Gastric Ulcer Healing with Ranitidine and Cimetidine

A single-blind study of 339 patients in 19 centres compared the efficacy and tolerance of ranitidine in treating endoscopically confirmed gastric ulcers. Ranitidine (150 mg twice daily) was compared with cimetidine (1 g daily in divided doses) over 4 weeks, followed by a second 4-week treatment for any patient whose ulcer was not healed. In 292 patients who completed the study, endoscopy showed healing in 69% of patients receiving ranitidine and 59% receiving cimetidine after 4 weeks, and 90% and 88%, respectively, by 8 weeks. These results were not significantly different, and, similarly, healing rates for different ulcer sites did not differ. There were no serious adverse drug reactions during the study. Ranitidine is an effective and safe treatment for healing gastric ulcers, with a tendency to produce a faster healing rate than cimetidine during the first 4 weeks of treatment.     

Transforming Growth Factor Alpha and Epidermal Growth Factor in Protection and Healing of Gastric Mucosal Injury

Transforming growth factor alpha (TGF) and epidermal growth factor (EGF) present in the gastric mucosa are polypeptides with similar biologic activity. This study compares the activity of TGF and EGF in the protection against injury by 100% ethanol and stress and in healing of acute gastric ulcerations. TGF and EGF (12.5-100 μg/kg-h) infused subcutaneously 30 min before and during ethanol or stress decreased mucosal lesions dose-dependently. The ID₅₀ for ethanol- and stress-induced lesions after TGF were 40 and 70 μg/kg-h and after EGF 60 and 100 ug/kg-h. TGF and EGF infused subcutaneously into intact rats inhibited gastric acid secretion but did not affect the gastric blood flow or mucosal generation of prostaglandin E₂ (PGE₂). Both TGF and EGF also significantly enhanced the healing of stress-induced lesions and the restoration of DNA synthesis. Ethanol and stress reduced blood flow in the oxyntic mucosa by 68% and 51%, respectively, and this effect was partially reversed by EGF and TGF. Pretreatment with indomethacin (5 mg/kg intraperitoneally), which reduced mucosal generation of PGE₂ by 85%, decreased in part the protection by TGF and EGF against ethanol-induced damage and virtually abolished the protective action of these peptides against stress-induced injury. We conclude therefore that 1) TGF and EGF show similar and comparable gastroprotective activity against ethanol- and stress-induced damage; 2) the protection by TGF and EGF is accompanied by an increase in gastric blood flow which appears to be an essential factor in gastroprotection; 3) mucosal PG is necessary for manifestation of the protective activity of TGF and EGF against acute gastric damage; and 4) TGF and EGF enhance the healing of gastric lesions, possibly via stimulation of DNA synthesis and cell proliferation.     

A Synthetic Prostaglandin E2 Analogue,Enprostil, Hastens Gastric Emptying of Solids in Patients with an Active Duodenal Ulcer

The effect of gastric emptying of two doses (35 and 70μg) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 ± 0.38 min^?1· 10^?2 after placebo to 2.77 ± 0.56 min^?1 · 10^?2 after 35 μg enprostil (p < 0.05 versus placebo) and to 3.65 ± 0.64 min^?1 · 10^?2 after 70 μg enprostil (p < 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 ± 6.9% after placebo, 35.2 ± 7.4% after 35 μ enprostil, and 24.1 ± 8.4% after 70 μg enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.     

丹参对胃溃疡大鼠血清一氧化氮含量和胃粘膜表皮生长因子受体表达的影响

目的：观察胃溃疡大量血清一氧化氮（NO）含量,溃疡周围粘膜上表皮生长因子受体（EGFR）表达,研究其与丹参改善微循环及促进胃粘膜上皮细胞增生之间的关系,进而阐明丹参抗胃溃疡的可能机制。方法：大鼠30只。随机分为对照组、模型组和丹参组,采用硝酸还原酶法测定动物血清NO含量,免疫组织化学方法测定胃粘膜EGFR表达,结果：丹参组NO含量较模型组显著升高,EGFR表达亦较模型组显著增强（P＜0．05）。结论：丹参可能通过NO、EGFR等介导改善胃溃疡大胃粘膜微循环及促进胃粘膜上细胞增生,从而发挥抗胃溃疡作用。     

