Helicobacter pylori infection increases serum nitrate and nitrite more prominently than serum pepsinogens

Background. Helicobacter pylori infection causes chronic gastritis and results in increased serum concentrations of pepsinogens I and II as well as gastrin, while the ratio of pepsinogen I to II (I : II) is decreased. Inducible nitric oxide synthase (iNOS) is induced in H. pylori‐associated gastritis and may modulate inflammation. However serum nitrate and nitrite (NOx) concentrations in patients with H. pylori‐induced chronic gastritis have not been reported. We examined differences in serum NOx between H. pylori‐negative and positive volunteers relative to differences in pepsinogens and gastrin. Materials and methods. Sera from 80 healthy asymptomatic volunteers younger than 36 years were analyzed for anti‐H. pylori antibody, NOx, gastrin and pepsinogens. Results. In H. pylori antibody‐positive subjects serum NOx concentrations were higher than in negative subjects (p < .005). In H. pylori‐negative subjects, NOx correlated with pepsinogen II (r = .405, p < .05). In subjects with low pepsinogen I or II, NOx was higher in H. pylori‐positive than negative subjects (p < .001). In subjects with high pepsinogen I : II (6 or higher), serum NOx was higher in H. pylori‐positive than in negative subjects. Conclusions. H. pylori‐induced gastritis increases serum NOx concentrations more prominently than those of pepsinogen. In H. pylori‐negative subjects, serum correlates with serum pepsinogen II.     

Predictive factors for improvement of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication: a three-year follow-up study in Korea

Background and Aims: To date, data on the effects of anti‐Helicobacter therapy on the improvement of atrophic gastritis (AG) and intestinal metaplasia (IM) have been conflicting. This study was performed to investigate whether eradication of H. pylori could lead to the improvement of AG and IM, and the prognostic factors associated with the improvement of AG and IM. Methods: Four hundred patients consisting of H. pylori‐negative (n = 116) and H. pylori‐positive (n = 284) groups were followed up 1 and 3 years after initial H. pylori tests. Serum levels of pepsinogen (PG), bacteria, environmental factors, and genetic polymorphisms were determined. Results: The grade of corpus atrophy decreased at 1 and 3 years after successful eradication (p < .001 and p = .033, respectively). However, there was no significant change in the IM in the antrum and in the corpus. Prediction factors for the improvement of corpus AG by H. pylori eradication were baseline low PG I/II ratio (≤3), high salt intake, and corpus‐predominant gastritis. IM improvement was also associated with spicy food intake and high baseline grade of IM, in addition to these factors. In addition, IL‐1B‐511 C/T and IL‐6‐572 C/G alleles were found to inhibit IM improvement. However, H. pylori‐negative and noneradicated group did not show any significant change in AG or IM. Conclusion: Corpus AG was reversed by H. pylori eradication, and improvement of IM by H. pylori eradiation was more definite in patients with severe IM, low PG I/II ratio, and corpus‐predominant gastritis, suggesting that H. pylori eradication is valuable even in severe cases.     

Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell kinetics: implication for gastric carcinogenesis

Background. Cyclooxygenase (COX)‐2 induced by Helicobacter pylori is thought to enhance gastric carcinogenesis by affecting the maintenance of epithelial homeostasis. Materials and Methods. Gastric biopsies from 160 subjects, 97 with nonulcer dyspepsia (47 H. pylori negative, 50 H. pylori positive) and 63 with gastric cancer were examined immunohistochemically for COX‐2 expression, cell proliferation and apoptotic indices. Results. COX‐2 expression in corpus was significantly higher in H. pylori positive than in negative non‐ulcer dyspepsia (NUD) (p < .05). Regardless of site, gastric cancer subjects had higher COX‐2 expression in both antrum and corpus compared with H. pylori negative and positive NUD (p < .005). Proliferation was higher in cancer and H. pylori positive than in negative NUD (p < .0001). Moreover, cancer had enhanced proliferation than H. pylori positive NUD in corpus greater (p = .0454) and antrum lesser (p = .0215) curvatures. Apoptosis was higher in H. pylori positive than in negative NUD (p < .05). However, both had a higher index than the cancer subjects (p < .0001). Apoptosis : proliferation ratio was higher in corpus of H. pylori negative than in positive NUD in greater (p = .0122) and lesser (p = .0009) curvatures. However, both had a higher A:P ratio than cancer cases (p = .0001). A negative correlation between COX‐2 expression and A:P ratio was found in corpus greater (r = –.176, p= .0437) and lesser (r = –.188, p= .0312) curvatures. Conclusion. The expression of COX‐2 is associated with disruption in gastric epithelial kinetics and hence may play a role in gastric carcinogenesis.     

Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?

Background. Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. Patients and Methods. We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody‐negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B₁₂, and circulating antibodies to H. pylori and to intrinsic factor were also determined. Results. We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p = .01). Mean levels of gastrin were increased (p < .0001), while those of pepsinogen were reduced (p < .001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti‐H. pylori antibodies were detected in 46 parietal cell antibody‐positive subjects (58%) compared with 26 controls (39%) (p = .03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p < .001 vs. controls). Mean levels of gastrin were markedly increased (p < .0001) and those of pepsinogen I decreased (p < .0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody‐positive subjects (58%) (p = .003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p < .001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. Conclusions. The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level.     

Mechanism of action of low recurrence of gastritis caused by Helicobacter pylori with the type II urease B gene

Background. Low recurrence of gastritis is seen in patients infected with Helicobacter pylori carrying the type II urease B gene, compared with H. pylori carrying types I and III. The underlying mechanism has been studied in terms of the urease activity and interleukin (IL)‐8 production capacity of different strains of H. pylori. Materials and Methods. Forty‐five patients infected with different strains of H. pylori (type I; 15, type II; 15 and type III; 15) were enrolled in the study. H. pylori was isolated from gastric mucosa and cultured in the presence of urea at pH 5.5 to evaluate urease activity. The capacity of different strains of H. pylori to induce IL‐8 mRNA and IL‐8 from a human gastric cancer cell line and human peripheral blood mononuclear cells was evaluated. Results. The urease activity of type II H. pylori[523 ± 228 µg of ammonia/dl/10⁸ colony‐forming units (CFU)/ml] was significantly lower than that of type I (1355 ± 1369 µg of ammonia/dl/10⁸ CFU/ml) and type III (1442 ± 2229 µg of ammonia/dl/10⁸ CFU/ml) (p < .05). Gastric cancer cells cocultured with type II H. pylori produced lower levels of IL‐8 mRNA compared with type I and type III H. pylori. The levels of IL‐8 were also significantly lower in cultures induced by type II H. pylori compared with those induced by type I and type III H. pylori. Peripheral blood mononuclear cells also produced lower levels of IL‐8 when cocultured with type II compared with type I H. pylori. Conclusions. These results indicate that both the lower level of urease activity and the low IL‐8‐inducing capacity of type II H. pylori might underlie the lower recurrence rate of gastritis caused by type II H. pylori.     

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children

Background. Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal‐stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods. Thirty‐six children aged 10–17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2–3 months after H. pylori eradication. Meal‐stimulated serum gastrin response was assessed before and 12 months after eradication. Results. H. pylori gastritis was typically antrum‐predominant. Acid secretion was greater in H. pylori‐positive patients with duodenal ulcer than in gastritis‐only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori‐positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre‐ and post‐H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal‐stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions. H. pylori infection in children is associated with a marked but reversible increase in meal‐stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.     

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status

Background: The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated. Materials and Methods: Serum pepsinogen, H. pylori antibody concentration, and fasting gastric pH (as an indicator of acid secretion) were measured in 231 patients undergoing upper gastrointestinal endoscopy. “Atrophic” pepsinogen was defined as pepsinogen‐I < 70 ng/mL and pepsinogen‐I/II ratio <3. Other levels of pepsinogen were defined as “normal”. Fasting gastric pH was analyzed in subjects stratified by pepsinogen level and by H. pylori antibody concentration. Results: Helicobacter pylori antibody concentration showed no significant relationship with fasting gastric pH when all subjects were analyzed together. In H. pylori‐seronegative subjects, fasting gastric pH was within the normal range, irrespective of the extent of mucosal atrophy. In H. pylori‐seropositive subjects, H. pylori antibody concentration was positively correlated with fasting gastric pH in subjects with “normal” pepsinogen, but inversely correlated in those with “atrophic” pepsinogen. Particularly in subjects with low H. pylori antibody concentration and atrophic mucosa, a group reportedly at high risk of noncardia cancer, the most impaired acid secretion was shown among subjects with atrophic mucosa. Conclusions: The relationship between acid secretion and H. pylori antibody concentration differs depending on the presence of mucosal atrophy. Our findings provide a possible rationalization for measuring both serum pepsinogen levels and H. pylori antibody concentration in gastric cancer screening.     

