Effect of single and repeated doses of oral omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels

The effect of omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels was studied in 12 healthy volunteers. Omeprazole, 40 mg enteric-coated granules, or placebo was given once daily for nine days in a double-blind crossover study design. Twenty-four hours after a single dose of omeprazole, mean basal and mean pentagastrin-stimulated acid output decreased significantly. This effect was more pronounced after nine days of treatment. Basal pepsin output was significantly reduced only in those subjects with basal anacidity during omeprazole treatment. Stimulated pepsin output was slightly reduced after a single dose but unaltered after nine days of omeprazole. Fasting serum gastrin and serum pepsinogen I levels increased significantly during omeprazole treatment. It is concluded that omeprazole is a potent and selective inhibitor of gastric acid secretion, probably without a direct effect on pepsin secretion. However, in cases of basal anacidity during omeprazole administration, basal pepsin secretion is reduced. During omeprazole treatment, fasting serum levels of gastrin and pepsinogen I rise.Omeprazole was supplied by A. B. Hässle, Mölndal, Sweden.     

Effect of regular and decaffeinated coffee on serum gastrin levels

We evaluated the hypothesis that the noncaffeine gastric acid stimulant effect of coffee might be by way of serum gastrin release. After 10 healthy volunteers drank 50 ml of coffee solution corresponding to one cup of home-made regular coffee containing 10 g of sugar and 240 mg/100 ml of caffeine, serum total gastrin levels peaked at 10 min and returned to basal values within 30 min; the response was of little significance (1.24 times the median basal value). Drinking 100 ml of sugared water (as control) resulted in occasional random elevations of serum gastrin which were not statistically significant. Drinking 100 ml of regular or decaffeinated coffee resulted in a prompt and lasting elevation of total gastrin; mean integrated outputs after regular or decaffeinated coffee were, respectively, 2.3 and 1.7 times the values in the control test. Regular and decaffeinated coffees share a strong gastrin-releasing property. Neither distension, osmolarity, calcium, nor amino acid content of the coffee solution can account for this property, which should be ascribed to some other unidentified ingredient. This property is at least partially lost during the process of caffeine removal.     

Effect of restorative proctocolectomy on gastric acid secretion and serum gastrin levels

PURPOSE: The aim of the present study was to analyze gastric acid secretion after restorative proctocolectomy, because it has been shown that ileal resection or exclusion may increase gastric acid secretion. An increased output of gastric acids may decrease the intestinal passage time and contribute to looser stools. METHODS: Eleven patients who had elective colectomy and ileoanal pouch because of ulcerative colitis were investigated. Eight patient were males. Eight S-pouches and three J-pouches were constructed. Gastric acid secretion (retention, basic, and stimulated) was studied, together with serum gastrin, pentagastrin, and pepsinogen, in patients before colectomy and after having had the pelvic pouch functioning for 12 months. RESULTS: A significant increase, compared with preoperative levels, in retention, basic, and stimulated gastric acid secretion was found after 12 months with the pouch functioning. Levels of serum gastrin, pentagastrin, and pepsinogen were unchanged. CONCLUSION: Restorative proctocolectomy leads to a significant increase in gastric acid secretion. These findings may be of importance with regard to intestinal passage time and consistency of the stools.     

Effect of fundusectomy on serum and antral gastrin levels in rats.

In adult male rats, fundusectomy decreased acid secretion but significantly increased total antral gastrin and both fasting and food-stimulated serum gastrin levels. The rise in fasting serum gastrin could be inhibited by antral acidification, suggesting that decreased acidity caused postfundusectomy hypergastrinemia. The mechanism for the increase in total gastrin in antral tissue is probably the same. These studies provide a useful experimental model for the increasing of antral gastrin and for the production of hypergastrinemia.     