人胃癌细胞膜表皮生长因子受体的表达

用~(125)Ⅰ标记的人类表皮生长因子(~(125)Ⅰ-EGF)与分离制备的胃癌和癌旁组织细胞膜进行放射配体结合试验。胃癌细胞膜~(125)Ⅰ-EGF结合量为13.5±3.84fmol/mg膜蛋白,癌旁组织为6.15±1.65fmol/mg膜蛋白,两者差异显著(22例,t=8.25,P<0.01)。高分化组胃癌~(125)Ⅰ-EGF结合量显著低于低分化组胃癌(P<0.05)。Scatchard分析表明,胃组织细胞膜EGF受体是一种单一亲和力的受体。胃癌~(125)Ⅰ-EGF最大结合力(B_(max)=26.15±2.17fmol/mg膜蛋白)高于癌旁正常组织(B_(max)=19.87±2.81 fmol/mg膜蛋白),两者差异显著(t=2.95,P<0.05)。胃癌EGF受体的亲和力(K_D=11.13±0.22nM)大于癌旁正常组织(K_D=1.79±0.23nM),两者差异显著(t=3.59,P<0.05)。本研究表明,胃癌细胞膜表面EGF受体在数量和亲和力两方面都有显著改变,提示在胃癌的发生发展过程中,EGF受体与其配体所形成的自/旁分泌增殖环可能起着重要的生长调节作用     

Expression of Hepatocyte Growth Factor and c-Met Receptor in Gastric Mucosa during Gastric Ulcer Healing

Background: Ethanol is generally believed to inhibit extracellular Ca 2+ influx, thereby inhibiting gastric muscle contraction. Recently, we observed that verapamil inhibited only the amplitude of spontaneous phasic contractions, whereas ethanol inhibited both amplitude and frequency. In our objective to investigate the mechanism of ethanol's inhibition of gastric motility, the involvement of various protein kinases in ethanol-inhibited spontaneous phasic contractions of the stomach muscle strips was tested. Methods: Circular muscle strips (2.0 × 0.2 cm) were prepared from the corpus of cat stomach in order to measure isometric contraction in a chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 °C) bubbled with 5% CO 2 in O 2. Results: Spontaneous phasic contraction was not affected by various receptor antagonists (1 μM atropine, 1 μM hexamethonium, 1 μM phentolamine and 1 μM propranolol) or 1 μM tetrodotoxin. EGTA and verapamil dose-dependently inhibited only the amplitude of spontaneous phasic contractions and not the frequency. Ethanol dose-dependently inhibited both the amplitude and frequency of phasic contractions. The amplitude and frequency of spontaneous phasic contractions were significantly inhibited by protein kinase C and tyrosine kinase inhibitors. However, neither protein kinase C activator nor various phosphatase inhibitors blocked the inhibitory effect of ethanol. Conclusions: Ethanol appears to inhibit spontaneous phasic contractions by a mechanism other than the inhibition of protein kinase C or tyrosine kinase or the inhibition of extracellular Ca 2+ influx.     

表皮生长因子和胃泌素在胃癌组织中的表达及意义

目的 探讨表皮生长因子(EGF)和胃泌素(GAS)在胃癌组织中的表达,及其相互关系与意义.方法 选取我院2003年1月～2009年12月经病理确诊的胃癌(GC)70例,慢性浅表性胃炎(CSG)25例,经过纳入标准及排除标准的筛选而作为研究对象.采用免疫组织化学Envision方法,检测EGF、GAS在各组胃黏膜组织中的...     

乳香提取物对大鼠乙酸胃溃疡愈合质量的影响

目的:研究乳香提取物对大鼠乙酸胃溃疡愈合质量的影响.方法:用冰醋酸制备大鼠慢性胃溃疡模型,随机分为6组,分别灌服0.85%氯化钠溶液、乳香提取物、雷尼替丁等.用苏木精-伊红染色、粘液组织化学染色和苦味酸-酸性品红染色对大鼠愈合性胃溃疡再生粘膜厚度、再生粘膜粘液含量、囊状扩张腺体数量、炎症细胞浸润数量等进行定量观察.结果:乳香提取物组再生粘膜厚度增加、囊状扩张腺体数量减少和粘液高碘酸无色品红(PAS)含量增加;肉芽组织胶原含量增加,炎症细胞浸润数量减少.结论:乳香提取物能提高溃疡再生粘膜结构和功能成熟度,提高溃疡愈合质量.     

