Helicobacter pylori infection is associated with reduced circulating ghrelin levels independent of body mass index

BACKGROUND: Ghrelin stimulates growth hormone and has orexigenic and adipogenic effects. Plasma ghrelin levels are reduced in obesity and possibly in Helicobacter pylori infection. AIM: To investigate whether there was a relation between H. pylori infection, body mass index (BMI) and serum ghrelin or leptin levels. METHODS: University students undergoing an annual health check-up were invited to participate. H. pylori status was based on the presence of specific IgG H. pylori antibodies in urine. Fasting serum ghrelin, leptin levels, and pepsinogen I and II levels were measured by enzyme immunoassay (EIA). RESULTS: Eight hundred and one students volunteered. There was no significant difference in the height and BMI between those with and without H. pylori infection. The population of ghrelin study consisted of 132 (66 H. pylori-positive and 66 H. pylori-negative) students matched for age, sex, and BMI. The ghrelin level in the H. pylori-positive group was significantly lower (median 55 pmol/l) compared to the H. pylori-negative group (103 pmol/l) (p < .00001). Leptin, triglyceride, total cholesterol, and HDL-cholesterol were not different between the two groups, whereas LDL-cholesterol levels were significantly higher (106 versus 100 mg/dl) (p = .03) in the H. pylori-positive group. Leptin levels correlated with the BMI (r = 0.53) (p < .00001). Among H. pylori-positive subjects, ghrelin correlated only with pepsinogen I levels (r = 0.26, p = .04). CONCLUSIONS: H. pylori infection was associated with a reduction in circulating ghrelin levels independent of sex and BMI.     

Host Single Nucleotide Polymorphisms of MMP-9 −1562/TIMP-1 372 Have Gender Differences in the Risk of Gastric Intestinal Metaplasia After Helicobacter pylori Infection

Background:  Helicobacter pylori infection causes chronic gastric inflammation and intestinal metaplasia (IM), related with deregulation of Wnt pathway and over-expressions of COX-2, matrix metalloproteinase (MMP), and tissue inhibitors of matrix metalloproteinase (TIMP). We thus test the host genomic predispositions related to the risk of IM after H. pylori infection.
Methods:  We enrolled 296 H. pylori -infected patients to provide gastric biopsies for histology and genomic DNA for genotypes of single nucleotide polymorphisms (SNPs), including APC , COX-2 , IL-1B , IL-1RN , IL-10 , MMP-2 , MMP-9 , TIMP-1 , and TIMP-2 determined by sequence specific oligonucleotide probe, sequence specific primers, restriction fragment length polymorphism, or real-time polymerase chain reaction.
Results:  There was no association between the presence of IM and SNPs in APC , COX-2 , IL-1B , IL-1RN , IL-10 , MMP-2 , and TIMP-2 . The risk of IM was increased up to 2.29-folds in males with TIMP-1 372 C, and 3.03-fold in females with T carrier ( p  < .05). The combination genotype of MMP-9 − 1562/ TIMP-1 372 as CC/C and CT/T in males had a 4.5-fold increased risk of IM, as compared to CC/T ( p  < .05). Females with such combination genotype as CC/T-carrier had a 3-fold risk of IM than males with CC/T ( p  < .05). In contrast, males' combination genotype as CC/C had a 3-fold risk of IM than females with CC/CC ( p =  .05).
Conclusions:  The host MMP-9 − 1562/ TIMP-1 372 SNPs had gender differences in the risk of IM after H. pylori infection, and could possibly serve as a host factor to identify the risk group harboring gastric precancerous changes after H. pylori infection.     

Functional Role of Metaplastic Paneth Cell Defensins in Helicobacter pylori-Infected Stomach

Background and Aims:  Chronic gastritis is caused by Helicobacter pylori infection, and gastritis is classified as inflammation, atrophy, and intestinal metaplasia. Detailed pathologic studies have shown that H. pylori settles on the surface of gastric mucosa, and that it is eliminated from metaplastic mucosa. However, its mechanism of natural protection is not well known.
Methods:  Antimicrobial human enteric defensin expression was determined in the RNA and protein levels. Recombinant enteric defensins were produced with a bacterial expression system and their anti- H. pylori activities were assessed by bactericidal assay.
Results:  Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. HD-5 protein was coexpressed with trypsin, which is considered to be an activating enzyme of HD-5. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. The recombinant defensins showed killing activity against H. pylori at a low concentration in vitro.
Conclusions:  The human defensins that are expressed in the metaplastic Paneth cells eliminate H. pylori . Metaplastic change may be a purposive development of the human stomach.     

