Role of Th22 cells in Helicobacter pylori-related gastritis and peptic ulcer diseases.

Helicobacter pylori (H. pylori) has been shown to be one of the leading causes of peptic ulcer diseases (PUDs) and gastritis. T helper-22 (Th22) cells and its most important cytokine, interleukin-22 (IL-22) are importantly active in inflammation and inflammatory tissues. Since inflammation is one of the main attributes of infection caused by H. pylori and resulting complications (gastritis and gastrointestinal ulcer), this study was designed to evaluate the Th22 cells count and the IL-22 protein expression in people suffering from PUD and gastritis. The present study was conducted on 55 patients with gastritis, 47 patients with PUD and 48 uninfected subjects. After preparation of section and extraction of protein from antral biopsies, immunohistochemistry and western blot methods were used to evaluate the Th22 cells and IL-22 protein expression level, respectively. According to findings, the Th22 cells count and the IL-22 protein expression level in the infected subjects were siginficantly more than in the uninfected subjects. It should be noted that the Th22 cells count and the IL-22 protein expression level in the infected subjects with PUD were significantly greater than those in the infected subjects with gastritis. In addition, the Th22 cells count had positive correlation with the density of H. pylori, chronic inflammation score and acute inflammatory score in the infected subjects with PUD. The Th22 cells count had positive correlation with the Th17 cells count and inverse correlation with the Treg cells count in the infected subjects with PUD and gastritis. Our data demonstrated that abnormal hyper-activation of Th22 cells as well as its correlation with the Th17 cells during infection caused by H. pylori might damage tissues through immunopathological responses.

Helicobacter pylori outer membrane vesicles involvement in the infection development and Helicobacter pylori-related diseases.

Helicobacter pylori - (H. pylori) play a role in the pathogenesis of gastritis, gastric and duodenal ulcers as well as gastric cancer. A possible involvement of outer membrane vesicles (OMVs) produced by H. pylori in the distribution of bacterial antigens through the gastric epithelial barrier and their role in the development of local and systemic host inflammatory and immune responses has been suggested. OMVs contain various biologically active compounds, which internalize into host cells affecting signaling pathways and promoting apoptosis of gastric epithelial and immunocompetent cells. OMVs-associated H. pylori virulence factors may strengthen or downregulate the immune responses leading to disease development. This review describes the biological importance of H. pylori OMVs and their role in the course of H. pylori infections, as well as H. pylori related local and systemic effects.

Rise and fall of peptic ulceration: A disease of civilization?

Humans and Helicobacter pylori have evolved and adapted over tens of thousands of years. Yet peptic ulcer disease appeared to be rare prior to the 19th century. The prevalence of peptic ulcer disease increased between 1850 and 1900 and culminated in a cohort at high risk that was born at the end of the 19th century. This coincided with the provision of safe water and improvements in sanitation and personal hygiene. One hypothesis for the emergence of peptic ulcer disease focuses on the rate of development of atrophic gastritis induced by H. pylori. The hypothesis developed in this article focuses on delay in the age of acquisition of H. pylori to a time when immune and inflammatory responses to the infection were more mature. Whereas the acquisition of H. pylori in infancy usually resulted in mild pangastritis, hypochlorhydria, and a low risk for peptic ulcer disease, delayed acquisition could cause either more severe pangastritis (predisposing to gastric ulceration) or gastritis largely restricted to the antrum of the stomach (predisposing to duodenal ulceration). The decline in the prevalence of peptic ulcer disease over the past 100 years parallels the decline in the prevalence of H. pylori. The epidemic of ulcer disease in the first half of the 20th century seems likely to be an adverse effect of important public health measures undertaken in the latter half of the 19th century.

Frequency of Celiac Disease in Children with Peptic Ulcers.

