20. (Nutmeg) on Helicobacter pylori induced gastritis in albino rats

    African Journals Online (AJOL)

    The anti-Helicobacter pylori (H. pylori) activities of dichloromethane and methanol extracts of Myristica fragrans Houtt. seed (nutmeg) was studied to authenticate ... Analysis of variance (ANOVA) tested the effect of the groups on the treatment days and revealed a significant difference between the treatments at p< 0.05.

  1. 49 Marked susceptibility of South African Helicobacter pylori strains ...

    African Journals Online (AJOL)

    Objectives. Helicobacter pylori-associated infection is common in South Africa, as in other developing countries. Antibiotic resistance is recognised as a major cause of treatment failure. We studied the susceptibility and resistance patterns of H. pylori to guide empiric treatment and prevent the emergence of resistance.

  2. RECOVERY OF HELICOBACTER PYLORI FROM WATER BY IMMUNOMAGNETIC CAPTURE

    Science.gov (United States)

    A few reports have been written stating that H. pylori can be found in waters. However, detection and identification of H. pylori from water samples remains a very difficult task. One method that seems to work successfully is immunomagnetic capture. Water samples were concentr...

  3. SURVIVAL OF HELICOBACTER PYLORI IN A NATURAL FRESHWATER ENVIRONMENT

    Science.gov (United States)

    The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...

  4. Systematic review: Helicobacter pylori infection and impaired drug absorption.

    Science.gov (United States)

    Lahner, E; Annibale, B; Delle Fave, G

    2009-02-15

    Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

  5. Helicobacter pylori gastritis in HIV-infected patients: a review.

    Science.gov (United States)

    Nevin, Daniel T; Morgan, Christopher J; Graham, David Y; Genta, Robert M

    2014-10-01

    The risk factors for acquiring Helicobacter pylori and Human Immunodeficiency Virus (HIV) infections are different: H. pylori is transmitted by gastro- or fecal-oral routes and is associated with low socioeconomic conditions, while HIV is transmitted through sexual intercourse, infected body fluids, and transplacentally. If the host responses to these infections were independent, the prevalence of H. pylori should be similar in HIV-infected and non-infected patients. Yet, several studies have detected a lower prevalence of H. pylori in patients with HIV infection, whereas other studies found either no differences or greater rates of H. pylori infection in HIV-positive subjects. To review studies that addressed the issue of these two simultaneous infections and attempt to determine whether reliable conclusions can be drawn from this corpus of often contrasting evidence. Electronic literature search for relevant publications, followed by manual search of additional citations from extracted articles. The initial search yielded 44 publications; after excluding case reports, reviews, narrowly focused articles, and duplicate reports, there remained 29 articles, which are the corpus of this review. With one exception, all studies reported higher rates of H. pylori infection in HIV-negative subjects. Five studies also examined the CD4 lymphocyte counts and found an inverse correlation between the degree of immunosuppression and the prevalence of active H. pylori infection. Current evidence suggests that it is likely that H. pylori needs a functional immune system to successfully and persistently colonize the human gastric mucosa. © 2014 John Wiley & Sons Ltd.

  6. Campylobacter pylori as possible factor in peptic ulcer recurrence

    NARCIS (Netherlands)

    Rauws, E. A.

    1989-01-01

    The author reviews the literature up to 1988 about the close association of Campylobacter pylori with chronic active gastritis, duodenitis and peptic ulcer disease. No firm data however demonstrate that Campylobacter pylori causes duodenal ulcer but long term eradication of this bacterium prevents

  7. Campylobacter pylori and its role in peptic ulcer disease

    NARCIS (Netherlands)

    Tytgat, G. N.; Rauws, E. A.

    1990-01-01

    In almost all patients with genuine nondrug-induced duodenal or gastric ulcer there is evidence of gastric Campylobacter pylori colonization and concomitant inflammation. C. pylori is only demonstrable in the duodenal cap when there is "gastric mucus metaplasia." Suppression or eradication of C.

  8. Helicobacer pylori detection using local (in-house) rapid Urease ...

    African Journals Online (AJOL)

    Background: Since the discovery of Helicobacter pylori (H. pylori) by Robin Warren and Barry Marshall in 1982 and its subsequent association with diseases like antral (type B) gastritis, peptic ulcer disease (PUD), gastric cancer and gastric Mucosal Associated Lymphoid Tissue (MALT) lymphoma, various invasive as well ...

  9. Helicobacter pylori and histopathological changes of gastric mucosa ...

    African Journals Online (AJOL)

    Helicobacter pylori and histopathological changes of gastric mucosa in Uganda population with varying prevalence of stomach cancer. ... Results: The severity of gastritis correlated with the presence of H. pylori in Ganda and Nyarwanda but not in Nkole. Intestinal metaplasia (IM) was observed in Nyarwanda and Nkole and ...

  10. Biofilm formation enhances Helicobacter pylori survivability in vegetables.

    Science.gov (United States)

    Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow

    2017-04-01

    To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Correlation of Serum Anti- Helicobacter pylori Immunoglobulin A (IGA)

    African Journals Online (AJOL)

    Background: The seroprevalence of anti-H. pylori IgA antibodies has been reported to vary among populations and in relation to strains of Helicobacter pylori bacterium. However, there has been conflicting reports on the association between IgA serological status and the histological variables of chronic gastritis. This study ...

