Changes In Serum Gastrin Research Articles

Evaluation of the effects of medium-term (57-day) omeprazole administration and of omeprazole discontinuation on serum gastrin and serum chromogranin A concentrations in the horse.

Rebound gastric hyperacidity (RGH) secondary to hypergastrinemia has been suggested to contribute to the rapid recurrence of equine squamous gastric disease (ESGD) in horses after discontinuation of omeprazole. To evaluate changes in serum gastrin and chromogranin A (CgA) concentrations in response to medium-term (57-day) omeprazole treatment and after omeprazole discontinuation. Fourteen mature Thoroughbred racehorses in simulated race training. Horses received 2.28 g of oral omeprazole PO q24h for 57 days within a 61-day period, excluding a withholding period applied mid-protocol during which treatment was stopped as part of a concurrent study. Serum samples were collected on day 0 before omeprazole treatment, on day 1 of each week of the treatment period, and for an additional 5 weeks after discontinuation of treatment. Serum gastrin and CgA concentrations were analyzed using radioimmunoassay (RIA) and ELISA, respectively. Median serum gastrin concentrations increased 2.5-fold from baseline to day 7 (P < .001) but did not increase further during the omeprazole treatment period. Median serum gastrin concentrations returned to baseline within 2 to 4 days after administration of the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. Serum gastrin concentrations increased in response to omeprazole treatment but returned to baseline within 2 to 4 days after the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. Our results do not support the use of tapering protocols in horses.

Clinical effects of acupoint catgut embedding with quadruple therapy on Hp (+) chronic atro-phic gastritis of spleen and stomach deficiency syndrome

To evaluate the clinical effects of acupoint catgut embedding combined with quadruple therapy on Helicobacter pylori (Hp)-positive (+) chronic atrophic gastritis (CAG) of spleen and stomach deficiency syndrome and explore the underlying mechanism. Hp (+) CAG patients with spleen and stomach deficiency syndrome were randomly divi-ded into a control group (n=68) and a treatment group (n=71). In addition to the routine quadruple therapy for two weeks, the patients in the control group received oral Weifuchun Tablets (4 tablets once, tid.), and those in the treatment group underwent acupoint catgut embedding at Pishu (BL20), Weishu (BL21), Zhongwan (CV12), and Zusanli (ST36), once a week. The two groups were treated for three months in total. The scores of traditional Chinese medicine (TCM) symptoms and signs, clinical efficacies, quality of life scale scores (PRO scores and HAMA scores), endoscopic and histopathologic scores, Hp eradication rates detected by 13C breath test, and the recurrence rates after six months of the two group were compared. The changes in serum gastrin 17 (G-17), pepsinogen Ⅰ (PGⅠ) and pepsinogen Ⅱ (PGⅡ) were detected by ELISA, and PGⅠ/PGⅡ was calculated. There was no significant difference in the eradication rate of Hp between the two groups after treatment (P>0.05), but the recurrence rate after six months in the treatment group was lower than that of the control group (P<0.05). After treatment, the scores of TCM symptoms and signs, endoscopic and histopathologic scores, PRO scores, and HAMA scores were decreased in both groups (P<0.01), while serum levels of G-17, PG Ⅰ, PG Ⅱ, and PG Ⅰ/PG Ⅱ were increased (P<0.05, P<0.01). The treatment group was superior to the control group in alleviating stomach discomfort by pressing or warmth, decreasing the total score of TCM symptoms and signs, relieving anorexia, mottled gastric mucosa, mucosal ulcer, chronic inflammation, and activity, improving anxiety, and regulating G-17 (P<0.05, P<0.01). The effective rates of the treatment group and the control group were 40.85% (29/71) and 23.53% (16/68)，the treatment group was higher than the control group (P<0.05). Acupoint catgut embedding combined with quadruple therapy in the treatment of Hp (+) CAG of spleen and stomach deficiency syndrome is significant in clinical efficacy and low in recurrence rate, which is presumedly achieved by repairing gastric mucosa and sensitizing the secretion of G-17 and pepsinogen.

Pharmacodynamics and pharmacokinetics of DWP14012 (fexuprazan) in healthy subjects with different ethnicities.

