Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran

Background: Helicobacter Pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H.pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics. Objectives: In this study we aimed to assess the effect of S. boulardii supplementation on H.pylori eradication among children in our region. Patients and Methods: In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H.pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces Boulardii and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05. Results: 24 children completed the study. The mean HpSA reduced from 0.40 ± 0.32 to 0.21 ± 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 ± 0.19 decrease in the study group whereas the same value was 0.0048 ± 0.12 for the controls, again stating a significant difference (P = 0.01). Conclusions: Saccharomyces boulardii has a positive effect on reducing the colonization of H.pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy.

Determinación de la frecuencia de infección por helicobacter pylori y parasitosis en preescolares de 2 a 4 años que acuden a los centros de desarrollo infantil del municipio de la ciudad de Cuenca. Julio, 2015

El presente estudio se enfocó en la determinación de la frecuencia de Helicobacter pylori y parasitosis intestinal en los niños y niñas de 2 a 4 años que asisten a los Centros de Desarrollo Infantil del Municipio de la ciudad de Cuenca. Las muestras de heces fueron receptadas en los Centros de Desarrollo Infantil con la colaboración de los padres de familia y los educadores. Los exámenes coprológicos se llevaron a cabo en el Laboratorio Clínico del Centro de Diagnóstico de la Facultad de Ciencias Médicas de la Universidad de Cuenca cumpliendo normas de control de calidad y bioseguridad. La identificación de los parásitos intestinales se realizó a través del examen coproparasitario en fresco y la técnica inmunocromatográfica se empleó para la determinación cualitativa de Helicobacter pylori. Los resultados del estudio evidenciaron una prevalencia de 26,1% de infección por Helicobacter pylori y de 19,3% para parasitosis intestinal en los Centros. En las parasitosis infantiles, el quiste de Entamoeba histolytica se identificó como el agente etiológico en el 58,8% de los casos

Frecuencia de la infección por Helicobacter Pylori en población asintomatica de 10-80 años. Cuenca - Azuay 1997

Se realiza un estudio clínico descriptivo en 210 personas asintomáticas voluntarias, con el fin de establecer la prevalencia por grupos etáreos de la infección por H. Pylori en personas asintomáticas entre los 10 y 80 años a través de la determinación de IgG, por el método de ELISA en suero sanguíneo. Se clasifican a los individuos de acuerdo a si presentan o no factores de riesgo, principalmente hacinamiento, en el aseo de manos, higiene bucal y convivencia con animales domésticos. Se concluye que la prevalencia de resultados positivos es del 63.3 por ciento en el examen serológico y es mayor sobre los 40 años sin que exista diferencia de sexo, siendo los principales factores de riesgo la convivencia con el gato y el cepillado dental no adecuado. En los pacientes con prueba serológica positiva a los que se realizó la endoscopía [40], se encontró un resultado histopatológico con reporte de gastritis aguda en el 42.5 por ciento y de gastritis crónica en el 30 por ciento; la positividad de H. pylori histopatológicamente fue del 52.5 por ciento. Las pruebas de sensiblidad de la ureasa y de la IGG fueron del 90.47 por ciento y del 95.2 por ciento, respectivamente y la especificidad de 84.2 en ambas pruebas

Antimicrobial activity of the essential oils of Dittrichia viscosa subsp viscosa on Helicobacter pylori

Dittrichia viscosa subsp. viscosa (Compositae) is found on edges, wood clearings and in waste places of the Iberian Peninsula. Aerial parts of D. viscosa were collected at flowering phase in September-October 2001 around Lisbon, Portugal and the essential oils isolated by hydro-distillation for 4 h using a Clevenger-type apparatus. The oils were analyzed by gas chromatography and gas chromatography-mass spectrometry. Preliminary examination of the essential oils allowed the identification of 32 components. Only four components reached percentages over 5%: fokienol (11.8%), T-muurorol (7.9%), (E)-nerolidol (5.5%) and delta-cadinene (5.0%). The essential oils were tested against Helicobacterpylori and Listeria monocytogenes. Essential oils did not have antimicrobial activity against L. monocytogenes. The essential oil at 0.88 to 22.22 mu g.ml(-1) did not inhibit the growth of H. pylori, affected the growth slightly at 44.40 mu g.ml(-1), and completely inhibited the growth at 88.80 to 133.20 mu g.ml(-1) Results show that use of D. viscosa essential oil in the treatment of gastric disorders caused by H. pylori can be effective.