  12. Short report: evaluation of Helicobacter pylori eradication with bismuth sucralfate

    NARCIS (Netherlands)

    Reijers, M. H.; Noach, L. A.; Tytgat, G. N.

    1994-01-01

    In a pilot study we have evaluated the clinical efficacy of bismuth sucralfate to eradicate H. pylori. Ten consecutive patients with chronic dyspepsia and H. pylori associated gastritis were treated with bismuth sucralfate (220 mg bismuth per tablet, 4 tablets per day for 4 weeks). If a 14C urea

  13. Catalase epitopes vaccine design for Helicobacter pylori : A ...

    African Journals Online (AJOL)

    Catalase, an important enzyme in the virulence of H. pylori, could be a suitable candidate for vaccine design because it is highly conserved, which is important for the survival of H. pylori; it is expressed in high level and it is exposed on the surface of the bacteria. In this study, we designed epitope-based vaccine for catalase ...

  14. changing patterns of the prevalence of helicobacter pylori among ...

    African Journals Online (AJOL)

    study described the prevalence of H. pylori among large numbers of ... the gastric antrum for Rapid Urease Test (RUT) in identifying H. Pylori. Data on patient characteristics, clinical diagnosis and findings upon endoscopy were analyzed by simple ..... factors to be taken into account when planning treatment include compli-.

  15. Possible association between Helicobacter pylori infection and vocal fold leukoplakia.

    Science.gov (United States)

    Chen, Min; Chen, Jian; Yang, Yue; Cheng, Lei; Wu, Hai-Tao

    2018-03-06

    Several studies have indicated the larynx as possible Helicobacter pylori (H. pylori) reservoirs. This study explored the association between H. pylori and vocal fold leukoplakia. The case-control study involved 51 patients with vocal fold leukoplakia and 35 control patients with vocal polyps. Helicobacter pylori was detected in tissues by the rapid urease test, nested polymerase chain reaction (PCR), and single-step PCR. The H. pylori-specific immunoglobulin antibodies were detected in plasma by enzyme-linked immunosorbent assay (ELISA). Helicobacter pylori-positive rate of vocal fold leukoplakia and vocal polyps was 23.5% versus 11.4% (P = .157), 37.2% versus 14.3% (P = .020), 27.5% versus 8.6% (P = .031), and 70.6% versus 68.6% (P = .841) detected by rapid urease test, nested PCR, single-step PCR, and ELISA, respectively. Regression analysis indicated that H. pylori infection (P = .044) was the independent risk factor for vocal fold leukoplakia. Helicobacter pylori infection exists in the larynx and may be associated with vocal fold leukoplakia. © 2018 Wiley Periodicals, Inc.

  16. Molecular Mechanisms of Antibiotic Resistance in Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique)

    2004-01-01

    textabstractAn estimated 4 to 5 million individuals in the Netherlands are actively infected with Helicobacter pylori. Eradication of this bacterium becomes more difficult as the prevalence of antibiotic resistance is increasing worldwide. Most H. pylori infections are now diagnosed by

  17. Prevalence Of Helicobacter pylori In Gastric Biopsies Of Patients ...

    African Journals Online (AJOL)

    The prevalence of Helicobacter pylori infection as seen at the University of Benin Teaching Hospital (UBTH) Benin City Nigeria was 16% which was significant using the students T-test (P<0.05). Eighty one gastric biopsy specimens received in the microbiology laboratory were cultured on chocolate agar. Of the H. pylori ...

  18. Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsukamoto

    2017-08-01

    Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

  19. Innovative Perspectives of Integrated Chinese Medicine on H. pylori.

    Science.gov (United States)

    Ye, Hui; Shi, Zong-Ming; Chen, Yao; Yu, Jing; Zhang, Xue-Zhi

    2018-06-08

    Helicobacter pylori (H. pylori) treatment requires the development of more effective therapies, mainly owing to the challenges posed by the bacterial resistance to antibiotics. In China, critically high infection and antibiotic resistance rates have limited the application of classic H. pylori eradication therapies. Consequently, researchers are attempting to find new solutions by drawing from traditional medicine. This article reviews basic scientific and clinical progress in the use of integrated Chinese and Western medicine (IM) to treat H. pylori; describes the conflicting results between in vivo and in vitro studies in this regard; discusses the observed clinical effects of IM, with emphasis on traditional patent medicines; and proposes a role for IM in both the diagnosis and treatment of H. pylori, including the use of tongue manifestation as an early diagnostic method and capitalizing on IM's direct and indirect methods for enhancing antibiotic effect.

  20. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Monika Burns

    Full Text Available Helicobacter pylori (H.pylori, a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA, enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40 were used; half were placed on a moderately iron deficient (ID diet immediately post-weaning, and the other half were maintained on an iron replete (IR diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet. All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001. Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05, independent of infection status. At 12 months postinfection, hematocrit (Hct and hemoglobin (Hgb concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA.