Reactive Nitrogen Species Mediate DNA Damage in Helicobacter pylori-Infected Gastric Mucosa

Background:  Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori . 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells.
Methods:  Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori -positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system.
Results:  In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa ( p  = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG ( p  = .004 and .007, respectively).
Conclusions:  Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori -induced DNA damage in gastric mucosa.     

Comparison of a Stool Antigen Test and Serology for the Diagnosis of Helicobacter pylori Infection in Mass Survey

Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non-invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey.
Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori- specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori , and the level of PGs I and II was also measured to determine the presence of atrophic gastritis.
Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p  < .05) in 303 subjects with severe atrophic gastritis.
Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori , would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined.     

Helicobacter pylori Infection and Family History of Gastric Cancer Decrease Expression of FHIT Tumor Suppressor Gene in Gastric Mucosa of Dyspeptic Patients

Background:  The expression of a fragile histidine triad (FHIT) protein is lost in stomach tumors. The study aimed at determining whether FHIT expression is affected by Helicobacter pylori infection, strain virulence ( vacA and cagA genes) and histopathological changes in the gastric mucosa of patients with functional dyspepsia having first-degree relatives with gastric cancer.
Materials and Methods:  Eighty-eight never-smoking patients with functional dyspepsia were selected for the study, and 48 of them had first-degree relatives with gastric cancer. Bacterial DNA amplification was used to identify H. pylori colonization. The level of FHIT gene expression was determined by qRT-PCR (mRNA) and Western blot (FHIT protein) analyses.
Results:  For patients having first-degree relatives with gastric cancer FHIT expression was lower (mRNA by ca. 40–45% and protein by 30%) compared with the control patients ( p  < .05). H. pylori infection decreased the FHIT mRNA level by 10–35% and the protein level by 10–20%. Bacterial strain vacA (+) cagA (+) lowered FHIT mRNA by ca. 30–35% in the antrum samples of both groups and in corpus samples of patients with first-degree relatives with gastric cancer ( p  < .05). The FHIT mRNA level was twice as high in control H. pylori- negative patients with intestinal metaplasia, compared with those with non-atrophic gastritis.
Conclusions:  The decreased FHIT gene expression associated with hereditary factors and with H. pylori infection, especially with vacA (+) cagA (+)-positive strains, may be related to gastric carcinoma development.     

Effect of cagA status on the sensitivity of enzyme immunoassay in diagnosing Helicobacter pylori-infected children

Background. The aims of our study were twofold. First, we sought to evaluate in symptomatic children the influence of the Helicobacter pylori genotype on gastritis, abdominal pain, and circulating anti– H. pylori IgG antibodies (anti– H. pylori IgG) or pepsinogen A (PGA) and C (PGC). Additionally, we sought to assess anti– H. pylori IgG, PGA, and PGC patterns in a large cohort (N = 921) of asymptomatic children.
Materials and Methods. In 183 symptomatic children, H. pylori infection and the presence of gastritis were evaluated by histology. In a subgroup of 20 H. pylori –positive children, the H. pylori genotype was evaluated also by polymerase chain reaction. Nine hundred and twenty-one asymptomatic children, aged 11 to 14 years, were studied by anti– H. pylori IgG, PGA, and PGC serum determination.
Results. The infection was found in 33 of 183 symptomatic children; among the 20 H. pylori –positive children for which the H. pylori genotype was available, cag A was present or absent in equal percentages. H. pylori infection was associated with more severe gastritis and higher serum levels of anti– H. pylori IgG and PGC but not with abdominal pain. In infected children, higher levels of anti– H. pylori IgG and the presence of abdominal pain were associated with infections caused by cag A-positive strains. In the cohort of 921 asymptomatic children, raised levels of anti– H. pylori IgG, PGA, and PGC were found in approximately 5% of the cases.
Conclusions. Infection with cag A-positive H. pylori strains can be associated with increased frequency of reported abdominal pain and higher circulating levels of anti– H. pylori IgG. The serological assessment of H. pylori IgG using H. pylori antigens containing significant amounts of cagA protein may, therefore, underestimate the true prevalence of infection.     

