Relationship between vitamin B12, folate and homocysteine levels and H. pylori infection in patients with functional dyspepsia: A cross-section study

ABSTRACT: BACKGROUND: H. pylori infection has been associated with many micronutrient deficiencies. There is a dearth of data from communities with nutritional deficiencies and high prevalence of H. pylori infection. The aim of this study was to determine the impact of H. pylori infection on serum levels of vitamin B12, folate and homocysteine in patients with functional dyspepsia (FD). METHODS: One hundred and thirty-two patients with FD undergoing gastroscopy were enrolled. The serum was analyzed for B12, folate and homocysteine levels before gastroscopy. H. pylori infection was diagnosed by histopathological examination of gastric biopsies and urea breath test. An independent sample t-test and the Mann-Whitney test were used to compare mean serum concentrations of biomarkers between H. pylori-positive and H. pylori-negative groups of patients. A Chi-square test was performed to assess the differences among proportions, while Spearman's rho was used for correlation analysis between levels of B12 and homocysteine. RESULTS: The mean age of the group was 40.3 +/- 11.5 (19-72) years. Folate deficiency was seen in 43 (34.6%), B12 deficiency in 30 (23.1%) and hyperhomocysteinemia in 60 (46.2%) patients. H. pylori was present in 80 (61.5%) patients with FD while it was absent in 50 (38.5%). Mean serum levels of B12, folate and homocysteine in the H. pylori-positive group of patients were not significantly different from the levels in the H. pylori-negative group (357 +/- 170 vs. 313 +/- 136 pg/mL; p = 0.13), (4.35 +/- 1.89 vs. 4.42 +/- 1.93 ng/mL; p = 0.84); (15.88 +/- 8.97 vs. 16.62 +/- 7.82 mumol/L; p = 0.24); respectively. B12 deficiency ([less than or equal to]200 pg/mL) was 23.8% in the H. pylori-positive patients versus 22.0% in the H. pylori-negative patients. Folate deficiency ([less than or equal to]3.5 ng/mL) was 33.8% in the H. pylori-positive group versus 36% in the H. pylori-negative group. Hyperhomocysteinemia (>15 mumol/L) was present in 46.2% of H. pylori-positive patients compared to 44% in the H. pylori-negative group. Correlation analysis indicated that serum B12 levels were inversely associated with serum levels of homocysteine in patients with FD (rho = 0.192; p = 0.028). CONCLUSIONS: This study demonstrated an inverse relationship between serum levels of B12 and homocysteine in patients with FD. Moreover, no impact of the presence of H. pylori was found on B12, folate and homocysteine levels in such patients.     

Gender Difference of Circulating Ghrelin and Leptin Concentrations in Chronic Helicobacter pylori Infection

Background:  Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined whether demographic background, Helicobacter pylori infection, or its related gastritis severity could be associated with circulating ghrelin and leptin levels.
Methods:  This study prospectively enrolled 341 dyspeptic patients (196 females, 145 males), who had received endoscopy to provide the gastric specimens over both antrum and corpus for histology reviewed by the updated Sydney's system. The fasting blood sample of each patient was obtained for total ghrelin and leptin analysis.
Results:  Without H. pylori infection, there were similar ghrelin levels between female and male patients. In the H. pylori -infected patients, the males had lower plasma ghrelin levels than females (1053 vs. 1419 pg/mL, p  < .001). Only in males, not in females, the H. pylori infection and its related acute and chronic inflammation scores were significantly associated with a lower ghrelin level ( p  ≤ .04). The multivariate regression disclosed that only the chronic inflammation score independently related to a lower ghrelin level. Only in males, the ghrelin levels ranked in a downward trend for the gastritis feature as with limited-gastritis, with antrum-predominant gastritis, and with corpus-gastritis (1236, 1101, and 977 pg/mL). Leptin level was not related to H. pylori -related gastritis, but positively related to body mass index.
Conclusion:  There should be a gender difference to circulating total ghrelin levels, but not leptin levels, in response to H. pylori infection and its related chronic gastritis.     