  1. The Association of Helicobacter pylori Infection with Hashimoto's Thyroiditis

    Directory of Open Access Journals (Sweden)

    Maryam Alsadat Salami

    2013-05-01

    Full Text Available Autoimmune thyroid diseases (ATD are multifactorial conditions that result from genetic predisposition in combination with environmental risk factors. Helicobacter pylori infection as an environmental risk factor has been proposed to imitate the antigenic components of the thyroid cell membrane and may play a leading role in the onset of the autoimmune diseases, such as Hashimoto thyroiditis. The aim of this study was to investigate the association between Helicobacter pylori (HP infection and Hashimoto's thyroiditis (HT. The participants in this case-control study included 43 patients affected by Hashimoto's thyroiditis, and 40 healthy individuals without history of autoimmune disease as the control group. Anti HP IgG and anti-TPO antibodies were determined using ELISA method. Results were considered positive when the IgG anti-HP value was higher than 30 IU/ml and the anti-TPO autoantibody value was higher than 75 IU/ml. The mean TSH level was 18.3±16.8 IU/ml for patients and 2.8±1.2 IU/ml for the control group (P<0.001. 46.5% of the patient group and 10.8% of the control group were infected with HP. The association between HP and Hashimoto's thyroiditis was statistically significant (Odds Ratio=7.2, 95%, Confidence Interval: 2.0- 28.8, P<0.001. The findings show that, there is an association between HP and Hashimoto's thyroiditis. To establish a definite correlation between them, more detailed studies with a more specialized examination and precise consideration regarding species of HP, genetic polymorphism of the host and investigation of environmental factors are needed.

  2. The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence.

    Science.gov (United States)

    Haley, Kathryn P; Delgado, Alberto G; Piazuelo, M Blanca; Mortensen, Brittany L; Correa, Pelayo; Damo, Steven M; Chazin, Walter J; Skaar, Eric P; Gaddy, Jennifer A

    2015-07-01

    During infectious processes, antimicrobial proteins are produced by both epithelial cells and innate immune cells. Some of these antimicrobial molecules function by targeting transition metals and sequestering these metals in a process referred to as "nutritional immunity." This chelation strategy ultimately starves invading pathogens, limiting their growth within the vertebrate host. Recent evidence suggests that these metal-binding antimicrobial molecules have the capacity to affect bacterial virulence, including toxin secretion systems. Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, or calgranulin A/B) binds zinc and represses the elaboration of the H. pylori cag type IV secretion system (T4SS). However, there are several other S100 proteins that are produced in response to infection. We hypothesized that the zinc-binding protein S100A12 (calgranulin C) is induced in response to H. pylori infection and also plays a role in controlling H. pylori growth and virulence. To test this, we analyzed gastric biopsy specimens from H. pylori-positive and -negative patients for S100A12 expression. These assays showed that S100A12 is induced in response to H. pylori infection and inhibits bacterial growth and viability in vitro by binding nutrient zinc. Furthermore, the data establish that the zinc-binding activity of the S100A12 protein represses the activity of the cag T4SS, as evidenced by the gastric cell "hummingbird" phenotype, interleukin 8 (IL-8) secretion, and CagA translocation assays. In addition, high-resolution field emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that S100A12 represses biogenesis of the cag T4SS. Together with our previous work, these data reveal that multiple S100 proteins can repress the elaboration of an oncogenic bacterial surface organelle. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. The accuracy of the Helicobacter pylori stool antigen test in diagnosing H-pylori in treated and untreated patients

    NARCIS (Netherlands)

    Arents, NL; van Zwet, AA; Thijs, JC; de Jong, A; Pool, MO; Kleibeuker, JH

    Objective and design To evaluate the performance of the Helicobacter pylori stool antigen test (HpSA test) in detecting H. pylori infection and monitoring the effect of treatment. This was done in two separate studies using either a biopsy or the C-13-urea breath test based 'gold standard' (in

  4. Helicobacter pylori Stool Antigen test: a reliable non-invasive test for the diagnosis of Helicobacter pylori infection in children

    NARCIS (Netherlands)

    van Doorn, O. J.; Bosman, D. K.; van't Hoff, B. W.; Taminiau, J. A.; ten Kate, F. J.; van der Ende, A.

    2001-01-01

    OBJECTIVE: To evaluate the Helicobacter pylori Stool Antigen (HpSA) test for the diagnosis of H. pylori infection in children. DESIGN AND SETTING: Prospective cohort study in an academic medical centre. PATIENTS AND METHODS: A total of 106 consecutive children who underwent gastroscopy were

  5. Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster.

    Science.gov (United States)

    Wang, Ming-yi; Shao, Chen; Li, Jie; Yang, Ya-Chao; Wang, Shao-bo; Hao, Jun-ling; Wu, Chun-mei; Gao, Xiao-zhong; Shao, Shi-he