Atrophic Changes of Gastric Mucosa Are Caused by Helicobacter pylori Infection Rather Than Aging: Studies in Asymptomatic Japanese Adults

Background. The current study was designed to evaluate the effect of aging and Helicobacter pylori infection on the gastric mucosa in asymptomatic Japanese adults.
Materials and Methods. Eighty-five asymptomatic healthy adults were recruited from a health-screening center in Sapporo. All subjects underwent endoscopy and gastric biopsy, and serum was obtained for IgG antibodies to H. pylori , serum gastrin, and pepsinogen levels.
Results. The prevalence of atrophic change of the gastric mucosa assessed by pathological findings increased with age (49% in the 30- to 39-year-old group compared to 89% in those 60 years and older, p < .001). The frequency of intestinal metaplasia also increased with age (38% in the 30- to 39-year-old group compared to 82% in those 60 years and older, p < .001). In contrast, the frequency of atrophic gastritis and intestinal metaplasia was extremely low in the H. pylori seronegative group regardless of age. Mean serum gastrin level in H. pylori -positive adults was significantly greater than in those who were H. pylori -negative (114.3 ± 11.2 compared to 65.8 ± 6.5 pg/ml, p < .03). The serum pepsinogen I-II ratio was significantly lower in those with H. pylori infection than in those without (3.1 compared to 6.6, p < .0001).
Conclusions. These results suggest that the chronological changes in the gastric mucosa in Japanese individuals are either entirely related to H. pylori infection or the process is greatly accelerated by H. pylori infection.     

A Population-Based Epidemiologic Study of Helicobacter Pylori Infection and its Association with Systemic Inflammation

Background:  Infection with Helicobacter pylori is associated with a variety of non-gastrointestinal sequelae. These may be mediated by an increase in systemic inflammation. We assessed if serologic evidence of infection with H. pylori is associated with increased serum C-reactive protein (CRP) levels.
Methods:  The study design consisted of a randomly selected, cross-sectional population-based study of 2633 individuals phenotyped in 1991, of whom 2361 participants provided serum samples to permit measurement of H. pylori 's serologic status and CRP levels.
Results:  Male gender (odds ratio (OR): 1.65; 95% confidence interval (CI): 1.23–2.21), age (OR per year: 1.05; 95% CI: 1.04–1.06), height (OR per meter: 0.05; 95% CI: 0.01–0.24), current smoking habit (compared with never smokers, OR: 1.46; 95% CI: 1.13–1.88), and less affluent socioeconomic status were associated with increased odds of being seropositive for H. pylori . Helicobacter pylori infection was associated with increased risk of having an elevated serum CRP (above 3 mg/L) after adjustment for gender, age, height, smoking status, and socioeconomic status (OR: 1.32; 95% CI: 1.05–1.67). Similar associations were seen using a threshold for elevated serum CRP of greater than 1 mg/L.
Conclusions:  Our data suggest that infection with H. pylori is associated with increased systemic inflammation. This suggests one potential mechanism to explain the extra-gastrointestinal conditions associated with H. pylori infection.     

NMR-based metabonomics for detection of Helicobacter pylori infection in gerbils: which is more descriptive

Background:  Helicobacter pylori , the human pathogenic gram-negative microaerophilic bacterium, causes chronic gastric infection in more than half of the human population regardless of race. The infection of microbe is not yet controllable to pose a substantial public health impact and a growing social burden. The management of H. pylori infection primarily necessitates accurate and timely diagnosis at case level, on-demand supervision of pathologic progression, and reliable evaluation of the impact of pharmacologic interventions on the patients' population.
Methods:  The characterization of H. pylori infection on gerbils model was performed by metabolic profiling, employing ¹H NMR spectroscopy compounding multivariate pattern recognition strategies. In the same manner, urine samples were individually collected from 10 gerbils infected with H. pylori GS13, and from 10 uninfected control animals equally accessible to feed and water.
Results:  The resultant metabolic profiles indicate that H. pylori infection disturbs carbohydrate metabolism to elevate the levels of α- and β-glucose, and cis -aconitate (a TCA cycle intermediate). In addition to the energy metabolism alteration, the colonization of H. pylori in gerbil stomach generates a remarkable deviation of amino acid metabolism as indicated by depletion of taurine and arginine, and elevation of proline and glutamine in the animal urine. Moreover, the H. pylori infection modifies the gut microbiota as highlighted by a range of microbial-related metabolites such as indoxyl sulfate and hippurate.
Conclusions:  These findings demonstrate that the ¹H NMR-based urine metabolic profiling is a promising technique capable of providing an accurate, noninvasive, and rapid diagnosis of H. pylori infection.     