Helicobacter pylori infection in connective tissue disorders is associated with high levels of antibodies to mycobacterial hsp65 but not to human hsp60

Background. To investigate whether the Helicobacter pylori status influences levels of antibodies against mycobacterial heat shock protein (hsp) 65 and human hsp60 in systemic autoimmune diseases and to study the concentration of anti‐H. pylori antibodies in autoimmune patients and healthy controls. Materials and Methods. Antibodies against human heat‐shock protein hsp60, mycobacterial heat‐shock protein hsp65 were analyzed by ELISA. Anti‐Helicobacter antibodies were determined by enzyme immunoassay. Results. There was a markedly higher prevalence of H. pylori infection in undifferentiated connective tissue disease (82%) (n = 33) and systemic sclerosis (78%) (n = 55) but not in systemic lupus erythematosus (n = 49), polymyositis/dermatomyositis (n = 14), rheumatoid arthritis (n = 21) or primary Raynaud's syndrome (n = 26) compared with controls (59%) (n = 349). In autoimmune diseases H. pylori infection was associated with elevated levels of antihsp65 (p = .008) but not of antihsp60. Anti‐hsp65 levels were significantly higher in H. pylori‐infected (n = 129) than in uninfected patients (n = 69) (p = .0007). Conclusions. These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.     

Enterocromaffin-like cell tumor induced by Helicobacter pylori infection in Mongolian gerbils

Background. Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori‐infected stomachs of Mongolian gerbils for a long time. Materials and Methods. Five‐week‐old‐male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals . Results In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes. Conclusions. H. pylori infection caused not only gastric carcinomas but also enterochromaffin‐like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.     

The association of intestinal parasitosis and H. pylori infection in children and adults from a Mexican community with high prevalence of parasitosis

Background. ABSTExperimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. Materials and Methods. The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. Results. In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). Conclusions. Intestinal parasitic infections and serum IgE levels showed an age‐dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence.     

Helicobacter pylori infection may be implicated in the topography and geographic variation of upper gastrointestinal cancers in the Taihang Mountain high-risk region in northern China

Backgrounds: Helicobacter pylori infection is prevalent in China. Chronic infection of the bacterial not only causes distal stomach cancer, but also confers risk to gastric cardia adenocarcinoma. Because H. pylori infection is inversely associated with esophageal adenocarcinoma, globally the infection rate is significantly correlated with the ratio of squamous carcinoma to adenocarcinoma of the esophagus. These agree with the topography of upper gastrointestinal cancer observed in the Taihang Mountain high‐risk region where both gastric cardia and non‐cardia adenocarcinoma coincide with esophageal squamous cancer, but with almost no distal esophageal adenocarcinoma. Moreover, as altitude increases from plain to mountains, we observed progressively increasing incidence rates of gastric adenocarcinomas in recent years in the region. Because H. pylori infection is a definite carcinogen to gastric adenocarcinoma and is more prevalent in the mountain than in plain areas due to undeveloped living conditions, the observation gives the impression as though H. pylori infection is implicated. Aims: This article aims to note the role of H. pylori infection in upper gastrointestinal cancer in the Taihang Mountain high‐risk region in northern China. Materials and Methods: First the unique topography and geographic variation of upper gastrointestinal cancer in the region is described to indicate a possible role of H. pylori infection, then we review studies on prevalence of H. pylori infection in the high‐risk region and describe difference in socioeconomic development and water hygiene between the plains and the mountains as related to the prevalence of H. pylori infection. Results: Coincidence of gastric cancer in the region and a progressively increasing rate of the cancer from the plain towards the mountains indicate H. pylori infection may be implicated in upper gastrointestinal cancer. Conclusion: International collaboration is needed to study H. pylori and upper gastrointestinal cancer in the region when rapid industrialization is just beginning.     

