Effect of omeprazole on intragastric and duodenal bulb acidity in duodenal ulcer patients

Intraluminal pH was measured simultaneously in the stomach and duodenal bulb with six small, glass electrodes tied together at 1.5-cm intervals. Ten patients with duodenal ulcer disease were studied under fasting conditions and for 3 h after a standard liquid meal on three occasions: day 1, before treatment; day 8, when the proton pump blocker omeprazole had been taken in a daily dose of 30 mg for 7 days consecutively, including the day of the pH study; day 9, 24 h after the last dose of omeprazole. Mean hydrogen ion activity and the percentage of time with pH below 3 was calculated from the digital pH data sampled at a frequency of 1 per second from each electrode. On day 8, five of the patients were permanently anacidic (pH greater than 4) in the stomach and duodenum, while the food-stimulation broke off anacidity for shorter periods in the other five patients. The pH pattern in the duodenal bulb was markedly altered in all patients with disappearance of the typical pH fluctuations, and a decrease in the time that the pH was below 3 from a median value of 30% before treatment to 0% in seven patients and close to 0% in three patients. On day 9, a large patient-to-patient variation was observed in gastric pH: three patients were still anacidic, four were markedly suppressed, but three patients reached near pre-treatment acidity. Duodenal bulb acidity was still decreased significantly on day 9 in all patients, with post-prandial pH below 3 for less than 5% of the time, compared with 30% before treatment.     

Gastric histamine in a chronic duodenal ulcer model induced by partial thoracic irradiation

In a new model, chronic duodenal ulcers are generated by irradiating the lower mediastinum of mice with single doses of X-rays. Histamine, a potent secretagogue, may have a role in the aetiology. Seven days after irradiation, the lag period for ulcerogenesis, mice were given a gastric perfusion test. In mice given irradiation to the lower mediastinum tissue histamine in the oxyntic region of the stomach assayed after perfusion was significantly lower than that of controls. Acid and peptic activity were not different from controls. Histamine release may mediate the abscopal ulcer without increasing acid and peptic activity.     

解郁清胃汤对胃溃疡患者血清中IL-6、IL-8及TNF-α的影响

目的 探讨解郁清胃汤对肝胃郁热证胃溃疡患者的治疗效果及其对IL-6、IL-8及TNF-α的影响.方法 选取2012年1月至2014年11月来本院消化内科就诊的胃溃疡患者87例,随机分为对照组和观察组,对照组43例,观察组44例.对照组患者口服奥美拉唑肠溶片、阿莫西林胶囊及克拉霉素胶囊,2周1个疗程;观察组使用院内自拟中药处方解郁清胃汤加减治疗,2周为1个疗程.4个疗程后观察两组患者溃疡面愈合情况及不良反应情况,同时比较两组患者治疗前后血清中IL-6、IL-8及TNF-α的含量.结果 治疗后观察组患者血清中的IL-6、IL-8及TNF-α含量分别为(102.24±9.08) ng/L、(33.02±3.60) ng/L及(21.86±2.21)ng/L,对照组患者血清中的IL-6、IL-8及TNF-α含量分别为(127.32±9.22) ng/L、(46.26±4.86) ng/L及(29.43±3.23) ng/L,两组患者血清中炎性因子水平与治疗前比较差异均有统计学意义(P＜0.05),并且观察组的IL-6、IL-8及TNF-α含量明显低于对照组(P＜0.05);观察组溃疡面愈合总有效率为93.2％,对照组溃疡面愈合总有效率为79.1％,观察组显著优于对照组(P＜0.05),观察组出现不良反应的患者例数也明显少于对照组(P＜0.05).结论 解郁清胃汤对肝胃郁热证胃溃疡疗效确切,值得临床推广应用.     

Effect of Helicobacter pylori eradication on duodenal ulcer scar in patients with no clinical history of duodenal ulcer

BACKGROUND: Helicobacter pylori eradication has become the standard treatment for duodenal ulcer. However, there is no relevant evidence for antibacterial treatment of the white scar stage of duodenal ulcer (duodenal ulcer scar) in patients with no past history of duodenal ulcer. AIM: To investigate whether H. pylori eradication could decrease duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer. PATIENTS AND METHODS: We prospectively enrolled 66 patients with duodenal ulcer scar: 53 were H. pylori-positive and 13 were H. pylori-negative. H. pylori-positive patients were randomly assigned into two groups (two-to-one allocation): 36 patients were assigned to the treatment group and 17 to the follow-up group. Thirteen H. pylori-negative patients were followed up according to the study protocol. Follow-up endoscopy was performed to evaluate ulcer scar changes and H. pylori status 6 weeks after anti-H. pylori treatment and then every 6 months for up to 30 months. RESULTS: Active duodenal ulcer recurrence was identified in seven of 23 H. pylori-positive/non-cured patients (30%). There was no duodenal ulcer recurrence in 43 H. pylori-negative/cured patients (0%), which was significantly different in terms of duodenal ulcer recurrence (P=0.001). CONCLUSIONS: H. pylori eradication is effective at preventing active duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.     