AIM: The aim of the present study is to investigate the frequency of celiac disease in children with peptic ulcers and to compare it with that of non-celiac peptic ulcers in terms of clinical and laboratory values. METHODS: Upper gastrointestinal endoscopy was performed in 1769 patients at the Department of Pediatric Gastroenterology, The Faculty of Medicine, Cukurova University, Turkey, between January 2012 and January 2017. These cases consisted of subjects presenting with various GIS symptoms and indicated for endoscopy (with chronic diarrhea, delayed growth and development, abdominal pains, GIS bleeding, etc.). The levels of immunoglobulin A (IgA) serum anti-tissue transglutaminase antibodies, IgA anti-endomysial antibodies (EMA), and IgA serum were estimated in the patients with peptic ulcers. RESULTS: Celiac disease was diagnosed with serology, endoscopy, and histopathology in 250 (14%) of all cases undergoing endoscopy. Peptic ulcers were diagnosed in 74 patients (4.2%) of all cases undergoing endoscopy. tTGA and EMA (+) levels were determined in 22 (29%) of the 74 patients with peptic ulcers, and then the presence of peptic ulcers was investigated in the upper gastrointestinal system using gastrointestinal endoscopy, followed by histopathological confirmation of celiac disease. HP infection was present in 14 (63%) of the patients with celiac disease and in 23 (44%) of non-celiac peptic ulcers; the difference was not statistically significant (p = 0.12). In the total ulcer group, 10.8% (8/74) of patients with celiac peptic ulcers were negative for HP infection, whereas 21% (8/37) of HP-negative patients with ulcers had celiac disease. CONCLUSION: There exists a high risk of celiac disease in children with peptic ulcers. We thus recommend celiac disease to be investigated, particularly in HP-negative patients with peptic ulcers but with no history of NSAID use.

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

BACKGROUND: 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. METHODS AND MATERIALS: 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-ß1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS: The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, 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-ß1 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-ß1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.

The Gastric Mucosa from Patients Infected with CagA+ or VacA+ Helicobacter pylori Has a Lower Level of Dual Oxidase-2 Expression than Uninfected or Infected with CagA-/VacA- H. pylori.

BACKGROUND: Helicobacter pylori (H. pylori) is a well-recognized gastroduodenal pathogen and class I carcinogen. Dual oxidase-2 (DUOX2), a member of NADPH oxidase family, has several critical physiological functions, including thyroid hormone biosynthesis and host mucosal defense. AIM: To investigate the effect of H. pylori infection on DUOX2 gene expression in human stomach. MATERIALS AND METHODS: The biopsies were obtained from patients who underwent endoscopic diagnosis. The patient serum was assayed for two virulence factors of H. pylori, CagA IgG and VacA. The inflammation in gastric mucosa was analyzed with histology. Real-time quantitative PCR was used to detect the expression of three members of NADPH oxidase, NOX1, NOX2, and DUOX2, as well as lactoperoxidase (LPO) in the gastric mucosa. NOX2, DUOX2, and myeloperoxidase (MPO) protein levels were quantified by Western blots or immunohistochemistry. RESULTS: The H. pylori-infected gastric mucosa had more severe inflammation than uninfected samples. However, the expression of DUOX2 mRNA and protein was lower in gastric mucosa of patients with H. pylori infection compared to the uninfected. Among the H. pylori-infected patients, those having CagA IgG or VacA in the serum had lower DUOX2 expression levels than those infected with H. pylori without either virulence factor. The NOX2 and MPO levels were higher in those patients infected with H. pylori irrespective of the virulence factors than those uninfected patients. NOX1 and LPO mRNA were undetectable in the gastric mucosa. CONCLUSION: CagA+ or VacA+ H. pylori in the stomach of patients may suppress DUOX2 expression to promote its own survival. Increased NOX2 could not eliminate H. pylori infection.

[SYSTEMIC CYTOKINOTHERAPY, USING BETALEUKIN IN A COMPLEX TREATMENT OF AN ACUTE GASTRODUODENAL ULCER BLEEDING].