Role of Helicobacter pylori Infection in the Treatment and Outcome of Chronic Urticaria

Introduction:  Chronic urticaria is thought to have numerous causative factors including a large variety of infectious conditions, food intake, and drugs. The impact of Helicobacter pylori infection has been studied with ambiguous results. The aim of this study was to investigate the course of chronic urticaria in H. pylori -positive patients undergoing eradication compared to H. pylori -negative urticaria patients.
Patients and Methods:  We included 74 urticaria patients with positive H. pylori breath test and 74 age- and sex-matched H. pylori -negative controls. All urticaria patients underwent an extensive diagnostic work-up to search for trigger foci. H. pylori -infected patients were submitted to eradication therapy. Mean follow-up time was 58 months.
Results:  Neither the prevalence of H. pylori nor the eradication therapy had an influence on the clinical course of chronic urticaria. In 81.1% of H. pylori -infected patients at least one additional infectious focus was found. Nevertheless, it could be shown that individuals that described any kind of symptom relief presented with higher serum IgE levels at diagnosis (198.1 vs 115.7 kU/L, p = .027) but this effect was independent of H. pylori infection.
Conclusions:  In conclusion there is no evidence that eradication of H. pylori improves the outcome in patients with chronic urticaria. The high rate of spontaneous remission and the coexisistance of multiple foci will always obscure the evaluation of any specific antimicrobial therapy.     

Prevalence and risk factors for Helicobacter pylori infection in Chinese populations

Background:  The prevalence of Helicobacter pylori is higher in developing countries. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China.
Methods:  A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 1457 individuals in Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and laboratory tests for H. pylori infection (¹³C-urea breath test and serum IgG antibodies to H. pylori ) were used and performed, respectively.
Result:  Among 1371 subjects who completed questionnaires and H. pylori detection, 851 (62%) were H. pylori positive. The prevalence reached a peak at the age of 30–40 years (67%). There was no sex difference. The annual family income level was shown to be positively correlated with the risk of H. pylori infection. The prevalence of H. pylori infection was also associated with family size, education level, and several diet-related factors, such as the number of times cooked rice and potatoes eaten per week, and a family history of stomach diseases. Compared to nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and belching) presented a low prevalence of H. pylori infection. No association between H. pylori prevalence and smoking or drinking was found. Using multivariate logistic regression analysis, annual family income and education level were the independent predictors for H. pylori infection.
Conclusion:  High prevalence of H. pylori infection was found in areas with a high risk of gastric cancer and was related to several risk factors. The underlying mechanisms need to be further investigated.     

Sex-associated differences in the leptin and ghrelin systems related with the induction of hyperphagia under high-fat diet exposure in rats

Leptin and ghrelin are known to be main hormones involved in the control of food intake, with opposing effects. Here we have explored whether changes in the leptin and ghrelin system are involved in the long-term effects of high-fat (HF) diet feeding in rats and whether sex-associated differences exist. Male and female Wistar rats were fed until the age of 6 months with a normal-fat (NF) or an HF-diet. Food intake and body weight were followed. Gastric and serum levels of leptin and ghrelin, and mRNA levels of leptin (in stomach and adipose tissue), ghrelin (in stomach), and NPY, POMC, and leptin and ghrelin receptors (OB-Rb and GHS-R) (in the hypothalamus) were measured. In both males and females, total caloric intake and body weight were greater under the HF-diet feeding. In females, circulating ghrelin levels and leptin mRNA expression in the stomach were higher under HF-diet. HF-diet feeding also resulted in higher hypothalamic NPY/POMC mRNA levels, more marked in females, and in lower OB-Rb mRNA levels, more marked in males. In addition, in females, serum ghrelin levels correlated positively with hypothalamic NPY mRNA levels, and these with caloric intake. In males, hypothalamic OB-Rb mRNA levels correlated positively with POMC mRNA levels and these correlated negatively with caloric intake and with body weight. These data reflect differences between sexes in the effects of HF-diet feeding on food intake control systems, suggesting an impairment of the anorexigenic leptin-POMC system in males and an over-stimulation of the orexigenic ghrelin-NPY system in females.     