Probiotics-containing yogurts suppress Helicobacter pylori load and modify immune response and intestinal microbiota in the Helicobacter pylori-infected children

Background: The benefits of probiotics to the pediatric Helicobacter pylori infection remain uncertain. We tested whether the H. pylori‐infected children have an altered gut microflora, and whether probiotics‐containing yogurt can restore such change and improve their H. pylori‐related immune cascades. Methods: We prospectively included 38 children with H. pylori infection confirmed by a positive ¹³C‐urea breath test (UBT) and 38 age‐ and sex‐matched noninfected controls. All of them have provided the serum and stool samples before and after 4‐week ingestion of probiotics‐containing yogurt. The serum samples were tested for the TNF‐α, IL‐10, IL‐6, immunoglobulin (Ig) A, G, E, pepsinogens I and II levels. The stool samples were tested for the colony counts of Bifidobacterium spp. and Escherichia coli. The follow‐up UBT indirectly assessed the H. pylori loads after yogurt usage. Results: The H. pylori‐infected children had lower fecal Bifidobacterium spp. count (p = .009), Bifidobacterium spp./E. coli ratio (p = .04), serum IgA titer (p = .04), and pepsinogens I/II ratio (p < .001) than in controls. In the H. pylori‐infected children, 4‐week yogurt ingestion reduced the IL‐6 level (p < .01) and H. pylori loads (p = .046), but elevated the serum IgA and pepsinogen II levels (p < .001). Moreover, yogurt ingestion can improve the childhood fecal Bifidobacterium spp./E. coli ratio (p = .03). Conclusions: The H. pylori‐infected children have a lower Bifidobacterium microflora in gut. The probiotics‐containing yogurt can offer benefits to restore Bifidobacterium spp./E. coli ratio in children and suppress the H. pylori load with increment of serum IgA but with reduction in IL‐6 in H. pylori‐infected children.     

Clinical application of 20 MHz endosonography and anti-Helicobacter pylori immunoblots to predict regression of low-grade gastric MALToma by H. pylori eradication

Aim. We tested whether serial 20 MHz endosonography (EUS) and anti‐Helicobacter pylori immunoblots can predict the complete regression of gastric MALToma by H. pylori eradication. Methods. The serums of 17 MALToma patients, including 15 with low grade and two with high grade, were collected before therapy. Fifteen patients with low‐grade MALToma and 18 nonMALToma patients, all infected with H. pylori, have been followed with serum sampling, endoscopy, and EUS on enrollment, on the 2nd, 6th, and 12th months after anti‐H. pylori therapy. All sera were tested for anti‐H. pylori immunoblots, including 19.5, 26.5, 30, 35, 89, 116 KDa (CagA), FldA. The DNAs were extracted serially from the biopsy of MALToma patients before and after therapy to perform polymerase chain reaction (PCR) for the immunoglobulin heavy‐chain gene monoclonality. Results. MALToma patients had higher prevalence rates of anti‐FldA protein, 19.5 and 30 KDa antibodies of H. pylori (p < 0.01). After H. pylori eradication, MALToma patients had negative seroconversion of 19.5, 26.5, 30, and 35 KDa antibodies (p < 0.05), but not in CagA and FldA. The PCR monoclonality occurred in 80% (12/15) of the MALToma patients before therapy, but did not correlate with any seroconversion of anti‐H. pylori immunoblots after therapy (p > 0.05). Complete regression of MALToma was observed in 73.3% (11/15) of patients. Evaluation with 20 MHz EUS, for the initial tumor depth and its normalization on the 6th month had 90.9% sensitivity and 100% specificity to predict the complete regression. Discussion. The negative seroconversions of the smaller‐molecular‐weight proteins, but not CagA and FldA, correlate with regression of MALToma by H. pylori eradication. 20 MHz EUS can effectively predict the therapeutic response of MALToma.     

