Does omeprazole-induced hypergastrinaemia contribute to the enhanced healing of aceticacid-induced gastric ulcers in rats?

We examined the effects of omeprazole and SDZ CO-611 (an orally active somatostatin analogue) alone and in combination, on ulcer healing, gastric acid secretion and the serum gastrin level in rats. Two or 4-weeks’ treatment with oral omeprazole significantly enhanced spontaneous healing and/or prevented delayed healing (caused by indomethacin) of acetic acid ulcers, with the inhibition of gastric acid secretion and hypergastrinaemia. While oral SDZ CO-611 had no effect on spontaneous ulcer healing, it significantly prevented delayed ulcer healing. On SDZ CO-611 treatment, gastric acid secretion was significantly inhibited but basal gastrin level remained unchanged. Hypergastrinaemia induced by a single treatment with oral omeprazole was markedly suppressed by SDZ CO-611 for >12 h. SDZ CO-611, administered together with omeprazole for 2 or 4 weeks, did not affect the enhanced ulcer healing or the antisecretory effect of omeprazole, despite a greater than 60% decrease. We conclude that omeprazole-induced hypergastrinaemia does not contribute to the mechanism by which omeprazole enhances ulcer healing. This paper was presented at the Section of IUPHAR GI Pharmacology Symposium on ‘Biochemical pharmacology as an approach to gastrointestinal disorders (basic science to clinical perspectives)’, October 12–14, 1995, Pécs, Hungary.     

Agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ: A new compound with potent gastroprotective and ulcer healing properties

Pioglitazone, a specific ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ), was recently implicated in the control of inflammatory processes and in the modulation of the expression of various cytokines such as tumor necrosis factor alpha (TNF-α), but its role in the mechanism of gastric mucosal integrity has not been studied extensively. This study was designed to determine the effect of pioglitazone on gastric mucosal lesions induced in rats by topical application of 100% ethanol and by 3.5 h of water immersion and restraint stress (WRS) with or without pretreatment with indomethacin (5 mg/kg i.p.) to inhibit cyclooxygenase-1 (COX-1) and COX-2 enzyme activities and L-NNA (20 mg/kg i.p.) to suppress nitric oxide (NO)-synthase. In addition, the effect of pioglitazone on ulcer healing in rats with chronic acetic acid ulcers (ulcer area 28 mm²) was determined. Rats were killed 1 h and 3.5 h after ethanol administration or WRS exposure or at day 9 upon ulcer induction, and the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was determined by H₂-gas clearance technique and the mucosal PGE₂ generation and gene expression and plasma concentration of TNF-α and IL-1β were also evaluated. Pre-treatment with pioglitazone dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID₅₀) being 10 mg/kg and 7 mg/kg, respectively. The protective effect of pioglitazone was accompanied by the significant rise in the GBF, an increase in PGE₂ generation and the significant fall in the plasma TNF-α and IL-1β levels. Strong signals for IL-1β-and TNF-α mRNA were recorded in gastric mucosa exposed to ethanol or WRS, and these effects were significantly decreased by pioglitazone. Indomethacin which suppressed PG generation by about 90%, while augmenting WRS damage, and L-NNA, that suppressed NO-synthase activity, significantly attenuated the protective and hyperaemic activity of this PPAR-γ ligand. In the chronic study, pioglitazone significantly reduced the area of gastric ulcers on day 9 and significantly raised the GBF at the ulcer margin. The acceleration of ulcer healing by PPAR-γ ligand was accompanied by a significant increase in the expression of PECAM-1 protein, a marker of angiogenesis. We conclude that (1) pioglitazone exerts a potent gastroprotective and hyperaemic actions on the stomach involving endogenous PG and NO and attenuation of the expression and release of proinflammatory cytokines TNF-α and IL-1β, and (2) PPAR-γ ligand accelerates ulcer healing, possibly due to the enhancement in angiogenesis at ulcer margin.     

Helicobacter pylori attenuates the delay in ulcer healing induced by aspirin and selective COX-2 inhibitor