DWP14012 (fexuprazan), a novel potassium-competitive acid blocker, is under development for the treatment of acid-related disorders. To compare the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of DWP14012 among healthy subjects of Korean, Caucasian and Japanese descent. A randomised, double-blind, placebo-controlled, single- and multiple-dose study was conducted. Ten subjects in each dose group (40, 60 or 80mg for Koreans; 40 or 80mg for Caucasians; 20, 40 or 80mg for Japanese) were randomly assigned to DWP14012 or a placebo. Twenty-four-hour intragastric pH measurements and serial blood samples were collected for PK/PD evaluation. The PK/PD parameters were compared between each ethnicity. The extent of gastric acid suppression was similar among the ethnicities; the mean percentages of time that the intragastric pH was above 4 after multiple doses of 40mg in the Korean, Caucasian and Japanese subjects were 64.3%, 62.8% and 70.3%, respectively, and the corresponding values for the 80mg dose were 94.8%, 90.6% and 90.6% respectively. The changes in serum gastrin were not clinically significant between all three ethnicities. The systemic exposure of DWP14012 was similar between the three ethnicities after the 40mg doses but slightly lower in Caucasian and Japanese subjects after the 80mg doses. Gastric acid suppression by DWP14012 showed a clear exposure-response relationship in the three ethnicities. Gastric acid suppression by DWP14012 was similar among the Korean, Caucasian and Japanese subjects in this study, and the PK, PK-PD relationships and safety were also similar among the three ethnicities. DWP14012 could be used without consideration of ethnicity.

Effect of Helicobacter pylori eradication on gastroesophageal function.

To elucidate the cause of possible occurrence of reflux esophagitis after Helicobacter pylori eradication, gastric and esophageal function among H. pylori infected Japanese patients were evaluated both before and after eradication therapy. Nine H. pylori-positive patients were studied before and 6 months after successful H. pylori eradication. Studies included gastric emptying, esophageal manometry, gastric and esophageal pH monitoring as well as measuring serum levels of gastrin, pepsinogen I and pepsinogen II. Helicobacter pylori eradication was associated with a significant change in serum gastrin and pepsinogen levels, consistent with the improvement in mucosal inflammation. There was no significant change in gastric emptying, fasting or postprandial lower esophageal sphincter (LES) pressure, esophageal primary peristaltic contractions, frequency of transient LES relaxation, or gastroesophageal reflux, as assessed by 24 h pH monitoring. The percent time of the gastric pH>4 at night decreased significantly. A 41-year-old male developed erosive gastroesophageal reflux disease (GERD) (Los Angeles Classification Grade A) after eradication. Physiological studies showed he had abnormal esophageal motility prior to H. pylori eradication. With the exception of gastric pH at night, most patients did not experience a significant change in gastric or esophageal function after H. pylori eradication. Development of GERD post H. pylori eradication likely reflects an increase in the acidity of the refluxate superimposed on pre-existing abnormalities in gastroesophageal motility.

An evaluation of human recombinant α interferon in patients with metastatic gastrinoma

Background: Metastatic gastrinoma is becoming increasingly recognized in patients with Zollinger-Ellison Syndrome. The mean 5-year survival of these patients is < 20%. Chemotherapeutic regimens are of limited benefit. The aim of this study was to evaluate the use of Interferon in these patients because a preliminary report suggested it might be effective. Methods: The efficacy and toxicity of interferon was assessed in 13 consecutive Zollinger-Ellison syndrome patients with liver metastases. Patients were treated with human recombinant α interferon (5 million IU, subcutaneously [SC]) daily and followed up at 3-month intervals with multiple imaging studies. At each follow-up, toxicity of therapy was assessed and fasting serum gastrin concentrations were obtained. Results: No patient showed a reduction in tumor size at any follow-up. One patient died after 2 months. At 6 months, six patients (46%) had stable tumor size in the liver, although new bone metastases developed in one patient. Three patients showed stable disease for up to 21 months. Changes in serum gastrin correlated with tumor response at 6 months. All patients developed some side effects of therapy. Thirty-one percent required dose reduction, and one patient (8%) had to have interferon therapy interrupted briefly. Conclusions: These results fail to define a therapeutic role for interferon in the treatment of metastatic gastrinoma.

Changes in gastric hormones associated with gastric outlet obstruction. An experimental study in rats.

To determine the effect of persistent narrowing of the gastric outlet on peptic ulcer disease, changes in gastric hormones induced by pyloric stenosis were studied in an experimental model in the rat. Pyloric stenosis was created by constricting the pylorus to a 4-mm channel. Changes in serum gastrin and plasma somatostatin concentrations, in the length of the lesser curvature, in the size of the fundic and pyloric regions, and in the G-cell and D-cell counts were determined after 4 and 8 weeks (PS4W and PS8W) and compared with those of control groups. The size of the stomach, the serum gastrin concentration, and the corrected G-cell count (indexed to stomach size) were greater in PS8W than in PS4W rats, and both were greater than in respective controls (p < 0.005). Serum somatostatin concentrations were not different, but the total D-cell count and the corrected D-cell count were higher in PS4W and PS8W rats than in controls. Moreover, the total D-cell count and the corrected D-cell count were greater in PS8W than in PS4W (p < 0.05, p < 0.005).

