Relationship of Helicobacter pylori infection with gastrointestinal motility

The interest of gastroenterologists in the relationship between Helicobacter pylori and gastrointestinal motility emerges from the observation that Helicobacter pylori may be involved in the pathogenesis of functional dyspepsia and that a relatively large percentage of patients with dyspepsia may show impaired gastrointestinal motility. A number of studies have been published on the interaction between Helicobacter pylori infection and gastrointestinal motility with controversial results, and, therefore, there are no definite conclusions, as yet, as to whether Helicobacter pylori is able, at all, or in which degree, to influence the motility of the upper gastrointestinal tract. Motility of the upper gastrointestinal tract has been studied in Helicobacter pylori positive and negative individuals by means of manometry, scintigraphy, radio-opaque markers or by other, recently developed, procedures such as breath tests, ultrasonography, and barostat. The vast majority of studies do not support the hypothesis that Helicobacter pylori may influence gastrointestinal motility. Nearly all these studies are, however, affected by methodological problems related to the small numbers of patients, different methodological approaches, and to the well-known difficulties in studying both gastrointestinal motility and functional dyspepsia.     

Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans

Galanin was infused intravenously in 8 healthy volunteers at a dose of 40 pmol/kg.min for 1 h to investigate the pharmacologic effects of this peptide on postprandial gastrointestinal motility and gut peptide release in humans. Galanin strongly inhibited gastrointestinal motility. Gastric emptying was significantly delayed, with the time taken to empty 50% of the gastric contents increasing from 59.0 +/- 4.8 min (control infusion) to 99.3 +/- 4.7 min (galanin infusion). Mouth-to-cecum transit time increased from 67.5 +/- 6.9 to 126.3 +/- 18.5 min. Galanin potently suppressed the initial postprandial rise in plasma concentrations of glucose, insulin, peptide tyrosine tyrosine, neurotensin, enteroglucagon, pancreatic glucagon, somatostatin, and pancreatic polypeptide, but did not change gastric inhibitory polypeptide, motilin, peptide histidine methionine, and gastrin concentrations compared with control. The results indicate that an infusion of galanin has potent effects on the gastrointestinal tract in humans. The changes in motor activity in particular suggest that the local galaninergic innervation could have an important physiologic role in the control of human gastrointestinal propulsive motor activity.     

Effect of intraduodenai infusion of tocamphyl on pancreatic exocrine secretion and gastrointestinal hormone release in rats

Tocamphyl is a synthetic choleretic that is derived from a root extract ofCurcuma longa, L. We investigated the effect of tocamphyl on pancreatic exocrine secretion and bile flow, and on the release of some gastrointestinal hormones, by administering it intraduodenally using anesthetized rats. Tocamphyl stimulated pancreatic exocrine secretion in terms of volume and amylase output in a dose-related manner. Neither a CCK-receptor antagonist, CR1505 (loxiglumide), nor atropine sulfate infused intravenously suppressed the stimulatory effects of tocamphyl on pancreatic exocrine secretion and bile flow. The stimulatory effect on bile flow was stronger than that on pancreatic exocrine secretion. Plasma secretin levels were augmented with the increasing doses of tocamphyl, but CCK levels were not. These results indicate that intraduodenally administered tocamphyl stimulates pancreatic exocrine secretion and bile flow, and suggest that the stimulatory action is, at least in part, mediated by secretin, but not by either CCK or the cholinergic pathway.     

Effect of age and Helicobacter pylori infection on gastric acid secretion

BACKGROUND: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. METHODS: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4. RESULTS: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. CONCLUSIONS: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.     

Helicobacter pylori infection and related gastrointestinal diseases

Helicobacter pylori has been implicated in the pathogenesis of a number of digestive tract disorders, such as chronic active gastritis, peptic ulceration, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. Disease outcome is dependent on many factors, including bacterial genotype, host physiology and genetics, and environmental factors such as diet. Researchers continue to explore the complexities of H. pylori infection, seeking to explain why some individuals have asymptomatic infection, whereas others experience clinical disease. The importance of treating H. pylori infection in patients with gastrointestinal problems has been confirmed in recent years, with clinical trials showing that cure of infection can prevent duodenal ulcer and, to a lesser extent, gastric ulcer recurrence; cure early stage mucosa-associated lymphoid tissue lymphoma; and reduce the chances of developing gastric cancer in high-risk individuals.     