Results of surgical treatment for an acute ulcer gastroduodenal bleeding in 120 patients, ageing 16-75 yrs old, were analyzed. In 20 of them a gastric ulcer was a cause of bleeding, while in 84--a duodenal ulcer, and in 16--a coexistent gastroduodenal ulcer. The bleeding activity was estimated in accordance to J. Forrest classification. In 57 patients (a comparison group) preoperatively and postoperatively a complex of a standard basal conservative therapy without immunocorrection was conducted, and in 63 (the main group)--a systemic cytokinotherapy (SCKTH), using betaleukin, was applied postoperatively additionally in a complex of therapy. A content of CD3+, CD4+, CD8+, CD19+, IgA, IgM, IgG was estimated in dynamics, as well as circulating immune complexes, phagocytic index, phagocytic number. There was established, that a dysbalance depth in the immune status have had depended upon the blood loss severity. The SCKTH application is pathogenetically substantiated, it promotes the immune status normalization, as well as a more favorable course of postoperative period and the results of treatment improvement.

CCL20/CCR6-mediated migration of regulatory T cells to the Helicobacter pylori-infected human gastric mucosa.

BACKGROUND: Helicobacter pylori-induced peptic ulceration is less likely to occur in patients with a strong gastric anti-inflammatory regulatory T cell (Treg) response. Migration of Tregs into the gastric mucosa is therefore important. OBJECTIVE: To identify the homing receptors involved in directing Tregs to the gastric mucosa, and investigate how H pylori stimulates the relevant chemokine responses. DESIGN: Gastric biopsy samples and peripheral blood were donated by 84 H pylori-infected and 46 uninfected patients. Luminex assays quantified gastric biopsy chemokine concentrations. Flow cytometry was used to characterise homing receptors on CD4(+)CD25(hi) Tregs. H pylori wild-type and isogenic mutants were used to investigate the signalling mechanisms behind CCL20 and IL-8 induction in gastric epithelial cell lines. Transwell assays were used to quantify Treg migration towards chemokines in vitro. RESULTS: CCL20, CXCL1-3 and IL-8 concentrations were significantly increased in gastric biopsy samples from H pylori-infected patients. CCR6 (CCL20 receptor), CXCR1 and CXCR2 (IL-8 and CXCL1-3 receptors) were expressed by a higher proportion of peripheral blood Tregs in infected patients. Most gastric Tregs expressed these receptors. H pylori induced CCL20 production by gastric epithelial cells via cag pathogenicity island (cagPAI)-dependent NF-κB signalling. Foxp3(+), but not Foxp3(-), CD4 cells from infected mice migrated towards recombinant CCL20 in vitro. CONCLUSIONS: As well as increasing Treg numbers, H pylori infection induces a change in their characteristics. Expression of CCR6, CXCR1 and CXCR2 probably enables their migration towards CCL20 and IL-8 in the infected gastric mucosa. Such qualitative changes may also explain how H pylori protects against some extragastric inflammatory disorders.

Peptic ulcer disease in Helicobacter pylori-infected children: clinical findings and mucosal immune response.

OBJECTIVES: Peptic ulcer disease (PUD) is highly prevalent among adults but less common in children. Helicobacter pylori infection, the main cause of PUD, is, however, acquired extremely early in life. The aim of the study was to analyze clinical characteristics of children with PUD in a country with a high prevalence of the disease and to evaluate which host factors could determine this clinical outcome. METHODS: Children referred for upper gastrointestinal (GI) endoscopy with suspicion of peptic diseases were included prospectively during an 8-year period. Antral biopsies were performed to determine H pylori presence and mucosal cytokines profile. RESULTS: A total of 307 children between 3 and 18 years old were enrolled. Of the total, 237 children (46% boys) with complete data were included. H pylori infection was confirmed in 133 (56.1%) participants. Duodenal ulcer (DU) was diagnosed in 32 patients (13.5%); among them 29 were infected with H pylori (90.6%). Infected children had a nodular appearance of the gastric mucosa more often than noninfected children. Noninfected children had fewer lymphoid follicles and less inflammatory infiltrate than infected children. Only mucosal polymorphonuclear cell infiltration was more intense in DU-infected children as compared with non-DU-infected children. DU-infected children had higher levels of mucosal interferon-γ than noninfected and non-DU-infected patients. Non-DU-infected children had also higher levels of mucosal interleukin-10 than noninfected patients (P < 0.05). CONCLUSIONS: PUD in children, especially DU, is strongly associated with H pylori infection in developing countries. There is no distinctive clinical presentation of children with PUD. T-helper cytokine balance may influence clinical outcomes in children.