Prevalence of Helicobacter pylori Infection and Identification of Risk Factors in Rural and Urban Beijing, China

Background:  The prevalence of Helicobacter pylori is higher in developing countries such as China. The aim of this study was to investigate the prevalence of H. pylori in one rural and one urban region of Beijing, China.
Materials and Methods:  Healthy individuals in rural Pinggu and urban Haidian voluntarily participated in this study. The diagnosis of H. pylori infection was reached using the ¹³C-urea breath test. Associations between H. pylori and sex, age, living area (i.e. rural vs urban), education level, smoking, and alcohol consumption were evaluated.
Results:  Of the 1232 included subjects, 54.7% of tested individuals residing in Pinggu and 41.3% in Haidian were positive for H. pylori . In urban region, more individuals were negative for H. pylori (429 of 731), whereas in the rural region, more individuals were positive for H. pylori ( p <  .05). Univariate analysis identified geographic area and lower education and annual income as significant factors associated with H. pylori . Men in rural areas were more likely than women in rural areas to be infected, and both men and women in the rural area were more likely to be positive for H. pylori than men and women in the urban area (all p  < .05).
Conclusions:  H. pylori infection is common in both rural and urban regions of Beijing. Residing in a rural area, having a lower family income, and lower education level are significant risk factors associated with infection.     

Circulating T-cell response to Helicobacter pylori infection in chronic gastritis

Background. Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection.
Materials and Methods. The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE).
Results. The proliferative response in whole-blood cultures was similar for both H. pylori –positive and –negative subjects stimulated with H. pylori AGE. While an increase in interferon-γ (IFN-γ) production was observed from both H. pylori –positive and –negative subjects with gastritis, significantly higher levels of IFN-γ were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori –positive and –negative subjects with gastritis. After eradication of H. pylori , antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-γ. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4.
Conclusion. The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance.     

Effect of Helicobacter pylori Eradication on Incidence of Gastric Cancer in Human and Animal Models: Underlying Biochemical and Molecular Events

Background:  Gastric cancer remains one of the most common cancers worldwide. A strong association exists between Helicobacter pylori infection and the risk of developing noncardia gastric cancer. H. pylori eradication by antibiotic treatment is regarded as a primary chemoprevention strategy to reduce gastric cancer incidence.
Aim:  To analyze the efficacy of H. pylori eradication in preventing gastric cancer in human and animal models, and to discuss whether biochemical, genetic, and epigenetic changes associated with H. pylori infection are reversible after curing the infection.
Results:  Several intervention trials have indicated that in some patients, H. pylori eradication leads to regression and prevents the progression of precancerous lesions. The eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. A few recent intervention studies in Japan have demonstrated significant prophylactic effects of eradication therapy on the development of gastric cancer, suggesting the use of eradication therapy in high-risk populations as a gastric cancer reduction strategy. However, gastric cancer may still develop despite successful eradication therapy. Studies in animal models have confirmed the use of eradication therapy at an early point of infection to prevent gastric cancer development.
Conclusion:  H. pylori eradication may not completely abolish the risk of gastric cancer. However, eradication therapy may be used in high-risk populations to reduce gastric cancer incidence. It can reverse many biochemical, genetic, and epigenetic changes that H. pylori infection induces in the stomach.     