Production of chemokines and reactive oxygen species by human neutrophils stimulated by Helicobacter pylori

Background. Bacteria have different characteristics in stimulation of human neutrophils to produce reactive oxygen species (ROS) and chemokines. This study examined the ability of Helicobacter pylori to induce production of ROS and chemokines by human neutrophils. Methods. H. pylori strains (1.5 × 10⁸ CFU/ml) were cocultured with 5 × 10⁴ neutrophils isolated from healthy subjects. Samples were incubated with human serum with or without IgG antibodies to H. pylori. ROS production was measured using luminol‐dependent chemiluminescence (LmCL), and the concentrations of chemokines (IL‐8, RANTES, MIP‐1α and MCP‐1) were measured by ELISA. Results. The mean of the highest LmCL (peak height; PH) value stimulated by H. pylori was 3318 in the absence of serum. PH increased to 4687 when incubated with anti‐H. pylori antibody‐positive sera (p < .001) but antibody‐negative sera did not affect LmCL response. The mean final concentration of IL‐8 produced in the absence of serum was 142.6 pg/ml. Increased IL‐8 production was seen by addition of antibody positive serum (p < .01). IL‐8 production was not significantly correlated with production of ROS. On the other hand, H. pylori stimulation did not induce neutrophil production of RANTES, MIP‐1α or MCP‐1. Conclusions. H. pylori was capable of inducing IL‐8 production by human neutrophils, but not C‐C chemokines. Production of C‐X‐C dominant chemokine by neutrophils is consistent with the pathological characteristics of H. pylori‐induced gastritis, where persistent neutrophil infiltration is present.     

Helicobacter pylori CagA Status,Mucosal Oxidative Damage and Gastritis Phenotype: A Potential Pathway to Cancer?

Background. Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori‐cagA‐positive strains are associated with the highest risk of gastric cancer. Aims. To ascertain whether cagA‐positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes. Patients and Methods. 118 patients were studied (65M/53F, age 61 ± 14 years). Twelve were H. pylori‐negative. Among the H. pylori‐positive patients, 34 were cagA‐positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling. The phenotype of the gastritis (atrophic compared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8‐hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR. Results. The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status (p = 0.036 antrum and p = 0.02 corpus). cagA‐positive infection significantly correlated with a higher prevalence of atrophic‐metaplastic lesions (p = 0.04). cagA‐positive patients had higher 8‐hydroxydeoxyguanosine levels than both cagA‐negative and H. pylori‐negative cases (p = 0.01). The 8‐hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis (p = 0.04). The odds ratio for cagA‐positive patients having 8OHdG levels above a cut‐off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered. Conclusions. cagA‐positive patients were characterized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer‐prone biological context.     

Age at acquisition of Helicobacter pylori in a pediatric Canadian First Nations population

Background. Few data exist regarding the epidem‐iology of Helicobacter pylori infections in aboriginal, including the First Nations (Indian) or Inuit (Eskimo) populations of North America. We have previously found 95% of the adults in Wasagamack, a First Nations community in Northeastern Manitoba, Canada, are seropositive for H. pylori. We aimed to determine the age at acquisition of H. pylori among the children of this community, and if any association existed with stool occult blood or demographic factors. Materials and Methods. We prospectively enrolled children resident in the Wasagamack First Nation in August 1999. A demographic questionnaire was administered. Stool was collected, frozen and batch analyzed by enzyme‐linked immunosorbent assay (ELISA) for H. pylori antigen and for the presence of occult blood. Questionnaire data were analyzed and correlated with the presence or absence of H. pylori. Results. 163 (47%) of the estimated 350 children aged 6 weeks to 12 years, resident in the community were enrolled. Stool was positive for H. pylori in 92 (56%). By the second year of life 67% were positive for H. pylori. The youngest to test positive was 6 weeks old. There was no correlation of a positive H. pylori status with gender, presence of pets, serum Hgb, or stool occult blood. Forty‐three percent of H. pylori positive and 24% of H. pylori negative children were < 50th percentile for height (p = 0.024). Positive H. pylori status was associated with the use of indoor pail toileting (86/143) compared with outhouse toileting (6/20) (p = 0.01). Conclusions. In a community with widespread H. pylori infection, overcrowded housing and primitive toileting, H. pylori is acquired as early as 6 weeks of age, and by the second year of life 67% of children test positive for H. pylori.     

