Intragastric nitric oxide/nitrite in Helicobacter pylori-infected subjects

BACKGROUND: Nitrite (NO2-) in swallowed saliva is reduced to nitric oxide (NO) and other nitrogen oxides by the intragastric acidity. This mechanism is probably important for the intragastric clearance of ingested micro-organisms and nitrosating compounds. The study examines the balance between intragastric NO and NO2- in relation to endogenous acid production and infection with Helicobacter pylori. METHODS: Six healthy H. pylori-negative and six H. pylori-positive volunteers with no known gastroduodenal pathology were examined after an overnight fast. Gastric NO was measured using a chemiluminescence technique and pH as well as NO2- were analysed in gastric aspirates. RESULTS: Gastric NO was slightly lower in H. pylori-positive subjects (1560 +/- 211 ppb) than in uninfected controls (2112 +/- 430 ppb; P > 0.05) during basal conditions, whereas both pH and NO2- concentration were similar in the two groups. During inhibition of acid secretion (omeprazole 20 mg b.i.d. over 5 days) median pH and mean NO2- concentration in gastric aspirates were significantly higher in H. pylori positives than in the controls. Furthermore, during omeprazole treatment the intragastric NO levels were almost absent in H. pylori positives, whereas approximately 50% remained in H. pylori-negative individuals. CONCLUSION: Proton-pump inhibition in H. pylori-infected individuals abolishes the intragastric chemical reduction of swallowed NO2- in the fasting stomach.     

Low yield of endoscopy in patients with persistent dyspepsia taking proton pump inhibitors

BACKGROUND: Options for the evaluation of dyspepsia include a Helicobacter pylori test-and-treat strategy, empiric acid suppression, and initial endoscopy. The aim of this study was to determine the yield of endoscopy in patients in whom empiric therapy is unsuccessful compared with patients who received no empiric therapy and to identify factors associated with endoscopic findings. METHODS: A total of 100 patients with dyspepsia referred for endoscopy completed a questionnaire that included a query concerning response to therapy. EGD findings were compared in patients taking an H2-receptor antagonist, patients taking a proton pump inhibitor, and those not receiving empiric therapy. RESULTS: There were fewer endoscopic findings in patients being treated with a proton pump inhibitor compared with those taking an H2-receptor antagonist or those not receiving therapy (p < 0.01). Fewer proton pump inhibitor recipients had esophagitis or ulcer compared with patients in the no therapy group. Lack of symptom relief (<20%) by acid suppression was highly associated with a normal endoscopy (17/17). CONCLUSIONS: Patients with persistent dyspepsia being treated with a proton pump inhibitor have fewer endoscopic abnormalities compared with patients with dyspepsia taking an H2-receptor antagonist and those receiving no therapy. For patients with partial symptom relief, proton pump inhibitor therapy may mask endoscopic findings, particularly esophagitis. Interruption of proton pump inhibitors before endoscopy may increase diagnostic yield. Endoscopy is unlikely to yield a positive finding in patients who experience no symptom relief while taking a proton pump inhibitor or H2-receptor antagonist.     

Intravenous proton pump inhibitors

Intravenous (IV) administration of a proton pump inhibitor (PPI) is a faster way to achieve gastric acid suppression than oral administration of the same agent. Peak suppression after IV administration occurs within hours, compared with several days later after oral administration. Thus the IV route of administration offers a faster onset of gastric suppression, achievement of intragastric pH closer to neutrality, and better bioavailability. The PPIs that have IV formulations in the United States (esomeprazole, lansoprazole, and pantoprazole) are approved for different indications; the key differences among them relate to their ability to reach specific gastric pH, time to maintain a specific gastric pH, and ease of use of the IV formulation (eg, reconstitution, requirement of inline filters, infusion times).     

Helicobacter pylori infection and the prevention of peptic ulcer with proton pump inhibitors in elderly subjects taking low-dose aspirin

