Molecular forms of gastrin in peptic ulcer: comparison of serum and tissue concentrations of G17 and G34 in gastric and duodenal ulcer subjects

We have studied the relationships between the main molecular forms of gastrin (G17 and G34) in the serum, antral and duodenal mucosa of duodenal (DU) and gastric (GU) ulcer patients. Fasting serum G17 was similar in both DU and GU (about 6 pmol/l) and in both groups increased about three-fold with feeding. In contrast, basal serum G34 was significantly higher in GU (29 pmol/l) than in DU (12 pmol/l) and the peak post prandial increase over basal of G34 was also higher in GU (57 pmol/l) compared with DU (10 pmol/l). In sharp contrast, in the same groups of DU and GU patients mean total antral gastrin concentrations were similar (about 12 nmol/g), and in both groups 95% of antral gastrin was G17, most of the remainder being G34. In both groups total duodenal gastrin concentrations were about 20% those in antral mucosa and about 70% of duodenal gastrin was attributable to G34. The higher serum G34 in GU could therefore be explained by increased secretion of duodenal gastrin, but further work is needed to examine whether there might also be preferential secretion of antral G34 in GU, or a difference in the metabolism (or volume of distribution) of gastrin variants in GU and DU.     

Abnormal processing of antral gastrin in active duodenal ulcer disease

The concentrations of gastrins containing the active C-terminal tetrapeptide amide (mainly gastrin-34 and gastrin-17) and the N-terminal tridecapeptide fragment of gastrin-17 were measured in antral and duodenal biopsy specimens. The antral concentration of the N-terminal gastrin fragment was much higher in patients with active duodenal ulcer (33.4 +/- 6.8 nmol g-1, mean +/- SEM, n = 15) than in controls (5.6 +/- 2.9 nmol g-1, n = 10), patients with gastric ulcer (5.6 +/- 1.8 nmol g-1, n = 10) or patients with pernicious anaemia (7.7 +/- 2.5 nmol g-1, n = 6). No differences were found between the groups regarding gastrin-34 and gastrin-17 concentrations. In duodenal extracts, the N- and C-terminal gastrin concentrations were similar in all groups of patients. These data suggest that the posttranslational processing of antral gastrin is abnormal in patients with active duodenal ulcer disease.     

Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects.

Acid-stimulating action and clearance of pure natural human big gastriin (HG-34-I) and little gastrin (HG-17-I) were assessed in four male subjects with inactive duodenal ulcer (DU) disease. Disappearance half-times for HG-17-I after intravenous infusion (5.2 min) or rapid intravenous injection (6.4 min) were six to eight times shorter than those for HG-34-I (41.5 and 37.8 min, respectively). Studies of clearance of synthetic human little gastrin (HG-17-I) were performed in three of these same four DU subjects, eight additional male DU subjects, and eleven normal male subjects. The disappearance halftime of synthetic HG-17-I averaged 6.2 min in both the DU subjects and the normal subjects. These data suggest that clearance of exogenous gastrin is not altered in patients with DU. Acid secretion in response to rapid intravenous injection of HG-34-I reached a higher peak and lasted longer than in response to an equimolar dose of HG-17-I; the total response to HG-34-I was about three times that to HG-17-I. During constant intravenous infusion, acid responses to equimolar exogenous doses of the two peptides were similar but the increment in molar concentration of circulating gastrin was six to eight times greater with HG-34-I than with HG-17-I. Chromatography of serum obtained during infusions of HG-34-I revealed no evidence of conversion to HG-17-I, nor was there any increase in circulating G-34 activity during infusions of HG-17-I. The increment in serum gastrin concentration required to produce half-maximal stimulation of gastric acid secretion (D50) was estimated in each subject for each gastrin from curves relating acid secretion to change in serum gastrin concentration produced by infusion of these peptides. After instilling peptone solution into the stomach, acid secretion was measured by intragastric titration, and increases in circulating G-17 and G-34 were determined by chromatography and radioimmunoassay of serum. Increases in circulating G-17 and G-34 in response to the peptone meal, taken together, were equivalent to 1.5 times the D50 determined from infusions of G-34 and G-17. Acid secretion during the same time period averaged 55% of maximal rates. Although G-34 comprised approximately three-fourths of the total molar concentration of circulating gastrin after stimulation, it was estimated to contribute less than half of the acid-stimulating activity.     

