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Peptic ulcers are caused by the interaction between bacterial and host factors. This study demonstrates enhanced expression of caspase-4 in peptic ulcer patient biopsies, indicating that pyroptosis and noncanonical inflammasome activity may be processes involved in peptic ulcer disease. We show that primary murine macrophages infected with Helicobacter pylori upregulate caspase-11 (the ortholog of human caspase-4), activate caspase-1, and secrete IL-1β. We demonstrate that misoprostol (a stable PGE 1 analogue) decreased IL-1β secretion and delayed lethality in vivo in a murine peritonitis model. PGE 2 was shown to inhibit caspase-11-driven pyroptosis and IL-1β secretion in macrophages. Overall, we provide evidence for a pathological role of caspase-4/11 in peptic ulcer disease and propose that targeting caspase-4 or inhibiting pyroptosis may have therapeutic potential in the management of peptic ulcers., (Copyright © 2020 The Authors.)

Helicobacter pylori causes persistent infection in the gastric epithelium of more than half of the world's population, leading to the development of severe complications such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Several virulence factors, including cytotoxin-associated gene A (CagA), which is translocated into the gastric epithelium via the type 4 secretory system (T4SS), have been indicated to play a vital role in disease development. Although infection with strains harboring the East Asian type of CagA possessing the EPIYA-A, -B, and -D sequences has been found to potentiate cell proliferation and disease pathogenicity, the exact mechanism of CagA involvement in disease severity still remains to be elucidated. Therefore, we discuss the possible role of CagA in gastric pathogenicity.

Background: The cure rate of Helicobacter pylori (HP)-positive peptic ulcer has appeared to downward trend, and the resistance of the ulcer relapse has become a hot issue., Methods: Hematoxylin and eosin staining was used to detect the repair of the damaged tissues in patients after treatment with the Chuyou Yuyang granule (CYYY). Elisa was used to analyze the expression of cytokine interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α) in the patients' serum. Western blot analysis was used to explore the mechanism of the CYYY. Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect the expression of microRNA-155a (miR-155a) and miR-146a in the blood of the patients and to confirm whether CYYY could cure peptic ulcer through regulation of miR-155a and miR-146a., Results: The damaged gastric mucosal tissues of ulcer patients were significantly repaired by treating with CYYY. The pro-inflammatory cytokine IL18 and TNF-α were notably repressed after treating with CYYY. In addition, CYYY played a key role in regulation of the Toll-like receptor (TLR4)/nuclear factor-κB (NF-κB) signal pathway and the expression of miR-155a and miR-146a., Conclusion: CYYY was a highly effective therapeutic method for peptic ulcer patients by inhibiting the activation of the TLR4/NF-κB signal pathway and suppressing the expression of miR-155a and miR-146a., (© 2019 Wiley Periodicals, Inc.)

Peptic ulcer is a lesion in the mucosa of the digestive tract affecting many people all around the world. Recent investigations have indicated that produced inflammatory cytokines such as TNF-α and IL-1β in response to gastric infection by Helicobacter pylori play an important role in the development of peptic ulcer. With regard to the significance of these cytokines in peptic ulcer development and the high prevalence of this disease in the developing countries, this study aimed to investigate the association of TNF-α and IL-1β with peptic ulcer in the presence of H. pylori. This case-control study enrolled 61 patients with peptic ulcer disease (PUD) as cases and 59 people without peptic ulcer (NPUD) as controls. Blood samples and endoscopic biopsies were collected. H. pylori infection was confirmed by using rapid urease test (RUT), specific IgG measurement and histopathological examination. Then, IL-1β and TNF-α levels were evaluated using enzyme linked immunosorbent assay (ELISA). The seropositivity of H. pylori was 62.5% in the studied population, while by considering RUT and histopathological examination along with specific-IgG antibody, H. pylori infection decreased to 56.7%. In addition, H. pylori infection was significantly (OR = 0.37; 95% CI = 0.17-0.82; P = .02) associated with peptic ulcer development. The TNF-α level in PUD and infected H. pylori subjects was significantly higher than that of control and un-infected H. pylori individuals. However, no significant difference of IL1β level was observed between PUD and control groups as well as between H. pylori infected and un-infected individuals. Interestingly, IL-1β level in PUD patients without H. pylori infection was significantly higher than infected ones. Moreover, a significant correlation between specific-IgG antibody with TNF-α level was observed. Taken together, our results showed that increased level of TNF-α could probably play pivotal role in pathogenesis of peptic ulcer in the presence of H. pylori infection. These findings also highlighted the importance of IL-1β in the absence of H. pylori infection in peptic ulcer development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: 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., Methods and Materials: 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., Results: 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., Conclusion: 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.)

Helicobacter pylori (H. pylori) infection is among the most prevalent human infections. CXCL12 is a well-known CXC chemokine involved in inflammation and play major roles in angiogenesis. There is currently very limited data on the role of CXCL12 in peptic ulcer disease. Hence, we aimed to explore whether CXCL12 is involved in the pathogenesis of peptic ulcer induced by H. pylori. In this study, we enrolled 102 H. pylori-infected patients, including 51 with active ulcer (GA) and 51 with healing ulcer (GH). We also recruited 50 healthy subjects as control, which did not show any sign or symptoms of chronic inflammatory diseases, infection, or immune-related disorders. Endoscopy was performed to determine the stage of the disease. ELISA was used for detection of H. pylori infection and CXCL12 measurement. We also employed western blotting to detect CXCL12 in ulcerative lesions of H. pylori. Demographic data were also collected by questionnaire. Our results demonstrated that CXCL12 serum levels in GA group (151.8±18.31pg/mL) were significantly higher than those in GH (36.89±6.78pg/mL) and control groups (33.77±9.12pg/mL) (P<0.0001). However, we did not observe a significant difference between GH and control groups. Moreover, overexpression of CXCL12 in gastric lesions of patients in GA group was confirmed by Western blot analysis. According to the result of the present study, it could be concluded that CXCL12 is involved in the pathogenesis and healing of H. pylori-induced peptic ulcer. CXCL12 serum levels may also be used to distinguish between GA and GH phases of the disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