Long term omeprazole therapy for reflux esophagitis:follow-up in serum gastrin levels,EC cell hyperplasia and neoplasia

AIM:To evaluate the long-term safety of omeprazole in patients of gastroesophageal reflux disease resistant to treatment with H2 receptor antagonist.METHODS:We prospectively followed 33 patients on omeprazole therapy for severe erosive esophagitis for 5-8 years, with periodic gastrin levels, H. pyloriinfection, gastric biopsies for incidence of ECL cell hyperplasia, carcinoids, gastric atrophy and neoplasia. A total 185 patient follow-up years and 137 gastric biopsies were done.RESULTS:Among the 33 patients, 36% reached their peak gastrin levels in an average of 8 months to one year, then drifted Down slowly over 1-2 year period to just above their baseline level, 24% of the patients had a peak gastrin level above 400ng·L(-1) and one patient had a peak level above 1000ng·L(-1). One patient had a mild ECL cell hyperplasia which was self limiting and did not show any dysplastic changes. Eighteen percent of patients were positive for H. pylori infection. The gastric biopsies did not show gastric atrophy, intestinal metaplasia or neoplastic changes.CONCLUSION:In a series of 33 patients followed for 5-8 years on omeprazole therapy for severe reflux esophagitis, we did not observe any evidence of significant ECL cell hyperplasia, gastric atrophy, intestinal metaplasia, dysplasia or neoplastic changes.     

Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis

Twenty-nine nongastrectomized and three partially gastrectomized patients with chronic reflux esophagitis resistant to 12 weeks' treatment with histamine H2-receptor antagonists were treated with a daily oral dose of 20-40 mg of omeprazole for 12-30 months. Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals. Serum gastrin levels significantly (P less than 0.01) increased threefold to fourfold during the first 1-2 months of the study when all patients ingested 40 mg of omeprazole daily. Dose reduction to 20 mg did not significantly decrease gastrin levels. Serum gastrin levels showed a trend to further increase after the first 3 months of treatment, reaching statistically significant differences for values from the 3-12-month period (P less than 0.05) and from the 3-24-month period (P less than 0.005). Women and patients with high basal serum gastrin levels before omeprazole treatment were more likely to achieve higher serum gastrin levels during omeprazole treatment. Serum pepsinogen A and C levels were significantly (P less than 0.01) increased at all time intervals during long-term treatment with omeprazole. No significant tendency toward higher serum pepsinogen C levels in time was observed. However, serum pepsinogen A levels and the ratio of pepsinogen A to pepsinogen C further increased significantly (P less than or equal to 0.05) during the initial 3-12-month period. However, this trend was not observed anymore afterward. Antrectomized patients did not show increases in serum gastrin and serum pepsinogen A and C levels, suggesting that hypergastrinemia may be involved in the observed hyperpepsinogenemia.     

Effect of antral instillation of bile salts on fasting serum gastrin levels

There have been several reports that bile salts instilled into a dog's alkalinized antral pouch cause acid secretion in a denervated fundic pouch. Antral gastrin release was assumed, but serum gastrin levels were not measured. In a randomized crossover study, serum gastrin levels were measured by radioimmunoassay during the infusion of a solution of bile salts (5 mM, pH 5.5, 280 mOsm, 37° C), or an identical saline solution without bile salts, into the pH-controlled (5.5), antrum of 8 volunteers. The mean baseline serum gastrin level (±se) was 18.7±1.0 and 20.5±0.9 pg/ml for the bile salt and control periods, respectively (NS). The serum gastrin rose promptly after bile salt infusion, but not after saline. The mean (±se) integrated gastrin response was 81±17 pg · min/ml during the bile salt infusions, but essentially zero (–3.3±22 pg · min/ml) during control infusions (P<0.02). The 40% rise in serum gastrin in the initial 15-min bile salt period was higher than in the control period (P=0.016). Thus we have shown, for the first time an increase in serum gastrin during the antral instillation of bile salts in man. The potential physiologic and/or patholgic importance of this finding has not been established.Dr. Levine was the recipient of National Health Service Award 5 F32 AM 05543-02.This paper was presented in part at the Annual Meeting of the American Gastroenterological Association in Las Vegas, Nevada, 1978.     