Helicobacter pylori (H. pylori) and NSAIDs are recognized as major pathogenic factors in peptic ulcer disease. However, whether these two factors exert synergistic or antagonistic effects on ulcer healing has not yet been fully explained. In this study, the effects of aspirin (ASA) alone and rofecoxib, a specific prostaglandin cyclooxygenase (COX)-2 inhibitor, were compared with that of ASA and rofecoxib applied in combination with H. pylori on gastric acid secretion and healing of acetic acid ulcers in rats. The H. pylori colonization of gastric mucosa was determined by viable bacterial culture and histology. The area of ulcers was determined by planimetry, the gastric blood flow (GBF) was measured using the H₂-gas clearance method and the gastric mucosal generation of PGE₂ and plasma gastrin levels were assessed by radioimmunoassay. ASA or rofecoxib applied alone delayed significantly the healing of chronic gastric ulcers and this effect was accompanied by a marked decrease in the GBF at the ulcer margin and gastric mucosal PGE₂ generation without significant influence of gastric acid output. H. pylori that produced moderate gastric inflammation at the ulcer margin as confirmed by bacterial culture, prolonged significantly the healing of these ulcers and decreased the GBF at the ulcer margin and gastric acid output while elevating significantly the gastric mucosal PGE₂ generation and plasma gastrin levels. H. pylori attenuated significantly the ASA- and rofecoxib-induced inhibition of ulcer healing and accompanying fall in the GBF at the ulcer margin and reversed, in part, the ASA- and rofecoxib-induced alterations in PGE₂ generation. We conclude that H. pylori attenuates the delay in ulcer healing induced by ASA and rofecoxib due to enhancement in the generation of endogenous PGE₂ and gastrin release, as well as suppression of acid secretion which may limit deleterious influence of NSAID on ulcer healing.     

Preventive and curative effects of curcumin on the development of gastric inflammatory diseases in rats

Preventive and curative effects of curcumin on experimental acute and chronic gastric ulcers were investigated to validate its clinical application on a remedy for peptic ulcer. Intraduodenal administration of curcumin, 5–20 mg/kg, inhibited gastric acid secretion in pylorus-ligated rats, and oral administration prevented ethanol-induced acute gastric mucosal lesions. Curcumin (20–80 mg/kg, p.o.) dose-dependently prevented both serotonin-induced gastric mucosal lesions and compound 48/80-induced gastric mucosal lesions in rats. Furthermore, oral administration of curcumin, 10–80 mg/kg, twice daily for 10 days, significantly accelerated the healing of acetic acid-induced chronic gastric ulcer and promoted mucosal regeneration in the ulcerated portion in a dose-related manner. Cimetidine prevented the formation of ethanol-induced gastric mucosal lesions, but not of serotonin-induced and compound 48/80-induced gastric mucosal lesions. Consecutive administration of cimetidine showed a marked acceleration in the healing of acetic acid-induced ulcer. Aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, showed anti-ulcerogenic effects similar to those oberved for curcumin. The present results indicate that curcumin exhibits gastric cytoprotection in the acute lesion models and ulcer healing promotion in the chronic ulcer model. The preventive and curative effects of curcumin might be due to an increase in the mucosal defensive mechanism through its antioxidant property and inhibition of NO or cytokine-mediated inflammation.     

复方铝酸铋颗粒对IL-1β致乙酸胃溃疡复发模型抑制作用的研究

目的 探讨复方铝酸铋颗粒(得必泰)对IL-1β致乙酸胃溃疡复发模型的抑制作用.方法 采用雷贝拉唑干预乙酸致大鼠胃溃疡的溃疡愈合模型,将大鼠随机分为空白组、模型组、雷贝拉唑组及得必泰组.予0.9%氯化钠溶液、雷贝拉唑及得必泰+雷贝拉唑混悬液灌胃干预溃疡愈合大鼠7周后,再予大鼠腹腔注射IL-1β诱导溃疡复发形成.检测各组大鼠血清学及病理学指标.结果 与模型组比较,雷贝拉唑组及得必泰组溃疡复发率及溃疡指数差异有统计学意义(P<0.01).与模型组比较,雷贝拉唑组PGE2、EGF含量升高,GAS明显下降(P<0.05或P<0.01);得必泰组PGE2、EGF升高和GAS下降均差异有统计学意义(P<0.05或P<0.01).得必泰组具有一定的优势倾向;雷贝拉唑组及得必泰组大鼠未复发典型溃疡的胃黏膜形态及病理组织学形态均较模型组好.结论 得必泰联合雷贝拉唑对IL-1β致乙酸胃溃疡复发具有抑制作用.     

Antiulcer activity of cod liver oil in rats

Objective:

Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o.) on gastric and duodenal ulcers.

Materials and Methods:

The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100 µg/kg, p.o.) were used as standard drugs.

Results:

Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose (0.5 g/kg, p.o.).

Conclusion:

Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats.     