There was held an useful eradication of Helicobacter Pylon in 20 patients with peptic ulcers (Omeprazole, Clarithromycin and Amoxicillin in normal doses). A five - year monitoring period revealed clinical manifestations of relapse in 50% of cases and endoscopic manifestatiQns in 60% of cases (15% - ulcers and 45% - gastral erosions). Relapse of peptic ulcers was accompanied with change of clinical course, it became oligo- or asymptomatic in 83% of patients. Relapse of peptic ulcers was fixed in 45% of patients (15% - in patients with ulcer and 30% - in patients with gastral erosions), at that, erosions were caused by NSAIDs in a half of cases, accompanied with a weak degree of contamination and inflammation of gastral rnucosa.

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.

Objective: To understand the junction protein expression of gastric mucosa including occlusal proteins (occludin), closed protein-4 (claudin-4), zonula occluden-1(ZO-1), epithelial cadherin (E-cadherin), and β ring protein (β-catenin) and the clinical significance in children with Helicobacter pylori (Hp) infection., Method: Seventy patients in whom gastric endoscopy was performed because of nausea, vomiting, abdominal pain, bloating, acid reflux, melena, and other gastrointestinal symptoms were enrolled in this study from Dec. 2010 to Apr. 2013 in our hospital. Informed consent was signed by their parents, and the study was in accordance with the principles of medical ethics. Hp positivity was confirmed if both respiratory urea test (RUT) and Hp were positive by gastric mucosal pathology. Gastric mucosal samples from 70 patients were enrolled in this study, 23 of them were Hp negative, 47 of them were Hp positive (24 cases without peptic ulcer, 23 cases with peptic ulcer). The mRNA levels and protein expression of tight junction protein of gastric mucosa were measured by RT-PCR and Western blot respectively. The location and semi quantitative content of E-cadherin and β-catenin in gastric mucosa were detected by immunohistochemical staining method., Result: The mRNA level of E-cadherin, β-catenin, ZO-1 in the Hp positive group regardless of peptic ulcer was significantly lower than that in the Hp negative group. Hp positive without peptic ulcer group were 0.0008, 0.0040, 0.0014, respectively; Hp positive with peptic ulcer group were 0.0010, 0.0090, 0.0013, respectively; Hp negative group were 0.0137, 0.0423, 0.0198, respectively (F values were 36.956, 39.893, 38.962, respectively, all P<0.05). The expression of claudin-4 mRNA in Hp positive group with peptic ulcer increased significantly, the difference among Hp positive group with peptic ulcer, Hp positive group without peptic ulcer and Hp negative group was statistically significant (0.1438 vs. 0.0926 vs. 0.0789) (F value was 11.964, P<0.05), while the difference of occludin mRNA levels among the three groups was not statistically significant.Immunohistochemistry results showed that the score of E-cadherin, β-catenin positive cell in the Hp positive patients were also significantly lower than that in the Hp negative group (t values were 3.981 and 2.340, all P<0.05, respectively). Western blot results showed that the protein levels of β-catenin in Hp positive group with peptic ulcer were significantly lower than that in Hp negative group, while the protein levels of E-cadherin in Hp positive patients regardless of peptic ulcer were decreased significantly in Hp negative group., Conclusion: Our results revealed that the tight junction protein E-cadherin, β-catenin, ZO-1 expression of gastric mucosa were decreased in children with Hp infection, while claudin-4 expression was increased in Hp positive patients with peptic ulcer, suggesting that damage to gastric epithelial barrier function may be the main pathogenesis of Hp associated gastric diseases in children.

Objective: Helicobacter pylori (H. pylori) infection is the main cause of gastroduodenal ulcer. The molecular mechanisms that underlying this progress are still not very clear. MicroRNAs (miRNAs) are small noncoding RNAs that function as negative regulator of numerous target genes at posttranscriptional level. miRNAs plays important roles in the development of many infection related diseases. The roles of miRNAs in the development of H. pylori-infected gastroduodenal ulcer haven't been well studied yet., Materials and Methods: The miRNA and mRNA profiles in normal gastroduodenal biopsy, H. pylori-infected gastroduodenal biopsy and H. pylori-infected gastroduodenal ulcer biopsy samples were compared and analyzed to identify potential related miRNAs and their target genes. The differential expression of the identified miRNAs and their target gene were validated in an independent set of H. pylori positive gastroduodenal ulcer biopsy samples by immunohistochemistry staining and RT-PCR. Then microRNA mimics were transfected to gastric epithelial cells infected with H. pylori 26695 (cagA+). RT-PCR and Western blotting were performed to confirm the target gene of the identified microRNAs., Results: The integrative analysis and immunohistochemistry staining validation indicated that miR-155 and miR-146b, as well as their predicted target gene IL6, are up-regulated in H. pylori positive gastroduodenal ulcer. Further experiments in gastric epithelial cells revealed that H. pylori 26695 (cagA+) infection induces IL6 overexpression. But the overexpression of IL6 is weaken due to negative regulation by miR-155 and miR-146b., Conclusions: This study indicated that the up-regulation of miR-155 and miR-146b decreases H. pylori (cagA+)-introduced IL6 overexpression, which might weaken the cleanup of H. pylori (cagA+) and contributes to ulcer.