Is there any relationship between Le(b) antigen expression and Helicobacter pylori infection?

INTRODUCTION: Helicobacter pylori infection is one of the main causes of peptic ulcer. There are some blood groups acting as receptors for the pathogen. Based on this view and previous attempts, we tried to examine the relationship between Lewis blood group and H. pylori infection. MATERIALS AND METHOD: Blood and saliva samples were collected from 60 patients with established peptic ulcer induced by H. pylori. Secretory status of each patient was determined by both direct agglutination and saliva tests. RESULTS: Seventy-two percent of the patients were secretor and expressed Lewis B antigen. This rate in control group was 61%. Statistical analysis showed no significant difference between the two groups. CONCLUSION: This study did not find any correlation between Le(b) antigen expression and presence of H. pylori-induced peptic ulcer. It is now recommended that other factors like Lewis(x) and sialyl Lewis(x) should be investigated in binding, colonization and virulence of H. pylori infection in the future.

Higher circulating levels of anti-phosphatidylserine antibody in peptic ulcer patients infected with CagA-positive strains of Helicobacter pylori.

BACKGROUND: The CagA-positive strains of H. pylori were associated with the higher risk of peptic ulcer (PU) diseases. The aim of this study was to evaluate the serum concentrations of anti-phosphatidylserine (anti-PS) and anti-cardiolipin (anti-CL) antibodies in H. pylori-infected PU patients, H. pylori-infected asymptomatic (AS) carriers, and a healthy non-infected group and also to determine their correlation with the bacterial virulence factor CagA. METHODS: A total of 100 H. pylori-infected PU patients (80 patients were positive for anti-CagA antibody and 20 patients were negative for anti-CagA antibody), 65 H. pylori-infected AS carriers (40 subjects were positive for anti-CagA antibody and 25 subjects were negative for anti-CagA antibody) and 30 healthy H. pylori-negative subjects (as a control group) enrolled in the study. Serum samples of participants were tested for the levels of anti-PS and anti-CL antibodies by ELISA. RESULTS: The mean serum levels of anti-PS antibody in the PU group (13.46 +/- 2.90 RU/mL) was significantly higher than that observed in the H. pylori-infected AS group (1.57 +/- 0.38 RU/mL, p < 0.001) and healthy uninfected control group (0.77 +/- 0.32 RU/mL, p < 0.001). No significant difference was observed for the mean serum levels of anti-PS antibody between the AS group and uninfected control group. In the PU group, the mean serum levels of anti-PS antibody was significantly higher in patients with a positive test for anti-CagA antibody (16.46 +/- 3.55 RU/mL) in comparison to patients with a negative test for anti-CagA antibody (2.74 +/- 1.29 RU/mL; p < 0.01). The differences of the mean serum levels of anti-CL antibody were not significant between PU, AS, and control groups. CONCLUSIONS: These results showed higher serum levels of anti-PS antibody in patients with PU disease, especially in those infected with the CagA+ strains of H. pylori. Clinical significance of the anti-PS antibody in H. pylori-infected PU patients can be considered in additional follow up studies.

A role for altered phagosome maturation in the long-term persistence of Helicobacter pylori infection.