    2015-07-01

    The duodenal ulcer promoting gene (dupA), located in the plasticity region of Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system (T4SS) with vir genes around dupA. In the study, we investigated the association between the dupA cluster status and the virulence of H. pylori in a littoral region of Northeast China. Two hundred and sixty-two H. pylori strains isolated from the chronic gastritis were examined to evaluate the dupA cluster status, cag PAI genes and vacA genotype using PCR and Western blot. Histopathologic evaluations of biopsy specimens were performed to analysis the association between the dupA cluster and the inflammatory response. IL-8 productions in gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured, respectively, to analysis the association between the dupA cluster status and IL-8 production. We found that gastric mucosal inflammatory cell infiltration was significantly higher in patients with dupA-positive H. pylori, including H. pylori with complete dupA cluster (2.71 ± 0.79) and incomplete dupA cluster (2.09 ± 0.61) than in patients with dupA-negative strain (1.73 ± 0.60, p dupA cluster. Gastric mucosal IL-8 levels were higher in the complete dupA cluster group than in other groups (p dupA cluster (1527.9 ± 180.0 pg/ml) than in those with an incomplete dupA cluster (1229.4 ± 75.3 pg/ml, p dupA negative (1201.9 ± 92.3 pg/ml, p dupA cluster in H. pylori is associated with inflammatory cell infiltration and IL-8 secretion, and H. pylori strain with a complete dupA cluster seems to be more virulent than other strains with the incomplete dupA cluster or dupA negative.

  6. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Cheng, Tain-Lu [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-02-05

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

  7. Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.

    Science.gov (United States)

    Saniee, Parastoo; Shahreza, Somayeh; Siavoshi, Farideh

    2016-04-01

    Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT). Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed. Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test. Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests. © 2015 John Wiley & Sons Ltd.

  8. Treatment of children with Helicobacter pylori infection and malabsorption syndromes with probiotics: Comparison with conventional methods

    International Nuclear Information System (INIS)

    Ghoos, Y.; Brunser, O.; Lawson, F.; Muzeke, A.; Ndjaye, M.F.

    2000-01-01

    It is stated that in developing countries a high rate of Helicobacter pylori infection among newborns and young children occurs. It is further assumed that this incidence may lead to inhibition of defense mechanism (inhibition of acid secretion) against bacteria, per orally ingested. This may result in excessive colonisation of the small intestine by bacteria. This situation may become a major cause for chronic malnutrition and diarrhoea syndrome with failure to thrive. This project aims at determining the occurrence of Helicobacter pylori infection in children at young age. It is aimed also at tracing the relationship between the Helicobacter pylori infection and the state of undernourishment. Finally it is aimed at comparing the usefulness of pre-/probiotics as anti-infection treatment. The methods used to demonstrate above mentioned parameters are based on stable isotopes, 13 CO 2 and H 2 breath tests mainly. To assess nutritional status and progress in growth conventional anthropometric techniques will be used, complementary to the results obtained by stable isotopes. It is put forward that the use of pre-/probiotics, instead of antibiotics, will suppress upper gastrointestinal infection and restore the intestinal cell capacity to assimilate all food ingredients. (author)

  9. Treatment of children with Helicobacter pylori infection and malabsorption syndromes with probiotics: Comparison with conventional methods

    Energy Technology Data Exchange (ETDEWEB)

    Ghoos, Y [UZ Gasthuisberg, Gastrointestinal Pathophysiology, Leuven (Belgium); Brunser, O [Institute of Nutrition and Food Technology, Santiago (Chile); Lawson, F [Clinique Padre Pio, Cotonou (Benin); Muzeke, A [Faculte de Medicine, University of Kinshasa, Kinshasa (Congo); Ndjaye, M F [Cercle Senegalais Gastroenterologie, Dakar (Senegal)

    2000-07-01

    It is stated that in developing countries a high rate of Helicobacter pylori infection among newborns and young children occurs. It is further assumed that this incidence may lead to inhibition of defense mechanism (inhibition of acid secretion) against bacteria, per orally ingested. This may result in excessive colonisation of the small intestine by bacteria. This situation may become a major cause for chronic malnutrition and diarrhoea syndrome with failure to thrive. This project aims at determining the occurrence of Helicobacter pylori infection in children at young age. It is aimed also at tracing the relationship between the Helicobacter pylori infection and the state of undernourishment. Finally it is aimed at comparing the usefulness of pre-/probiotics as anti-infection treatment. The methods used to demonstrate above mentioned parameters are based on stable isotopes, {sup 13}CO{sub 2} and H{sub 2} breath tests mainly. To assess nutritional status and progress in growth conventional anthropometric techniques will be used, complementary to the results obtained by stable isotopes. It is put forward that the use of pre-/probiotics, instead of antibiotics, will suppress upper gastrointestinal infection and restore the intestinal cell capacity to assimilate all food ingredients. (author)

  10. In silico approach towards identification of potential inhibitors of Helicobacter pylori DapE.

    Science.gov (United States)

    Mandal, Rahul Shubhra; Das, Santasabuj

    2015-01-01

    Helicobacter pylori is a gastric mucosal pathogen and is associated with diseases like peptic ulcer and gastric cancer. To combat H. pylori infection, there is an urgent need for new class of antibiotics due to the emergence of drug-resistant strains. Enzymes involved in bacterial lysine biosynthetic pathways may be potential targets for antibacterial drug development, since lysine is an essential component of the bacterial peptidoglycan cell wall. No pathway exists for lysine biosynthesis in humans; hence, the inhibitors targeting bacterial enzymes may have selective toxicity. dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a critical enzyme of this pathway and deletion of DapE gene is lethal to H. pylori, since the organism has no alternative pathway for lysine biosynthesis. In this study, we reported a 3D model structure of H. pylorie DapE, which consisted of a catalytic domain and a dimerization domain generated by MODELLER software. We also confirmed the stability of the modeled structure through 10 ns molecular dynamics simulation using GROMACS software. Next, to identify potential small molecule inhibitors of DapE, drug-like small molecule-screening library was generated. This was performed by Tanimoto-based similarity searching in the PubChem Database with DapE substrate L,L-SDAP as a query molecule, followed by fragment-based docking approach using GLIDE XP. This approach identified two potential substrate-competitive small molecule inhibitors of DapE. These new molecules may provide a starting point to search for novel therapeutics.

