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Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the regulation of coagulation and inflammation. In addition to inhibiting the fibrinolytic system, TAFI may also regulate the bradykinin and complement systems. We hypothesized that TAFI also plays a role in defense mechanisms of the gastric mucosa during Helicobacter pylori infection. This study comprised 65 patients with gastroduodenal disorders: 41 patients with H. pylori infection, 13 without, and 11 patients with cured H. pylori infection. The gastric intramucosal concentrations of TAFI were measured by enzyme immunoassay. The gastric levels of TAFI and plasminogen activator inhibitor-1 were significantly increased in patients with H. pylori compared to those without infection or cured H. pylori. The presence of TAFI was detected in gastric mucosal epithelial cells. The concentration of TAFI was correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity. These results show that TAFI is present in the gastric mucosa and that it may play a role in the pathogenesis of H. pylori infection-associated gastroduodenal disorders.

Helicobacter pylori colonize the stomach of over half the world's population. While 80-90% H. pylori-infected individuals have clinically asymptomatic gastritis, 10-15% develop peptic ulcer, and 1-2% gastric malignancies. These variable clinical outcomes have led to an interest in prognostic indicators. The current disease paradigm suggests that host genetics and bacterial virulence both play important roles in modulating the final outcome of H. pylori infection. Elucidation of the interaction between host and bacterium is essential to clarify pathogenesis and to develop new strategies for prevention and treatment. Proteomic technology is a powerful tool for simultaneously monitoring proteins and protein variation on a large scale in biological samples. It has provided an unprecedented opportunity to survey a cell's translational landscape comprehensively, and the results may allow in-depth analyses of host and pathogen interactions. Using this high-throughput platform and taking advantage of complete sequences for both the H. pylori and the human genome in available databases, we have identified several crucial proteins that have pathogenic and prognostic potential. Among them, antibodies to AhpC and GroEs of H. pylori could be utilized for identification of patients who are at high risk of disease complications after H. pylori infection. Evolving proteomic technologies, together with appropriate clinical phenotyping and genotype information should enhance understanding of disease pathogenesis and lead to more precise prediction of variable disease outcomes. It will also facilitate development of biomarkers for diagnosis, treatment, and prevention of H. pylori infection.

Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.

Objectives: Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H. pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection., Methods: We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E2 and F2alpha synthesis rates., Results: Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori-infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H. pylori-infected participants than in noninfected subjects (p = 0.03), and two H. pylori-infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E2 plus F2alpha) synthesis rates than their noninfected counterparts (108 +/- 6 ng/g/min versus 75 +/- 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants., Conclusions: Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion.

It is highly probable that nutritionally-related geographic and socioeconomic factors may modulate the conversion of early stages of Helicobacter pylori-associated chronic active gastritis (chronic superficial gastritis [CSG] and chronic deep gastritis [CDG]) to chronic atrophic gastritis (CAG). The factors would be diets low in antioxidant vitamins and other micronutrients. In regions of the world and population groups with high socioeconomic level in which these modulating factors are absent, chronic active gastritis tends to stay in its early stages of CSG or CDG and to predispose to duodenal ulcer. On the contrary, in regions and population groups with low socioeconomic level in which the modulating factors are present, the frequency of CAG increases markedly. When CAG becomes severe and diffuse, hypochlorhydria ensues. Hypochlorhydria decreases the predisposition to duodenal ulcer, while CAG, a precancerous lesion, predisposes to gastric cancer of the intestinal type. The real role of the modulating factors already mentioned could be elucidated doing a multicentric study to determine endoscopically and histologically, in large series of dyspeptic patients from various regions of the world and with different socioeconomic levels, prevalence rates of duodenal ulcer, gastric ulcer, gastric cancer, Helicobacter pylori-associated CAG and intestinal metaplasia of the gastric mucosa, and to correlate these prevalence rates with blood levels of antioxidant capacity and related micronutrients. Latin America, because of its diversity in regions, geographic characteristics and population socioeconomic levels, seems to be the ideal place to conduct a study of that type. If the study could be performed, it would undoubtedly constitute an important contribution to a better understanding of Helicobacter pylori-associated gastroduodenal pathology.

It is unclear why Helicobacter pylori produces different diseases in different persons. High and low acid secretion rates probably contribute to duodenal ulceration and gastric carcinogenesis, respectively. Both of these changes seem to be corrected by eradicating Helicobacter pylori. We are therefore exploring the basic mechanisms and asking why patients react differently? Helicobacter pylori products and certain cytokines released in Helicobacter pylori gastritis release gastrin from G-cells but inhibit parietal cells. Also tumour necrosis factor alpha inhibits somatostatin-cells and interleukin 1 beta inhibits enterochromaffin-like cells. The net result is that antral gastritis tends to increase, whilst corpus gastritis tends to decrease acid secretion. Corpus atrophy further lowers acid through loss of parietal cells. Factors postulated to increase corpus gastritis include host genetics, early acquisition of Helicobacter pylori, more aggressive strains, poor general health and diets high in salt or lacking in antioxidant vitamins. Further research should address the interaction of bacterium, host and environment with a view to preventing the serious clinical outcomes.

Helicobacter pylori infection is often associated with gastrointestinal diseases, such as chronic gastritis, peptic ulcer, and gastric cancer. After total gastrectomy, positive to negative seroconversion of the H. pylori IgG antibody assayed by enzyme-linked immunosorbent assay (ELISA) was found in 10/15 patients (67%) an average of 8.5 months after surgery. Therefore, the IgG antibody persists for a long time after total removal of the stomach in about 30% of patients. Immunoglobulin A (IgA) is a major component of the local immunity of the stomach mucosa and has a short half-life. Therefore, tissue H. pylori IgA antibodies in biopsy specimens from patients with various gastric diseases were assayed by ELISA and compared with the bacterial culture, serum IgG antibody (ELISA), and [13C]urea breath test results from 144, 170, and 123 endoscopic examinations, respectively. Positivity and negativity of tissue H. pylori IgA coincided with the culture results in 67% of the examinations, and positive IgA antibody but negative culture results were found in 23%. The coincidence of tissue IgA and serum IgG antibodies against H. pylori was 64% and that of negative tissue IgA but positive serum IgG antibody results was 36%. Positivity and negativity of tissue H. pylori IgA antibody coincided with the [13C]urea breath test results in 72%. One month after completion of treatment of peptic ulcer patients for H. pylori infection with lansoprazole and benexate HCl betadex plus amoxicillin, 6/9 (67%) patients showed positive to negative conversion of the tissue IgA antibody, in contrast to no IgG antibody seroconversion. In conclusion, the tissue H. pylori IgA antibody assay is useful for detection of local immunity against H. pylori in the stomach and during follow-up after treatment.