Prognostic Role of Host Cyclooxygenase and Cytokine Genotypes in a Caucasian Cohort of Patients with Gastric Adenocarcinoma

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H. pylori-infection and antibody immune response in a rural Tanzanian population

Abstract Background: Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare. Methods: Sera collected during a household-based survey in rural Tanzania in 1985 were tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models. Results: Of 788 participants, 513 were aged ≤17 years. H. pylori seropositivity increased from 76% at 0–4 years to 99% by ≥18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2–31.4 for 10–17 vs. 0–4 years), higher birth-order (11.1; 3.6–34.1 for ≥3rd vs. 1st born), and having a seropositive next-older sibling (2.7; 0.9–8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7–5.6), consistent with a Th2- dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3–4.4). Conclusion: H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa.

Comparative Transcriptomics of H. pylori Strains AM5, SS1 and Their hpyAVIBM Deletion Mutants: Possible Roles of Cytosine Methylation

Helicobacter pylori is an important human pathogen and one of the most successful chronic colonizers of the human body. H. pylori uses diverse mechanisms to modulate its interaction with the host in order to promote chronic infection and overcome host immune response. Restriction-modification genes are a major part of strain-specific genes present in H. pylori. The role of N-6 -adenine methylation in bacterial gene regulation and virulence is well established but not much is known about the effect of C-5 -cytosine methylation on gene expression in prokaryotes. In this study, it was observed by microarray analysis and RT-PCR, that deletion of an orphan C-5 -cytosine methyltransferase, hpyAVIBM in H. pylori strains AM5and SS1 has a significant effect on the expression of number of genes belonging to motility, adhesion and virulence. AM Delta DhpyAVIBM mutant strain has a different LPS profile and is able to induce high IL-8 production compared to wild-type. hpyAVIBM from strain 26695 is able to complement mutant SS1 and AM5 strains. This study highlights a possible significance of cytosine methylation in the physiology of H. pylori.

The nuclease activities of both the Smr domain and an additional LDLK motif are required for an efficient anti-recombination function of Helicobacter pyloriMutS2

Helicobacter pylori, a human pathogen, is a naturally and constitutively competent bacteria, displaying a high rate of intergenomic recombination. While recombination events are essential for evolution and adaptation of H.pylori to dynamic gastric niches and new hosts, such events should be regulated tightly to maintain genomic integrity. Here, we analyze the role of the nuclease activity of MutS2, a protein that limits recombination during transformation in H.pylori. In previously studied MutS2 proteins, the C-terminal Smr domain was mapped as the region responsible for its nuclease activity. We report here that deletion of Smr domain does not completely abolish the nuclease activity of HpMutS2. Using bioinformatics analysis and mutagenesis, we identified an additional and novel nuclease motif (LDLK) at the N-terminus of HpMutS2 unique to Helicobacter and related epsilon-proteobacterial species. A single point mutation (D30A) in the LDLK motif and the deletion of Smr domain resulted in approximate to 5-10-fold loss of DNA cleavage ability of HpMutS2. Interestingly, the mutant forms of HpMutS2 wherein the LDLK motif was mutated or the Smr domain was deleted were unable to complement the hyper-recombination phenotype of a mutS2(-) strain, suggesting that both nuclease sites are indispensable for an efficient anti-recombinase activity of HpMutS2.

General practitioners' habits and knowledge in relation to the management of H. pylori-associated dyspepsia and their views about a locally available 13-carbon urea breath test

We report the results of general practitioners' views on Helicobacter pylori-associated dyspepsia and use of screening tests in the community. The use of office serology tests in screening is of concern as independent validation in specialist units has been disappointing.

Structural analysis of glycans and development of microarrays from Helcobacter pylori cell surface glycome