INTRODUCTION: The role of Helicobacter pylori infection on the risk of low-dose aspirin-related gastroduodenal damage and on the efficacy of the prevention therapy in elderly chronic users of low-dose aspirin is still controversial. AIM: To evaluate in symptomatic elderly chronic users of low-dose aspirin: (1) the association between H. pylori infection and the prevalence of upper gastrointestinal lesions; and (2) the effect of H. pylori infection on the efficacy of proton pump inhibitors in the prevention of aspirin-related gastroduodenal lesions. PATIENTS AND METHODS: Two hundred and forty-five symptomatic elderly who were taking aspirin 75-300 mg daily, at least during the last 3 months, were evaluated by endoscopy. A structured interview was carried out to evaluate gastrointestinal symptoms and the use of proton pump inhibitors. H. pylori infection was diagnosed according to histology and the rapid urease test on gastric biopsies. RESULTS: One hundred and twelve patients were H. pylori-positive and 133 patients were H. pylori-negative. A significantly higher prevalence of peptic ulcers was observed in H. pylori-positive than in H. pylori-negative subjects (36.6% versus 15.8%, P = 0.0002). The use of proton pump inhibitors was associated with a significant decreased risk of peptic ulcer both in H. pylori-positive (absolute risk reduction, ARR = -36.2, 95% confidence interval: -51.2 to -21.3, P < 0.001) and H. pylori-negative patients (ARR = -12.6, 95% confidence interval: -23.9 to -1.2, P = 0.03). However, the number of patients who needed to be treated in order to gain a reduction of one peptic ulcer (number needed to treat, NnT) was lower in H. pylori-positive than in H. pylori-negative patients (NnT = 3 versus 8). CONCLUSIONS: In symptomatic elderly chronic users of low-dose aspirin, H. pylori infection may influence the prevalence of peptic ulcers and the cost-effectiveness of the proton pump inhibitor prevention therapy.     

Comparative study: Vonoprazan and proton pump inhibitors in Helicobacter pylori eradication therapy

AIM To compare the effectiveness and safety of vonoprazan-based therapy with proton pump inhibitor(PPI)-based therapies to treat Helicobacter pylori(H. pylori).METHODS We retrospectively analysed data from first-line(vonoprazan or PPI with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 d)(n = 1353) and second-line(vonoprazan or PPI with 250 mg metronidazole and 750 mg amoxicillin twice daily for 7 d)(n = 261) eradication treatments for H. pylori- positive patients with associated gastrointestinal diseases from April 2014 to December 2015 at Hattori Clinic, Japan. The primary endpoint was the eradication rate, which was assessed with a full analysis set. The secondary endpoints were adverse events and related factors.RESULTS After the first-line treatments, the eradication rates for vonoprazan, esomeprazol, rabeprazole, and lansoprazole were 87.9%(95%CI: 84.9%-90.5%), 71.6%(95%CI: 67.5%-75.5%), 62.9%(95%CI: 52.0%-72.9%), and 57.3%(95%CI: 50.4%-64.1%), respectively. The vonoprazan eradication rate was significantly higher than that of the PPIs(P 0.01). Interestingly, smoking did not affect the H. pylori eradication rate in the vonoprazan group(P = 0.34), whereas it decreased the rates in the PPI groups(P = 0.013). The incidence of adverse events in the vonop-razan group was not different from the PPI group(P = 0.054), although the vonoprazan group exhibited a wider range of adverse events. Vonoprazan-based triple therapy was highly effective as a second-line treatment, with an eradication rate similar to that of PPI-based therapy.CONCLUSION Vonoprazan might be superior to PPIs in first-line H. pylori therapy, particularly for smokers. However, caution is required due to possible adverse events.     

Pharmacology of proton pump inhibitors

The gastric H,K-ATPase is the primary target for the treatment of acid-related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pK_a of about 4.0, which allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pK_a of about 1.0. PPIs are acid-activated prodrugs that convert to sulfenic acids or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. Because of covalent binding, their inhibitory effects last much longer than their plasma half-life. However, the short half-life of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. PPIs with longer half-life promise to improve acid suppression. All PPIs give excellent healing of peptic ulcers and produce good results in reflux esophagitis. PPIs combined with antibiotics eradicate Helicobacter pylori.     

Tnfluence of various proton pump inhibitors on intestinal metaplasia in noneradicated Helicobacter pylori patients

AIM: Intestinal metaplasia (IM) is more often found in patients with Helicobacter pylori(H pylori) infection, while eradication of H pylori results in significant reduction in the severity and activity of chronic gastritis. We aimed to determine in patients with unsuccessful eradication of H pylori the role of various proton pump inhibitors (PPIs)having different mechanisms in the resolution of IM.METHODS: We confirmed endoscopically and pathohistologically (Sydney classification) the IM in 335 patients with gastritis before and after medication for eradication of H pylori(Maastricht Protocol 2002). H pylori infection was determined by using histology, urease test and culture. Control endoscopy and histology were done after 30 d and thereafter (within 1 year). Unsuccessful eradication was considered if only one of the three tests (histology, urease and culture) was negative after therapy protocol. We used omeprazole, pantoprazole,lansoprazole in therapy protocols (in combination with two antibiotics).RESULTS: We found no significant difference in resolution of IM by using different PPI between the groups of eradicated and noneradicated patients (P＜0.4821 and P＜0.4388,respectively).CONCLUSION: There is no significant difference in resolution of intestinal metaplasia by different proton pump inhibitors.     