老年人消化性溃疡与慢性萎缩性胃炎的相关性研究

目的研究老年人消化性溃疡与慢性萎缩性胃炎的相关性。方法对十二指肠溃疡（DU）、胃溃疡（GU）和复合性溃疡（CU）的老年患者胃窦、胃窦胃体交界处和胃体黏膜以及慢性胃炎（CG）患者胃窦黏膜活检标本进行组织学检查,统计各自胃黏膜的萎缩、肠化生、慢性炎症、活动性和幽门螺杆菌（Hp）感染的发生率。结果 DU患者胃窦、胃窦胃体交界处和胃体黏膜的萎缩发生率分别为54.0%、8.0%和16.0%,肠化生发生率分别为19.0%、6.0%和4.0%。其胃窦黏膜肠化生的发生率明显低于相应的GU、CU或CG者。3种消化性溃疡和CG患者均存在胃窦部慢性炎症,且老年消化性溃疡患者胃体部炎症的发生率较高,其胃炎活动性以胃窦部为主,且均较CG者高。结论老年人消化性溃疡均可有胃窦部灶性萎缩和肠化生发生,但DU胃窦黏膜肠化发生率最低,这可能是老年DU患者罹患胃癌危险性较低的原因之一。     

幽门螺杆菌感染与十二指肠胃上皮化生及胃泌素之间关系的研究

目的　通过对幽门螺杆菌 (Hp)感染与十二指肠胃上皮化生 (DGM )及胃泌素 (GAS)关系的研究 ,探讨Hp导致十二指肠溃疡 (DU)的发病机制。 方法　检测了 12 1例患者内镜、病理、Hp感染及DGM情况。同时测定了其中 6 6例患者的血清GAS浓度。结果　球部有溃疡者 ,胃及球部Hp检出率均显著高于球部无溃疡者 (P <0 .0 0 1) ;但球部Hp检出率在DU与CU、GU与CG之间无差别 (P >0 .0 5 ) ;球部有溃疡者DGM的检出率显著高于球部无溃疡者 (P <0 .0 0 1) ,且前者的DGM程度更重 (P <0 .0 0 1) ,但在DU与CU、GU与CG之间无差别 (P >0 .0 5 ) ;胃部Hp阳性者DGM的发生率 (73.0 % )显著高于胃部Hp阴性者 (37.5 % ,P <0 .0 0 1) ,DGM( )及以上者在Hp阳性组发生率 (47.2 % )也高于Hp阴性组 (2 1.9% ,P <0 .0 5 ) ;Hp阳性者血清GAS浓度显著高于Hp阴性者 (P <0 .0 1) ,但血清GAS浓度在Hp阳性的DU、CU、GU与CG之间无差别(P >0 .0 5 ) ;有DGM者血清GAS浓度也显著高于无DGM者 (P <0 .0 1) ,且随着DGM程度的加重 ,血清GAS浓度早递增趋势 ,两者呈正相关 (rs=0 .4 2 ,P <0 .0 1)。结论　Hp感染特别是十二指肠Hp定植及DGM是影响DU发生、发展的两大危险因素。Hp可影响DGM的发生与发展 ,其中部分可能通过增加血清GAS分泌的作用。     

Serum IL-8 as a possible marker for determining the status of<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in patients with untreated and treated peptic ulcer

Failure to eradicateHelicobacter pylori can lead to peptic ulcer recurrence and gastric malignancy. Therefore, the objective of this study was to develop a noninvasive method for determining whetherH pylori infection was eradicated with antibiotic-based triple therapy. A total of 17 patients with duodenal ulcer (DU) and 17 with gastric ulcer (GU) were evaluated both before and after treatment. Outcomes included serum levels of interleukin-8 (IL-8), pepsinogen I, and gastrin, and the Wilcoxon signed rank test was used to test significance. Changes in these parameters were also correlated with disease status. In those patients where both GU and DU healing occurred as a result of treatment, most showed an increase in serum IL-8 and a decrease in serum pepsinogen. Serum gastrin levels were not significantly changed in either group. Posttreatment increases in serum IL-8 were seen in 15 of 17 (88%) recovered DU patients and 14 of 17 (82%) recovered GU patients (P < .05 for each). Posttreatment decreases in pepsinogen I were found in 15 of 17 DU and 15 of 17 GU patients (P < .05 for each). These preliminary findings suggest that an increase in serum IL-8 and possibly a decrease in pepsinogen I may be useful in identifying the successful eradication ofH pylori infection in patients with peptic ulcer treated with antibiotics. A more systematic analysis of these putative diagnostic markers is now warranted.     

Role of serum fasting gastrin in screening for hypergastrinemic syndromes in duodenal ulcer disease.

Basal serum gastrin levels were measured in 237 patients with endoscopically confirmed duodenal ulcer and were higher than normal in 16 cases. Protein meal gastrin stimulation was performed on this group of 16 patients and on a control group of 48 patients with normal basal gastrin concentrations but high rates of either ulcer recurrence or of complications (e.g., bleeding or perforation); 21 patients from the two groups were also tested for serum gastrin inhibition with secretin. Four cases (25%) of antral G-cell hyperfunction were found in the first group, plus 1 case compatible with Zollinger-Ellison syndrome (6.2%). Only 1 case (2%) of antral G-cell hyperfunction was found among the 48 controls. These results suggest the clinical utility of routine basal gastrin measurement in screening for hypergastrinemic patients with duodenal ulcer disease.     