  11. Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.

    Science.gov (United States)

    Ritter, Birgit; Kilian, Petra; Reboll, Marc Rene; Resch, Klaus; DiStefano, Johanna Kay; Frank, Ronald; Beil, Winfried; Nourbakhsh, Mahtab

    2011-02-01

    Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

  12. Ulcerogenic Helicobacter pylori strains isolated from children: a contribution to get insight into the virulence of the bacteria.

    Directory of Open Access Journals (Sweden)

    Inês Vitoriano

    Full Text Available Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD. In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA "on" status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence

  13. Indications for treatment of Helicobacter pylori infection: a systematic overview.

    Science.gov (United States)

    Veldhuyzen van Zanten, S J; Sherman, P M

    1994-01-15

    To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates

  14. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    Science.gov (United States)

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  15. Helicobacter pylori - a seasoned pathogen by any other name

    Directory of Open Access Journals (Sweden)

    Ahmed Niyaz

    2009-12-01

    Full Text Available Abstract Helicobacter pylori is a well known inhabitant of human stomach which is linked to peptic ulcer disease and gastric adenocarcinoma. It was recently shown in several studies that H. pylori can be harnessed as a surrogate marker of human migration and that its population structure and stratification patterns exactly juxtapose to those of Homo sapiens. This is enough a testimony to convey that H. pylori may have coevolved with their host. Several protective effects of H. pylori colonization have been considered as evidence of a presumed symbiotic relationship. Contrary to this assumption is the presence of a strong virulence apparatus within H. pylori; why a co-evolved parasite would try inflicting its host with serious infection and even causing cancer? The answer is perhaps embedded in the evolutionary history of both the bacterium and the host. We discuss a hypothetical scenario wherein H. pylori may have acquired virulence genes from donors within its environment that varied with change in human history and ecology. The H. pylori genomes sequenced to date portray fairly high abundance of such laterally acquired genes which have no assigned functions but could be linked to inflammatory responses or other pathogenic attributes. Therefore, the powerful virulence properties and survival strategies of Helicobacter make it a seasoned pathogen; thus the efforts to portray it as a commensal or a (harmless 'bacterial parasite' need rethinking.

  16. Prevalence of Helicobacter pylori in Northern Jordan: Endoscopy based study

    International Nuclear Information System (INIS)

    Bani-Hani, Kamal E.; Hammouri, Shadi M.

    2001-01-01

    Helicobacter pylori infection is considered the most common infection worldwide and is associated with many other disorders. The aim of this study is to determine the prevalence of this infection among patients undergoing endoscopy in Northern Jordan. Between November 1998 and September 2000, all patients referred from the Gastro-esophageal Clinic to the Endoscopy Unit at Princess Basma Teaching Hospital, Irbid, Northern Jordan were enrolled in this prospective study. For each patient clinical and epidemiological data was collected and endoscopy was performed. At least 3 antral biopsies were obtained from each patient, and these were examined histologically for the presence of gastritis and stained for Helicobacter pylori using modified Giemsa stain. A total of 197 consecutive patients (113 females) with a mean age of 40.2 years (range 15-91 years) were studied. Abdominal pain was the highest presenting symptom. Gastritis 91% and esophagitis 42% were the most frequent endoscopic findings. Gastritis was documented histologically in 183 (93%) of patients. Helicobacter pylori was found in 161 patients (82%), with all of these having histological gastritis. The 11 patients with gastric ulcer, compared to the 51 out of the 59 (86%) patients with duodenal ulcer, showed Helicobacter pylori in their biopsies. The prevalence of Helicobacter pylori infection in patients subjected to an upper gastrointestinal endoscopy in Jordan is high. This study confirms that Helicobacter pylori is significantly associated with gastritis and peptic ulcer. Further studies are needed to determine the types of Helicobacter pylori strains present in Jordan. (author)

  17. In vitro antagonistic activity of Lactobacillus casei against Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Shymaa Enany

    2015-01-01

    Full Text Available Helicobacter pylori is one of the most common causes of chronic infections in humans. Curing H. pylori infection is difficult because of the habitat of the organism below the mucus adherent layer of gastric mucosa. Lactobacilli are known as acid-resistant bacteria and can remain in stomach for a long time than any other organism, we aimed in this study to examine the efficacy of Lactobacillus casei as a probiotic against H. pylori in humans. Particularly, L. casei was opted as it is considered to be one of the widely used probiotics in dairy products. One hundred and seven strains of H. pylori were isolated from dyspeptic patients and were tested for their antibiotic susceptibility to metronidazole (MTZ, clarithromycin (CLR, tetracycline (TET, and amoxicillin (AMX by the disc diffusion method. The strains were examined for their susceptibility toward L. casei - present in fermented milk products - by well diffusion method. It was found that 74.7% strains were resistant to MTZ; 1.8% to MTZ, TET, and CLR; 3.7% to MTZ and CLR; 4.6% to MTZ and TET; and 0.9% were resistant to MTZ, TET, and AMX. The antibacterial activity of L. casei against H. pylori was determined on all the tested H. pylori isolates including antibiotic resistant strains with different patterns. Our study proposed the use of probiotics for the treatment of H. pylori infection as an effective approach.