Effects of sex and age on serum GH binding protein levels in normal adults

OBJECTIVE: The effects of sex and age on serum growth hormone binding protein (GHBP) levels during adulthood were investigated. DESIGN: The levels of GHBP, insulin-like growth factor-I (IGF-I), and growth hormone (GH) were determined and analysed as a function of sex and age. PATIENTS: We studied 101 normal adults (45 men, aged 20-77 years; 56 women, aged 20-80 years). MEASUREMENTS: GHBP levels were determined using an Ultrogel AcA 44 minicolumn. RESULTS: During the second and third decade, GHBP levels were not different between men (22.8 +/- 1.1%) (mean +/- SE) and women (23.2 +/- 0.8%). After the age of 40 years, however, GHBP levels in men were significantly decreased (19.1 +/- 0.7%), and were lower than those in women (22.7 +/- 0.9%). IGF-I levels correlated positively with GHBP levels in men (r = 0.51, P less than 0.01) but not in women (r = 0.16, NS). CONCLUSIONS: These results indicate that both sex and age may have some effects on the GH-GH receptor-IGF-I axis.     

严重脓毒症早期性激素水平与器官损伤的相关性及对预后的影响

目的:探讨严重脓毒症患者早期血清性激素水平与器官损伤之间的相关性及对预后的影响。方法:回顾性分析53例男性严重脓毒症患者的临床资料,收集患者72 h内血清睾酮(T)、雌二醇(E2)和催乳素(PRL)水平,并进行Marshall和APACHEⅡ评分,4周后根据存活情况分为存活组和死亡组,另外选择同期20例男性健康体检者作为对照组。结果:存活组32例,死亡组21例;存活组的血清T低于死亡组和对照组(均P0.01),血清E2和PRL水平高于死亡组和对照组(均P0.05),Marshall和APACHEⅡ评分均低于死亡组(均P0.01);死亡组血清E2显著低于对照组(P0.01),血清T和PRL与对照组无显著差异(P0.05),但呈降低趋势;生存组和死亡组Marshall评分与血清T呈正相关(r=0.637),与血清E2和PRL呈负相关(r分别为-0.732和-0.654,均P0.05)。结论:严重脓毒症早期患者血清T、E2和PRL水平与器官功能的损伤程度密切相关,血清高E2、PRL和低T水平可能具有保护器官的作用。     

Effect of age on gastric acid secretion and serum gastrin concentrations in healthy men and women

The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates.     

The effects of omeprazole on interdigestive motility and early postprandial levels of gastrin and secretin.

Ten healthy men participated in a crossover study, and the experiments took place after 10 days of treatment (40 mg omeprazole every morning). Blood samples were drawn at fixed intervals during a complete migrating motor complex (MMC) cycle. The manometric pressure tube was removed after passage of the second duodenal phase III, and an omelet (1400 KJ) tagged with 99mTc was ingested, followed by 150 ml of water tagged with 111In-diethylenetriaminepentaacetic acid. Mean plasma gastrin (pmol/l) in phases I, II, and III in the omeprazole group was 18.8, 23.3, 19.9, respectively. The corresponding figures for the placebo group were 9.3, 9.6, 9.5, respectively. All mean values for the omeprazole group were significantly higher (p less than 0.01). Mean plasma gastrin in the omeprazole group was significantly higher in phase II than in phase I (p less than 0.05). Mean plasma secretin (pmol/l) in phases I, II, and III in the omeprazole group was 1.6, 1.4, 1.1, respectively. The corresponding figures for the placebo group were 2.0, 1.7, 2.2, respectively. Mean plasma secretin in the omeprazole group was significantly lower in phases I and III (p less than 0.05). The mean incremental integrated postprandial gastrin response (pmol.30 min/l) was significantly higher in the omeprazole group (475.0 versus 97.5) (p less than 0.05). The immediate postprandial mean value of secretin was significantly lower in the omeprazole group (p less than 0.05). We conclude that 40 mg omeprazole elicits i) a phase-related increase in fasting plasma gastrin, ii) a decrease in secretin in phases I and III, iii) an augmented meal-stimulated gastrin response, and iv) a secretin response characterized by a significantly lower mean in the immediate postprandial period.     

Effect of loxiglumide on basal and gastrin- and bombesin-stimulated gastric acid and serum gastrin levels.

