Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation

Adherence of Helicobacter pylori to the gastric epithelium is believed to be an important step in the induction of active inflammation of the mucosal layer. However, structural evidence showing a quantitative relationship between the adherence of H. pylori and severity of gastric mucosal inflammation is lacking. We therefore investigated the correlations between severity of gastritis and adherence of morphologically different forms of H. pylori. Fifty-seven biopsy specimens from the gastric bodies of patients with H. pylori-induced gastritis were examined. The severity of gastritis and the adherence and structure of H. pylori were determined with the use of light and scanning electron microscopy. We also investigated the ability of H. pylori organisms with different structural features to induce interleukin-8 secretion by human gastric adenocarcinoma (AGS) cells in vitro because production of interleukin-8 is related to H. pylori-associated gastritis. Furthermore, serum pepsinogen concentrations and cytotoxin-associated protein status in relation to adherence of H. pylori to the epithelial surface were examined. The results indicated that H. pylori organisms, which adhered firmly to the epithelial surface, were consistently long, tightly coiled bacilli. Histologically, those gastric mucosa samples with H. pylori firmly attached showed severe gastritis. H. pylori bacilli of greater length induced higher levels of interleukin-8 secretion. The serum pepsinogen I/II ratio showed a significant negative correlation with the grade of H. pylori adhesion (r = -0.401, P <.01). We also noted a significant correlation between cytotoxin-associated protein status and the adherence of H. pylori (r = 0.344, P <.05). A quantitative correlation was found between adherence of H. pylori and gastric inflammation. Both adherence and the induction of inflammation were found to be related to the structure of H. pylori.     

Regional peptic acid activity in gastroduodenal ulcers

The acid peptic activity in different parts of the gastroduodenal area using an original method was investigated in 25 patients with duodenal ulcer, 39 patients with gastric ulcer and 14 controls. Acidity and proteolytic activity in the gastroduodenal area were different and correlated with morphofunctional peculiarities of the mucosa. The acid peptic activity in the zone of ulceration in mediogastric and anthropyloric ulcers did not exceed that in persons without gastroduodenal pathology. The acid peptic activity in the proximal part of the duodenum was higher in the patients with duodenal ulcer than in the controls.     

幽门螺杆菌感染相关的低胃酸分泌与胃癌发生

流行病学资料强烈提示,幽门螺杆菌(H.pylori)感染是胃癌发生的重要因素之一,国际癌症联合会将其定义为Ⅰ类致癌原。尽管目前关于H.pylori感染导致胃癌发生的机制并不十分清楚,但早在H.pylori致癌假说提出之前,长期低胃酸分泌可诱发胃癌的结论早已得到公认,故推测H.pylori感染相关的低胃酸分泌在H.pylori致癌机制中起到了关键的作用。H.pylori感染诱导产生的持续性胃黏膜免疫炎症反应可以引起T细胞释放大量细胞因子,最终导致胃黏膜的损伤和生理功能(胃酸分泌)的改变。目前认为,H.pylori感染患者中仅少部分进展至胃癌,宿主的胃酸分泌状态和胃内共栖菌群构成是决定H.pylori感染患者不同临床结局的重要因素。因此,本文将重点讨论H.pylori相关低胃酸分泌与胃癌的关系,以及胃内菌群在其中的作用。     

Relationship between mucosal levels of Helicobacter pylori-specific IgA, interleukin-8 and gastric inflammation

Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced inflammation. Current information on the relationship between H. pylori-induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA-positive strains of H. pylori and those with toxin-negative or cagA-negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration (P<0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori. However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage.     

Effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion in rats

The effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion was investigated in rats. The effect of three doses of omeprazole given orally once daily for 25 days was investigated. In controls median ulcer healing was 19.6% after 25 days. Omeprazole increased median ulcer healing from 36% at 145 mumole/kg/day to 80% at 580 mumole/kg/day. Basal and pentagastrin stimulated gastric acid secretion decreased dose-dependently by nearly 90% at a dose of 580 mumole/kg/day 22-24 hr after the last dose of omeprazole. Cimetidine given twice daily, in a dose that initially inhibits gastric acid secretion by 95%, reduced acid secretion by only 50% 11 hr after the last dose. Median ulcer healing after treatment with cimetidine for 25 days was 41%. This study demonstrates that omeprazole has a more long-acting inhibitory effect on gastric acid secretion compared to cimetidine and accelerates healing of chronic gastric ulcers dose-dependently in rats.     

Helicobacter pylori-related immunoglobulins in sarcoidosis.