Clinical pharmacology of etintidine in patients with duodenal ulcer

Summary The gastric antisecretory activity of etintidine, a new histamine H₂-receptor antagonist, was evaluated in 5 patients with quiescent duodenal ulcer disease. Meal-stimulated acid secretion was measured after 100 and 300 mg oral doses of etintidine, 100 and 300 mg oral doses of cimetidine, and placebo. Reductions from placebo in four-hour gastric acid secretion were 49, 65, 80, and 94%, with 100 mg cimetidine, 100 mg etintidine, 300 mg cimetidine, and 300 mg etintidine, respectively. Drug concentrations in plasma were determined by HPLC. The pharmacokinetics of the 2 drugs were similar. We analyzed sigmoid-shaped concentration-response curves to both agents; the concentrations causing 50% inhibition of meal-stimulated gastric acid secretion were 0.44±0.04 and 0.15±0.04 µg/ml for cimetidine and etintidine, respectively. However, characteristics of these curves were such that the potency difference diminished at higher concentrations.     

Pharmacokinetics of cimetidine in patients with unresponsive duodenal ulcer

The pharmacokinetics of cimetidine after an oral dose of 400 mg were measured in 18 patients with duodenal ulcer, 9 refractory and 9 responders. The peak plasma concentration of cimetidine (2.13 +/- 0.17 micrograms/ml vs 1.43 +/- 0.04 micrograms/ml), the area under the plasma concentration curve (A.U.C.) between 0 to 8 hours after cimetidine (8.49 +/- 0.29 micrograms/ml/h vs 5.83 +/- 0.25 micrograms/ml/h), and the time span in which cimetidine was above 0.5 micrograms/ml (I.C.50) (401 +/- 8.86 min vs 296 +/- 20 min) were all found to be greater in responding patients than in non-responders to the therapy. No differences were detectable between the two groups in urinary excretion, T 1/2 of cimetidine or percentage inhibition (1%) of maximal pentagastrin-stimulated acid output (MAO). The results indicate that clinical healing of duodenal ulcer after cimetidine is related principally to the drug's pharmacokinetics, i.e. to its absorption from the small bowel, and that some other therapeutic approaches might be tried before surgery in cases of duodenal ulcer refractory to cimetidine.     

Gastric histology and plasma gastrin response to a meal in patients with duodenal ulcer disease after five years treatment with ranitidine

Fifty asymptomatic patients with duodenal ulcer disease, aged 31-82 years, who had received ranitidine maintenance therapy continuously for five or more years without a symptomatic recurrence, were studied. Fasting plasma gastrin concentrations were normal (mean 24 pmol/L, S.D. +/- 22) while the post-prandial gastrin response was variable with maximum plasma concentrations ranging from 16 to 309 pmol/L. Endoscopy revealed six asymptomatic peptic ulcers. Histological examination of gastric biopsies showed mild, superficial inflammatory cell infiltration of the fundic mucosa, but more extensive inflammatory cell infiltration with some atrophy of the mucosal glands in the antral mucosa. Patchy intestinal metaplasia was evident in the antral mucosa of 18 patients. No fundic ECL cell hyperplasia was seen. Helicobacter pylori were detected in the corpus and antrum of most patients. These results suggest that maintenance treatment with ranitidine for 5 years is not associated with either significant hypergastrinaemia or with changes in the fundic mucosa which could be interpreted as pre-malignant.     

Cimetidine and ranitidine in duodenal ulcer

Two histamine H2 antagonists, cimetidine and ranitidine, given in doses of 1 g daily and 200 mg daily to 18 and 20 patients respectively proved equivalent in promoting healing of duodenal ulcer. No adverse effects occurred during the trial, though serum urea and creatinine concentrations tended to rise slightly during treatment with cimetidine but not ranitidine. Choice between the two drugs is likely to be influenced by overall patterns of adverse effects rather than considerations of individual potency.     

