Duodenal defence mechanisms: role of mucosal bicarbonate secretion

The duodenal epithelium secretes bicarbonate at higher rates than does the stomach (or more distal small intestine) and the duodenal secretion is currently accepted as the most important defence mechanism against acid discharged from the stomach. HCO₃ ^- entering the continuous layer of visco-elastic mucus gel on top of the epithelial surface maintains pH in its cell-facing portion at neutrality at acidities encountered in the healthy duodenum. The secretion is decreased in patients with acute and chronic duodenal ulcer disease and is inhibited by non-steroidal anti-inflammatory agents. Studies of the neurohumoral control of the duodenal alkaline secretion and of acid/base transport processes and intracellular signaling in duodenal enterocytes are currently of great research interest.     

Helicobacter pylori attenuates the delay in ulcer healing induced by aspirin and selective COX-2 inhibitor

Helicobacter pylori (H. pylori) and NSAIDs are recognized as major pathogenic factors in peptic ulcer disease. However, whether these two factors exert synergistic or antagonistic effects on ulcer healing has not yet been fully explained. In this study, the effects of aspirin (ASA) alone and rofecoxib, a specific prostaglandin cyclooxygenase (COX)-2 inhibitor, were compared with that of ASA and rofecoxib applied in combination with H. pylori on gastric acid secretion and healing of acetic acid ulcers in rats. The H. pylori colonization of gastric mucosa was determined by viable bacterial culture and histology. The area of ulcers was determined by planimetry, the gastric blood flow (GBF) was measured using the H₂-gas clearance method and the gastric mucosal generation of PGE₂ and plasma gastrin levels were assessed by radioimmunoassay. ASA or rofecoxib applied alone delayed significantly the healing of chronic gastric ulcers and this effect was accompanied by a marked decrease in the GBF at the ulcer margin and gastric mucosal PGE₂ generation without significant influence of gastric acid output. H. pylori that produced moderate gastric inflammation at the ulcer margin as confirmed by bacterial culture, prolonged significantly the healing of these ulcers and decreased the GBF at the ulcer margin and gastric acid output while elevating significantly the gastric mucosal PGE₂ generation and plasma gastrin levels. H. pylori attenuated significantly the ASA- and rofecoxib-induced inhibition of ulcer healing and accompanying fall in the GBF at the ulcer margin and reversed, in part, the ASA- and rofecoxib-induced alterations in PGE₂ generation. We conclude that H. pylori attenuates the delay in ulcer healing induced by ASA and rofecoxib due to enhancement in the generation of endogenous PGE₂ and gastrin release, as well as suppression of acid secretion which may limit deleterious influence of NSAID on ulcer healing.     

Reactions from Rat Gastric Mucosa During One Year of Helicobacter pylori Infection

The aim of the present study was to investigateresponses from the gastric mucosa of rats duringlong-term H. pylori infection. Twenty-fourSprague-Dawley rats were inoculated with a mouse-adaptedstrain of human H. pylori (vacA⁺,cagA⁺), 16 uninfected rats served ascontrols. Three to six rats from each group were killedtwo weeks or two, six, or 12 months later. At sacrifice,blood was sampled and the gastric mucosa was taken for bacterial culture,histology, immunocytochemistry and in situhybridization. H. pylori colonized the antrum in 23/24inoculated rats; with time the density of bacteriaincreased. The inflammation in the antral mucosa was mildto moderate and was dominated by infiltration oflymphocytes and macrophages. Serum H. pylori-specificIgG_2a was significantly increased in theinfected rats. The frequency of epithelial cell apoptosis wassignificantly increased in the early months ofinfection. The mucosal expression of trefoil peptidemRNA remained unchanged. We conclude that after one year of H. pylori infection in rats, themucosal responses were rather mild, indicating that theanimals may adapt to the infection by mechanisms whichremain to be identified.     