Background: The infection of Helicobacter pylori (H. pylori) is one of the most important causes of gastric ulcer disease. The role of hydrogen sulfide (H2S) production in H. pylori-induced gastric ulcer disease., Aim: The expression of cystathionine-γ-lyase (CSE) was determined, and correlated with the severity of gastric ulcer disease., Methods: One hundred and eight patients were selected based on the determination of gastric ulcer and the infection of Helicobacter pylori (H. pylori), including 36 normal control, 36 patients with H. Pylori-negative gastric ulcer, and 36 patients with H. Pylori-positive gastric ulcer. RT-PCR determination was performed to determine the expression of CSE, NF-κB and IL-8., Results: The expression of CSE, NF-κB and IL-8 was higher in the gastric ulcer group than control group (p<0.05). Compared with the H. pylori-negative gastric ulcer, the expression of CSE, NF-κB and IL-8 was higher than H. pylori-positive gastric ulcer group (p<0.05). For H. pylori-negative gastric ulcer group, the expression of CSE positively correlated with the expression of NF-κB (r=0.98, p<0.05) and IL-8 (r=0.95, p<0.05). For H. pylori-positive gastric ulcer group, the expression of CSE also positively correlated with the expression of NF-κB (r=0.99, p<0.05) and IL-8 (r=0.85, p<0.05)., Conclusion: The expression of CSE was positively correlated with the severity of gastric ulcer.

The Purpose of the Study: To study the genetic diversity of H. pylori in patients with chronic gastritis, peptic ulcer disease, chronic pancreatitis., Materials and Methods: The study involved 490 patients with gastric ulcer, duodenal ulcer, chronic superficial gastritis, chronic atrophic gastritis, chronic pancreatitis. Diagnosis of H. pylori infection was carried out by the following methods: morphological, urea breath test serological (determining the concentration of IgG antibodies to H. pylori and immunoblotting) and by polymerase chain reaction. For genotyping of H. pylori using sets of primers with a mixture of CagA, VacA s1/ s2, VacA m1, VacA m2, IceA1, IceA2, BabA. To perform immunoblotting using Anti-Helicobacter pylori EUROLINE-Western blot (IgG), based on the Western blot method using test strips with antigens separated by electrophoresis cell extract H. pylori. Statistical computer processing was performed using software packages Statistic for Windows 6.0., Results: The virulent genotype of H. pylori was determined in 92% cases of duodenal ulcer. In chronic non-atrophic and atrophic gastritis virulent genotypes of H. pylori were not detected. In case of uncomplicated duodenal ulcer we revealed isolated (vacA m2) and combined (vacA s1/ s2) genotypes of H.pylori in 23% of cases, of them monogenotip VacAm2 (vacuolating-associated cytotoxin) was determined in 83%. In complicated duodenal ulcer the combined genotype of H. pylori (vacAs1/ s2; vacAs1/ s2 + vacAm1 + vacAm2; vacAs1/ s2 + vacAm2) and mixed genotype of H. pylori (vacAs1/ s2 + cagA, vacAs1/ s2 + iceA2, vacAm1 + cagA + iceA2) were determined in 77% of the samples. In cases of chronic pancreatitis the vacuolating cytotoxin VacA was detected in 35.7%, such as in the control group it was 81.8%. Genes encoding the production of urease (subunit A) were found in 85.7% of chronic pancreatitis patients, in the control group--54.5%. Genes encoding the synthesis of outer membrane proteins of H. pylori such as p26, p19, p17 were detected in 82.1% of patients with chronic pancreatitis, in patients of the control group--54.5%. H. pylori outer membrane proteins with molecular weights of 30 and 33kDa (p30 and p33) were detected in 85.7% of patients with chronic pancreatitis., Conclusion: The bacterium H. pylori, which is the main cause of acid diseases, realizes effect through its pathogenicity factors. Waste products of H. pylori have a direct damaging effect on the mucous membrane of the stomach and duodenum, contributing to the release of lysosomal enzymes, a number of cytokines. They are cause the development of inflammatory processes in the mucosa. Lipopolysaccharide of outer membrane of H. pylori cause immune response of the human body and the development of chronic inflammation at the system level. Set of pathogenicity factors of H. pylori determine the nature and severity of the pathological processes triggered by the bacterium at different levels of the microorganism.

Background: The ratio of Helicobacter pylori/NSAID-negative gastric ulcers is increasing. Idiopathic gastric ulcers have unique clinical and endoscopic features, and are associated with more bleeding complications and a higher mortality. Alterations in gastric mucin expression and sialylation pattern may be important in ulcer pathogenesis., Aims: The purpose of this study was to determine the expression pattern of membrane-bound mucins and side chain sugars in H. pylori associated-, NSAID-, and idiopathic-gastric ulcers., Methods: We randomly selected 92 patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for T-cell CD4/CD8, MUC1, MUC4, MUC17, and ECA and SNA lectins staining was performed on sections from the ulcer margins. Inflammation score was assessed according to the Sydney system., Results: Bleeding and mortality rates were significantly higher in group 4. CD4 positive T cell count was higher in H. pylori positive patients (P = 0.009). Staining intensity of MUC17 was higher in group 1 than in group 4, foveola and glands alike, with 11.50 ± 3.47 versus 6.80 ± 4.02, and 9.61 ± 4.26 versus 7.59 ± 3.26, respectively (P < 0.0001). This was a mirror image with MUC1. SNA lectin staining was increased in group 4, in parallel to MUC1 expression, indicating more abundant α2-6 sialylation in that group., Conclusions: Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was demonstrated for MUC1. This observation might be important, since different mucins with altered sialylation patterns likely differ in their protection efficiency against acid and pepsin.