Helicobacter pylori is a bacterial pathogen that affects more than half of the world’s population with gastro-intestinal diseases and is associated with gastric cancer. The cell surface of H. pylori is decorated with lipopolysaccharides (LPSs) composed of three distinct regions: a variable polysaccharide moiety (O-chain), a structurally conserved core oligosaccharide, and a lipid A region that anchors the LPS to the cell membrane. The O-chain of H. pylori LPS, exhibits unique oligosaccharide structures, such as Lewis (Le) antigens, similar to those present in the gastric mucosa and are involved in interactions with the host. Glucan, heptoglycan, and riban domains are present in the outer core region of some H. pylori LPSs. Amylose-like glycans and mannans are also constituents of some H. pylori strains, possibly co-expressed with LPSs. The complexity of H. pylori LPSs has hampered the establishment of accurate structure-function relationships in interactions with the host, and the design of carbohydrate-based therapeutics, such as vaccines. Carbohydrate microarrays are recent powerful and sensitive tools for studying carbohydrate antigens and, since their emergence, are providing insights into the function of carbohydrates and their involvement in pathogen-host interactions. The major goals of this thesis were the structural analysis of LPSs from H. pylori strains isolated from gastric biopsies of symptomatic Portuguese patients and the construction of a novel pathogen carbohydrate microarray of these LPSs (H. pylori LPS microarray) for interaction studies with proteins. LPSs were extracted from the cell surface of five H. pylori clinical isolates and one NCTC strain (26695) by phenol/water method, fractionated by size exclusion chromatography and analysed by gas chromatography coupled to mass spectrometry. The oligosaccharides released after mild acid treatment of the LPS were analysed by electrospray mass spectrometry. In addition to the conserved core oligosaccharide moieties, structural analyses revealed the presence of type-2 Lex and Ley antigens and N-acetyllactosamine (LacNAc) sequences, typically found in H. pylori strains. Also, the presence of O-6 linked glucose residues, particularly in LPSs from strains 2191 and NCTC 26695, pointed out to the expression of a 6-glucan. Other structural domains, namely ribans, composed of O-2 linked ribofuranose residues were observed in the LPS of most of H. pylori clinical isolates. For the LPS from strain 14382, large amounts of O-3 linked galactose units, pointing to the occurrence of a galactan, a domain recently identified in the LPS of another H. pylori strain. A particular feature to the LPSs from strains 2191 and CI-117 was the detection of large amounts of O-4 linked N-acetylglucosamine (GlcNAc) residues, suggesting the presence of chitin-like glycans, which to our knowledge have not been described for H. pylori strains. For the construction of the H. pylori LPS microarray, the structurally analysed LPSs, as well as LPS-derived oligosaccharide fractions, prepared as neoglycolipid (NGL) probes were noncovalently immobilized onto nitrocellulosecoated glass slides. These were printed together with NGLs of selected sequence defined oligosaccharides, bacterial LPSs and polysaccharides. The H. pylori LPS microarray was probed for recognition with carbohydratebinding proteins (CBPs) of known specificity. These included Le and blood group-related monoclonal antibodies (mAbs), plant lectins, a carbohydratebinding module (CBM) and the mammalian immune receptors DC-SIGN and Dectin-1. The analysis of these CBPs provided new information that complemented the structural analyses and was valuable in the quality control of the constructed microarray. Microarray analysis revealed the occurrence of type-2 Lex and Ley, but not type-1 Lea or Leb antigens, supporting the results obtained in the structural analysis. Furthermore, the H. pylori LPSs were recognised by DC-SIGN, a mammalian lectin known to interact with this bacterium through fucosylated Le epitopes expressed in its LPSs. The -fucose-specific lectin UEA-I, showed restricted binding to probes containing type-2 blood group H sequence and to the LPSs from strains CI-117 and 14382. The presence of H-type-2, as well Htype- 1 in the LPSs from these strains, was confirmed using specific mAbs. Although H-type-1 determinant has been reported for H. pylori LPSs, this is the first report of the presence of H-type-2 determinant. Microarray analysis also revealed that plant lectins known to bind 4-linked GlcNAc chitin oligosaccharide sequences bound H. pylori LPSs. STL, which exhibited restricted and strong binding to 4GlcNAc tri- and pentasaccharides, differentially recognised the LPS from the strain CI-117. The chitin sequences recognised in the LPS could be internal, as no binding was detected to this LPS with WGA, known to be specific for nonreducing terminal of 4GlcNAc sequence. Analyses of the H. pylori LPSs by SDS-PAGE and Western blot with STL provided further evidence for the presence of these novel domains in the O-chain region of this LPS. H. pylori LPS microarray was also applied to analysis of two human sera. The first was from a case infected with H. pylori (H. pylori+ CI-5) and the second was from a non-infected control.The analysis revealed a higher IgG-reactivity towards H. pylori LPSs in the H. pylori+ serum, than the control serum. A specific IgG response was observed to the LPS isolated from the CI-5 strain, which caused the infection. The present thesis has contributed to extension of current knowledge on chemical structures of LPS from H. pylori clinical isolates. Furthermore, the H. pylori LPS microarray constructed enabled the study of interactions with host proteins and showed promise as a tool in serological studies of H. pyloriinfected individuals. Thus, it is anticipated that the use of these complementary approaches may contribute to a better understanding of the molecular complexity of the LPSs and their role in pathogenesis.

Melhora sintomática em pacientes com dispepsia funcional após a erradicação do helicobactet pylori : resultados de estudo de 12 meses, randomizado, duplo-cego, controlado complacebo

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Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação do Helicobacter em cães oriundos do Biotério Central da Unesp - Campus de Botucatu

Pós-graduação em Bases Gerais da Cirurgia - FMB

Polimorfismos gênicos de citocinas e receptores envolvidos no processo inflamatório da carcinogênese gástrica e alterações nos níveis de expressão gênica

Pós-graduação em Genética - IBILCE