Head-to-head comparison of H_2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model.RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs,1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vsstandard dose H2RAs, 1.59 (95%CI, 1.44-1.75);standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis.CONCLUSION: H2RAS are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.

Efficacy of the H2-receptor antagonist famotidine on chronic spontaneous urticaria in children

Urticaria is a common pediatric skin disorder. Histamine H1-receptor antagonists are effective in chronic as well as acute urticaria. When H1-anti-histamines are ineffective, add-on use of H2-receptor antagonists is thought to give better symptom relief. However, there are few reports on the therapeutic efficacy in pediatric patients. We retrospectively reviewed the medical records of pediatric patients with chronic spontaneous urticaria (csU) who met the following criteria. They were consulted our outpatient clinic between April 2010 and March 2012;were unsuccessfully treated with H1 antihistamines;and were treated with add-on H2-receptor antagonist (famotidine). In six patients who met the inclusion criteria (mean age 6.1 ± 5.1 years), urticaria activity score was significantly decreased from 4.3 ± 0.8 just before administration of famotidine to 1.3 ± 1.0 on the first outpatient visit within 4 weeks after the first administration of famotidine

Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins

AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the afferent neurons, including transient receptor potential vanilloid subtype 1 （TRPV1）. METHODS： Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol （60% in 150 mmol/L HCl） in a volume of 1 mL for rats or 0.3 mL for mice. RESULTS： Both lafutidine and capsaicin （1-10 mg/kg, po） afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2＋]i in rat TRPV1-transfected HEK293 cells while lafutidine did not. CONCLUSION： These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1.

A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients with non-erosive reflux disease

AIM： To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H2-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease （NEED）.METHODS： This is a single center, prospective, randomized, open-label trial of on-demand therapy with rabeprazole （group A） vs ranitidine （group B） for 4 wk. Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gas- troesophageal reflux disease （GERD） symptoms and a normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A （n = 44） were al-lowed a maximum rabeprazole dose of 20 mg twice daily, while those in group B （n = 39） were allowed a maximum ranitidine dose of 300 mg twice daily. Ef- ficacy was assessed by patient evaluation of global symptom relief, scores of the SF-36 quality of life （QoL） questionnaires, total number of pills used, and number of medication-free days.RESULTS： Among the 83 patients who were enrolled in the study, 76 patients （40 in the rabeprazole group and 36 in the ranitidine group） completed the 4-wk trial. Baseline characteristics were comparable between both groups. After 4 wk, there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups （71.4% vs 65.4%, respectively; P = 0.9）. There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups （rabeprazole 22.40±27.53 vs ranitidine 17.28 ± 37.06; P = 0.582）. There was no significant difference in the mean number of pills used （rabeprazole 35.70±29.75 vs ranitidine 32.86±26.98; P = 0.66）. There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION： Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD. Both medications were associated with improved quality of life.

A Prospective, Multicentric, Post Marketing Surveillance to Evaluate Efficacy & Safety of Ranitidine HCl (150 & 300 mg IR/CR) in Indian Patients with Gastroesophageal Reflux Disease (PROGRADE)

Purpose: Ranitidine hydrochloride (HCl) remains an important medication for treating acid-peptic ailments such as Gastroesophageal reflux disease (GERD). The main objective of this Post Marketing Surveillance (PMS) clinical study was to test the efficacy and safety of Ranitidine HCl in Indian patients suffering from GERD. Patients and Methods: Data of 2446 patients (1307 males;1121 females) from 21 centers across India were analyzed. Patients received either of the three treatments: Ranitidine HCl 150 mg twice a day (BID) (ARM-A), Ranitidine HCl 300 mg once daily (OD) or BID (ARM-B), and Ranitidine HCl 300 mg OD (ARM-C). Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) score and Heartburn Severity score were used to assess the drug’s efficacy. The adverse events reported by patients or investigators were analyzed to assess the safety profile of Ranitidine. Results: Of the 2446 subjects screened, 2428 were enrolled. There was a significant reduction in GSAS scores from baseline to the end of the study visit in all three ARMs. The GSAS scores reduced from 2.02 to 0.23 in ARM-A, 2.01 to 0.24 in ARM-B, and 2.07 to 0.26 in ARM-C patients. In ARM A, 72.82% had 24 hours heartburn-free days, and 66.89% had 7 consecutive heartburn-free days, which was more significant than the other two ARMs. 128 (5.27%) patients reported ADRs due to Ranitidine HCl at different doses. The most frequently reported ADR was constipation (17.18%), followed by oliguria (14.06%), cold (13.28%), and dysuria (12.5%). Of 128 ADRs, 113 (88.28%) were mild, and only 11 (8.59%) ADRs were related to the study drug. No severe ADRs were reported during the study. Conclusion: Ranitidine HCl 150/300 mg tablet was found to be an effective and safe H2-receptor antagonist for treating GERD in Indian Patients.