  18. Peptide Extracts from Cultures of Certain Lactobacilli Inhibit Helicobacter pylori.

    Science.gov (United States)

    De Vuyst, Luc; Vincent, Pascal; Makras, Eleftherios; Leroy, Frédéric; Pot, Bruno

    2010-03-01

    Helicobacter pylori inhibition by probiotic lactobacilli has been observed in vitro and in vivo. Carefully selected probiotic Lactobacillus strains could therefore play an important role in the treatment of H. pylori infection and eradication. However, the underlying mechanism for this inhibition is not clear. The aim of this study was to examine if peptide extracts, containing bacteriocins or other antibacterial peptides, from six Lactobacillus cultures (Lactobacillus acidophilus La1, Lactobacillus amylovorus DCE 471, Lactobacillus casei YIT 9029, Lactobacillus gasseri K7, Lactobacillus johnsonii La1, and Lactobacillus rhamnosus GG) contribute to the inhibition of H. pylori. Peptide extracts from cultures of Lact. amylovorus DCE 471 and Lact. johnsonii La1 were most active, reducing the viability of H. pylori ATCC 43504 with more than 2 log units within 4 h of incubation (P < 0.001). The four other extracts were less or not active. When six clinical isolates of H. pylori were tested for their susceptibility towards five inhibitory peptide extracts, similar observations were made. Again, the peptide extracts from Lact. amylovorus DCE 471 and Lact. johnsonii La1 were the most inhibitory, while the three other extracts resulted in a much lower inhibition of H. pylori. Protease-treated extracts were inactive towards H. pylori, confirming the proteinaceous nature of the inhibitory substance.

  19. The Helicobacter pylori theory and duodenal ulcer disease. A case study of the research process

    DEFF Research Database (Denmark)

    Christensen, A H; Gjørup, T

    1995-01-01

    should be selected for H. pylori eradication treatment. CONCLUSION: Descriptive clinical studies and laboratory studies of disease mechanisms were the prevailing types of research about H. pylori. Comparatively few therapeutic intervention studies were done; this fact may have hampered the acceptance......OBJECTIVES: To describe the medical research process from the time of the generation of a new theory to its implementation in clinical practice. The Helicobacter pylori (H. pylori) theory, i.e. the theory that H. pylori plays a significant causal role in duodenal ulcer disease was chosen as a case....... MATERIAL: Abstracts from 1984 to 1993, identified in the CD-Rom, Medline system, ("Silverplatter"), using the search terms Campylobacter pylori and Helicobacter pylori, and reviews and editorials about H. pylori in some of the most widespread clinical journals. RESULTS: 2204 papers on H. pylori were...

  20. Severe gastritis decreases success rate of Helicobacter pylori eradication.

    Science.gov (United States)

    Kalkan, Ismail Hakki; Sapmaz, Ferdane; Güliter, Sefa; Atasoy, Pınar

    2016-05-01

    In several studies, different risk factors other than antibiotic resistance have been documented with Helicobacter pylori eradication failure. We aimed in this study to investigate the relationship of gastric density of H. pylori, the occurrence/degree of gastric atrophy, and intestinal metaplasia (IM) with success rate of H. pylori eradication. Two hundred consecutive treatment naive patients who received bismuth containing standart quadruple treatment due to H. pylori infection documented by histopathological examination of two antral or two corpal biopsies entered this retrospective study. The updated Sydney system was used to grade the activity of gastritis, density of H. pylori colonization, atrophy, and IM. Stages III and IV of operative link for gastritis assessment (OLGA) or the operative link on gastric intestinal metaplasia assessment (OLGIM) stages was considered as severe gastritis. H. pylori eradication was determined via stool H. pylori antigen test performed 4 weeks after the end of therapy. The presence of gastric atrophy and IM was significantly higher in patients with eradication failure (p = 0.001 and 0.01, respectively). Severe gastritis (OLGA III-IV and OLGIM III-IV) rates were higher in eradication failure group. A multiple linear regression analysis showed that OLGA and OLGIM stages were to be independent risk factors for eradication failure (p = 0.03 and 0.01, respectively). Our results suggested that histopathologically severe gastritis may cause H. pylori eradication failure. In addition, we found that H. pylori density was not a risk factor for treatment failure in patients who receive quadruple treatment.