Serum Gastrin Increases with Increasing Dietary Calcium But Not with Increasing Dietary Fat or Fiber in Fischer-344 Rats

We studied the effects of dietary calcium, fat and fiber on serum gastrin in Fischer-344 rats in a full factorial experiment as part of a larger study of diet and colon cancer risk factors. Nine- to 10-wk-old male rats were fed standard or experimental diets for 4 wk. Wheat bran was the sole source of fiber. Wheat bran levels were 0, 2.5, 10 and 20%; fat levels were 1, 5 and 10%; calcium levels were 0.18, 0.52 and 1.04% of diet weight. On d 29 serum was collected and stored at -80 degrees C until analyzed. There was a significant (P less than 0.0001) dose-dependent increase in serum gastrin from 102 to 173 ng/L, with increasing calcium. No other significant changes in serum gastrin were noted with the dietary changes. A long-term change in the level of serum gastrin, caused by dietary modification, will influence the trophic effect that gastrin has on colonic mucosa as well as on colon carcinomas. We speculate that calcium supplementation, although slowing colonic proliferation, might have an undesirable effect on the growth of early undetected colonic tumors.

Gastrin and Pepsinogen Changes During an Ostertagia ostertagi Challenge Infection in Calves

Daily changes in serum gastrin and pepsinogen concentration have been studied during two types of infection with Ostertagia ostertagi in calves. In a first experiment two calves were trickle infected (10 times 10,000 L3 Ostertagia) and two animals received a single infection of 100,000 L3 Ostertagia. Gastrin and pepsinogen changes are discussed in relation to adult wormburdens. The second experiment involved 8 calves and was designed to investigate pepsinogen and gastrin changes following a challenge infection in previously sensitized calves. The high dosed group was infected with 5,000 L3 O. ostertagi during 30 days, the low dosed group received 500 L3 O. ostertagi and group 3 served as uninfected control. At day 41 post infection all animals were treated with oxfendazole and on day 61 challenged with 100,000 L3 O. ostertagi. Only in the high dosed group a distinct pepsinogen and gastrin reaction was noticed. Both parameters dropped to almost preinfection levels after treatment. Two days post challenge a moderate rise (+/- 1,000 mU tyr) of the pepsinogen concentration was observed in the previously infected animals and gastrin showed a temporary slight increase in several animals 8 to 10 days post challenge. The effect of treatment and challenge infection is discussed in relation to gastrin and pepsinogen changes and immunity.

Effects of diet and feeding on postprandial serum gastrin and insulin concentration in adult horses.

Gastrin is the only hormone known to stimulate secretion of hydrochloric acid. It also has trophic effects on specific parts of the mucosa of the gastrointestinal tract. Using radioimmunoassay techniques, postprandial serum gastrin and insulin concentrations were measured in six adult horses to establish effects of different diets on gastrin concentrations. Insulin concentrations were measured to provide support to the patterns of gastrin secretion because patterns of insulin secretion were already known. The horses were fed coastal bermuda hay, or twice daily 5 kg of a complete pelleted ration, 5 kg of commercial sweet feed or 5 kg of the sweet feed together with hay. There was little change in serum gastrin or insulin concentrations after feeding hay alone. Rations containing more readily available nutrients (pellets, sweet feed) produced significant increases in postprandial serum gastrin and insulin concentrations. Gastrin concentrations also varied according to the duration of feeding each diet, but this was not seen with insulin. These results indicated that gastrin secretion, and therefore possibly gastric acid secretion, were markedly influenced by dietary composition and duration of feeding a diet. There appeared to be some adaptation of the stomach (gastrin secretion) to changes in diet, but this was not accompanied by indications of adaptation in the endocrine pancreas (insulin secretion).

Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

To determine whether intravenous infusion of individual amino acids stimulated gastric acid secretion in man, graded doses of phenylalanine, tryptophan, glycine, alanine, histidine, and NaCl control were infused on separate days in nine healthy subjects. Intravenous infusion of phenylalanine and tryptophan significantly stimulated gastric acid secretion to 50 and 52%, respectively, of the acid secretory response to intragastric peptone. Intravenous alanine and histidine were without effect, whereas glycine produced a slight response. Serum gastrin concentrations did not significantly change during intravenous amino acid infusion, except in response to 0.1 M phenylalanine. However, the increase in serum gastrin occurred 2 h after acid secretion had significantly increased in response to the 0.025 M phenylalanine infusion. Plasma amino acid concentrations were measured during intravenous amino acid infusion and in response to a steak meal in five of the subjects. At a time when acid secretion was significantly increased during intravenous infusion of phenylalanine and tryptophan, plasma amino acids were similar to, or less than, that observed after the steak meal, suggesting that circulating levels of these three amino acids have a physiologic effect on gastric secretion in man. Intravenous infusion of a combination of graded doses of phenylalanine plus a continuous infusion of 0.01 M tryptophan shifted the dose-response curve to the left and resulted in a significantly greater response than to either amino acid alone. In five subjects with parietal cell vagotomy, intravenous phenylalanine and tryptophan stimulated acid secretion, whereas histidine was without effect, similar to normal subjects. These studies indicate that intravenous infusion of small amounts of phenylalanine (0.025 M, 3.1 mmol/h) and tryptophan (0.01 M, 1.25 mmol/h) stimulated gastric acid secretion at plasma concentrations similar to those observed after a steak meal, suggesting a physiologic role for circulating levels of these amino acids on gastric acid secretion. Because acid secretion increased at a time when serum gastrin was unchanged and since there was no correlation between changes in serum gastrin and acid secretion, the responses to phenylalanine and tryptophan are probably mediated by a nongastrin-related mechanism(s). Since both phenylalanine and tryptophan stimulated secretion in vagotomized subjects, the response is vagally independent. These observations suggest that circulating levels of these two amino acids have either a direct or indirect effect on or near the human parietal cell.

Effect of thyrotropin-releasing hormone on gastro-intestinal secretions in dogs

Thyrotropin-releasing hormone (TRH) immunoreactivity has been shown previously to be distributed throughout the gastrointestinal tract and the pancreas. This study demonstrated that TRH given intravenously suppresses, in a dose-related manner, sham-feeding induced food intake and inhibits gastric secretion provoked by infusion of pentagastrin or instillation of 10% liver extract into the stomach. TRH also reduces pancreatic response to secretin, caerulein, feeding a meat meal or duodenal acidification. The findings that TRH inhibits gastric and pancreatic secretions induced by exogenous and endogenous stimulants, and that the inhibition by TRH of post-prandial secretion is not accompanied by any change in serum gastrin, indicate that TRH probably acts directly on the exocrine stomach and pancreas.

Human lower esophageal sphincter responses to synthetic human gastrins 34 (G-34) and 17 (G-17)

Gastrin is a potent stimulant of human lower esophageal sphincter pressure (LESP), but previous studies have indicated that G-17 is not likely to be the major physiologic regulator of LESP in humans. The effects of big gastrin (G-34) on human LESP have not been reported previously. This study was conducted to determine the pharmacologic and possible physiologic effects of G-34 on LESP in normal human subjects. Equimolar rapid injections of synthetic human G-17 and G-34 in doses ranging from 6.25 to 100 pmol/kg resulted in similar dose-related increases in LESP that commenced within 2 min after injection of either peptide. After rapid intravenous injection, the threshold change in serum gastrin for stimulation of LESP was more than 100 fmol/ml for both peptides. The LESP returned to baseline within 15 min after G-17, but remained elevated for more than 45 min after G-34. The magnitude of LES responses to equal increments of G-34 was less at 30 min than at 10 min, indicating a loss of sensitivity to this peptide over time. Continuous intravenous infusion of G-34, 100 pmol · kg−1 · hr−1, and of G-17, 200 pmol · kg−1 · hr−1, significantly increased LESP above control values and produced similar peak responses. During G-17 and G-34 infusions, the threshold change in serum gastrin estimated to produce any increase in LESP was 30–50 fmol/ml, half maximal responses were obtained at approximately 140 fmol/ ml, and maximal responses were achieved with increases of 210–290 fmol/ml above baseline values. Intragastric instillation of 10% peptone resulted in a mean peak increase in total gastrin of 58 fmol/ml, well below the change in serum gastrin necessary for half maximal LESP responses. Neither the peptone meal nor the control saline meal produced a significant increase in LESP in these subjects. It is concluded that: (a) circulating G-17 and G-34 have similar potency for stimulation of human LESP, (b) the total change in serum G-17 and G-34 after a peptone meal approached the threshold stimulation of LESP for these forms of gastrin but was accompanied by no significant increase in LESP, and (c) G-17 and G-34 are not likely to be physiologic regulators of the human LES.