Helicobacter pylori infection induces chronic inflammation of the gastric mucosa and thus profoundly affects gastric physiology. In the acute phase of infection, gastric acid secretion is transiently impaired. The morphological damage of the gastric mucosa, changes in gastric hormone release, and disruption of neural pathways all contribute to influence gastric acid secretion in a distinct manner. Changes in gastric acid secretion, whether impaired or increased, are intimately related with the topographic phenotypes of gastritis and the presence of atrophy or absence of corpus atrophy. The interplay of gastritis phenotype and acid secretion are key determinants in disease outcomes. Corpus-predominant gastritis and corpus atrophy are accompanied by hypochlorhydria and carry the highest risk for gastric cancer, whereas antrum-predominant gastritis with little involvement of the corpus-fundic mucosa is associated with hyperchlorhydria and predisposes to duodenal ulcer disease., (Copyright © 2011 S. Karger AG, Basel.)

Helicobacter pylori is a Gram-negative bacterium that infects over 50% of the world's population. This organism causes various gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer. H. pylori possesses lipopolysaccharides that share structural similarity to Lewis blood group antigens in gastric mucosa. Such antigenic mimicry could result in immune tolerance against antigens of this pathogen. On the other hand, H. pylori colonizes gastric mucosa by utilizing adhesins that bind Lewis blood group antigen-related carbohydrates expressed on gastric epithelial cells. After colonization, H. pylori induces acute inflammatory responses mainly by neutrophils. This acute phase is gradually replaced by a chronic inflammatory response. In chronic gastritis, lymphocytes infiltrate the lamina propria, and such infiltration is facilitated by the interaction between L-selectin on lymphocytes and peripheral lymph node addressin (PNAd), which contains 6-sulfo sialyl Lewis X-capped O-glycans, on high endothelial venule (HEV)-like vessels. H. pylori barely colonizes gland mucous cell-derived mucin where alpha1,4-GlcNAc-capped O-glycans exist. In vitro experiments show that alpha1,4-GlcNAc-capped O-glycans function as a natural antibiotic to inhibit H. pylori growth. These findings show that distinct sets of carbohydrates expressed in the stomach are closely associated with pathogenesis and prevention of H. pylori-related diseases, providing therapeutic potentialities based on specific carbohydrate modulation.

Helicobacter pylori infection, peptic ulcer and gastric cancer are common problems in Egypt. We investigated the prevalence of cagA-positive Helicobacter pylori infections among Egyptian adults in relation to presentation (e.g. dyspepsia vs asymptomatic controls) in Minofyia, Egypt. Patients included men or women seeking care for at least 3 months of upper gastrointestinal symptoms. Helicobacter pylori status was determined by rapid urease test and gastric histopathology in patients and by anti-Helicobacter pylori IgG antibodies in controls. CagA status was determined using an anti-cag A ELISA. 99 Helicobacter pylori infected patients were entered including 90 dyspeptic patients (30 each with gastric cancer, peptic ulcer, and non-ulcer dyspepsia) and 9 non-dyspeptic healthy controls. Age ranged from 27 to 78 y (mean 49.5 y); 50% were men. Anti-cagA antibodies were present in 62.2% of dyspeptic patients compared with 11% of asymptomatic controls (p = 0.004). Anti-cagA antibodies were more prevalent among dyspeptic patients with gastric cancer or peptic ulcer (73.3%) compared to those with non-ulcer dyspepsia (40%) (p = 0.004). The prevalence of cagA in Egypt was related to the clinical presentation of Helicobacter pylori infection being lowest in asymptomatic controls (11.1%) and increasingly prevalent in non-ulcer dyspepsia (40%), peptic ulcer (66.7%), and gastric cancer (89%).

Purpose of Review: This review attempts to contextualize some of the clinically important publications of the last 2 years as they relate to the broad topic of dyspepsia and peptic ulcer disease, both Helicobacter pylori and nonsteroidal anti-inflammatory drug-related., Recent Findings: This review includes findings which provide insight with regard to the triaging of dyspeptic subjects, information on new proton pump inhibitor drugs and H. pylori eradication 'rescue regimens'. The 'COX-2 debacle' is discussed and new data relating to the efficacy of co-therapy strategies for the prevention of nonsteroidal anti-inflammatory drug gastropathy are presented, while the use of antiplatelet agents as 'safe' substitutes for aspirin cardioprophylaxis is questioned. The important issue of proton pump inhibitor safety and nonsteroidal anti-inflammatory drug enteropathy are addressed., Summary: The review provides a summary and interpretation of literature pertaining to the above issues, and should provide a point of departure for clinical decision-making relevant to these issues.

Modern gastroenterology started in early 19(th) century with the identification by W. Prout of the inorganic (hydrochloric) acid in the stomach and continued through 20(th) century with the discoveries by I.P. Pavlov of neuro-reflex stimulation of gastric secretion for which he was awarded first Nobel Prize in 1904. When concept of nervism or complete neural control of all digestive functions reached apogeum in Eastern Europe, on the other side of Europe (in United Kingdom), E. Edkins discovered in 1906 that a hormone, gastrin, may serve as chemical messenger in stimulation of gastric acid secretion, while L. Popielski revealed in 1916 that histamine is the most potent gastric secretagogue. K. Schwartz, without considering neural or hormonal nature of gastric secretory stimulation, enunciated in 1910 famous dictum; "no acid no ulcer"; and suggested gastrectomy as the best medication for excessive gastric acid secretion and peptic ulcer. In early 70s, J.W. Black, basing on earlier L. Popielski's histamine concept, identified histamine-H(2) receptors (H(2)-R) and obtained their antagonists, which were found very useful in the control of gastric acid secretion and ulcer therapy for which he was awarded in 1972 second Nobel Prize in gastrology. With discovery by G. Sachs in 1973 of proton pumps and their inhibitors (PPI), even more effective in gastric acid inhibition and ulcer therapy than H(2)-R antagonists, gastric surgery, namely gastrectomy, practiced since first gastric resection in 1881 by L. Rydygier, has been considered obsolete for ulcer treatment. Despite of the progress in gastric pharmacology, the ulcer disease remained essentially "undefeated" and showed periodic exacerbation and relapses. The discovery of spiral bacteria in the stomach in 1983 by B.J. Marshall and R.J. Warren, Australian, clinical researches, awarded in 2005 the Nobel Prize for the third time in gastrology, has been widely considered as a major breakthrough in pathophysiology of gastritis and peptic ulcer, which for the first time can be definitively cured by merely eradication of germ infecting stomach. This overview presents the mechanism of induction of gastritis and peptic ulcer by the H. pylori infection and describes accompanying changes in gastric acid and endocrine secretion as well as the effects of germ eradication on gastric secretory functions and gastroduodenal mucosal integrity.