Effect of plaunotol on release of plasma secretin and pancreatic exocrine secretion in humans

Plaunotol, an acyclic diterpene alcohol is a new antiulcer agent derived from the leaves of the plau-noi plant. We investigated the effect of plaunotol on the release of endogenous secretin with radioimmunoassay and exocrine pancreatic secretion, using a dye dilution technique with polyethylene glycol 4,000 as a nonabsorbable marker in eight human volunteers. Intrajejunal administration of plaunotol (pH 6.5) in three different doses (80, 160, and 320 mg/30 min) resulted in significant increases in both plasma secretin concentration and pancreatic bicarbonate secretion in a dose-related manner (r = 0.819 and 0.701, p less than 0.001, respectively). Bicarbonate outputs produced by plaunotol correlated well with plasma secretin concentrations (r = 0.727, p less than 0.001). Amylase output was also increased significantly by plaunotol. However, the response was not dose-dependent from that of bicarbonate output. These results indicate that endogenous secretin is released by plaunotol in humans and suggest that the increased pancreatic bicarbonate secretion can be attributed to the increased plasma secretin concentration.     

Helicobacter pylori, NSAIDs and gastrointestinal haemorrhage.

Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) cause the majority of bleeding ulcers. Whether the presence of H. pylori infection would affect the risk of ulcers in patients taking NSAIDs is important for both theoretical and practical reasons. However, the results have been so conflicting that there is no consensus on the management of patients requiring NSAIDs who are infected with H. pylori. The controversy is largely due to the variable study design and marked heterogeneity of the study population. Studying the interaction between H. pylori and NSAIDs without considering these factors often leads to erroneous conclusions. Current evidence suggests that H. pylori contributes to an increased ulcer risk for patients who are about to start NSAID treatment, whereas NSAIDs probably account for the majority of ulcer disease in patients who are already taking long-term NSAIDs. In the light of the reduced gastric toxicity of COX-2 inhibitors, the relative importance of H. pylori in the pathogenesis of ulcers is expected to increase. Furthermore, recent evidence suggests that H. pylori contributes to ulcer bleeding associated with low-dose aspirin. Among H. pylori-positive patients with a history of ulcer bleeding who are taking low-dose aspirin, the eradication of H. pylori has been shown to be comparable to omeprazole in preventing recurrent bleeding.     

Thyrotropin-releasing hormone inhibits pancreatic enzyme secretion in humans

Recent studies have shown that thyrotropin-releasing hormone is present in gastrointestinal tissues and has effects on gastrointestinal motility and secretion. In the present study, we have investigated in healthy subjects the effects of various doses of thyrotropin-releasing hormone on secretin-cholecystokinin-stimulated pancreatic secretion. Intravenous infusion of thyrotropin-releasing hormone at doses of 4, 20, and 100 microgram/30 min, administered during a constant pancreatic stimulation with secretin (0.5 Clinical Units/kg/h) and cholecystokinin (0.5 Ivy dog units/kg/h), produced a significant decrease in lipase and chymotrypsin secretion without affecting volume and bicarbonate secretion. The decrease appeared immediately with the lowest dose of TRH employed, and was progressively more marked with increasing doses of the hormone. Compared with the control experiments, the maximal inhibition of lipase output reached -17.6%, -37.2%, and -43%, and the maximal inhibition of chymotrypsin output -18.2%, -39.3%, and -44.9%, for the three doses of thyrotropin-releasing hormone employed, respectively. It is concluded that TRH has a marked inhibitory effect on the enzymatic component of the pancreatic secretion stimulated by submaximal doses of secretin and cholecystokinin. The physiologic importance of this effect remains to be defined.     

Local and systemic antibody responses in humans with Helicobacter pylori infection.