Functiono-morphologic substantiation of the diagnostic value of the atropine test in patients with duodenal ulcer

The basal production of hydrochloric acid, pepsin, the level of immunoreactive gastrin-17 in the blood serum and gastric juice, endocrine G-, EcI- and Ec-cells of the gastric mucosa were studied in 42 patients with duodenal peptic ulcer. Patients with a negative atropine test were characterized by a high production of hydrochloric acid, hypergastrinemia, an elevated secretion of gastrin with gastric juice, hyperplasia of G- and EcI-cells. In a positive atropine test these indices were lower with the exception of a great amount of Ec-cells in the antral mucosa. Thus the atropine test reflected the functional-morphological arrangement of the secretory apparatus of the gastric mucosa and was of diagnostic value.     

Blood flow and morphofunctional status of gastroduodenal mucosa in different phases of peptic ulcer

AIM: To investigate gastric and duodenal mucosal blood flow (MBF) in different phases of gastric ulcer (GU) and duodenal ulcer (DU) and its relation both to Helicobacter pylori (HP) infection and mucosal disorders. MATERIAL AND METHODS: Upper endoscopy and histological examinations (score of inflammation, atrophy, metaplasy) were performed in 407 patients with DU and 103 with GU. Gastric and duodenal MBF were assessed by the hydrogen gas clearance technique in 102 DU and 95 GU patients. HP was detected by histology. Gastric secretion was measured in the interdigestive period and after stimulation by pentagastrin. RESULTS: Lowering of MBF in gastric antrum and duodenum was observed in DU and GU patients only with score 3 of HP infection. DU healing is accompanied with a decrease of HP value and improvement of mucosal histology. At the same time MBF exhibits a significant rise: in the duodenum (by 45%) at the stage of white scar; in gastric antrum (by 26%) and body (by 40%) at healing stage, but a decrease in white scar. During healing of GU gastric MBF reached maximum in active ulcer but in white scar MBF was significantly lower. MBF at ulcer margin and MBF in ulcer crater was the same (30 ml/min/100 g) with MBF in the region of white scar with enhanced inflammation (score 2.1) before GU relapse. CONCLUSION: Changes of MBF in different phases of ulcer are, in part, determined both by HP and by mucosal morphological disorders. The ratio MBF increase in ulcer healing/MBF reduction in ulcer relapse is the same (30% from optimal) and it is restitution entity. The MBF level of 30 ml/min/100 g was assessed as crucial in ulcerogenesis. Lowering MBF in mucosa with remaining inflammation in the scar region may predict GU relapse.     

Tumour necrosis factor alpha stimulates gastrin release from canine and human antral G cells: possible mechanism of the Helicobacter pylori–gastrin link

There is evidence that gastric Helicobacter pylori ( Hp ) infection promotes duodenal ulceration by releasing gastrin. We therefore asked how Hp releases gastrin. Tumour necrosis factor alpha (TNF-α) is up-regulated in Hp gastritis and stimulates hormone release from pituitary cells, so we tested its effect on primary cultures of canine antral G cells and human antral fragments. TNF-α pretreatment (100ngmL^–1) of canine G cells significantly increased both basal (by 89%: P <0.01) and bombesin-stimulated (by 39% P <0.05) gastrin release. A similar pattern of increase was seen following TNF-α (20ngmL⁻¹) pretreatment of human antral fragments: basal gastrin release was increased by 38% ( P  < 0.05) and bombesin-stimulated by 26% ( P  < 0.05). This effect persisted during immunoblockade with anti-somatostatin antibody S6. We propose that TNF-α provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.     

Comparison of acid secretory responsiveness to gastrin heptadecapeptide and of gastrin heptadecapeptide pharmacokinetics in duodenal ulcer patients and normal subjects.

Serum gastrin concentrations and gastric acid secretion were measured during intravenous infusion of gastrin heptadecapeptide (G-17) (0, 7, 22.1, 70, 221, and 700 pmol/kg X h) in 15 duodenal ulcer patients and 15 healthy controls. Ulcer patients developed higher serum gastrin concentrations during G-17 infusion due to nearly twofold slower clearance of gastrin (8.8 vs. 15.7 ml/kg X min; P less than 0.01). Despite slower clearance of G-17, ulcer patients had plasma elimination half-times for G-17 similar to controls (6.0 vs. 6.1 min, respectively). Thus, calculated volume of distribution for G-17 was lower in ulcer patients than controls (78.5 vs. 140.7 ml/kg; P less than 0.025). For any serum gastrin during gastrin-17 infusion, acid secretion (millimoles per hour) was higher in ulcer patients than in controls. However, when acid secretion was expressed as a percentage of peak acid output to G-17 (to correct for differences in parietal cell mass), curves relating acid secretion to serum gastrin were identical in ulcer patients and controls.     