施维舒、法莫替丁治疗十二指肠白点综合征疗效观察

目的：为探讨十二指肠白点综合征的治疗效果，对３２例患者进行了治疗前后对比观察；方法：经内镜诊断的３２例患者均服用施维舒和法莫替丁，疗程８周；结果：腹痛，消化不良症状缓解，总有效率８３８％；胃镜下十二指肠白点减少，病理组织学上炎症细胞浸润明显减少，总好转率为５４６％；结论：内镜及病理组织学证实十二肠白点综合征为一种炎性疾病，临床上服用胃粘膜保护剂施维舒和Ｈ２受体拮抗剂法莫替丁可改善症状。

肾素-血管紧张素系统阻断剂与代谢综合征患者脂联素水平的关系

目的探讨肾素-血管紧张素系统(RAS)阻断剂与代谢综合征(Mets)患者血浆脂联素水平的关系。方法53例Mets患者随机分为3组,ACEI组15例予贝那普利(5 mg/d),ARB组15例予坎地沙坦(4 mg/d),对照组23例避免应用影响RAS的相关药物,服药期为4周,检测并比较治疗前后血浆脂联素(APN)、空腹血糖(FBG)、空腹胰岛素(FINS)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、肌酐(CR)、丙氨酸转氨酶(ALT)、胆红素(BIL)和胰岛素抵抗指数(HOMA-IR)的水平。结果ACEI组的FBG和LDL-C、ARB组的CR治疗后低于治疗前(P<0.05);ACEI组和ARB组APN水平治疗后高于治疗前(P<0.01),而3组中FINS、HOMA-IR、TC、ALT和BIL在治疗前后变化差异无统计学意义(P>0.05)。治疗前CR、TC、ALT和BIL是APN水平的影响因素;治疗后FBG和TC是APN水平的影响因素。结论APN可能是ACEI和ARB治疗Mets及其并发症的潜在靶点。

Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.

Angiogenesis related gene expression profiles of EA.hy926 cells induced by irbesartan： a possible novel therapeutic approach

Background Angiogenesis occurs commonly in various physiological and pathological processes. Improving blood supply through promoting angiogenesis is a novel approach for treating ischemic diseases. Angiotensin II type 1 receptor blockers （ARBs） dominate the management of hypertension, but evidence of their role in angiogenesis is contradictory. Here we explored the angiogenic effects of ARBs through characterizing gene expression of the human umbilical vein endothelial cell line EA.hy926 exposed to irbesartan. Methods The human umbilical vein endothelial cell line EA.hy926 was grown for 72 hours after treatment with different concentrations of irbesartan. The cell proliferative capacity was assessed by CCK8 assay at 24, 48 and 72 hours. Gene expression levels in EA.hy926 cells responding to irbesartan were measured under optimal proliferation conditions by microarray analysis using Affymetrix U133 plus 2.0. The differential expression of genes involved in angiogenesis was identified through cluster analysis of the resulting microarray data. Quantitative RT-PCR and Western blotting analyses were used to validate differential gene expression related to the angiogenesis process. Results In the 104, 105, 106 mol/L treatment groups, cell proliferation studies revealed significantly increased proliferation in EA.hy926 cells after 24 hours of irbesartan treatment. However, after 48 and 72 hours of treatment with different concentrations of irbesartan, there was no significant difference in cell proliferation observed in any treatment group. We selected the group stimulated with irbersartan at a concentration of 10.6 mol/L for microarray experiments. Statistical analysis of the microarray data resulted in the identification of 56 gene transcripts whose expression patterns were significantly correlated, negatively or positively, with irbesartan treatment. Cluster analysis showed that these genes were involved in angiogenesis, extracellular stimulus, binding reactions and skeletal system morphogenesis. Of these 56 genes we identified seven genes （VEGF, KDR, PTGS2, PLXND1, ROB04, LM02, and COL5A1） involved in the angiogenesis process, qRT-PCR analysis of these genes confirmed the microarray results. Protein expression of three VEGF pathway genes （VEGF, KDR, and PTGS2） was further confirmed by Western blotting. Conclusions Our study showed that irbesartan may induce angiogenic effects in vascular endothelial cells. It suggested that the mechanism of angiogenic effects of ARBs might be attributed to the signaling cascade from angiotensin receptors in the VEGF pathway. It also provided evidence indicating that ARBs could be used as a novel therapeutic approach to treat chronic ischemic heart disease as well as anti-hypertensive agents.

Early effects of oral administration of omeprazole and roxatidine on intragastric pH

Objective： The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress- related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods： Ten Heficobacterpylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral admini- stration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period. Results： During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole （median： 4.45 vs. 2.65; P=0.0367）. Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg （median： 90.6% vs. 55.2%, P=-0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively）. Conclusions： In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.