胃散对胃溃疡模型大鼠胃黏膜保护作用的研究

目的 研究胃散对胃溃疡大鼠胃黏膜的保护作用。方法 采用乙酸烧灼型胃溃疡模型、幽门结扎型胃溃疡模型、乙醇损伤型胃溃疡模型,检测溃疡指数、胃酸总酸度、胃酸分泌速度和胃蛋白酶活性,综合考察胃散对胃溃疡模型大鼠胃黏膜的保护作用。结果 胃散在1、0.5、0.25 g/kg剂量下,对乙酸烧灼型胃溃疡有非常显著的促愈合作用;对幽门结扎型胃溃疡的形成有显著的抑制作用;对乙醇损伤的胃黏膜也有显著的保护作用;对胃液总酸度、胃酸分泌速度和胃蛋白酶活性有明显抑制作用,显著增加胃液分泌量。结论 胃散具有增加胃液分泌、抑制胃酸分泌、抑制胃蛋白酶活性、保护胃黏膜和防止胃溃疡的作用。     

Mouse model of Helicobacter pylori infection: studies of gastric function and ulcer healing

BACKGROUND: Helicobacter pylori infection in humans is a major risk factor for peptic ulcer, but studies on the relation between H. pylori infection and gastric pathology are limited due to a deficiency of convenient animal models resembling this infection in humans. METHODS: We studied the effects of inoculation of conventional BALB/c mice with CagA and VacA positive (type I) H. pylori or CagA and VacA negative H. pylori (type II) strains on gastric secretion and healing of chronic acetic acid-induced ulcers in mouse stomachs. The ulcer area, gastric blood flow, plasma interleukin (IL)-1beta and IL-12, as well as plasma gastrin and gastric luminal somatostatin were determined. Gastric mucosal biopsy samples were also taken for assessment of the presence of viable H. pylori using a rapid urease test, H. pylori-culture and the RT-PCR analysis of the signal for H. pylori CagA. RESULTS: Gastric acid and pepsin secretion was reduced by over 50% immediately after H. pylori inoculation and accompanied by a significant increment in plasma gastrin and fall in gastric luminal somatostatin content observed over all test days, particularly in mice infected with type I H. pylori. The area of ulcers in vehicle-treated controls decreased significantly starting from day 2 after ulcer induction and then continued to decline for a further 14 days to heal almost completely after 28 days. In contrast, the ulcers were present until day 28 in all mice infected with type I or type II H. pylori strains, being significantly larger, especially with type I H. pylori infection. The gastric blood flow at the ulcer margin and ulcer crater in vehicle-treated mice gradually increased with decreasing ulcer size, after 14 and 28 days reaching a value which was not significantly different from that in vehicle-administered mice. In contrast, the gastric blood flow in type I H. pylori and, to a lesser extent, in type II H. pylori infected mice was significantly lower than in vehicle controls, both at the margin and at the crater of ulcers at all tested days. Histological changes such as oedema or congestion of surface epithelium were found after 7 days whereas mucosal inflammatory infiltration appeared after 14 days with a further increase after 28 days, especially in type I H. pylori and to a lesser extent in type II H. pylori infected mice. Plasma IL-1beta and IL-12 were significantly elevated at all tested days of ulcer healing and their increments were significantly higher in type I than in type II H. pylori infection. CONCLUSIONS: Conventional mice with gastric ulcers can be successfully infected by both toxigenic and nontoxigenic H. pylori strains, and this infection causes an immediate suppression of gastric secretion and markedly delays the healing of ulcers due to the fall in mucosal microcirculation in the ulcer region, cytokine release and an impairment in the gastrin-somatostatin link that appears to be independent of gastritis and more pronounced with infection of toxigenic than nontoxigenic strains.     

胃甘胶囊对实验性胃溃疡的保护作用

目的:研究胃甘胶囊对实验性胃溃疡的作用.方法:采用水浸应激性、利血平型、幽门结扎型及乙酸型胃溃疡模型研究胃甘胶囊抗胃溃疡作用;以幽门结扎收集胃液观察对胃液分泌的影响.结果:胃甘胶囊对小鼠水浸应激性、利血平型及大鼠幽门结扎型胃溃疡均有明显的保护作用;对大鼠乙酸型胃溃疡有明显的促进愈合作用;能抑制大鼠胃酸的分泌并促进胃粘液分泌.结论:胃甘胶囊有抑制实验性胃溃疡的作用,该作用可能与其抑制胃酸分泌、促进胃粘液分泌有关.     