BACKGROUND/PURPOSE: The purpose of this study was to determine serum antibody titers against a common bacterial antigen, Helicobacter pylori (H. pylon), in subjects with sarcoidosis, comparing those titers to those present in a healthy population. SUBJECTS AND METHODS: With the approval of the Institutional Review Board of the University of Missouri-Kansas City, patients with sarcoidosis (pulmonary and extrapulmonary) who visited the Truman Medical Center-Hospital Hill pulmonary clinic were recruited to enter the study. A serum sample was frozen at -70 degrees C for later testing (n = 20). Specific information collected on subjects included corticosteroid use, use of histamine2 blockers and antacids, date of first diagnosis, and stage of sarcoidosis. Normal controls and demographically matched individuals who lacked pulmonary diseases, including sarcoidosis, were also recruited. Serum samples were processed as above. Antibody capture enzyme immunoassay was completed for H. pylori and urease antigens by serum dilution assay for each subject, from which titers for antigen-specific immunoglobulin (Ig)G and IgA were calculated. Nonspecific serum IgE was also measured. RESULTS: An increased incidence of high-titer IgG antibody directed against H. pylori antigens was found in subjects with sarcoidosis compared with controls. The sarcoidosis and control groups were significantly different with respect to IgG and IgA against H. pylori, both at p = .001. IgG directed against urease was also significantly different between sarcoidosis and control patients (p = .001), but IgA directed against urease was very low in all subjects and did not yield significant differences between groups. CONCLUSIONS: Specific H. pylori and urease IgG antibodies exceeded those expected in the population studied. The data suggest that in pulmonary sarcoidosis, the relationship of H. pylori and its products to sarcoid granuloma formation warrants further investigation.     

Sialic acid secretion of patients with gastric and duodenal ulcers in the dose-response pentastrin test.

The secretion of HCl and sialic acid into the gastric juice was investigated in 13 patients with gastric, 52 with duodenal ulcers and 27 control patients, during the dose-response pentagastrin test. The basal output of sialic acid was clearly highest in patients with gastric ulcers, and the differences between these and other groups of patients were significant. During pentagastrin stimulation a significant initial decrease was found in patients with gastric ulcers with small doses, and the minimum was reached with a dose of 0.1 micrograms/kg/h. After increasing the dose, an increase in sialic acid output occurred in all groups, reaching its maximum with a pentagastrin infusion rate of 1.0 micrograms/kg/h. The basal concentration of sialic acid was also highest in patients with gastric ulcers. In all groups the concentration decreased during the stimulation, which obviously depended on the sialic output not increasing in the same relationship as the volume of gastric secretion.     

Effects of substance P on cholinergically stimulated gastric acid secretion and mucosal blood flow in rats

Effects of substance P (SP) on gastric acid secretion and mucosal blood flow (MBF) were examined in anesthetized Wistar rats. Intravenous infusion of graded doses of SP (5 and 10 nmol/kg/min) had no effects on either the basal gastric acid secretion or on the MBF. When gastric acid secretion was increased by giving a supramaximal dose of bethanechol (10 micrograms/kg/min), a muscarinic parasympathetic stimulant, SP had no effect on the gastric acid secretion but did decrease the MBF. On the other hand, when gastric acid secretion was increased by left cervical vagus nerve stimulation (0.5 mA, 3 Hz, 0.5 msec duration), SP inhibited both acid secretion and MBF, in a dose-dependent manner. The inhibitory effects of SP on the vagally stimulated gastric responses were not affected by pretreatment with phentolamine (5 mg/kg i.m.), propranolol (10 mg/kg i.m.), mepyramine (20 mg/kg i.m.) or indomethacin (30 mg/kg i.v., followed by 4 mg/kg/hr). These findings suggest that SP acts directly on the gastric vascular system and decreases gastric MBF, and that this substance also acts on the parasympathetic neurons in the gastric wall and inhibits the vagally stimulated gastric acid secretion. The inhibitory effects of SP on the gastric acid secretion do not appear to be mediated by adrenergic or by histamine H-1 receptor-, prostaglandin-involved mechanisms.     

Role of endogenous prostaglandins in gastric secretion and mucosal defense

Prostaglandins are found in high concentration in the gastric mucosa and gastric juice. Exogenous prostaglandins inhibit acid secretion, stimulate mucus and bicarbonate secretion, alter mucosal blood flow, and provide dramatic protection against a wide variety of agents which cause acute mucosal damage. The physiological role of prostaglandins is still being elucidated. There is now strong evidence that endogenous prostaglandins modulate acid secretion by blocking the histamine-stimulated increase in cyclic AMP within the parietal cell. This function is probably controlled by intraluminal pH. It is likely that mucus and bicarbonate secretion by both stomach and duodenum are influenced by endogenous prostaglandins. A physiological role of prostaglandins in mucosal protection is less certain. Prostaglandins are released by trivial injury, and this probably serves a defensive function. A mucosa which is prostaglandin-depleted is more susceptible to damage, but does not spontaneously ulcerate. It is conceivable that peptic ulcer disease may be in part caused by an impaired mucosal prostaglandin response to food.     