Impairment of Gastric Ulcer Healing by Alendronate,a Nitrogen-Containing Bisphosphonate,in Rats

Bisphosphonates such as alendronate have been developed as antiresorptive agents capable of treating diseases related to bone remodeling. In the present study, we examined the effect of alendronate on the healing of acetic acid-induced gastric ulcers in rats and investigated the mechanism involved in this action both in vivo and in vitro using the rat gastric epithelial cell line (RGM1). Acetic acid-induced gastric ulcers healed spontaneously, with up-regulation of COX-2/prostaglandin E₂ production as well as expression of vascular endothelium-derived growth factor (VEGF) and basic fibroblast growth factor (bFGF) in ulcerated mucosa. The healing of ulcers was impaired by indomethacin (2 mg/kg, s.c.) or alendronate (60 mg/kg, p.o.) given once daily for 7 days, starting 3 days after acid application. Indomethacin, but not alendronate, inhibited mucosal prostaglandin E₂ production. Alendronate as well as indomethacin decreased the protein expression of both VEGF and bFGF in ulcerated mucosa, resulting in a reduction of angiogenesis in the ulcer base. Supplementation of recombinant bFGF significantly reverted the delay in ulcer healing caused by alendronate. On the other hand, the size of cell-free areas in RGM1 cells in vitro decreased with time after wound induction, and this process was promoted by epidermal growth factor (EGF; 10 ng/ml). Co-incubation with alendronate (1 mM) did not affect the spontaneous healing but significantly suppressed the accelerated wound healing caused by EGF. These results suggest that alendronate impairs the healing of gastric ulcers in rats, and this effect may be related to down-regulation of VEGF and bFGF, the important growth factors for vascularization/granulation, as well as suppression of the stimulatory action of EGF on epithelial proliferation/migration.     

胃灵颗粒对大鼠乙酸胃溃疡愈合质量的影响

目的 :研究胃灵颗粒对大鼠乙酸慢性胃溃疡愈合质量的影响。方法 :用冰醋酸制备大鼠乙酸慢性胃溃疡模型 ,随机分为 5组 ,分别灌服蒸馏水 ,雷尼替丁 ,低、中、高剂量胃灵颗粒 ,用苏木精 -伊红染色对大鼠愈合性胃溃疡再生粘膜进行定量观察 ,并测胃壁结合粘液量、胃酸、胃蛋白酶活性。结果 :胃灵颗粒组改善胃粘膜的组织损伤 ,并提高胃壁结合粘液量 ,减少胃酸的排出。结论 :胃灵颗粒能提高溃疡愈合质量 ,是临床抗消化性溃疡复发的可能机制之一。     

Effect of Ranitidine on the Content of Glyceroglucolipids in Gastric Secretion of Patients with Gastric and Duodenal Ulcer

The glyceroglucolipids content of basal and pentagastrin-stimulated gastric secretion was measured in male patients with gastric (12) and duodenal (12) ulcer. Six patients in each group received twice daily for a period of 4 weeks 150 mg of ranitidine, whereas the other patients received placebo. The glyceroglucolipids output in the basal secretion of patients with gastric and duodenal ulcer before treatment was similar and increased 2.7-fold after pentagastrin stimulation. In all patients treated with ranitidine, the mean output of glyceroglucolipids after pentagastrin stimulation increased from 1.38 to 2.05 μmol/h (P < 0.05). This increase, however, was more pronounced in the duodenal ulcer group than in the gastric ulcer patients. No change in glyceroglucolipids output was noted in the patients treated with placebo. The ratio of glyceroglucolipids to HCl increased significantly (P < 0.02) only in the ranitidine-treated patients.     

表皮生长因子治疗糖尿病足溃疡的研究进展

糖尿病足是糖尿病常见的慢性并发症之一,15%的糖尿病患者可能发生足部溃疡。溃疡创面局部生长因子及受体活性下降和数量的绝对或相对缺乏是其难以愈合的病理生理基础。表皮生长因子(EGF)通过促进细胞迁移、增殖及细胞外基质合成等参与溃疡创面愈合。外源性EGF作为一种新的治疗手段,局部应用于糖尿病足溃疡取得显著效果。通过组织工程学技术,EGF释药方式不断改善,并可与其他生长因子联合应用,具有广泛前景。     