The effect of the specific cholecystokinin-receptor antagonist loxiglumide on basal and bombesin-, and gastrin 17-I-stimulated gastric acid secretion and serum gastrin levels was studied in 12 healthy subjects. Loxiglumide (10 mg.kg-1.h-1) significantly augmented basal gastric acid output from 1.8 +/- 0.3 to 3.9 +/- 0.6 mmol H+/h (P less than 0.005) but did not significantly influence integrated basal serum gastrin concentrations (2 +/- 21 vs. 32 +/- 21 pmol L-1.h-1). Both gastric acid secretion and integrated serum gastrin concentrations stimulated by bombesin infusion (92.6 pmol.kg-1.h-1) were significantly augmented by loxiglumide [from 4.0 +/- 0.3 to 10.0 +/- 1.3 mmol H+/h (P less than 0.005) and from 1251 +/- 93 to 2558 +/- 206 pmol.L-1.h-1 (P less than 0.005), respectively]. Gastric acid output and serum gastrin concentrations during infusion of 5 pmol.kg-1.h-1 of synthetic human gastrin 17-I (9.6 +/- 2.9 mmol H+/h and 1045 +/- 177 pmol.L-1.h-1) and during infusion of 15 pmol.kg-1.h-1 of gastrin 17-I (14.5 +/- 3.1 mmol H+/h and 2412 +/- 312 pmol.L-1.h-1) were not significantly influenced by loxiglumide (10.3 +/- 2.3 mmol H+/h and 1291 +/- 257 pmol.L-1.h-1 for the 5-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide and 13.6 +/- 3.4 mmol H+/h and 2611 +/- 305 pmol.L-1.h-1 for the 15-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide). These data indicate that endogenous cholecystokinin inhibits gastric acid secretion under basal conditions and gastrin release and gastric acid secretion during infusion of bombesin in humans and suggest that the augmented effect of loxiglumide on bombesin-stimulated gastric acid secretion may be explained largely by enhanced gastrin release.     

Effect of long-term, continuous versus alternate-day omeprazole therapy on serum gastrin in patients treated for reflux esophagitis.

BACKGROUND: Proton pump inhibitors have been proven to have a major role in the management of peptic diseases, especially the long-term control of reflux esophagitis. The potent inhibitory effect of omeprazole on gastric acid secretion is frequently associated with hypergastrinemia, and gastrin and its intermediates have been reported to promote gastrointestinal cellular functions and cell growth. Experimental data suggest that gastrin may affect the proliferation of colon cells and some other cancer cells. However, so far the direct role of gastrin in tumorigenesis is unclear. Although most clinical studies on long-term treatment with omeprazole or other proton pump inhibitors do not report serious adverse effects, the issue of prolonged hypergastrinemia and tissue growth is unsettled, and many clinicians are reluctant to recommend long-term use of omeprazole or of other proton pump inhibitors. STUDY: We examined the effect of long-term omeprazole treatment on serum gastrin levels in patients with reflux esophagitis when given either 20 mg daily (group 1) or on alternate days (group 2). During the follow-up period, clinical remission was monitored and maintained in all patients in group 1 and in the majority of patients in group 2. RESULTS: The mean serum gastrin level was significantly elevated in group 1 (mean +/- SE, 159 +/- 23.6 pg/mL; range, 45-620 pg/mL; n = 31) as compared with the alternate-day treatment group (group 2) (66 +/- 4.8 pg/mL; range, 37-115 pg/mL; n = 21) (p < 0.005). In controls, serum gastrin levels showed similar values to those found in group 2 (54 +/- 4.3 pg/mL; range, 27-94 pg/mL; n = 20). Fourteen patients (45%) in group 1 had serum gastric ranging from 140 to 620 pg/mL, and 8 (25%) had a 6-fold or greater increase in serum gastrin. The follow-up treatment period ranged between 3 and 60 months (mean +/- SE, 16.1 +/- 2.1 months) for group 1 and 3-36 months (9.7 +/- 1.4 months) for group 2. Upon multivariate adjustment for age and duration of treatment, a significantly lower mean serum gastrin level was observed in the alternate-day group as compared with the daily treated group. CONCLUSION: Alternate-day, long-term treatment with omeprazole may be adequate to maintain remission in patients with reflux esophagitis. This regimen can assure serum gastrin levels within the normal range, thus reducing the potential risk of prolonged, sustained hypergastrinemia and profound hypochlorhydria.