Acid inhibitory potency of twice a day omeprazole is not affected by eradication of Helicobacter pylori in healthy volunteers

Background & Aims. The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. Materials and Methods. We undertook 24‐hour pH‐metry in 12 H. pylori‐positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. Results. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH ≥ 3, as well as increasing the area under the H⁺ concentration‐time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL‐1α, IL‐8, IL‐13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H⁺ concentration‐time curve ‘without omeprazole’ minus ‘with omeprazole’, when comparing ‘after’ versus ‘before’ eradication of H. pylori. Conclusions. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity ‘with’ versus ‘without’ omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.     

Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study

Background: Recent studies indicate a potential role of Saccharomyces boulardii in the prevention of Helicobacter pylori treatment‐related side‐effects and also in improvement of eradication rate. Our aim is to investigate the efficacy and safety of S. boulardii in the prevention of side‐effects related to H. pylori eradication. The secondary aim of the study was to define the effect of S. boulardii on the eradication success of anti‐H. pylori therapy. Materials and methods: One hundred and twenty‐four patients with H. pylori infection (male/female: 44/80, mean age: 48 ± 14.25 year) receiving 14 days of triple therapy (clarithromycin 500 mg b.i.d., amoxicillin 1000 mg b.i.d., and lansoprazole 30 mg b.i.d.) were randomly assigned to S. boulardii or placebo. Dyspeptic symptoms were recorded by using modified Glasgow Dyspepsia Questionnaire (GDQ). Side‐effect profile and tolerability were assessed using a symptom‐based questionnaire. H. pylori status was rechecked after 6 weeks after completion of eradication therapy. Results: H. pylori eradication rate, although higher in the treatment group, was statistically similar in treatment and control groups: 71% (44/62) versus 59.7% (37/62), respectively (p > .05). Nine (14.5%) patients in the treatment group and 19 (30.6%) patients in the placebo group experienced diarrhea (p < .05). Epigastric discomfort was more frequent in the control group [9 (14.5%) versus 27 (43.5%), respectively (p < .01)]. Diffuse abdominal pain, abdominal gas, taste disturbance, urticaria, nausea symptoms were similar in both groups. GDQ scores after treatment were significantly better for treatment group (mean ± SD, range: 1.38 ± 1.25 (0–5) vs. 2.22 ± 1.44 (0–6), respectively; p < .01). Conclusion: S. boulardii improved anti‐H. pylori antibiotherapy‐associated diarrhea, epigastric discomfort, and treatment tolerability. In addition, S. boulardii supplement decreased post‐treatment dyspepsia symptoms independent of H. pylori status. However, S. boulardii had no significant affect on the rate of H. pylori eradication.     

Helicobacter-induced gastritis in mice not expressing metallothionein-I and II

Background. Helicobacter pylori a primary cause of gastritis and peptic ulcer disease, is associated with increased production of reactive oxygen species within the gastric mucosa. Metallothionein (MT), a low‐molecular‐weight, cysteine‐rich, metal‐binding ligand, has been shown to sequester reactive oxygen species and reduce tissue damage. This study investigates the role of MT in H. pylori‐induced gastritis in mice. Materials and Methods. Control (MT+/+) and MT‐null (MT–/–) mice were inoculated with either 1 × 10⁸H. pylori or H. felis, and were infected for 4, 8 and 16 weeks or 8 weeks, respectively. H. pylori load was determined by culture. Myloperoxidase activity and MT levels were also determined. Results. The stomachs of H. felis‐infected mice were more severely inflamed than those of H. pylori‐infected mice. H. felis‐induced gastritis was more severe (p = .003) in MT–/– than in MT+/+ mice. MT–/– mice also had higher (60%; p < .05) H. pylori loads than MT+/+ mice 4 weeks after infection but not 8 or 16 weeks after infection. Myloperoxidase activity with H. pylori was similar between MT+/+ and MT–/– mice. Thirty‐three per cent greater (p < .05) myloperoxidase activity was observed in MT–/– than in MT+/+ mice infected with H. felis. In MT+/+ mice infected with H. pylori, liver MT was increased by 33 and 39% (p < .05) at 8 and 16 weeks, respectively, whereas gastric MT increased by 46% (p < .05) at 4 weeks and declined to baseline levels at 8 and 16 weeks. Conclusions. Mice lacking MT are more susceptible to H. pylori colonization and gastric inflammation, indicating that MT may be protective against H. pylori‐induced gastritis.