消化性溃疡幽门螺杆菌(Hp)清除前后血Hp抗体、PG、GAS 变化的研究

幽门螺杆菌(Helicobacter pylori,Hp)阳性消化性溃疡患者在Hp清除前后血清抗Hp-IgG,抗Hp-IgM,胃蛋白酶原(Pep-sinogen,PG)和胃泌素(Gastrin,GAS)水平如何?奥美拉唑,硫糖铝,罗红霉素治疗Hp感染的消化性溃疡的效果如何?本课题对上述问题进行了研究。1材料与方法1.1一般资料病例选     

The Role of the Beta-Adrenergic Receptor in the Secretion of Gastrin: Studies in Normal Subjects and in Patients with Duodenal Ulcers

Intravenous infusion of isoproterenol, a beta-adrenergic receptor stimulatory agent, increased serum gastrin concentration significantly more in patients with a duodenal ulcer than in healthy subjects. The rise in pulse rate, blood glucose concentration and in serum insulin was the same in both groups of subjects. Gastrin secretion was also increased significantly more in the patients than in the control subjects after a beef-meal. Basal serum gastrin concentrations were higher in the patients than in the control subjects and correlated to the rise in serum gastrin during both tests in the patients with a duodenal ulcer. Isoproterenol and meal stimulated gastrin secretion, expressed as percent of the basal value, were twice as high in the patients as in the control subjects. The combined administration of isoproterenol and the meal had an additive effect on the rise in serum gastrin. Isoproterenol stimulated gastrin secretion was completely suppressed by propranolol, a beta-adrenergic receptor blocking agent, which had no effect on meal stimulated gastrin secretion. It is concluded that the mechanism of the hypersecretion of gastrin in patients with a duodenal ulcer did not involve a specific abnormality of the beta-adrenergic receptor or the receptor which recognized proteins and their digested products. There is no established role of beta-adrenergic receptor activity in the hypersecretion of gastrin in patients with duodenal ulcers. It is suggested that the beta-adrenergic receptor may have some yet unknown function unrelated to the acute secretory response of gastrin.     

Reactions of humoral and cellular immunity in peptic ulcer in relation to the condition of the gastric mucosa

A total of 160 persons including 50 patients with duodenal ulcer (DU) and 38 with gastric ulcer (GU) were examined for antibodies to the parietal cells of the stomach (PCA) and cell cellular immunity responses to autologous antigen from the gastric mucosa. It was shown that both PCA of the stomach and cell immunity responses in patients with GU and DU occurred in an insignificant number of cases. No differences were revealed in the humoral and cellular immunity in GU and DU persons with and without concomitant gastritis or in the stage of exacerbation and ulcer cicatrization.     

Synergistic interaction between an H2-receptor antagonist and enprostil on 24-hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.     

Gastric Acid Secretion is Abnormally Sensitive to Endogenous Gastrin Released after Peptone Test Meals in Duodenal Ulcer Patients

We studied 25 duodenal ulcer patients and 14 age- and sex-matched normal controls to determine whether gastric acid secretion in duodenal ulcer patients is abnormally sensitive to stimulation by gastrin endogenously released in response to meals. Acid response to saline and to 0.5, 1.0, 2.0, 4.0, and 8.0% peptone infused into the stomach was measured by 30 min intragastric titration. Total serum gastrin (G-total) and serum heptadecapeptide gastrin (G17), fasting and 30 min after each test meal, were measured by specific radioimmunoassays. In 19 ulcer patients and 11 normal subjects (controls), acid response to graded doses (11, 33, 100, and 300 pmol kg⁻¹ h⁻¹) of G17-I were also measured.     

十二指肠球部溃疡合并幽门螺杆菌感染时胃局部胃泌酸、生长抑素和前列腺素E_2含量的变化

该研究通过测定十二指肠球部溃疡合并幽门螺杆菌感染患者胃液、胃窦粘膜胃泌素、生长抑素、前列腺素E_2的含量,观察幽门螺杆菌根除后上述指标变化,并与浅表性胃炎患者对照,探讨幽门螺杆菌感染在十二指肠球部溃疡发病中的作用。     

Inhibition of gastrin secretion by hypertonic solutions in patients with pernicious anaemia and duodenal ulcer

Abstract. Serum gastrin increased in patients with pernicious anaemia after a beef-meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to appoximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride.
There was no rise in beef-meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef-meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients.
Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concentrations were attained.
The inhibitory effects of 10 g of glucose given orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments.
It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo-receptors located in the small intestine.