Evaluation of Two String Tests for Obtaining Gastric Juice for Culture, Nested-PCR Detection, and Combined Single- and Double-Stranded Conformational Polymorphism Discrimination of Helicobacter pylori

We have compared two gastric string tests forobtaining gastric juice for culture of Helicobacterpylori and for nested-PCR detection and PCR-basedcombined single- and double-stranded conformationalpolymorphism (SDSCP) discrimination of infecting strains.String test specimens were obtained from oneseropositive volunteer for 13 consecutive weeks. Thedistal 10 cm of each string was suspended in 1 ml salineand quantitatively cultured. An additional ninevolunteers with histories of upper-gastrointestinalcomplaints were given a string test for culture andnested-PCR assay. H. pylori isolates and/or gastricjuice from each volunteer were extracted for DNA andanalyzed by PCR-based SDSCP. Quantitative culture showedthat the Entero-test was four times as sensitive as theGastro-test but was more prone to contamination by oral flora. However, the two string testsare equally sensitive by PCR assays. Thus, theGastro-test is more suitable for culture detection of H.pylori, since it is less prone to oral contamination and its shorter length is better tolerated.SDSCP analysis of H. pylori DNA from four PCR-positivevolunteers without requiring culture showed fourdistinct profiles, indicating different infectingstrains. SDSCP analysis of strains isolated before andafter treatment of one volunteer had the same SDSCPprofile, suggesting endogenous reinfection by the samestrain.     

Helicobacter pylori-Induced Gastritis May Contribute to Occurrence of Postprandial Symptomatic Hypoglycemia

In our clinical experience, postprandialsymptomatic hypoglycemic (PSH) patients with H. pylorigastritis showed a substantial improvement in theirhypoglycemic symptoms after the eradication of H.pylori. Therefore, in this study we have investigatedwhether H. pylori gastritis may contribute to theoccurrence of PSH. For this purpose, we have evaluatedthe following parameters in 12 PSH patients with H. pylori gastritis before and one month afterthe eradication therapy: (1) the number and severity ofPSH attacks that occurred in a one-month period using a30-day diary, (2) the total symptom score following a mixed meal using a visual analog scalequestionnaire (VASQ), and (3) the glucose and insulinresponses to the mixed meal. After the eradication of H.pylori, the serum insulin responses at 30 and 60 min decreased (P < 0.001 in both), whereasthe plasma glucose levels at 150, 180 and 210 minincreased significantly (P < 0.001 for 180 min and P< 0.01 in others) following the mixed meal. The number and severity score of PSH attacks thatoccurred in a one-month period and the area under curvefor symptom score in VASQ decreased significantly (P< 0.001 in all). These results suggest that H. pylori gastritis may contribute to theoccurrence of PSH.     

Mechanisms of peptic ulcer recurrence: role of inflammation

The mechanism of peptic ulcer recurrence is still unclear. Since ulcerogenic factors such as Helicobacter pylori, non-steroidal anti-inflammatory drugs and stress can increase expression of inflammatory cytokines in gastric mucosa, gastric mucosal inflammation may play key roles in ulcer recurrence. In acetic acid-induced gastric ulcers, persistent infiltration of neutrophils into scarred mucosa, which is caused by prostaglandin deficiency, affects future ulcer recurrence. In a rat model of ulcer recurrence which we developed, inflammatory cytokines such as interleukin (IL)-1 are key mediators of ulcer recurrence. In this model, IL-1 increases expression of adhesion molecules on both leukocytes and endothelial cells, and cytokines, leading to neutrophil infiltration into scarred mucosa. Gastric acid also plays important roles in recurrence of gastric ulcer in this model. Acid regulates inflammatory processes, including expression of adhesion molecules and inflammatory cytokines during ulcer recurrence. This review focuses on recent advances in understanding of the mechanisms underlying development of gastric ulcer recurrence.     