The authors present the results of laser-based 13C-urea breath test (13C-UBT) application in diagnostics of Helicobacter pylori-associated diseases (chronic gastritis, duodenitis, and peptic ulcer). 13C-UBT data distribution before and after eradication therapy, as well as age distribution, were obtained. Correlations between the nosological forms and the rate of contamination were established.

Although Helicobacter pylori infects 50% of the total human population, only a small fraction of the infected people suffer from severe diseases like peptic ulcers and gastric adenocarcinoma. H. pylori strains, host genotypes and environmental factors play important role in deciding the extent and severity of the gastroduodenal diseases. The bacteria has developed a unique set of virulence factors to survive in the extreme ecological niche of human stomach. Together these virulence factors make H. pylori one of the most successful human pathogenic bacteria colonizing more than half of the human population. Understanding the mechanism of action of the major H. pylori virulence factors will shed light into the molecular basis of its pathogenicity.

Background: To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin-8 (IL-8), histological inflammation through eradication therapy, and interactions among these parameters., Methods: Twenty-eight H. pylori-positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and 13C-urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL-8 were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Histology was assessed by the Sydney system., Results: H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients' backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL-8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL-8., Conclusions: These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide-immune interactions in the gastric mucosa exist in H. pylori infection.

Objective: Helicobacter pylori infection causes gastric diseases, but the responsible mechanisms are not completely understood. They can involve DNA and tissue damage induced by reactive oxygen and nitrogen species. Our aim is to investigate the effects of bacterial eradication on oxidative stress by measuring changes of relevant markers., Methods: Antral biopsies were obtained from 34 patients with chronic atrophic gastritis and peptic ulcer disease before and after bacterial eradication. The expression of inducible nitric oxide synthase (iNOS) and levels of nitrotyrosine (NTYR) and 8-hydroxy-2'-deoxyguanosine were assessed immunohistochemically as markers of nitric oxide (NO) production and of damage to proteins and DNA, respectively., Results: Before treatment, the percentages of patients with staining were: 56 for iNOS in inflammatory cells, 79 and 61 for NTYR and 8-hydroxy-2'-deoxyguanosine in foveolar cells, respectively, and 82 for 8-hydroxy-2'-deoxyguanosine in lymphoid follicles. NTYR staining was associated with the intensity of inflammation (p = 0.04) and gastritis activity (p = 0.07). The prevalence of 8-hydroxy-2'-deoxyguanosine tended to be associated with that of NTYR. After successful H. pylori eradication, the prevalence of iNOS and NTYR (in mild gastritis) staining decreased (p < 0.001 and p < 0.06, respectively). 8-Hydroxy-2'-deoxyguanosine staining disappeared in 24% of cases but appeared in 18% of previously negative cases despite eradication., Conclusion: Targets of oxidative stress associated with H. pylori infection are inflammatory and deep foveolar cells and lymphoid follicles. This is the first report of 8-hydroxy-2'-deoxyguanosine localization in gastric mucosa. Oxidative stress is reduced by bacterial eradication in the first stages of mild gastritis. Moderate-severe gastritis may be a step that is reversible for iNOS, but partly irreversible for NTYR and 8-hydroxy-2'-deoxyguanosine.

Background: The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-kappaB activation in gastric cancer cell lines, there is little information on cellular localization of NF-kappaB in H. pylori-infected gastric mucosa., Methods: H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-kappaB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-kappaB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1beta levels as measured with enzyme-linked immunosorbent assay with the degree of NF-kappaB expression., Results: NF-kappaB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-kappaB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-kappaB expression also correlated with mucosal IL-8 levels but not with IL-8., Conclusions: H. pylori infection increases the expression of NF-kappaB in gastric mucosa, suggesting that NF-kappaB is involved in inflammatory responses to H. pylori.

Aims: To investigate interleukin (IL)-12 (p40) and IL-10 mRNA expression levels in the gastric mucosa in relation to H pylori cag status, peptic ulceration, and histopathology., Methods: In 81 dyspeptic patients, antral and corpus biopsies were taken for reverse transcriptase polymerase chain reaction (RT-PCR) and histology. G3PDH (control) and IL-10 and IL-12 were coamplified in a duplex PCR and the ratios of cytokines to G3PDH were determined. Bacterial ureA and cagA status was determined by RT-PCR., Results: IL-10 mRNA expression in both the antral and corpus mucosa was greater (p < 0.01) in cagA positive infection than in H pylori negative patients with histologically normal mucosa. No increase in IL-10 mRNA expression was observed in cagA negative infection. Both in the antral and corpus mucosa, IL-12 mRNA expression was greater (p < 0.05) in cagA positive than in cagA negative infection and uninfected patients with normal gastric mucosa. In cagA positive infection, there was a correlation between IL-10 and IL-12 mRNA expression in both the antral mucosa (r = 0.515, p < 0.01) and the corpus mucosa (r = 0.6, p < 0.005). IL-12 mRNA expression in the antral mucosa was significantly more frequent in H pylori positive patients with duodenal ulcer than in those with gastric ulcer or nonulcer dyspepsia. No difference was observed in IL-10 mRNA expression in relation to endoscopic diagnosis., Conclusions: CagA positive H pylori infection is associated with increased IL-10 and IL-12 mRNA expression. The increased expression of IL-12 mRNA in the majority of patients with duodenal ulcer suggests that Th1 responses may predominate and play a role in the pathogenesis of duodenal ulceration.