The vigorous host immune response that is mounted against Helicobacter pylori is unable to eliminate this pathogenic bacterium from its niche in the human gastric mucosa. This results in chronic inflammation, which can develop into gastric or duodenal ulcers in 10% of infected individuals and gastric cancer in 1% of infections. The determinants for these more severe pathologies include host (e.g., high IL-1ß expression polymorphisms), bacterial [e.g., cytotoxicity-associated gene (cag) pathogenicity island], and environmental (e.g., dietary nitrites) factors. However, it is the failure of host immune effector cells to eliminate H. pylori that underlies its persistence and the subsequent H. pylori-associated disease. Here we discuss the mechanisms used by H. pylori to survive the host immune response and, in particular, the role played by altered phagosome maturation.

[Correction of the immunity disorders in patients while surgical treatment of coexistant gastroduodenal ulcers].

There were examined 64 patients, suffering combined gastroduodenal ulcers. Subpopulations of lymphocytes, using monoclonal antibodies, were used to estimate the patients immune status. The investigation was performed in a dynamics: immediately after admittance to hospital, on the operation day and on the tenth postoperative day. In 33 patients (the main group) reamberin was applied in a complex of surgical treatment and in 31 (the comparison group)--the conventional medicinal preparations. In all the patients before the treatment conduction there were revealed the cell immunity chain disorders like in a secondary immune deficiency state (SIDS). The SIDS elimination and the immunological indices improvement were promoted by incorporation of reamberin in the complex of surgical treatment.

[Dynamics of the main immunological indices in patients, suffering gastroduodenal ulcers, complicated by hemorrhage].

A deep clinical, immunological, microbiological analysis was performed in patients, suffering gastroduodenal ulcer, complicated by hemorrhage. Immunodeficiency state with the signs of autoimmunization was noted in the patients. These changes were most severe in a severe blood loss, the local endoscopic hemostasis instability, high risk of the hemorrhage recurrence occurrence, presence in a periulcer zone mucosa of a conditionally pathogenic and pathogenic microflora with a Klebsiella pneumoniae and Streptococcus beta-haemoliticus predominance. The analysis of the data obtained permits to prognosticate the pathologic process severity course and to improve the program of treatment.

Reduced small-intestinal injury induced by indomethacin in interleukin-17A-deficient mice.

BACKGROUND AND AIMS: The pathogenesis of enteropathy induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL-17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL-17A gene. METHODS: Male C57BL/6 (wild-type) and homozygous IL-17A(-/-) C57BL/6 mice were subjected to this study. Indomethacin (10 mg/kg) was subcutaneously administered to induce small-intestinal damage. Indomethacin-induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines. RESULTS: The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory-associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein-1 (MCP-1), and granulocyte-colony stimulating factor (G-CSF), were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL-17A(-/-) mice compared with wild-type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP-1, and G-CSF levels. CONCLUSION: These findings demonstrate that IL-17A contributes to the development of indomethacin-induced small intestinal injury through upregulation of G-CSF, KC, and MCP-1. IL-17A might be a promising new therapeutic target to treat NSAID-induced enteritis.

[CD25-positivity and efficacy of roncoleukin in complex treatment of patients with gastroduodenal ulcers complicated by hemorrhage].

In 72 patients, suffering gastroduodenal ulcer disease recombinant interleukin-2 (LL-2) Roncoleukin ("Biotech", Russia) was applied in complex of treatment. The main populations of immunocytes, containing cellular-tissue receptor IL-2 CD25, were investigated in specimen from various zones of gastroduodenal mucosa and peripheral blood. There was established the trustworthy hyperexpression of CD25 in patients while gastrointestinal hemorrhage. Roncoleukin inclusion into the complex of treatment of patients have promoted more effective normalization of affinity of various immunocytes type towards IL-2 receptors, clinical signs occurrence of the disease elimination and the ulcer defect epithelization acceleration.

Development of an in-house capture ELISA: An attempt to detect CagA antigen in sera of Helicobacter pylori infected patients.