Organ-specific autoantibodies in children with Helicobacter pylori infection

BACKGROUND: We compared the prevalence of organ-specific autoantibodies in a group of Helicobacter pylori infected children and a group of uninfected children and investigated the relationship between the presence of relevant autoantibodies and the status of the target organs. PATIENTS AND METHODS: One hundred and twenty-four children with dyspepsia (54 boys, 70 girls; mean age 10.5 years; range 4-19) underwent gastroscopy: 56 had H. pylori infection (31 girls, 25 boys), while 68 (37 girls and 31 boys), were H. pylori-negative. All sera were tested for the presence of: parietal cell autoantibodies (PCA), intrinsic factor autoantibodies (IFA), microsomial autoantibodies, thyroglobulin autoantibodies, islet cell autoantibodies, glutamic acid decarboxylase autoantibodies, adrenal cortex autoantibodies, steroid-producing cell autoantibodies; gastrin, pepsinogen A, pepsinogen C and anti-H. pylori antibodies. The histological features and the ureA and cagA genes were also considered. RESULTS: The frequency of organ-specific autoantibodies was higher in patients with H. pylori infection than in uninfected patients (chi2-test p < .0001). Specifically gastric autoantibodies were significantly higher: seven of the 56 H. pylori-positive children were PCA-positive and one was IFA-positive (chi2-test p = .0004). The presence of autoantibodies was not associated with any clinical or biohumoral signs of disease. CONCLUSIONS: Our study detected a relationship between H. pylori infection in childhood and the presence of organ-specific autoantibodies unassociated with any clinical or biohumoral signs of disease. Helicobacter pylori infection in childhood could trigger the onset of clinical autoimmune gastritis, and/or other clinical autoimmune diseases.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Asymptomatic Helicobacter pylori infection increases asymmetric dimethylarginine levels in healthy subjects

BACKGROUND: Chronic infections have been demonstrated to be early factors of atherosclerosis and cardiovascular diseases, and their relevance increases when they are caused by agents with extremely broad spectrum of disease outcome such as Helicobacter pylori. The consequent endothelial impairment leads to a reduced bioavailability of nitric oxide. Increasing evidences have pointed out that the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine, defined as a risk factor for cardiovascular disease, may increase in infections and plays an important role impairing the vascular functions of the endothelium. Starting from these findings, we aim to investigate whether H. pylori may affect asymmetric dimethylarginine levels. MATERIALS AND METHODS: The study was carried out on a group of 186 subjects (age 46.2 +/- 14.9 years). We evaluated asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine, presence of H. pylori by 13C-urea breath test, and the main parameters of glyco and lipo metabolic balance. RESULTS: Increased levels of asymmetric dimethylarginine were found in H. pylori-positive subjects with respect to H. pylori-negative subjects (0.46 x/ / 1.13 versus 0.42 x/ / 1.23 mol/l, p < .001, respectively). No differences were detected in L-arginine levels between the two groups. Multiple regression analysis performed in H. pylori-positive subjects and H. pylori-negative subjects showed profound differences in the variables related to asymmetric dimethylarginine (R2 = 66.9%, p < .01 versus 34.3%, p < .01, respectively) and symmetric dimethylarginine (R2 = 39.2%, p < .01 versus 20.6%, p = .09, respectively) levels. CONCLUSIONS: Our data clearly demonstrate that H. pylori infection increases asymmetric dimethylarginine levels. Moreover, this infection causes a profound metabolic modification that alters the role of the known determinants of asymmetric dimethylarginine levels. We conclude that H. pylori infection must be taken into account as a cause of increased asymmetric dimethylarginine levels and that the eradication of H. pylori may therefore lead to a decrease in asymmetric dimethylarginine levels, which is a further reason for the reduction of the risk for cardiovascular disease in this large portion of population.     

Involvement of Helicobacter pylori infection and impaired glucose metabolism in the increase of brachial-ankle pulse wave velocity

BACKGROUND: The role of Helicobacter pylori in the pathogenesis of atherosclerosis remains controversial. The present study was designed to elucidate the pathogenic role of H. pylori in the early stages of atherosclerosis by measurement of brachial-ankle pulse wave velocity (baPWV) in relation to glucose metabolism. MATERIALS AND METHODS: baPWV level, anti-H. pylori antibody, fasting blood glucose (FBG), and glycosylated hemoglobin A1c (HbA1c) and other conventional risk factors for cardiovascular diseases were measured in 947 subjects who attended their annual medical check-up. RESULTS: Multiple regression analyses indicated that age, gender (male), body mass index, FBG, systolic blood pressure, and smoking habits were each independently related to baPWV values. In younger subjects (30-49 years), H. pylori seropositivity was significantly correlated with an increase of baPWV levels (r = 0.100, p = .0445). baPWV values in the H. pylori-positive subjects with impaired glucose metabolism (IG: FBG >or= 110 mg/dL and/or HbA1c >or= 5.9%) were significantly greater than those in the H. pylori-negative subjects with IG (p = .0078). Furthermore, H. pylori-positive subjects with IG were at higher risk for increase of baPWV, in younger (r = 0.203, p < .0001) as well as in older subjects (50-69 years, r = 0.099, p = .0009). CONCLUSIONS: These results suggest that H. pylori seropositivity is a potential risk factor for increased baPWV levels, and that H. pylori infection accelerates the effect of IG on an increase of baPWV, especially in younger subjects. Thus, the possible interaction between H. pylori infection and IG may contribute to the early development of atherosclerosis.     

Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori

This case control study presents data on the concentrations of nitrite and nitrate and a variety of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with gastritis, gastric ulcer and gastric cancer are studied and grouped according to infection by Helicobacter pylori. The 208 patients who underwent upper gastrointestinal endoscopic examination were classified as follows; H. pylori-positive gastritis (n = 32), H. pylori-negative gastritis (n = 32), H. pylori-positive ulcers (n = 34), H. pylori-negative ulcers (n = 34), 43 patients with H. pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy control individuals. Gastric fluids and blood samples were taken concomitantly. Cytokines and nitrite and nitrate determinations were attempted as soon as possible after collection of the samples. Nitrite and nitrate levels of serum and gastric fluids of H. pylori-positive gastritis and ulcers were higher than H. pylori-negative gastritis and ulcers. The concentrations of total nitrite and nitrate and cytokines (TNF-alpha, IL-2R, IL-6, and IL-8) in gastric fluids and sera of H. pylori-positive gastric cancer patients were higher than H. pylori-negative control groups. IL-1 beta level was significantly elevated in gastric fluid of infected cancer patients but not in serum. Taken together, the results suggest that an increase in cytokine-NO combination in gastric mucosa previously reported by many studies is not restricted to local infected gastric tissue but also detected in gastric fluid and sera of H. pylori-positive subjects and may have an important role in the pathogenesis and development of common gastric diseases.     

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.     

Helicobacter pylori-induced immunological responses in patients with duodenal ulcer and in patients with cardiomyopathies

The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease. The mucosal production of TNF-alpha, IL-6, IL-8 and IL-10 and the CagA status were investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antral mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). The local TNF-alpha, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H. pylori-positive (58 of 100) healthy blood donors. In complementary studies focusing on extragastric disease, it was found that 57% of patients with ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them had antibodies against human heat shock protein 60, too. This study suggests that, besides the bacterial virulence factor, the host response of an increased mucosal production of inflammatory cytokines can be relevant to the gastric pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart diseases the role of autoimmune processes induced by H. pylori cannot be excluded.     

Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura

BACKGROUND: Improvement in platelet counts has been reported after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura (ITP). We examined the levels of serum markers of gastritis and anti-CagA (cytotoxin-associated gene A) IgG antibody in patients with ITP to investigate whether these factors are associated with the platelet response after H. pylori eradication therapy. MATERIALS AND METHODS: One hundred and sixteen consecutive patients with ITP were assessed for H. pylori infection by (13)C-urea breath test and serum H. pylori antibody test. Patients with H. pylori infection received eradication therapy. Before and after eradication therapy, we evaluated serum levels of gastrin, pepsinogen (PG)-I, and PG-II and the anti-CagA IgG antibody titer. RESULTS: H. pylori infection was found in 67 (58%) of the 116 patients with ITP. Fifty-two infected patients received eradication therapy, which was successful in 44 patients (85%). Twenty-seven patients (62%) showed an increased platelet count and were identified as responders. The duration of ITP was shorter in responders than in nonresponders (p = .017). There was no difference of the levels of gastrin and PGs between responders and nonresponders. Before eradication therapy, the serum anti-CagA antibody titer did not differ significantly between responders and nonresponders. However, reduction in the anti-CagA antibody titer after eradication therapy was significantly greater in responders than in nonresponders (p = .013). CONCLUSIONS: H. pylori eradication therapy improves the platelet count in H. pylori-positive patients with ITP of short duration. Immune response of hosts to CagA protein of H. pylori may play a role in the pathogenesis of ITP.     

Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication

BACKGROUND: Helicobacter pylori infection has been reported to cause gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Recent studies have suggested that H. pylori infection may also associate with other diseases, including hematologic and dermatologic disorders, and cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive oxygen species (ROS) was determined in peripheral blood samples from 86 patients (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d) pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were also analyzed their ROS production in peripheral blood after H. pylori eradication. RESULTS: ROS production was significantly higher in individuals with H. pylori infection than in those without infection. Enhanced production of ROS was decreased significantly after eradication of H. pylori. No correlation was found between the extent of ROS production and sex, age, smoking status, alcohol ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION: These findings suggest that ROS production was enhanced in peripheral blood by H. pylori infection. Chemiluminescence analysis of blood samples using L-012 permits evaluation of systemic oxidative stress in patients with H. pylori infection.     

Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.     

幽门螺杆菌感染与血浆obestatin水平的关系研究

目的：obestatin是新发现的与肥胖相关的多肽,本研究探讨幽门螺杆菌（H．pylori）对体重指数（BMI）~LM浆obestatin水平的影响。方法：于我院体检中心入选健康体检者205例,所有入选者无明确的胃肠疾病史,无心脏、肾脏、肝脏、甲状腺等疾病病史,无急性感染等其他可能影响激素水平的因素。幽门螺杆菌的感染依据l3C呼气实验及血清学指标联合判定。应用放射免疫分析法测定血浆obestatin及血清胰岛素水平。血清血脂水平采用自动生化分析仪进行酶法测定。胰岛素抵抗采用胰岛素抵抗指数（HOMA-IR）评定,HOMA—IR=空腹胰岛素（p~IU／ml）x空腹血糖（mmol／L）／22．5。结果：在我们的75例研究对象中H．pylori阳性的检出率为39％,幽门螺杆菌感染阳性者与阴性者相比,体重指数（BMI）差异并无统计学意义,血浆obestafin水平无显著性的差异。按体重指数进行分组,BMI〉24kg／m2组与BMI〈24kg／m2相比血浆obestatin水平明显下降。结论：H．pylori的感染状态并没有显著影响个体的循环obestatin水平。BMI对血浆obestatin水平有影响。     

Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). Nitrotyrosine was determined by ECL Western blotting. It was additionally investigated whether the tissue levels of the cytokines correlated with the peripheral cytokine levels, and the CagA status of the patients. The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. There was a negative correlation between the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy specimens, considerable nitrotyrosine production was detected by ECL Western blotting. There was no significant difference in peripheral TNF-a and IL-6 production between the DU patients and healthy blood donors (n = 100; 58% of whom were also H. pylori-positive). Only the in vitro IL-8-producing capacity was higher in the peripheral blood of the DU group after ex vivo induction with H. pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This study suggests that besides the bacterial virulence factor, the host response, with an increased mucosal production of inflammatory cytokines and reactive oxygen and nitrogen species could be relevant to the gastric pathophysiology in H. pylori-induced DU. There is no generalized cytokine overproduction in these DU patients, but the moderate increase in in vitro IL-8 production might be of pathophysiological importance.     

Toll-like receptor (TLR2, TLR4 and TLR5) gene polymorphisms and Helicobacter pylori infection in children with and without duodenal ulcer

Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. Our aim was to investigate whether TLR4, TLR2, and TLR5 polymorphisms were associated with H. pylori susceptibility and risk for duodenal ulcer in children. Gastric biopsy specimens were obtained at endoscopy for evaluation of H. pylori status, TLR4, TLR2 and TLR5 polymorphisms from 486 children (254 H. pylori-negative and 232 H. pylori-positive: 72 with and 160 without duodenal ulcer). cagA status of H. pylori infection was investigated by PCR. The levels of gastric cytokines were detected by ELISA. H. pylori-positivity or duodenal ulcer were not associated with TLR2, TLR4 or TLR5 polymorphisms. Otherwise, the presence of TLR4 polymorphic allele was associated with infection by cagA-positive strains and with increased gastric levels of interleukin-8 and interleukin-10. TLR4 polymorphism might ultimately contribute to more severe consequences of the infection in adulthood since it was associated with susceptibility to cagA-positive H. pylori infection early in life.     

Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytokines which may improve knowledge concerning the outcome of gastric diseases caused by H. pylori. Antral biopsies from 42 dyspeptic patients including 27 H. pylori-positive and 15 H. pylori-negative patients were tested for apoptotic activity by the TUNEL assay, and immuno-histochemically for p53 and the proliferative marker Ki-67. H. pylori infection, bacteria load and inflammatory activity were associated with increased cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53 was significantly correlated to IFN-gamma, IL-8 and IL-10. The H. pylori-positive state was furthermore accompanied by varying degrees of altered distribution pattern of the markers studied, with occasional presence of apoptosis in the deeper pit zones, upward extension of Ki-67 and to a lesser degree of p53. Given a similar pattern of change in proliferation and apoptosis in some neoplastic lesions in other parts of the gastrointestinal tract, such studies in cell turnover may provide insights valuable in the investigations of potential precursors of gastric malignancies.     

Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents

Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa (AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone (GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min (from 2000 to 0800) in 23 AN and 21 controls 12-18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls (P < 0.0001) subsequent to decreased burst mass (P < 0.0001) and basal secretion (P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/creatinine (15% of variability). Valley leptin predicted cortisol half-life (22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition.     

CagA and VacA are immunoblot markers of past Helicobacter pylori infection in atrophic body gastritis

BACKGROUND AND AIM: Atrophic body gastritis (ABG) may be induced by H. pylori infection. It is difficult to diagnose H. pylori infection in this condition, since during progression of body atrophy the bacterium disappears. In 30% of patients with ABG no sign of H. pylori infection is detectable. We aimed to investigate whether patients with ABG, classified as H. pylori-negative by conventional methods (ELISA serology and Giemsa stain histology), have been previously exposed to the infection. METHODS: Case series consisted of 138 outpatients with ABG, of whom 31 are H. pylori negative (histology and ELISA serology), and 107 are H. pylori related (histology and ELISA serology positive: active infection, n = 29; only serology positive: past infection, n = 78). Thirty control subjects who were H. pylori negative at histology and ELISA serology were investigated. Immunoblotting of sera against H. pylori whole-cell protein lysate was performed. RESULTS: None of the control sera recognized CagA, VacA, heat-shock protein B, and urease B, yielding a specificity of 100%. All H. pylori-negative patients with ABG showed immunoblotting seroreactivity, including in each case either CagA or VacA. The concomitant seroreactivity against CagA and VacA was highly prevalent in the H. pylori-negative patients with ABG, comparable to those with active infection (77.4% vs. 86.2%) and with past infection (vs. 61.5%). CONCLUSIONS: Immunoblotting against CagA and VacA is able to prove past exposure to H. pylori infection in all patients with ABG defined as H. pylori-negative by conventional methods, suggesting a hidden role of H. pylori infection in gastric atrophy also in these patients.     

Intrafamilial transmission of Helicobacter pylori among the population of endemic areas in Japan

BACKGROUND: Helicobacter pylori (H. pylori) infection is a worldwide phenomenon related to several gastrointestinal diseases. However, because many aspects concerning the route of transmission remain unclear, we performed this epidemiologic study to clarify the route of intrafamilial transmission of H. pylori. MATERIALS AND METHODS: A retrospective study was performed in three widely separate areas in Japan to investigate the prevalence of H. pylori infection. In 1993, 613 residents were tested as were 4136 in 2002, including 1447 family members of 625 families. Antibody to H. pylori (anti-H. pylori) was determined by enzyme-linked immunosorbent assay. RESULTS: In 2002, the age-adjusted anti-H. pylori prevalence in Hoshino Village (67.5%) was significantly higher than in Kasuya Town (55.0%) and in Ishigaki City (54.7%) (p < .0001, p = .0039, respectively). The age-adjusted anti-H. pylori prevalence of Ishigaki City significantly decreased from 1993 (68.4%) to 2002 (52.5%), showing an age cohort effect. However, the prevalence did not significantly differ in children aged 0-6 years of Ishigaki City between 1993 (9.6%) and 2002 (10.3%). A familial analysis in 2002 demonstrated that the prevalence of anti-H. pylori was significantly higher in children with anti-H. pylori-positive (21.6%, 22 of 102) than with -negative mothers (3.2%, 3 of 95) (p < .0001, by Mantel-Haenszel test), whereas there was no significant difference between children with anti-H. pylori-positive and -negative fathers. Moreover, the prevalence was significantly higher in wives with anti-H. pylori-positive (64.0%, 208 of 325) than with -negative husbands (46.5%, 80 of 172) (p = .0071, by Mantel-Haenszel test) and in husbands with anti-H. pylori-positive (72.2%, 208 of 288) than with -negative wives (56.0%, 117 of 209) (p = .0106, by Mantel-Haenszel test). CONCLUSIONS: In the last decade, H. pylori infection decreased in the general population of Japan by improvement of general hygiene conditions, but did not differ in young children, most likely because of mother-to-child transmission.