The Influence of Helicobacter pylori Status on Circulating Levels of the Coagulation Factors Fibrinogen, von Willebrand Factor, Factor VII, and Factor VIII

Background. Helicobacter pylori (H. pylori) infection has been associated with an increased risk of developing ischemic heart disease (IHD). It has been suggested that a persisting low-grade acute phase response results from the chronic inflammation caused by H. pylori infection, which may give rise to increased circulating levels of certain coagulation factors.
Materials and Methods. One hundred three (53 male) nonconsecutive, randomly selected white subjects with symptoms of dyspepsia were recruited for study from an outpatient endoscopy clinic at Leeds General Infirmary. The presence of H. pylori was determined by histological and microbiological investigation, a rapid urease test, and a ¹³carbon urea breath test (¹³C-UBT). Fibrinogen was measured by the Clauss method, factor VIII:C (FVIII:C) and factor VII:C (FVII:C) were measured by clotting rate assays, and the von Willebrand factor (vWF) was determined by an enzyme-linked immunosorbent assay.
Results. No difference was found in levels of coagulation factors according to H. pylori status. Multiple regression models were used to account for the effect of covariates and H. pylori status on levels of FVII:C, FVIII:C, vWF, and fibrinogen, and again H. pylori status was not a significant determinant of levels of any of these coagulation factors. No difference occurred in full blood count, platelet count, white cell count, or plasma viscosity in individuals who were H. pylori -positive compared with those who were negative.
Conclusions. H. pylori infection is not associated with increased circulating levels of fibrinogen, FVII:C, vWF.Ag, or FVIII:C or hemorrheology in this patient group.     

Four modes of adhesion are used during Helicobacter pylori binding to human mucins in the oral and gastric niches

Background:  Helicobacter pylori causes peptic ulcer disease and gastric cancer, and the oral cavity is likely to serve as a reservoir for this pathogen. We investigated the binding of H. pylori to the mucins covering the mucosal surfaces in the niches along the oral to gastric infection route and during gastric disease and modeled the outcome of these interactions.
Materials and Methods:  A panel of seven H. pylori strains with defined binding properties was used to identify binding to human mucins from saliva, gastric juice, cardia, corpus, and antrum of healthy stomachs and of stomachs affected by gastritis at pH 7.4 and 3.0 using a microtiter-based method.
Results:  H. pylori binding to mucins differed substantially with the anatomic site, mucin type, pH, gastritis status, and H. pylori strain all having effect on binding. Mucins from saliva and gastric juice displayed the most diverse binding patterns, involving four modes of H. pylori adhesion and the MUC5B, MUC7, and MUC5AC mucins as well as the salivary agglutinin. Binding occurred via the blood-group antigen-binding adhesin (BabA), the sialic acid-binding adhesin (SabA), a charge/low pH-dependent mechanism, and a novel saliva-binding adhesin. In the healthy gastric mucus layer only BabA and acid/charge affect binding to the mucins, whereas in gastritis, the BabA/Le^b-dependent binding to MUC5AC remained, and SabA and low pH binding increased.
Conclusions:  The four H. pylori adhesion modes binding to mucins are likely to play different roles during colonization of the oral to gastric niches and during long-term infection.     

Serum Levels of Leptin As Marker For Patients At High Risk of Gastric Cancer

Background:  Serological screening for gastric cancer (GC) may reduce mortality. However, optimal serum markers for advanced gastric precursor lesions are lacking.
Aim:  To evaluate in a case–control study whether serum leptin levels correlate with intestinal metaplasia (IM) and can serve as a tool to identify patients at high risk for GC.
Materials and Methods:  Cases were patients with a previous diagnosis of IM or dysplasia, controls were patients without such a diagnosis. All patients underwent endoscopy. Fasting serum was collected for the measurement of leptin, pepsinogens I/II, gastrin, and Helicobacter pylori . Receiver operating characteristic (ROC) curves and their area under the curve (AUC) were provided to compare serum leptin levels with other serological markers.
Results:  One hundred nineteen cases and 98 controls were included. In cases, the median leptin levels were 116.6 pg/mL versus 81.9 pg/mL in controls ( p  = .01). After adjustment for age, sex and BMI, leptin levels remained higher in cases than in controls ( p  < .005). In multivariate analysis, male sex ( p  = .002), age (<0.001), low pepsinogen levels ( p  = .004) and high leptin levels ( p  = .04) were independent markers for the presence of IM. In addition, a ROC curve including age, sex and pepsinogen I levels had an AUC of 0.79 (95% CI (0.73–0.85)). Adding serum leptin levels increased the AUC to 0.81 (95% CI (0.75–0.86)).
Conclusions:  High leptin levels are associated with an increased risk of IM. Moreover, serum leptin levels are a significant independent marker for the presence of IM. However, in combination with the serological test for pepsinogen I the additional value of serum leptin levels is rather limited.