Immunization can prevent or cure an otherwise chronic helicobacter infection in several animal models despite the chronic nature of natural helicobacter infections. Differences in the antigenic specificity of the antibodies may contribute to the protection observed in these experimental animals. The goal of the present study was to compare the local and systemic antibody responses of humans with chronic Helicobacter pylori infection with those of an individual with spontaneous resolution of infection to find an immunological correlate of protection. Spontaneous resolution of infection was accompanied by a change in immunoblot profiles. Whereas a broad range of H pylori antigens was recognized in chronically infected patients (including the patient who ultimately cleared the infection spontaneously), resolution of infection in the absence of therapeutic agents resulted in the recognition of only several immunodominant antigens. The most dominant antigen was approximately 66 kDa in molecular mass. Immunoblot analysis demonstrated that these antibodies were specific for the structural subunits of the urease enzyme. These studies suggest that the success of antihelicobacter immunization may be due to the ability of vaccination to induce an immune response against antigens that are normally not immunodominant during the course of infection.     

Helicobacter pylori infection reduces intraluminal nitric oxide in humans

It has recently been demonstrated that nitric oxide (NO) is highly concentrated in the gastric lumen and plays an important role in defending against pathogenic microorganisms in the stomach. NO in the gastric lumen is mainly delivered by extrinsic sources from saliva. We studied whether Helicobacter pylori infection affected intraluminal NO levels in humans. H. pylori infection was diagnosed on the basis of histology and culture or (¹³C)-urea breath test. Air and gastric juice in the gastric lumen were collected endoscopically. The concentration of intraluminal NO was measured by a chemiluminescence system, using an NO analyzer. The concentration of nitrite in gastric juice was measured by the Griess reaction. The intraluminal concentration of NO in H. pylori-positive patients (198.2 ± 41 parts per billion [ppb] mean ± SE; n = 70) was significantly lower than that in H. pylori-negative patients (353.0 ± 57.9 ppb; n = 43; P < 0.05). In contrast, the concentration of nitrite in gastric juice in H. pylori-positive patients (57.7 ± 12.3 μM; n = 70) was significantly higher than that in H. pylori-negative patients (25.9 ± 6.4 μM; n = 43, P < 0.01). The intraluminal concentration of NO in H. pylori-positive patients was markedly increased and the concentration of nitrite in H. pylori-positive patients was markedly decreased following the completion of eradication therapy. Based on these results, we propose that a decrease in NO and excess nitrite production in the gastric lumen are associated with H. pylori infection and may play an important role in the pathogenesis of H. pylori-related abnormalities. Received: December 14, 1998 / Accepted: June 25, 1999     

Effect of age, Helicobacter pylori infection, and gastritis with atrophy on serum gastrin and gastric acid secretion in healthy men.

Gastric acid secretion has been considered to decline with increasing age but this view is being re-evaluated as the importance of Helicobacter pylori infection emerges. This study aimed to determine the effect of age, H pylori, and gastritis with atrophy on the serum gastrin concentration, gastric secretory volumes, and acid output in healthy, asymptomatic men. Young men (mean (SD) age 22.9 (0.6) years; n = 22) were compared with old men (72.9 (1.2) years; n = 28) in respect of basal serum gastrin and basal, sham fed, pentagastrin stimulated maximal and peak acid secretion. Antral, corpus, and fundal biopsy specimens were taken for histology and H pylori status (histology, culture, and rapid urease test). H pylori associated gastritis was present in three of 22 young (13.6%) and 16 of 28 old (57.1%) men. Gastritis with atrophy was present in 11 old subjects, 10 of whom were H pylori positive. These subjects had higher mean (SD) serum gastrin concentrations than old subjects without atrophy and young subjects (61.8 (9.2); 40.0 (2.9); 36.8 (2.3) pmol/l respectively; p < 0.001). H pylori infected subjects had higher gastrin values than uninfected subjects, overall (55.3 (5.9); 36.0 (1.8) pmol/l; p < 0.001) and in subjects without atrophy (45.3 (4.2); 36.0 (1.8) pmol/l; p < 0.03). In subjects without H pylori infection, gastrin values did not differ with age (old 37.1 (1.7); young 35.4 (2.1) pmol/l). The maximal gastric secretory volume was lower in old subjects with atrophy. Acid output (mmol/h) in subjects with atrophy was lower than in subjects with no atrophy (basal: 3.0(1.1); 5.1(0.7); p=NS; sham led: 5.4 (1.4); 9.3 (0.8); p<0.02; maximal: 18.9 (4.0); 31.4(1.8); p<0.002; peak: 25.1(5.3); 43.4(2.7); p<0.003). However, acid secretion in old subjects without atrophy was not different to that in young subjects, irrespective of H pylori status. These results did not differ when acid output was expressed as mmol/h/kg lean body mass or mmol/h/kg fat free body weight. Using multiple linear regression analysis, gastritis with atrophy was the only factor that had an independent negative effect on acid secretion. In healthy men without atrophy, gastric acid secretion is preserved with ageing and is independent of H pylori status. Atrophy, which is closely related to H pylori infection, is associated with a decline in acid secretion. Increased basal serum gastrin is related to both atrophy and H pylori infection but not to ageing per se.     