Quantitative effect of oral feeding on gastrointestinal myoelectric activity in the conscious dog

Gastrointestinal myoelectric activity was recorded in seven studies in five dogs during two hours of fasting immediately followed by feeding and subsequent recording for four hours. In four studies serial plasma samples were taken for radioimmunoassay of insulin and gastrin. In all animals there was a significant reduction (P less than 0.01) in gastric basic electrical rhythm (BER) frequency on feeding which was sustained throughout the postprandial period. There was no change in the duodenal BER. Feeding induced a significant (P less than 0.01) increase in overall jejunal and ileal (but not duodenal) spike activity. Ileal (but not jejunal) spike activity again increased significantly (P less than 0.05) after the first two post-prandial hours. The changes in serum gastrin or in serum insulin did not appear to account for most of the observed changes in myoelectric activity, suggesting that other humoral and/or neural factors mediate the response to food.

Role of gastrin and insulin in postprandial disruption of migrating complex in dogs.

The duration of the disruption of the interdigestive migrating myoelectric complex (MMC) by various test meals in dogs was correlated with changes in serum gastrin and insulin levels. The test meals consisted of milk protein, sucrose, arachis oil and medium chain triglycerides (MCT). Intravenous infusions of glucose 20% were also used. Electrical activity of the small intestine was registered by means of electrodes implanted over the entire length of the gut. Hormones were assayed by radioimmunoassay techniques. The insulin level rose significantly after both the glucose infusion and the sucrose meal. The rise was small after the milk protein meal and nothing after arachis oil and MCT. Gastrin level was not changed by arachis oil or MCT and rose slightly after sucrose and milk protein. The MMC was not disrupted by glucose infusions, but was disrupted for 5--7 h by archis oil and for 6--12 h by MCT. We conclude that in dogs neither gastrin nor insulin have an important role in the mechanism of disruption of the MMC after feeding.

Gastroesophageal sphincter pressure and serum gastrin: reaction to food stimulation in normal subjects and in patients with gastric or duodenal ulcer.

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and after the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal of similar weight to that of the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional normal subject and one duodenal ulcer patient the constant intravenous infusion of Aminosol for 2 h produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers, and, furthermore, that this effect is mediated by proteins in the gastrointestinal tract.

Gastroesophageal sphincter pressure and serum gastrin: reaction to food stimulation in normal subjects and in patients with gastric or duodenal ulcer.

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal similar in weight to the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional nromal and one duodenal ulcer, the constant intravenous infusion of Aminosol during 2 hours produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers; furthermore, that this effect is mediated by proteins in the gastrointestinal tract.

Action of norepinephrine on the serum gastrin level.

The authors have studied the influence of endogenous norepinephrine released during exercise on the level of serum gastrin. After a period of absolute rest, 10 volunteers in good health underwent a prolonged graded exercise corresponding to 60, then 80% of the maximum theoretical heart-beat frequency. Only norepinephrine was significantly high during the course of the second phase of muscular activity. No significant change in serum gastrin was observed during the entire test.

After Vagotomy Atropine Suppresses Gastrin Release by Food

Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement.

The Effect of Carbachol on Resting Gastro-Oesophageal Sphincter Pressure and Serum Gastrin in Normal Human Subjects

With the purpose of investigating the mechanism of action behind the rise in gastro-oesophageal sphincter pressure induced by cholinergic activity, serum gastrin and sphincter pressure were recorded in 8 normal human subjects before and in relation to administration of carbachol. Carbachol was given subcutaneously in a dose of 4.5 mug per kg body weight. Mean sphincter pressure recorded 15, 30, and 45 minutes after administration of carbachol was significantly higher than the basal mean. The administration of carbachol did not lead to significant changes in serum gastrin and a relationship between serum gastrin and sphincter pressure was not demonstrable. It is concluded, that the carbachol-induced rise in the basal sphincter pressure is not dependent on an increase in serum gastrin, but probably attributable to either direct cholinergic stimulation of the receptors or a cholinergically enhanced sensitivity of the receptors for gastrin. Moreover, it is concluded that carbachol in individual dosages may be a suitable adjuvant in the medical treatment of patients with gastro-oesophageal reflux.

Serum Gastrin and Secretin Levels After the Exalto-Mann-Williamson Procedure

The Exalto-Mann-Williamson procedure produces peptic ulceration in nearly 100% of experimental animals but the mechanism is unknown. To investigate the possible hormonal role of the gastric acid hypersecretion seen after this procedure, we investigated preoperative and postoperative serum gastrin and secretin concentrations. There was no significant change in serum gastrin; however, serum secretin concentrations increased to 2 1/2 times the preoperatve value, most likely secondary to the enhanced secretion of gastric acid. These data do not suppport the theory that alterations in circulating secretin or gastrin levels are responsible for the gastric acid hypersecretion following the Exalto-Mann-Williamson operation.