Background: Omeprazole is metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. In persons with a poor-metabolizer genotype for CYP2C19, the therapeutic efficacy of omeprazole may be increased., Objective: To investigate whether CYP2C19 genotype status is associated with cure rates for Helicobacterpylori infection and peptic ulcer achieved by using dual therapy with omeprazole and amoxicillin., Design: Prospective cohort study., Setting: University hospital and health service center in Hamamatsu, Japan., Patients: 62 patients with peptic ulcer and H. pylori infection., Intervention: Omeprazole and amoxicillin., Measurements: CYP2C19 genotype status and cure rates for H. pylori infection and peptic ulcer., Results: Cure rates for H. pylori infection were 28.6% (95% CI, 13.1% to 48.7%), 60% (CI, 38.6% to 83.0%), and 100% (CI, 66.4% to 100%) in the rapid-, intermediate-, and poor-metabolizer groups, respectively. Healing rates for both duodenal and gastric ulcer in the three groups were roughly parallel with cure rates for H. pylori infection., Conclusion: The results of the genotyping test for CYP2C19 seem to predict cure of H. pylori infection and peptic ulcer in patients who receive dual therapy with omeprazole and amoxicillin.

To elucidate the role of interleukin (IL)-6 and IL-8 in the pathogenesis of gastric ulcer in Helicobacter pylori-positive gastritis, in situ hybridization using digoxigenin-labeled cDNA probes for both cytokines was performed. Immunogold silver staining was added to further improve the sensitivity of this non-radioactive hybridization. The biopsy specimens were taken from eight patients with active gastric ulcer before treatment, in all of whom H. pylori was positive. Macrophages (the putative producers of these cytokines) were determined by immunohistochemistry using anti-CD68 monoclonal antibodies (KP-1). IL-6 mRNA was most abundantly expressed in the epithelium and in the infiltrating cells in tissue adjacent to gastric ulcer. Quantitative analysis disclosed a significant increase in cells positive for IL-6 mRNA near the ulcer margin compared to cells in the surrounding tissue. In contrast, cells positive for IL-8 mRNA were observed in equal proportions and evenly in the epithelium and over the entire layer of the gastric mucosa regardless of the presence of gastric ulcer. The majority of infiltrating cells positive for both IL-6 and IL-8 mRNA were thought to be macrophages because of their morphologic features and their immunohistochemical reactivity to CD68. These findings strongly suggest that IL-6 is overexpressed at the margin of gastric ulcer in H. pylori-positive gastritis.

The aim of this study was to evaluate the accuracy of the 14C-urea breath test by comparing the results to those obtained by endoscopy with mucosal biopsy. We also examined the value of the breath test result obtained prior to endoscopy in predicting peptic ulcer disease. Forty-two individuals underwent the 14C-urea breath test. Collections of expired C02 were analysed using a liquid scintillation counter. All individuals then underwent endoscopy with biopsy. Biopsy material was evaluated by the rapid urease method and by histology for the presence of H. pylori. Our results demonstrated that the 14C-urea breath test was 100% sensitive and specific when compared to the rapid urease test as the 'gold standard' for the detection of H. pylori. In comparison to pathology, the sensitivity remained 100% and the specificity was 89%. The results of the 14C-urea breath test had a poor predictive value for the determination of peptic ulcer disease. We conclude that the 14C-urea breath test can be easily performed at any medical facility equipped with a liquid scintillation counter and can accurately detect H. pylori. A negative breath test result could not exclude the presence of peptic ulcer disease.

Cytotoxin-associated gene A (CagA), expressed in about 60% of H. pylori isolates in Western countries, may play a role in the pathogenesis of peptic ulcer. In this study, we determined the prevalence and significance of the H. pylori cagA gene and protein expression in Taiwan. Genomic DNA from antrum biopsies and H. pylori isolates were analyzed for cagA using polymerase chain reaction, Southern hybridization, or colony hybridization. CagA seropositivity was analyzed using Helico blots. In addition, Western blotting was performed to detect the CagA protein. About 94% of antrum tissues from both asymptomatic subjects and duodenal ulcer patients and all 76 H. pylori isolates (21 asymptomatic subjects, 39 with duodenal ulcers, 13 with gastric ulcers, 2 with gastric cancers, and 1 with mucosa-associated lymphoid tissue [MALT] lymphoma) were positive for the cagA gene. Moreover 77 out of 78 H. pylori-positive serum and all 27 H. pylori lysates had anti-CagA antibodies or CagA protein, respectively. H. pylori isolated from patients with various upper gastrointestinal diseases in Taiwan contained the cagA gene and expressed CagA protein at high frequencies.

Objective: The relationship between Helicobacter pylori (H. pylori), xanthine oxidase (XO)-induced oxygen derived free radicals (ODFR) and histamine in the induction of human gastroduodenal disorders was investigated., Patients and Methods: Histamine concentration, XO and xanthine dehydrogenase (XD) activities were measured in endoscopically obtained biopsies from 66 symptomatic patients., Results: H. pylori infection was associated with lower oxyntic and duodenal histamine in 'normal' controls (group N) (p < 0.002 and p < 0.05, respectively). Patients with gastroduodenal disease tended to have reduced mucosal concentration of histamine, but comparing H. pylori positive and negative patients, infection did not lead to a further fall in histamine concentration. H. pylori positive duodenal ulcer (DU) patients tended to have higher XO activity than group N (p = 0.051) and had a significantly lowered activity of XD, the precursor of XO (p' < 0.05). Histamine concentration at the ulcer-edge was lower while XO activity was higher than in the distant normal mucosa (p < 0.05, respectively). Gastritis (group GL) with H. pylori also had lower XD than H. pylori positive group N (p' < 0.025) but no corresponding rise in XO activity. In group N, duodenal mucosal histamine and XD activity were inversely related (Rs = -0.51, p < 0.025)., Conclusions: These findings support the hypothesis that histamine, xanthine oxidase related ODFR, and H. pylori may be closely associated in the manifestations of chronic duodenal ulcer.

