Background: An inverse relation between Helicobacter pylori infection and asthma has been shown in epidemiological studies. Infection with H. pylori, or application of an extract of it before or... Show moreBackground: An inverse relation between Helicobacter pylori infection and asthma has been shown in epidemiological studies. Infection with H. pylori, or application of an extract of it before or after sensitization, inhibits allergic airway disease in mice. Objectives: The aim of this study was to investigate the effect of an extract of H. pylori on allergic airway disease induced by repeated allergen exposure in mice that were sensitized and challenged prior to extract application. Method: C57BL/6 mice were intranasally (i.n.) sensitized and challenged with house dust mite (HDM). After a minimum of 4 weeks, mice received the H. pylori extract intraperitoneally and were rechallenged i.n. with HDM. Allergen-specific antibodies were measured by ELISA. Cells present in the bronchoalveolar lavage fluid and dendritic cell (DC) subsets in the lung tissue were analyzed by flow cytometry. Tissue inflammation and goblet cell hyperplasia were assessed by histology. Cells of the mediastinal lymph node (mLN) were isolated and in vitro restimulated with HDM or H. pylori extract. Results: Treatment with H. pylori extract before rechallenge reduced allergen-specific IgE, the DC numbers in the tissue, and goblet cell hyperplasia. Cells isolated from mLN of mice treated with the extract produced significantly more IL-10 and IL-17 after in vitro restimulation with HDM. mLN cells of H. pylori-treated mice that were re-exposed to the H. pylori extract produced significantly more interferon gamma. Conclusions: An extract of H. pylori is effective in reducing mucus production and various features of inflammation in HDM rechallenged mice. (C) 2019 The Author(s) Published by S. Karger AG, Basel Show less
In this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were... Show moreIn this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were conducted in the Netherlands, Europe and Indonesia. We discuss diagnostic tests, therapeutic regimens, resistance and preventive measurements. We highlight clinical and pathophysiological aspects of the infection and describe which particular strains are prevalent and how transmission occurs. Presently, there are no established correlations between a Helicobacter pylori infection and recurrent abdominal pain, gastroesophageal reflux disease or growth retardation. We present data on the prevalence of Helicobacter pylori in young infants in the Netherlands and observe that children with at least one non-Dutch parent form a risk group. We assess risk factors in a Europe-wide study on gastroduodenal erosions and ulcers in childhood. In our study, Helicobacter pylori infection and gastrotoxic medications were relatively little implicated as etiology of that pathology. The prevalence of Helicobacter pylori infection in Indonesian young children is relatively high and points at an early acquisition of the infection. Finally, the resistance of Helicobacter pylori to clarithromycin and metronidazole was assessed for adults and children in the Netherlands. Low resistance rates were found, but the resistance in adults is increasing. We conclude that a test-and-treat regimen is justified for the Netherlands. Show less
The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric... Show moreThe studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were found. By successful H. pylori eradication, active and chronic inflammation decreased, accompanied by a significant decrease of mucosal MMP-9. MMP-2, MMP-7, MMP-8 and MMP-9, lipocalin-2, MMP-9/lipocalin-2 and TIMP-1 were significantly increased in tumour tissue of gastric cancer patients compared to normal gastric mucosa whereas only enhanced levels of MMP-2 and MMP-9/lipocalin-2 complexes were independently related to worse prognosis. Subsequently the genotype distribution of single-nucleotide polymorphisms (SNPs) of MMPs and TIMPs in gastric cancer was studied. The genotype distribution of MMP-7-181A>G was associated with H. pylori status and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2-303C>T correlated significantly with tumour-related survival. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7-181A>G and TIMP-2-303C>T polymorphism combination to have a major impact on patients survival outcome. Show less
This thesis sheds light on the clinical utility of serum markers of gastric atrophy, pepsinogen and gastrin, in general practice in the Dutch province of Zeeland. The biomarkers were used in... Show moreThis thesis sheds light on the clinical utility of serum markers of gastric atrophy, pepsinogen and gastrin, in general practice in the Dutch province of Zeeland. The biomarkers were used in studies on atrophic corpus gastritis, as surrogate outcome of gastric cancer. Attention was paid to seroepidemiological, aetiological and diagnostic aspects. Results of the thesis: - The seroprevalence of atrophic corpus gastritis in Zeeland appears to be 3.4%, which is higher than in other parts of the country (reference cohort studies, respectively 2.4% and 1.6%). The approximate relative risk of having corpus atrophy was higher(p Show less