The CagA protein one of the key virulence factors of Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer diseases. Unfortunately the cagA gene status can only be determined by PCR while serology is an alternative approach to detect antigens or antibodies. Our aim is to detect the CagA antigen in sera of infected subjects by the development of an in-house capture ELISA test. Gastric antral biopsies and serum samples were collected from 63 patients. PCR was used to determine the cagA status. Our previously developed recombinant CagA protein and monoclonal antibody were used for setting up the capture ELISA test. H. pylori positive [(38 gastritis, 14 duodenal ulcers (DU), 11 gastric ulcer (GU)] patients were determined by PCR. The cagA gene was detected in 21 (55%) of gastritis, 11 (78%) of DU and 7 (60%) of GU patients. The reagents used in setting up the capture ELISA test following optimization displayed high performance. This study showed that our developed in-house capture ELISA has the potential to detect the CagA antigen at very low concentrations even though not detected in our H. pylori infected patients sera but we are also intended to use it in saliva and stool samples.

Peptic Ulcer Disease is Associated with Increased Risk of Chronic Urticaria Independent of Helicobacter pylori Infection: A Population-Based Cohort Study.

BACKGROUND: Some studies showed patients with chronic urticaria have a higher rate of peptic ulcer disease (PUD). Whether PUD is a risk factor for chronic urticaria is unclear. OBJECTIVE: The objective of this study was to evaluate the incidence of and risk factors for chronic urticaria in patients with PUD using the Taiwan National Health Insurance Research Database. METHODS: We conducted a retrospective nationwide cohort study of the period 2000-2012 and involving 11,901 patients with PUD who underwent Helicobacter pylori (HP) therapy (PUD + HP group) and an equal number of matched patients without HP infection (PUD - HP group). Furthermore, we enrolled 23,802 patients without PUD for comparison (non-PUD group). The Cox proportional hazards regression model was used to analyze chronic urticaria risk after adjusting for potential confounding factors. RESULTS: The mean ages of the three groups were around 50 years. Approximately 42.6% were female. Chronic urticaria incidences in the PUD + HP and PUD - HP groups were both significantly higher than that in the non-PUD group. The hazard ratios of chronic urticaria in the PUD + HP group and the PUD - HP group were 1.34 (95% confidence interval 1.09-1.64) and 1.45 (95% confidence interval 1.19-1.79), respectively. The risk difference became significant 2 years after patients with PUD had the HP infection tests and persisted till the end of follow-up. The risk increase was significant in patients with PUD who were female or aged 40-64 years. There was no difference in the risk comparison between PUD + HP and PUD - HP groups. CONCLUSIONS: Peptic ulcer disease, independent of HP infection, is associated with an increased chronic urticaria risk. Patients with PUD who were female or aged 40-64 years are more likely to have chronic urticaria.

Malvidin Protects against and Repairs Peptic Ulcers in Mice by Alleviating Oxidative Stress and Inflammation.

Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg-1, Malvidin prevented gastric ulcer induction by ethanol, NSAID and repaired the tissue after 6 days of IR. Moreover, the anthocyanidin accelerated the healing of acetic acid-induced ulcer, increased the gene expression of EGF and COX-1, and downregulated MMP-9. Anthocyanin treatment mitigated the effect of polypharmacy on inflammation and oxidative stress observed in the intestine. Additionally, the compound downregulated cytokine expression and TLR4 and upregulated HMOX-1 and IL-10, exhibiting protective activity in the mouse gut. Malvidin thus prevented gastric and duodenal ulcers due to prominent anti-inflammatory and antioxidative effects on the gastrointestinal tract that were related to gene expression modulation and an increase in endogenous defense mechanisms.

[The level of serum cytokines in children infected with various strains of Helicobacter pylori].

Serum contents of 7 cytokines (IL-1, IL-1beta, IL-6, IL-8, TNF-alpha, INF-gamma, INF-alpha) were examined in 87 children aged 14-17 years according to presence of antibodies against Helicobacter pylori and cytotoxic CagA protein. There was a lack of difference in cytokine levels between infected and non-infected children. Thus H. pylori infection in children in contrast to adults does not cause changes in systemic cytokine secretion.