It is hypothesized that probable geographic factors of nutritional type, nonrelated to development or socioeconomic level, may modulate the conversion of Helicobacter pylori-associated active chronic gastritis from its early stages to chronic atrophic gastritis (CAG). The factors could be diets low in antioxidant vitamins and other micronutrients such as selenium. In regions of the world where these modulating factors are not present, active chronic gastritis tends to stay in its early stages and to predispose individuals to duodenal ulcer. On the contrary, in regions where the modulating factors are present, the frequency of CAG increases markedly. When CAG becomes severe and extensive, hypochlorhydria ensues. Hypochlorhydria decreases the predisposition to duodenal ulcer, while CAG, a precancerous lesion, predisposes individuals to gastric cancer of the intestinal type. The hypothesis could be tested in a multicenter, multiregional study to (1) determine endoscopically and histologically the prevalence rates of duodenal ulcer, gastric ulcer, gastric cancer, and H. pylori-associated CAG in large series of dyspeptic patients and (2) correlate these prevalence rates with blood levels of micronutrients in these patients.

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.

Helicobacter pylori (Hp) associated ulcer disease is a common form of gastric disorder involving mucosal damage and invasion of the mucosa by polymorphic inflammatory cells with concomitant changes in the epithelial cell structure. The bacteria are thought to adhere by specific junction zones to the epithelial cell surface resulting in the degeneration of the mucosal layer. Our study was undertaken to examine the relative status of tissue kallikrein (TK) in antral and fundic biopsies, endoscopically obtained from 10 patients suspected of having gastric disorders. For histological evidence of inflammation the tissue was stained with hematoxylin and eosin and classified as mild, active, chronic and chronic active gastritis. Hp infection was determined by Giemsa staining. For localisation of TK, slide-mounted tissue sections were subjected to PAP and immunofluorescent staining using a goat anti-human TK IgG antibody. The results revealed that in the antral control tissue, removed during partial antractomy, TK was immunovisualised along the luminal border of the deep pyloric glands. The surface epithelia and superficial glands showed no labelling. The fundic control tissue revealed an absence of TK in the superficial and surface epithelial glands, but was positive in the parietal cells. The fundic biopsy specimens showed similar immunoreactivity in these areas. By contrast, in the inflammed pyloric mucosa, there was a shift of TK localisation to the basal part of the glandular cells and there was also expression of TK in the superficial glands that showed histological evidence of regeneration. In the fundic biopsies there was no change observed in the sites of TK localisation (similar to control tissue). It was observed, that even though 8 of the 10 subjects exhibited Hp infection, the inflamed mucosa showed no discernable difference in the staining patterns between the infected and non-infected tissue sections. Our findings suggest an important role for a B1/B2 kinin antagonist in patients with gastritis.

We examined secretion, mRNA expression, and histologic localization of interleukin-8 (IL-*) and growth-related gene product-alpha (GRO alpha) in the Helicobacter pylori-infected gastric antral mucosa. Antral biopsies were obtained from an area of endoscopically intact mucosa. Significantly higher levels of IL-8 and GRO alpha were secreted in organ cultures from patients with H. pylori infection, and their elevation was prominent in patients with duodenal ulcer. There was a significant association between these alpha-chemokine levels and histologic grades of activity, inflammation, and H. pylori density. In fresh antral biopsies, IL-8 and GRO alpha mRNA expression was detected more frequently in H. pylori-infected patients compared with those without infection. Immunofluorescence microscopy showed localization of IL-8 and GRO alpha proteins in gastric epithelial cells and infiltrating CD68+ macrophages. In the chemotaxis assay, a significant positive correlation was found between neutrophil migration induced by the organ culture supernatants and their contents of IL-8 and GRO alpha. After H. pylori eradication, a significant decrease was observed in IL-8 and GRO alpha levels detected in organ cultures. In conclusion, mucosal alpha-chemokine activity correlates well with histologic severity of H. pylori-associated antral gastritis and can be used to predict the effects of H. pylori eradication therapy.

The efficacy and safety of combination therapy with amoxicillin, lansoprazole, and plaunotol for the eradication of Helicobacter pylori in patients on dialysis were evaluated. The study subjects comprised 15 dialysis patients in whom H pylori had been found in the gastric mucosa. The patients were given 500 mg amoxicillin once a day for 3 weeks, 30 mg lansoprazole once a day for 8 weeks, and 80 mg plaunotol three times a day for 24 weeks. Endoscopy was performed on entry and at 4 and 24 weeks after cessation of amoxicillin. The concentrations of serum gastrin and gastric juice ammonia also were measured. Fourteen patients completed the treatment protocol, one having dropped out because of nausea and diarrhea. H pylori was eradicated in 11 of the 14 patients 4 weeks after the end of amoxicillin therapy (eradication rate, 78.6%). All but one patient was free of H pylori 24 weeks after the amoxicillin was discontinued. Patients who became negative for H pylori had significantly decreased serum gastrin and gastric juice ammonia concentrations. Our findings indicate that a combination of amoxicillin, lansoprazole, and plaunotol can be used to eradicate H pylori in patients on dialysis.