  1. Helicobacter pylori eradication in complicated peptic ulcer: Beneficial in most?

    Directory of Open Access Journals (Sweden)

    Subair Mohsina

    2016-01-01

    Full Text Available Helicobacter pylori eradication therapy has a role in minimizing the complications of peptic ulcer disease, namely, bleeding, perforation, and obstruction. However, the precise role of H. pylori eradication therapy in the complicated ulcers remains inconclusive, especially in perforation and gastric outlet obstruction. The prevalence of H. pylori in peptic ulcer bleeding patients has been widely underestimated owing to the differences in diagnostic tests and patient characteristics, and hence, it is recommended that an initial negative test should be followed up by a delayed repeat testing to rule out false negativity. It is well established now that eradication of H. pylori in patients with bleeding ulcers reduces rebleeding and ulcer recurrence. Multiple studies have attributed high recurrence rates of duodenal ulcer following simple closure to a high prevalence of H. pylori infection. Eradication therapy decreases the recurrence rate of perforated ulcers, thus justifying the role of H. pylori eradication therapy following the primary surgical management of perforated ulcers. The role of H. pylori in duodenal ulcer with gastric outlet obstruction is yet to be evaluated clearly. There are some reports of resolution of gastric outlet obstruction following therapy for H. pylori, obviating the need for surgery. Clarithromycin-containing regimens are recommended as first-line in areas of low resistance, whereas bismuth-containing quadruple therapy is the first-line empirical treatment in areas of high clarithromycin resistance. Treatment of H. pylori is beneficial in most of the patients with complicated peptic ulcer disease, especially in reducing recurrence of ulcer with or without complications.

  2. Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis, and NSAID use.

    Science.gov (United States)

    Tahara, Tomomitsu; Shibata, Tomoyuki; Kawamura, Tomohiko; Ishizuka, Takamitsu; Okubo, Masaaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Arisawa, Tomiyasu; Ohmiya, Naoki; Hirata, Ichiro

    2016-02-01

    Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. We measured average telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa and assessed its relationship to H. pylori-related gastritis, DNA methylation, ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID users and 102 nonusers. Relative telomere length in genomic DNA was measured by real-time PCR. H. pylori infection status, histological severity of gastritis, and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation status was determined by methylation-specific PCR (MSP). Average relative telomere length of H. pylori-infected subjects was significantly shortened when compared to H. pylori-negative subjects (p = 0.002) and was closely associated with all histological parameter of gastritis (all p values gastritis and CDH1 methylation status. Also, telomere shortening is accelerated by NSAID usage especially in H. pylori-negative subjects.

  3. Polysaccharides as Bacterial Antiadhesive Agents and "Smart" Constituents for Improved Drug Delivery Systems Against Helicobacter pylori Infection.

    Science.gov (United States)

    Menchicchi, Bianca; Hensel, Andreas; Goycoolea, Francisco M

    2015-01-01

    The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context

  4. The expression of Helicobacter pylori tfs plasticity zone cluster is regulated by pH and adherence, and its composition is associated with differential gastric IL-8 secretion.

    Science.gov (United States)

    Silva, Bruno; Nunes, Alexandra; Vale, Filipa F; Rocha, Raquel; Gomes, João Paulo; Dias, Ricardo; Oleastro, Mónica

    2017-08-01

    Helicobacter pylori virulence is associated with different clinical outcomes. The existence of an intact dupA gene from tfs4b cluster has been suggested as a predictor for duodenal ulcer development. However, the role of tfs plasticity zone clusters in the development of ulcers remains unclear. We studied several H. pylori strains to characterize the gene arrangement of tfs3 and tfs4 clusters and their impact in the inflammatory response by infected gastric cells. The genome of 14 H. pylori strains isolated from Western patients, pediatric (n=10) and adult (n=4), was fully sequenced using the Illumina platform MiSeq, in addition to eight pediatric strains previously sequenced. These strains were used to infect human gastric cells, and the secreted interleukin-8 (IL-8) was quantified by ELISA. The expression of virB2, dupA, virB8, virB10, and virB6 was assessed by quantitative PCR in adherent and nonadherent fractions of H. pylori during in vitro co-infection, at different pH values. We have found that cagA-positive H. pylori strains harboring a complete tfs plasticity zone cluster significantly induce increased production of IL-8 from gastric cells. We have also found that the region spanning from virB2 to virB10 genes constitutes an operon, whose expression is increased in the adherent fraction of bacteria during infection, as well as in both adherent and nonadherent fractions at acidic conditions. A complete tfs plasticity zone cluster is a virulence factor that may be important for the colonization of H. pylori and to the development of severe outcomes of the infection with cagA-positive strains. © 2017 John Wiley & Sons Ltd.

  5. Unique mechanism of Helicobacter pylori for colonizing the gastric mucus.

    Science.gov (United States)

    Yoshiyama, H; Nakazawa, T

    2000-01-01

    Helicobacter pylori is a human gastric pathogen causing chronic infection. Urease and motility using flagella are essential factors for its colonization. Urease of H. pylori exists both on the surface and in the cytoplasm, and is involved in neutralizing gastric acid and in chemotactic motility. H. pylori senses the concentration gradients of urea in the gastric mucus layer, then moves toward the epithelial surface by chemotactic movement. The energy source for the flagella movement is the proton motive force. The hydrolysis of urea by the cytoplasmic urease possibly generates additional energy for the flagellar rotation in the mucus gel layer.

