BackgroundHelicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis.ResultsThe number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR = 3.08, 95% CI = 1.74 to 5.45, p < 10-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p = 0.04) and intestinal metaplasia (p = 0.007). Furthermore, patients infected by cagA strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer.ConclusionsOur results demonstrate that infection with H. pylori strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer.Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.

Helicobacter pylori cagA-positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL-1 gene cluster and tumor necrosis factor-a (TNFA)-307 polymorphisms, as well as cagA-positive status, are associated with gastric carcinoma in a non-Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori-positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme-linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B-511/-31, IL1RN (interleukin-1 receptor antagonist) and TNFA-307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2-pair primers. We found that the IL1RN2 polymorphic allele (OR 5 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA-positive status was the strongest independent factor associated with gastric carcinoma (OR 5 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA-positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma. ' 2005 Wiley-Liss, Inc.

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Helicobacter pylori infection is associated with peptic ulcer and gastric carcinoma. The oral cavity may be a reservoir for H. pylori; however, the results of studies on this subject are controversial. We employed single-step and nested polymerase chain reactions (PCR) to detect the presence of the vacA, ureA and 16S rDNA genes of H. pylori in the stomach, saliva and dental plaque of 30 subjects. The results were confirmed by sequencing. Nested 16S rDNA and ureA amplification was achieved in 80% of gastric, 30% of saliva and 20% of dental plaque specimens. Sequencing of 10, seven and four 16S rDNA products from stomach, saliva and dental plaque, respectively, showed > 99% identity with H. pylori. Sequencing of the other four oral cavity PCR products showed similarity with Campylobacter and Wolinella species. Additionally, the vacA genotype identified in the samples of different sites was the same within a given subject.H. pylori may be found in the oral cavity of patients with gastric infection, thus it could be a source of transmission. However, results obtained with detection methods based only on PCR should be interpreted with caution because other microorganisms that are phylogenetically very close to H. pylori are also present in the mouth.

Our analyses showed positive associations between proinflammatory polymorphisms at IL1RN and TNFA-307 loci and UC, as well as polymorphisms in the NOD2 gene and CD. These results highlight the importance of different genetic profiles associated with CD and UC.

We evaluated whether polymorphisms in genes coding molecules linked to the innate and adaptive immune response are associated with susceptibility to Helicobacter pylori infection. IL1B-511C-->T, IL1B-31T-->C, IL1RN allele 2, IL2-330T-->G, TNFA-307G-->A, TLR2Arg677Trp, TLR2Arg753Gln, TLR4Asp299Gly, and TLR5(392STOP) polymorphisms were determined in 541 blood donors. IL2-330T-->G allele carriers had a decreased H. pylori infection risk (OR=0.63, 95% CI=0.43-0.93) after adjustment for demographic and environmental factors. Hence, we investigated whether the polymorphism is functional by evaluating IL-2 serum concentration in 150 blood donors and 100 children. IL-2 pro-inflammatory and anti-inflammatory properties were indirectly investigated by determining serum IFN-gamma and IL-10/TGF-beta levels. The polymorphism was associated with increased mean IL-2 levels in H. pylori-positive adults (2.65 pg/mL vs. 7.78 pg/mL) and children (4.19 pg/mL vs. 8.03 pg/mL). Increased IL-2 was associated with pro-inflammatory activity in adults (IFN-gamma=18.61 pg/mL vs. 25.71 pg/mL), and with anti-inflammatory activity in children (IL-10=6.99 vs. 14.17 pg/mL, TGF-beta=45.88 vs. 93.44 pg/mL) (p<10(-3) for all). In conclusion, in the context of H. pylori infection, IL2-330 T-->G polymorphism is functional and is associated with decreased risk of infection in adults.

ObjectiveTo evaluate the usefulness and prognostic value of reactive hyperemia - peripheral arterial tonometry in patients with sepsis. Moreover, we investigated the association of reactive hyperemia - peripheral arterial tonometry results with serum levels of certain inflammatory molecules.MethodsProspective study, conducted in an 18-bed mixed intensive care unit for adults. The exclusion criteria included severe immunosuppression or antibiotic therapy initiated more than 48 hours before assessment. We measured the reactive hyperemia - peripheral arterial tonometry on inclusion (day 1) and on day 3. Interleukin-6, interleukin-10, high-mobility group box 1 protein and soluble ST2 levels were measured in the blood obtained upon inclusion.ResultsSeventeen of the 79 patients (21.6%) enrolled were determined to have reactive hyperemia - peripheral arterial tonometry signals considered technically unreliable and were excluded from the study. Thus, 62 patients were included in the final analysis, and they underwent a total of 95 reactive hyperemia - peripheral arterial tonometry exams within the first 48 hours after inclusion. The mean age was 51.5 (SD: 18.9), and 49 (62%) of the patients were male. Reactive hyperemia indexes from days 1 and 3 were not associated with vasopressor need, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, or 28-day mortality. Among the patients who died, compared with survivors, there was a significant increase in the day 3 reactive hyperemia index compared with day 1 (p = 0.045). There was a weak negative correlation between the day 1 reactive hyperemia - peripheral arterial tonometry index and the levels of high-mobility group box 1 protein (r = -0.287).ConclusionTechnical difficulties and the lack of clear associations between the exam results and clinical severity or outcomes strongly limits the utility of reactive hyperemia - peripheral arterial tonometry in septic patients admitted to the intensive care unit.

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