N alpha-methylhistamine: association with Helicobacter pylori infection in humans and effects on gastric acid secretion

Infection with the bacterium Helicobacter pylori is associated with altered gastric acid secretion and gastrointestinal disease. Recent work has suggested that N alpha-methylhistamine, produced by the bacterium and acting on histamine receptors in gastric tissue, might be involved. Gastric juice and tissue biopsies from infected patients have been analysed for the presence of N alpha-methylhistamine using a specific and sensitive assay based on gas chromatography mass spectrometry. N alpha-Methylhistamine was detected in five of seven samples of gastric juice from infected patients (5-180 pmol/ml) but was absent in nine uninfected subjects. The compound was not found in fundic and antral biopsies from both subject groups. Helicobacter pylori, cultured on agar and in broth with and without added histamine, was found not to produce detectable levels of N alpha-methylhistamine. Instillation of this compound at 10(-5) mol/l into the gastric lumen produced a significant increase in acid secretion in vivo while plasma gastrin concentration remained unchanged. N alpha-Methylhistamine in gastric juice appears therefore to be associated with infection, although this product is not generated directly by the bacterium. The concentrations found are below those required to affect acid secretion or gastrin production in vivo, although higher local concentrations may exist around a site of infection.     

Prevalence of Helicobacter pylori infection in stress-induced gastric mucosal injury

OBJECTIVE: To determine the role of Helicobacter pylori infection in critically ill patients admitted to the intensive care unit in the formation of gastric and duodenal mucosal injury in these patients. DESIGN AND SETTING: Prospective cohort analysis in an 18-bed mixed medical and surgical closed format ICU in a teaching hospital. PATIENTS: Fifty consecutive patients admitted to the intensive care unit for emergency reasons and requiring mechanical ventilation were included. INTERVENTIONS: H. pylori infection was detected by the laser-assisted ratio analyzer [13C]urea breath test (UBT). Gastric and duodenal mucosal lesions were assessed by upper gastrointestinal endoscopy and classified as minor (up to five erosions or submucosal hemorrhages) or major (more than five erosions or submucosal hemorrhages) mucosal injury. MEASUREMENTS AND MAIN RESULTS: Six patients were not eligible because the UBT could not be processed. Of the 44 eligible patients 22 were H. pylori positive by UBT and 22 H. pylori negative. Either minor or major gastric mucosal injury was found on endoscopy in 66 %. Of the 29 patients with minor mucosal injury 10 (34.5 %) were infected with H. pylori as indicated by positive LARA 13C-UBT. In contrast, of the 15 patients with major mucosal injury 12 (80%) were infected with H. pylori (p = 0.004). H. pylori was the only risk factor significantly associated with major mucosal injury in a multiple regression analysis (p = 0.019). CONCLUSION: The severity of gastric and duodenal mucosal injury in critically ill patients during mechanical ventilation is significantly correlated with the presence of H. pylori infection.     

Effects of the sympathoadrenal system on vagally induced gastric acid secretion and mucosal blood flow in rats

Effects of the sympathoadrenal system on vagally induced increases in gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized, gastric fistula rats. Greater splanchnic nerve stimulation reduced significantly both the gastric acid secretion and MBF. Stimulation of the splanchnic postganglionic nerve reduced to a greater extent the acid secretion than the MBF, while stimulation of the adrenal branch reduced both the acid secretion and MBF. Infusion of epinephrine also reduced both the acid secretion and MBF, but the reduction of MBF was the more prominent. Phentolamine, but not propranolol and alprenolol, reduced the inhibitory effects on both gastric functions of the splanchnic postganglionic nerve stimulation and adrenal branch stimulation or epinephrine infusion. These results suggest that catecholamines released from the splanchnic postganglionic nerve terminals inhibit gastric acid secretion through alpha adrenergic receptors in the stomach, independent of MBF, and that circulating catecholamines released from the adrenal medulla inhibit both the acid secretion and MBF through alpha adrenergic receptors in the stomach. The inhibition by greater splanchnic nerve stimulation is probably the sum of the effects induced by catecholamines released from the splanchnic postganglionic nerve terminals and from the adrenal medulla.