  6. Asymptomatic gastric heterotopia in the rectum with Helicobacter pylori infection.

    Science.gov (United States)

    Swatek, Jarosław; Wronecki, Lech; Ciechanek, Roman; Szumiło, Justyna

    2015-12-01

    Gastric heterotopia is very rare in the rectum - less than 50 cases have been reported so far. Only in six of them Helicobacter pylori has been observed in heterotopic mucosa. We report a case of a 58-year-old woman with asymptomatic gastric heterotopia in the rectum, incidentally revealed during colonoscopy as a small, sessile polyp. The presence of H. pylori was confirmed by immunohistochemistry. This finding supports the opinion that H. pylori may pass along the gastrointestinal tract in a viable form and that the fecal-oral route of transmission is possible.

  7. [Latin American contribution to the study of Helicobacter pylori].

    Science.gov (United States)

    Ramírez Ramos, Alberto; Sánchez Sánchez, Rolando

    2009-09-01

    We have reviewed Lilacs, PubMed and Google searching for original articles related to Helicobacter pylori published by Latin American investigators from 2003 to 2008. Contributions in the following fields by countries are: Molecular biology: Brasil, Chile, Colombia, Peru y Venezuela. Argentina, Brasil, Colombia, Cuba, Peru y Venezuela. Argentina, Bolivia, Brasil, Chile, Costa Rica, Colombia, Mexico, Peru y Venezuela. Helicobacter pylori and gastroduodenal diseases: Brasil, Cuba, Peru y Venezuela. Helicobacter pylori and extra digestive diseases: Brasil, Colombia and Venezuela. Pediatrics: Brasil, Cuba y Venezuela. Argentina, Brasil, Chile, Colombia, Costa Rica, Mexico, Peru y Venezuela.

  8. Prevalence of Helicobacter pylori and parasites in symptomatic children examined for Helicobacter pylori antibodies, antigens, and parasites in Yemen.

    Science.gov (United States)

    Bin Mohanna, Mabrook A; Al-Zubairi, Lutf M; Sallam, Abdul K

    2014-11-01

    To estimate the prevalence of Helicobacter pylori (H. pylori) and parasites in symptomatic children examined for H. pylori antibodies, antigens, and parasites in Yemen. A record-based study was carried out at Specialized Sam Pediatric Center in Sana'a, Yemen for 3 years between 2011-2013. Out of the 43,200 patients seen for different causes through that period, 1008 (2.3%) (females: 675 [67%]; males: 333 [33%]) had gastric complaints, and were subjected to an examination of blood and stool for H. pylori and parasites. Data regarding age and gender was also collected. The age of the patients ranged from 3-15 years. The prevalence of H. pylori among children examined for H. pylori was 65%, 30% of them were males, and 35% were females (chi square [I2]=142, p<0.01]). The prevalence in the 6-8 years age group was 83%, and it was 52% in the age group of 12-15 years. The prevalence of giardiasis was 10%, and amoebiasis was 25%. Prevalence of H. pylori infection among children was high, and was more prevalent in the age group of 6-8 years than in the other age groups. Females were more affected than males. Parasites (amoebiasis and giardiasis) infestation was less prevalent.

  9. Changes in gastric microbiota induced by Helicobacter pylori infection and preventive effects of Lactobacillus plantarum ZDY 2013 against such infection.

    Science.gov (United States)

    Pan, Mingfang; Wan, Cuixiang; Xie, Qiong; Huang, Renhui; Tao, Xueying; Shah, Nagendra P; Wei, Hua

    2016-02-01

    Helicobacter pylori is a gram-negative pathogen linked to gastric ulcers and stomach cancer. Gastric microbiota might play an essential role in the pathogenesis of these stomach diseases. In this study, we investigated the preventive effect of a probiotic candidate Lactobacillus plantarum ZDY 2013 as a protective agent against the gastric mucosal inflammation and alteration of gastric microbiota induced by H. pylori infection in a mouse model. Prior to infection, mice were pretreated with or without 400 µL of L. plantarum ZDY 2013 at a concentration of 10(9) cfu/mL per mouse. At 6 wk postinfection, gastric mucosal immune response and alteration in gastric microbiota mice were examined by quantitative real-time PCR and high-throughput 16S rRNA gene amplicon sequencing, respectively. The results showed that L. plantarum ZDY 2013 pretreatment prevented increase in inflammatory cytokines (e.g., IL-1β and IFN-γ) and inflammatory cell infiltration in gastric lamina propria induced by H. pylori infection. Weighted UniFrac principal coordinate analysis showed that L. plantarum ZDY 2013 pretreatment prevented the alteration in gastric microbiota post-H. pylori infection. Linear discriminant analysis coupled with effect size identified 22 bacterial taxa (e.g., Pasteurellaceae, Erysipelotrichaceae, Halomonadaceae, Helicobacteraceae, and Spirochaetaceae) that overgrew in the gastric microbiota of H. pylori-infected mice, and most of them belonged to the Proteobacteria phylum. Lactobacillus plantarum ZDY 2013 pretreatment prevented this alteration; only 6 taxa (e.g., Lachnospiraceae, Ruminococcaceae, and Clostridiaceae), mainly from the taxa of Firmicutes and Bacteroidetes, were dominant in the gastric microbiota of the L. plantarum ZDY 2013 pretreated mice. Administration of L. plantarum ZDY 2013 for 3 wk led to increase in several bacterial taxa (e.g., Rikenella, Staphylococcus, Bifidobacterium), although a nonsignificant alteration was found in the gastric microbiota