Aim: To investigate the association between Helicobacter pylori infection and serum pepsinogen (PG) 1 and 2 concentrations in various gastroduodenal diseases., Methods: Serum PG1 and 2 concentrations and antibodies to H pylori were measured by enzyme linked immunosorbent assay (ELISA); gastric mucosal pH was assessed and urease activity in biopsy tissue was determined. A comparison of the ELISA and urease test results permitted division of the cases into positive, false positive, false negative and negative categories for control, gastritis, and ulcer groups., Results: The gastric mucosal pH and serum PG2 in cases positive for H pylori were significantly increased in ulcer and gastritis cases compared with H pylori negative cases. Similar tendencies were observed for the false positive and false negative categories., Conclusions: A positive ELISA reaction for antibodies and an increased serum PG2 concentration are reliable indicators of H pylori infection.

Background: Helicobacter pylori is the cause of chronic (type B) gastritis, duodenal ulceration (DU), and gastric ulceration (GU). Smoking is associated with delayed ulcer healing. Epidermal growth factor (EGF) is produced in the salivary and Brunner's glands of the upper gastrointestinal tract, inhibits gastric acid secretion, and is a powerful mitogen., Materials and Methods: We sought to determine gastric luminal EGF (GL-EGF) in smokers and patients with Hp-associated DU and the effects of Hp eradication. Our aim was to determine GL-EGF in patients with GU and the effect of ulcer healing and to measure serum EGF in patients with Hp gastritis with or without DU disease., Results: GL-EGF was reduced in smokers compared to controls (p = .008). Subjects with HP gastritis had reduced GL-EGF compared to controls (p = .0002). There was no difference in GL-EGF between Hp-positive subjects who had DU and those with chronic gastritis alone. Eradication of Hp from those patients with DU had no effect on the low levels of GL-EGF. There was no difference between GL-EGF in Hp gastritis alone and in Hp-associated active GU. GL-EGF fell after ulcer healing (p = .04), a difference confirmed by analysis of paired samples from patients before and after ulcer healing (p = .03). There was no difference in serum EGF between controls and subjects with Hp infection. There was no difference in serum EGF in subjects with DU associated and non-ulcer-associated gastritis., Conclusions: Subjects with Hp gastritis, or those who smoke, had low concentrations of GL-EGF regardless of whether DU was present. Eradication of Hp did not return the concentrations of GL-EGF to normal in DU subjects. Individuals and Hp gastritis and inactive GU had low levels of GL-EGF compared to non-ulcer Hp infection. The relative increase in GL-EGF that occurred with ulceration of the gastric mucosa may have resulted from the development of an ulcer-associated cell lineage. Serum EGF did not play a role in the pathogenesis of Hp gastritis or of associated DU ulcer disease.

Objectives: Hepatocyte growth factor (HGF) is increasingly recognized for its role in a variety of hepatic and systemic diseases. Its relationship to gastritis has not been studied. We aimed at measuring gastric mucosal HGF levels in the presence or absence of Helicobacter pylori gastritis, in peptic ulcers, and in response to H. pylori eradication., Methods: Fifty one patients were studied. Patients were not entered if they had liver disease, malignancy, or any systemic illness. HGF was measured in gastric antral incubates using an enzyme-linked immunosorbent assay. Assessments were repeated 6 wk after a 2-wk course of anti-H. pylori triple therapy in 12 patients. Code numbers were used for blinding., Results: The median gastric mucosal HGF level was 36 ng/gm/tissue in patients with H. pylori gastritis (n = 33) compared with 19 ng/gm in 18 negative controls (p = 0.0024), 18 ng/gm after the eradication of H. pylori (p = 0.021), 23 ng/gm in all patients with ulcers (n = 10), and 26 ng/gm/tissue in H. pylori-positive ulcers (n = 7)., Conclusions: Gastric mucosal HGF levels were elevated in H. pylori gastritis and reduced by its eradication. These results are relevant to our understanding of the increased gastric cell proliferation in patients with H. pylori-related gastritis.

Duodenum exposed to above threshold gastric acid secretion may ulcerate if infected with Helicobacter pylori. Duodenal ulcers can be healed by suppressing acid secretion medically or surgically; their recurrence can be prevented by lifelong antisecretory drugs or by an elective vagotomy. However, duodenal and gastric ulcers can now be healed, and recurrence prevented, without operation by eradication of H. pylori.

We studied 128 patients with active peptic ulcer diagnosed by gastro-endoscopy four weeks after treatment with Xi Lei powder, PGE2 levels in both serum and gastro-duodenal mucosa were significantly higher than that before the treatment, the difference was significant (P < 0.01). The rate of negative conversion of Helicobacter pylori (HP) showed in 63.3% of cases. The distributed density of HP significantly reduced, the difference was significant (P < 0.01). These results indicated that Xi Lei powder could heal ulcer probably owing to the increasing of the PGE2 level in gastroduodenal mucosa, it inhibited the growth and reproduction of HP, and eliminated the HP, but did not inhibit the secretion of gastric acid and release the gastrin.

Etiologic role for HP appears to be best established in histologically proven gastritis. The major factors mediating gastritis induced by the colonization of the "gastric type" mucosa with HP are probably cytotoxins, cytokines and free radicals activated by this organisms. The deficiency of negative feedback in somatostatin-gastrin link in antral gastritis may result in an excessive gastrin release and increased gastric acid secretion with increased duodenal acid load under basal state and after meal. Recent NIH consensus 1994 proposes that: (1) ulcer patients with HP require treatment with antimicrobial agents whether on first presentation or on recurrence; (2) the value of treatment of HP infection in non-ulcer dyspepsia remains to be determined and (3) the asymptomatic subjects with HP infection do not require treatment with antimicrobial agents.

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.