Angiopoietin-1 inhibits endothelial permeability,neutrophil adherence and IL-8 production

1 Angiopoietin-1 (Ang1) is an angiogenic growth factor that binds to the Tie2 receptor on vascular endothelium, promoting blood vessel maturation and integrity. In the present study, we have investigated whether Ang1 also possesses anti-inflammatory properties by determining its effects on endothelial barrier function, neutrophil (PMN) adherence to endothelial cells (EC) and production of the PMN chemotactic factor interleukin-8 (IL-8). 2 Pretreatment of endothelial monolayers with Ang1 attenuated the permeability increase induced by thrombin in both lung microvascular cells and a human endothelial cell line. Similarly, Ang1 prevented the permeability-inducing effects of platelet-activating factor, bradykinin and histamine. 3 Pretreatment of EC with Ang1 also reduced the adherence of PMN to EC stimulated by thrombin. In contrast to its ability to counteract the increase in monolayer permeability brought about by various inflammatory agents, Ang1 did not affect the ability of histamine, PAF, or tumor necrosis factor-alpha to stimulate PMN adherence to EC. 4 In addition to its ability to inhibit PMN adherence, Ang1 diminished IL-8 production from EC challenged with thrombin in a concentration-dependent manner. 5 When EC were preincubated with the specific Rho kinase (ROCK) inhibitor Y-27632, we observed a reduction in PMN adherence in response to thrombin, as well as a decrease in thrombin-stimulated IL-8 production. Coincubation of monolayers with Y-27632 and Ang1 did not further attenuate the above-mentioned responses. However, Ang-1 failed to inhibit the activation of RhoA in response to thrombin, suggesting that inhibition of EC adhesiveness for PMN and IL-8 production by Ang1 does not result from reduced ROCK activation. 6 We conclude that Ang1 can counteract several aspects of the inflammatory response, including endothelial permeability, PMN adherence to EC as well as inhibition of IL-8 production by EC.     

Failure of secretin release in patients with duodenal ulcer.

The release of secretin was studied in 12 normal subjects and 23 patients suffering from proved duodenal ulceration. After infusing acid directly into the duodenum mean plasma levels (plus or minus S.E.M.) of secretin rose in normal subjects to 52.6 plus or minus 4.8 ng/1 at six minutes but to only 37.5 plus or minus 3.6 ng/1 in duodenal-ulcer patients, a significant difference. The impairment of secretin release was as great in patients with a recent onset as in those who had had symptoms of a duodenal ulcer for a long time, raising the possibility of it being a primary defect. Patients who smoked 20 or more cigarettes a day had a particularly reduced secretin release, in accord with the greater incidence of ulcers in heavy smokers.     

Trimoprostil plasma concentration-gastric acid inhibition relationships in duodenal ulcer patients

The effect of single 0.25 mg, 0.75 mg, 1.5 mg, and 3.0-mg oral doses of trimoprostil and placebo on the inhibition of meal-stimulated gastric acid secretion was investigated in duodenal ulcer patients. Drug and placebo were administered in a double-blind, randomized, crossover study under fasting conditions. A bactopeptone meal was administered 30 minutes after dosing. Gastric acid output was measured by intragastric titation (pH 5.5) and trimoprostil plasma concentrations were measured by a specific gas chromatography-negative chemical ionization-mass spectrometric method. Meal-stimulated gastric acid secretion was significantly reduced when compared to placebo for one hour after 0.25 mg, 1.5 hours after 0.75 mg, and for 2.5-3.0 hours after both 1.5 mg and 3.0 mg doses. The maximal inhibition of gastric acid ranged from 65% reduction after 0.75 mg to 74% after 1.5 mg to 82% after 3.0-mg doses. Trimoprostil was rapidly absorbed and eliminated; terminal elimination half-life ranged from 21 to 45 minutes. Both maximum concentration and area under the plasma concentration-time curve increased proportionately with an increase in the dose. The concentration-effect data at a given dose were simultaneously fit to a pharmacokinetic/pharmacologic effect model. An IC50 (plasma concentration needed to elicit a 50% inhibition effect) value of 0.2 ng/mL was observed at doses of 0.75 mg to 3.0 mg. Overall, trimoprostil was effective in inhibiting acid output in a dose-related manner in duodenal ulcer patients.     

Twenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.     

Omeprazole inhibition of nocturnal gastric secretion in patients with duodenal ulcer

We studied the effect of single 08.00 h doses of omeprazole or placebo on gastric acid secretion during the following night, 14 to 23 h after administration, in seven male subjects with duodenal ulcer. The drug was given orally, double-blind, in randomized order. Omeprazole 20 mg, 40 mg and 80 mg reduced mean total overnight acid output by 43%, 73% and 91% respectively and median pH increased from 1.4 with placebo to 1.6, 3.1 and 7.0 respectively. The inhibitory effect was maintained throughout the study period. No clinical side effects or abnormalities of laboratory screening tests were seen. Omeprazole is well tolerated and administration at 08.00 h produces prolonged dose related inhibition of acid output during the following night.     

Effect of quamatel on neutrophil properties, parameters of lipid peroxidation and the antioxidant defense system in blood of patients with duodenal ulcer and pancreatitis

The properties of neutrophils, the parameters of lipid peroxidation, and the characteristics of antioxidant protection (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity) were studied in the blood of patients with duodenal ulcer and pancreatitis in the course of quamatel administration. The pattern of changes induced by quamatel shows evidence of the antioxidant activity of the drug.