Relation between Helicobacter pylori infection and gastrointestinal symptoms and syndromes

Background—Helicobacter pylori is ahuman pathogen that colonises the gastric mucosa and causes permanentgastric inflammation.
Aims—To assess the symptoms of Hpylori infection in an adult unselected population.
Subjects—A random sample of 3589 adult Danes whowere examined in 1982 and 1987 (n=2987).
Methods—Abdominal symptoms within the precedingyear were recorded at both attendances. Circulating IgG antibodiesagainst H pylori in serum samples drawn in 1982 weremeasured by using in-house indirect enzyme linked immunosorbent assays (ELISA).
Results—People with increased levels of IgGantibodies to H pylori were more likely than uninfectedindividuals to report heartburn (odds ratio (OR) = 1.26, 95%confidence interval (CI) 1.03-1.54) and abdominal pain characterisedby daily length (OR= 1.33, 95% CI 0.92-1.91), nocturnal occurrence(OR = 1.62, 95% CI 1.19-2.19), spring aggravation (OR = 1.68, 95% CI0.70-4.05), and no relation to meals (OR = 0.62, 95% CI 0.43-0.91)or stress (OR = 0.69, 95% CI 0.50-0.95). The inclusion of people withincreased levels of IgG antibodies to H pylori, butwithout upper dyspepsia, at study entry significantly increased thelikelihood of reporting upper dyspepsia at follow up (OR = 1.71, 95%CI 1.24-2.36). People with epigastric pain and increased levels of IgMantibodies to H pylori only indicative of acute Hpylori infection were more likely to report nocturnal pain,heartburn, nausea, and vomiting.
Conclusions—H pylori infection mayprecede the development of dyspepsia and is associated with a varietyof gastrointestinal symptoms in people with no history of peptic ulcer disease.

Keywords:epidemiology; Helicobacter pylori;non-ulcer dyspepsia; symptomatology; upper dyspepsia

     

Duodenal ulcer, Helicobacter pylori, and gastric secretion.

Patients with chronic dyspepsia were categorised by macroscopic appearance at oesophagogastroduodenoscopy as having duodenal ulceration (DU), other diagnosed lesions such as reflux oesophagitis, carcinoma of stomach, etc, or no organic lesion (non-ulcer dyspepsia, NUD). Material was collected to identify gastric infection with Helicobacter pylori (H pylori) by CP urease test, culture, and histological examination and to make the microscopic diagnosis of active chronic gastritis. Each patient in the DU and NUD categories was then invited to volunteer for a gastric secretion study in which maximal gastric secretion in response to histamine was measured. Sixty two gastric secretion tests were performed (31 DU, 31 NUD). The presence of H pylori was associated with active chronic gastritis (100%). DU patients secreted more acid than the NUD patients. H pylori positivity was associated with decreased maximal gastric secretion in both groups. There was a positive correlation between smoking and maximal acid output shown only in H pylori negative but not in H pylori positive patients. These findings were clear cut when all corrections of maximal gastric secretion were made for pyloric loss, duodenogastric reflux, and stature. This study failed to show any aetiological link between H pylori and DU by increased maximal gastric secretion.     

Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea

BACKGROUND: Helicobacter pylori infection occurs throughout the world and causes gastroduodenal diseases in all age groups. The prevalence of H. pylori infection varies between countries and races. The aim of this study was to evaluate the seroprevalence of H. pylori infection in asymptomatic healthy people in South Korea. METHODS: From March 1998 to October 1998, 5732 asymptomatic subjects who responded to the self-assessment questionnaires from 54 hospitals in South Korea were enrolled in this study. The serum levels of antibodies for H. pylori immunoglobulinG were measured by using an ELISA test. RESULTS: The overall seroprevalence of H. pylori infection was 46.6% and there was no statistical difference between males (47.2%) and females (45.9%). In adults, a significant difference was observed between genders. According to the geographic areas, the high prevalent provinces were Kangwon (53.4%), Cheju (52.9%) and Cholla province (50.6%); Seoul (41.9%) was the lowest prevalent area. The seroprevalence increased with age and was highest when patients were aged in their 40s (78.5%). The characteristic feature of our study was that the infection rate was steeply increased in three age groups (10-12 year olds, 16-19 year olds and those aged in their 20s). In Seoul, there was no difference in the prevalence rate among the districts studied. CONCLUSIONS: This nation-wide seroprevalence of H. pylori infection in South Korea was 46.6%, which showed the transition from a developing country to a developed country. More studies on the epidemiological factors and the route of transmission of H. pylori infection should be warranted.     

Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans

OBJECTIVES: There are contradictory reports on the relationship between Helicobacter pylori and circulating ghrelin. We sought to clarify the influence of H. pylori infection on gastric and plasma ghrelin dynamics in humans. METHODS: Using endoscopic biopsies from the corpus of 56 H. pylori-infected patients and 25 uninfected subjects, ghrelin mRNA expression levels and gastric ghrelin peptide contents were measured by real-time polymerase chain reaction and radioimmunoassay, respectively. We also measured plasma ghrelin concentrations and analyzed the numbers of ghrelin immunoreactive cells in the fundic gland area. Fifty-one patients with H. pylori infection were treated with a 7-day triple therapy consisting of lansoprazole, clarithromycin, and amoxicillin. RESULTS: The gastric ghrelin mRNA expression level of H. pylori-positive patients (1.64 +/- 1.27 in arbitrary units) was significantly lower than in H. pylori-negative subjects (4.87 +/- 4.1, p < 0.0001). A similar trend was noted for ghrelin peptide contents (31.2 +/- 27.5 vs 81.2 +/- 64.1 ng/mg protein, respectively, p < 0.0001). There was no significant difference in the number of ghrelin immunoreactive cells/mm(2) in terms of H. plyori status. Plasma ghrelin concentrations in H. pylori-infected patients (144.6 +/- 7.8.8 fmol/ml) were significantly lower than in uninfected subjects (196.1 +/- 97.2, p < 0.05) and increased following cure of the infection. Plasma ghrelin levels correlated positively with the expression levels of ghrelin mRNA (r = 0.583, p < 0.0001) and peptide products (r = 0.574, p < 0.0001). There was a significant stepwise decrease in gastric ghrelin mRNA expression (p < 0.05), peptide contents (p < 0.01) and density of ghrelin immunoreactive cells (p < 0.05) with progression of histological severity of glandular atrophy in the corpus. The histological severity of chronic inflammation also negatively influenced the ghrelin mRNA expression (p < 0.001) and peptide production (p < 0.005). CONCLUSIONS: H. pylori infection has a negative impact on gastric and plasma ghrelin dynamics. Chronic inflammatory and atrophic changes associated with the infection may affect gastric ghrelin biosynthesis and contribute to the low circulating levels.