Influence of various proton pump inhibitors on intestinal metaplasia in noneradicated Helicobacter pylori patients

AM: Intestinal metaplasia (IM) is more often found in patients with Helicobacterpylori(Hpylori) infection, while eradication of H pylori results in significant reduction in the severity and activity of chronic gastritis. We aimed to determine in patients with unsuccessful eradication of Hpylori the role of various proton pump inhibitors (PPIs) having different mechanisms in the resolution of IM. METHODS: We confirmed endoscopically and pathohistologically (Sydney classification) the IM in 335 patients with gastritis before and after medication for eradication of H pylori (Maastricht Protocol 2002). H pylori infection was determined by using histology, urease test and culture. Control endoscopy and histology were done after 30 d and thereafter (within 1 year). Unsuccessful eradication was considered if only one of the three tests (histology, urease and culture) was negative after therapy protocol. We used omeprazole, pantoprazole, lansoprazole in therapy protocols (in combination with two antibiotics). RESULTS: We found no significant difference in resolution of IM by using different PPI between the groups of eradicated and noneradicated patients (P<0.4821 and P<0.4388, respectively). CONCLUSION: There is no significant difference in resolution of intestinal metaplasia by different proton pump inhibitors.     

Anaphylaxis to proton pump inhibitors

Proton pump inhibitors (PPI) are widely used for the treatment of peptic ulcer, but cases of anaphylactic reactions have rarely been described. We present a patient who experienced an episode of urticaria 30 minutes after oral intake of an omeprazole capsule. Skin prick tests to omeprazole, pantoprazole and lansoprazole were positive. Challenge test with lansoprazole was carried out and within 45 minutes the patient developed urticaria, facial edema, vomiting, and hypotension. Oral challenge with other imidazole derivatives (ketoconazole, cimetidine, metronidazole) were carried out with good tolerance. Serum tryptase levels determined 3 hours after the adverse reaction to lansoprazole were elevated. Specific IgE to PPI were not detected by an enzyme-linked immunosorbent assay technique. The clinical findings, positive skin prick test to PPI and elevated serum tryptase levels suggest that an IgE-mediated mechanism was implicated in the reactions to both omeprazole and lansoprazole. Skin prick tests may be a useful tool for detecting patients sensitized to PPI. An experimental protocol was used to detect specific IgE antibodies against PPI, which may explain RAST negativity. The previous findings suggest that cross-reactivity between PPI exists, but not with other imidazoles.     

Maastricht Ⅱ treatment scheme and efficacy of different proton pump inhibitors in eradicating Helicobacter pylori

AIM: The Maastricht Ⅱ criteria suggest the use of amoxicillin and clarithromycin in addition to a proton pump inhibitor over 7-10 d as a first line therapy in the eradication of Helicobacter pylori (Hpylori). For each proton pump inhibitor, various rates of eradication have been reported. The present study was to compare the efficacy of different proton pump inhibitors like omeprazole, lansoprazole and pantoprazole in combination with amoxicillin and clarithromycin in the first line eradication of Hpylonand to investigate the success of H pylonrieradication in our district. METHODS: A total of 139 patients were included having a Helicobacter pylori (+) gastroduodenal disorders diagnosed by means of histology and urease test. Besides amoxicillin (1000 mg twice a day) and darithromycin (500 mg twice a day), they were randomized to take omeprazole (20 mg twice a day), or lansoprazole (30 mg twice a day), or pantoprozole (40 mg twice a day) for 14 d. Four weeks after the therapy, the eradication was assessed by means of histology and urease test. It was evaluated as eradicated if the Hpyloriwas found negative in both. The complaints (pain in epigastrium, nocturnal pain, pyrosis and bloating) were graded in accordance with the Licert scale. The compliance of the patients was recorded. RESULTS: The eradication was found to be 40.8% in the omeprazole group, 43.5% in the lansoprazole group and 47.4% in the pantoprazole group. Sixty-three out of 139 patients (45%) had eradication. No statistically significant difference was observed between the groups. Significant improvements were seen in terms of the impact on the symptom scores in each group. CONCLUSION: There was no difference between omeprazole, lansoprazole and pantoprazole in H pylori eradication, and the rate of eradication was as low as 45%. Symptoms were improved independent of the eradication in each treatment group. The low eradication rates suggest that the antibiotic resistance or the genetic differences of the microorganism might be in effect. Further studies are required to verify these suggestions.     