左旋泮托拉唑镁对动物实验性胃溃疡的影响

目的研究左旋泮托拉唑镁 ((- ) PAN·Mg)对动物实验性胃溃疡的影响。方法应用小鼠束水应激型胃溃疡模型、小鼠阿斯匹林型胃溃疡模型、大鼠醋酸烧灼型胃溃疡模型、大鼠幽门结扎型胃溃疡模型 ,急性胃瘘大鼠模型 ,观察口服 (- ) PAN·Mg对胃溃疡的抑制作用及对胃酸分泌的影响 ,并与右旋、消旋体进行了比较。结果 (- ) PAN·Mg对动物实验型胃溃疡具有明显的保护作用 ,能显著抑制溃疡的发生 ,抑制胃酸分泌 ,对胃溃疡的抑制效果优于 (+) PAN·Mg和 (± ) PAN·Mg。 结论 (- ) PAN·Mg的抗动物实验性胃溃疡作用和抑酸作用强于右旋 ((+) PAN·Mg)与消旋泮托拉唑镁 ((± ) PAN·Mg) ,具有良好的新药开发前景     

脑室注射催产素对大鼠胃和十二指肠溃疡的作用

INTRODUCTION Central neurons that synthesize oxytocin are locatedin the supraoptic(SON) and paraventricular nuclei(PVN) of the hypothalamus. Magnocellular neurons inboth nuclei project to the posterior pituitary gland,     

吲哚美辛对大鼠胃功能的影响及作用机制研究

目的 研究吲哚美辛对大鼠胃酸分泌及胃蛋白酶活力的影响及其作用机制。方法 大鼠分为对照组和吲哚美辛低、中、高剂量组。测定各组大鼠胃酸分泌量及胃蛋白酶活力,测定血清胃泌素含量。结果 吲哚美辛可显著增加胃酸分泌量、增加胃酸分泌速度及增加胃蛋白酶活力,促进胃泌素分泌。结论 吲哚美辛可显著促进胃酸分泌,增加胃蛋白酶活力,这与其促进胃秘素分泌有关。     

复方猴头胶囊联合雷贝拉唑治疗胃溃疡的临床研究

目的探讨复方猴头胶囊联合雷贝拉唑钠片治疗胃溃疡的临床疗效。方法选取2018年2月—2019年2月在商洛市中心医院治疗的胃溃疡患者86例,按照治疗方法的差别分为对照组(43例)和治疗组(43例)。对照组口服雷贝拉唑钠肠溶片,20 mg/次,1次/d;治疗组在对照组基础上口服复方猴头胶囊,2 g/次,3次/d。两组患者经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者症候积分,血清胃泌素(GAS)、胃动素(MTL)、生长抑素(SS)、血管内皮生长因子(VEGF)、高迁移率族蛋白B1(HMGB-1)、表皮生长因子(EGF)、白细胞介素-1(IL-1)和白细胞介素-17(IL-17)水平,及幽门螺杆菌(Hp)根除率和溃疡愈合率。结果治疗后,对照组和治疗组临床有效率分别为81.40%和97.67%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者症候评分均显著下降(P0.05),且治疗组患者这些症候积分明显低于对照组(P0.05)。治疗后,两组患者血清MTL、GAS、HMGB1、IL-1和IL-17水平显著下降(P0.05),而SS、VEGF和EGF水平升高(P0.05),且治疗组患者这些细胞因子水平明显好于对照组(P0.05)。经治疗,治疗组患者Hp根除率和溃疡愈合率均明显高于对照组(P0.05)。结论复方猴头胶囊联合雷贝拉唑钠片治疗胃溃疡可有效改善患者临床症状、胃肠激素水平,降低机体炎症反应,促进溃疡愈合。     

Influence of aging on gastric ulcer healing activities of cimetidine and omeprazole

In this study, we compared the effects of cimetidine and omeprazole on the healing of acetic acid-induced gastric ulcers in 8-, 48-, and 96-week-old rats. The repeated oral administration of cimetidine or omeprazole for 14 consecutive days markedly accelerated the ulcer healing in 8- and 48-week-old rats. However, both drugs were ineffective in 96-week-old rats. The basal gastric acid secretion of 8-, 48-, and 96-week-old rats decreased with aging. A single oral administration of cimetidine or omeprazole strongly decreased basal gastric acid secretion in the three different ages of rats. Cimetidine and omeprazole produced a potent and sustained serum gastrin-elevating action in 8- and 48-week-old rats. However, the gastrin-elevating actions of both drugs in 96-week-old rats were much weaker than in the 8- and 48-week-old rats. These results indicate that cimetidine and omeprazole have potent gastric ulcer healing actions in 8- and 48-week-old rats, as well as potent serum gastrin-elevating actions, but both drugs are ineffective in 96-week-old rats, which have lost their gastrin-elevating actions.     