Proximal and Distal Gastric Distension in Normal Subjects and H. pylori-Positive and -Negative Dyspeptic Patients and Correlation with Symptoms

Aim of the study was to analyze gastricdistension with water in H. pylori-positive and-negative dyspeptic patients and normal subjects and thecorrelation with symptoms. Twenty dyspeptic patients and 19 normal subjects were studied. H. pylori wasdetermined in each dyspeptic patient with the rapid ureatest at endoscopy. Gastric distension was evaluated byreal-time ultrasonography with the ingestion of stepwise-increasing amounts of water up toa total of 600 ml. During distension, the symptom scorewas evaluated as well. The proximal stomach wassignificantly smaller in dyspeptic patients than in healthy controls, at 100-600 ml water (P <0.01). A larger distal stomach was observed at 500 and600 ml of water (P < 0.01). The score of bloating andfullness was greater in dyspeptics than in controls at 300 and 600 ml of water distension.The symptoms score was linearly correlated with proximaland distal gastric measurements in dyspeptic patientsand in controls. No significant difference was found in dyspeptic patients regarding theH. pylori status. In conclusion, dyspeptic patients showa defective adaptation of the whole stomach to waterdistension and an increased symptom perception score as compared to controls. H. pyloriinfection does not seem to be a determining factor inthese observed findings.     

Release Behavior of Amoxicillin from Glycol Chitosan Superporous Hydrogels

Two kinds of amoxicillin-containing glycol chitosan superporous hydrogels, drug-dispersed and drug-conjugated, were synthesized as candidates for an efficient drug-delivery system to eradicate Helicobacter pylori. The swelling and drug-release patterns were investigated for application as drug carriers to cure gastric disease. Both the swelling capacity and swelling kinetics decreased with decreasing network mesh size associated with increasing cross-linking density. The drug-conjugated system showed much slower drug-release patterns than the drug-dispersed system, thus prolonging the drug-delivery effect. This difference in drug-release kinetics is attributed to the difference in the main release mechanism, diffusion for the drug-dispersed and hydrolysis for the drug-conjugated system.     

化浊解毒清幽方加减治疗幽门螺杆菌相关性胃炎临床观察

【目的】观察基于"浊毒致病学说"所组方剂化浊解毒清幽方对幽门螺杆菌相关性胃炎(HPAG)患者的临床症状、胃镜下表现和幽门螺杆菌(HP)等的影响,寻求治疗HPAG有效的中医药基本方。【方法】采用随机双盲法将64例患者随机分为治疗组和对照组各32例。治疗组给予化浊解毒清幽方(蒲公英、白花蛇舌草、半枝莲、黄连、厚朴、枳实、白芍、木香、延胡索、三七、甘草)加减口服治疗,对照组给予"三联疗法"(雷贝拉唑胶囊+阿莫西林胶囊+甲硝唑片)治疗。对2组治疗前后的一般情况、胃镜下改变及根除HP情况等进行观察分析。【结果】治疗后,治疗组的临床症状疗效和胃镜疗效显著优于对照组,差异均有统计学意义(P<0.05);2组的抗HP感染疗效比较,差异无统计学意义(P>0.05),表明2组的抗HP感染疗效相仿。【结论】化浊解毒清幽方加减治疗HPAG疗效满意,值得临床进一步研究和推广。     

H. pylori Infection in HIV-Positive Patients (A Serohistological Study)

Sixty-seven consecutive patients infected withthe human immunodeficiency virus (HIV-1), 72% of whichwith overt AIDS, were examinated by upper endoscopy dueto various indications and evaluated for the prevalence of H. pylori infection. Theinfection was studied by performing both histologicalexamination of gastric biopsies and serological testingfor anti-H. pylori IgG antibodies. The H. pyloriprevalence rate was 55% in histology; no significantdifferences were observed in HIV-infected subjects andthose with overt AIDS (52% vs 63%, respectively; P =NS). Positive histological testing appeared to bedirectly related to the peripheral CD4⁺lymphocyte count (minimum rates of 43% were detected in6 patients with CD4⁺ < 100 ×10⁶/liter and maximum rates of 78% inpatients with CD4⁺ > 200 ×10⁶/liter, respectively; P < 0.05) and inversely related to the frequency ofantibiotic treatments performed over the six monthsprior to endoscopy. Low CD4⁺ counts were alsoapparently associated with low-grade H. pyloriinfection. Serological testing was positive for anti-H. pylori IgGantibodies in 39% of patients; compared to histology,serology displayed a sensitivity of 57% and aspecificity of 81%. The discrepancy between histologicaland serological positive results for H. pylori wasnoted to be higher in the more advanced phases of HIVinfection. Based upon our results, the serologicaltesting for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positivepatients.