Maastricht Ⅱ treatment scheme and efficacy of different proton pump inhibitors in eradicating Helicobacter pylori

AIM: The Maastricht Ⅱ criteria suggest the use of amoxicillin and clarithromycin in addition to a proton pump inhibitor over 7-10 d as a first line therapy in the eradication of Helicobacter pylori(H pylori). For each proton pump inhibitor, various rates of eradication have been reported. The present study was to compare the efficacy of different proton pump inhibitors like omeprazole, lansoprazole and pantoprazole in combination with amoxicillin and clarithromycin in the first line eradication of H pylori and to investigate the success of H pylori eradication in our district.METHODS: A total of 139 patients were included having a Helicobacter pylori(+) gastroduodenal disorders diagnosed by means of histology and urease test. Besides amoxicillin (1 000 mg twice a day) and clarithromycin (500 mg twice a day), they were randomized to take omeprazole (20 mg twice a day), or lansoprazole (30 mg twice a day), or pantoprozole (40 mg twice a day) for 14 d. Four weeks after the therapy, the eradication was assessed by means of histology and urease test. It was evaluated as eradicated if the H pylori was found negative in both. The complaints (pain in epigastrium, nocturnal pain, pyrosis and bloating)were graded in accordance with the Licert scale. The compliance of the patients was recorded.RESULTS: The eradication was found to be 40.8% in the omeprazole group, 43.5% in the lansoprazole group and 47.4% in the pantoprazole group. Sixty-three out of 139patients (45%) had eradication. No statistically significant difference was observed between the groups. Significant improvements were seen in terms of the impact on the symptom scores in each group.CONCLUSION: There was no difference between omeprazole, lansoprazole and pantoprazole in H pylori eradication, and the rate of eradication was as low as 45%.Symptoms were improved independent of the eradication in each treatment group. The iow eradication rates suggest that the antibiotic resistance or the genetic differences of the microorganism might be in effect. Further studies are required to verify these suggestions.     

嗜酸乳杆菌联合三联方案根除幽门螺杆菌的效果分析

目的通过嗜酸乳杆菌联合标准三联方案5周疗法,探讨嗜酸乳杆菌对提高三联方案幽门螺杆菌(Helicobacter pylori,H.pylori)根除率的作用。方法分析我院消化内科门诊H.pylori阳性初治患者134例临床资料。将134例患者分为治疗组和对照组,治疗组采用嗜酸乳杆菌+标准三联方案5周疗法,对照组采用标准三联方案1周疗法。结果所有患者均按时完成治疗,完成随访的117例患者中,治疗组61例,治愈53例,治愈率86.9%;对照组56例,治愈40例,治愈率71.4%;两组比较有统计学差异(P<0.05)。结论嗜酸乳杆菌能提高三联方案H.pylori根除率,患者服药副作用小,依从性好,具有应用价值。     

Agranulocytosis induced by proton pump inhibitors

We report the first published case of agranulocytosis induced by omeprazole and its recurrence with esomeprazole, the S-isomer form of omeprazole. Interestingly, we found an homozygotous mutation of CYP2C19*17, responsible for the metabolism of proton pump inhibitors.     

Persistent oxidative stress in the corpus mucosa is evoked by long-term treatment of H. pylori-infected patients with proton pump inhibitors

BACKGROUND/AIMS: To examine the influence of long-term treatment of H. pylori-infected patients with proton pump inhibitors (PPI) on the toxic oxidant production in the stomach. METHODOLOGY: Eight H. pylori-positive patients with gastric ulcer were enrolled, and tissue samples were obtained endoscopically from the antrum and corpus. The tissue contents of neutrophil myeloperoxidase (MPO) and oxygen-derived free radicals were quantified by ELISA and chemiluminescence (ChL) assay. The H. pylori density in the tissue specimens was scored by immunohistochemistry and the mucosal infiltration by neutrophils and monocytes was scored by histopathology. The effects of PPI on these parameters were evaluated by oral administration of lansoprazole (LPZ) at the dose of 30mg od for 8 weeks, followed by 15mg for 24 weeks. RESULTS: Eight-week treatment with LPZ significantly increased the corpus ChL by 400%, which remained unchanged at this level during the subsequent 24 weeks, but the antrum ChL decreased slightly following LPZ-treatment. No significant changes in the mucosal MPO activity or the histologically determined parameters of H. pylori density and neutrophil/monocyte infiltration were observed in either portion of the stomach. CONCLUSIONS: The mucosal oxidative stress level significantly increased in the corpus mucosa after long-term treatment with LPZ, which may be independent of inflammatory cell infiltration.