注射用雷贝拉唑钠对不同溃疡模型大鼠的影响

目的 比较注射用雷贝拉唑钠对不同溃疡模型大鼠的影响。方法 采用幽门结扎法收集胃液,测定注射用雷贝拉唑钠0.5、1.0、2.0、4.0、8.0 mg/kg对大鼠胃液酸度、胃酸总分泌量的影响。制备吲哚美辛引起的胃溃疡模型、醋酸性胃溃疡、大鼠反流性食管炎以及半胱胺型十二指肠溃疡,模型动物iv给予注射用雷贝拉唑钠后,对溃疡进行评分,计算溃疡抑制情况。结果 ①与模型组比较,注射用雷贝拉唑钠8 mg/kg组胃液分泌量,0.5、4.0、8.0 mg/kg组胃液酸度,2、4、8 mg/kg剂量组胃酸分泌量均显著降低（P<0.05、0.01）。②与模型组比较,0.5、1.0、2.0、4.0 mg/kg剂量组吲哚美辛引起的溃疡得分均显著降低（P<0.05、0.01）。③注射用雷贝拉唑钠1 mg/kg对大鼠醋酸性胃溃疡、反流性食管炎、半胱胺型十二指肠溃疡抑制率分别为18.2%、37.5%和23.4%,其中对反流性食管炎的抑制作用具有显著性差异（P<0.05）。结论 注射用雷贝拉唑钠抑制胃酸分泌,对吲哚美辛引起胃溃疡、反流性食管炎、十二指肠溃疡和醋酸性胃溃疡均有抑制作用。     

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.     

Inhibitory effects of devil’s claw (secondary root of <Emphasis Type="Italic">Harpagophytum procumbens</Emphasis>) extract and harpagoside on cytokine production in mouse macrophages

Successive oral administration (50 mg/kg) of a 50% ethanolic extract (HP-ext) of devil’s claw, the secondary root of Harpagophytum procumbens, showed a significant anti-inflammatory effect in the rat adjuvant-induced chronic arthritis model. HP-ext dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] in mouse macrophage cells (RAW 264.7). Harpagoside, a major iridoid glycoside present in devil’s claw, was found to be one of the active agents in HP-ext and inhibited the production of IL-1β, IL-6, and TNF-α by RAW 264.7.     

Effect of 11R, 16, 16-trimethyl prostaglandin E2 on meal-stimulated gastric acid secretion in duodenal ulcer subjects

The effect of varying oral doses of 11R, 16, 16-trimethyl prostaglandin E2 (TmPGE2) on meal-stimulated gastric acid secretion and serum gastrin concentrations was studied in 10 male subjects with asymptomatic duodenal ulcer disease. A liquid protein meal was infused intragastrically 0.5 h and 3.5 h after drug administration. TmPGE2 inhibited gastric acid secretion in a dose dependent manner during the first meal and no significant effect was observed during the second meal. Except for the highest dose, no TmPGE2 was detected in plasma 3 h after drug administration. The degree of inhibition of meal-stimulated gastric acid was positively correlated with the plasma level of TmPGE2, but it was not due to inhibition of postprandial gastrin release. The results indicate that oral TmPGE2 inhibits meal-stimulated gastric acid secretion but not gastrin release in humans with asymptomatic duodenal ulcer disease.     

Zollinger-Ellison syndrome and antral G-cell hyperfunction in patients with resistant duodenal ulcer disease

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16%vs duodenal ulcer 2%P= 0.0144). In the presence of duodenal ulcer disease resistant to H₂-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.     

Luminal Nalpha-methyl histamine stimulates gastric acid secretion in duodenal ulcer patients via releasing gastrin

Nalpha-methyl histamine is an unusual histamine metabolite which is produced in the stomach infected by Helicobacter pylori and which was shown in animals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence on gastric secretion and gastrin release in duodenal ulcer patients before and after H. pylori eradication. In this study, we compared the effects of intragastric administration of single or graded doses of Nalpha-methyl histamine on gastric acid secretion and plasma gastrin levels in 16 male duodenal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal histamine and gastrin contents were determined before and after H. pylori eradication. In H. pylori-infected duodenal ulcer patients, the intragastric application of Nalpha-methyl histamine failed to affect gastric acid secretion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and plasma gastrin levels, were significantly reduced. Nalpha-methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duodenal ulcer patients was found to increase dose-dependently gastric acid output reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v. infusion of 25 microg/kg h of histamine dihydrochloride. We conclude that Nalpha-methyl histamine is a potent luminally active stimulant of gastrin release and gastric acid secretion in H. pylori-eradicated patients when luminal histamine is low but is not effective in H. pylori infected patients when luminal histamine is enhanced, possibly due to desensitization of gastrin (G-cells) and acid-producing (parietal) cells by Nalpha-methyl histamine produced excessively in H. pylori-infected stomach.