消化性溃疡根除幽门螺杆菌前后血中前列腺素E_2和表皮生长因子变化的临床研究

重点研究消化性溃疡(Pu)中幽门螺杆菌(HP)与前列腺素E_2(PGE2)和表皮生长因子(EGF)之间的关系。胃镜证实良性消化性溃疡39例,HP均为阳性,男26例,女13例,平均年龄41.2岁,接受德诺、弗莱莫新、灭滴灵“三联”治疗。停药4周后复查胃镜了解PU和HP的治疗情况,并在治疗前和复查后分别给患者抽血2ml用放免方法检测PGE2和EGF的变化情况,结果HP根除前PGE_2高于正常组,EGF低于正常组;HP根除后,PGE_2和EGF均接近正常。说明HP的存在不仅起着溃疡的致病作用,而且影响保护胃肠粘膜的胃肠激素水平,同时可将PGE_2和EGF作为判断根除HP的疗效指标之一。     

Acute Effects of Smoking during Modified Sham Feeding in Duodenal Ulcer Patients: An Analysis of Nicotine,Acid Secretion,Gastrin, Catecholamines,Epidermal Growth Factor,Prostaglandin E2, and Bile Acids

Smoking is associated with an increased incidence of duodenal ulcer with a high relapse rate, and smokers tend to be slow healers. The etiology responsible for this remains unknown, and there is general disagreement as to whether smoking affects gastric secretion. The aim of the present study was to investigate both aggressive and protective factors in response to vagal stimulation induced by modified sham feeding (MSF) in duodenal ulcer patients when smoking versus not smoking. On smoking days, nicotine concentrations in plasma averaged about 15 ng/ml and were extremely high in saliva and gastric juice (>1300 and >800 ng/ml, respectively). MSF induced a significant decrease in intragastric pH during non-smoking (p = 0.01) but not during smoking. Acid output 1 h after MSF was lower on smoking than on non-smoking days (p = 0.02), as was volume secretion (p = 0.02). Plasma gastrin concentrations were significantly increased during MSF on non-smoking days (p = 0.04) but not on smoking days, the concentrations during the whole day being lower on smoking days (p = 0.002). Plasma catecholamine levels were unaffected by MSF, whether smoking or not. However, plasma concentrations of noradrenaline decreased during the smoking of a single cigarette (p = 0.03), whereas those of adrenaline were increased on smoking days (p = 0.02). Epidermal growth factor concentrations were decreased in gastric juice after MSF during non-smoking (p = 0.01) but not during smoking. Although prostaglandin E₂ (PGE₂) concentrations in gastric juice were unaffected by MSF, PGE₂ output increased after MSF whether smoking or not, the increment being non-significantly less during smoking (p = 0.09). Neither MSF nor smoking seemed to affect bile reflux. The results of this study indicate that factors other than stimulated gastric acid secretion are responsible for the increased ulcer susceptibility in smokers. Possibly, the very high nicotine concentrations in gastric juice affect the cytoprotective properties of the mucosa and may even have a direct toxic effect on the epithelial cells.     

表皮生长因子对胃粘膜保护作用的机理初探

报道表皮生长因子（ＥＧＦ）保护胃粘膜抵制损伤的作用。实验采用多普勒激光流量仪测定ＧＭＢＦ，将ＳＤ鼠随机分成两组（移出内源性ＥＧＦ组和未移出组）并应用不同剂量外源性ＥＧＦ，观察其对ＧＭＢＦ和胃损伤的影响。结果显示：移出组加重酒精诱发的胃损伤（Ｐ＜０．０５），对ＧＭＢＦ虽有所下降，但无统计学意义。在预先加用外源性ＥＧＦ织，胃粘膜损伤减轻，ＧＭＢＦ增加（二者Ｐ＜０．０５），而且ＧＭＢＦ增长与ＥＧＦ剂量（从３．２５μｇ～２５μｇ）呈正相关，相关系数ｒ＝０．６８，Ｐ＜０．００１；与损伤指数呈负相关，ｒ＝－０．７５，Ｐ＜０．００１。因此本文结论是ＥＧＦ对粘膜的保护可能是通过完整的ＧＭＢＦ所介导。     

Changes in Gastric Mucosal Blood Flow during Healing of EMR-Induced Ulcer

Abstract: We used the laser Doppler method to study the difference in gastric mucosal blood flow changes between peptic ulcer (65 cases) and artificial ulcer caused by endoscopic mucosal resection (35 cases) during their respective healing processes. At each endoscopic ulcer stage, blood flow at the ulcer margin and that in the surrounding mucosa were measured. In the artificial ulcer, which heals easily, blood flow at the ulcer margin was still high at the scarring stage as compared with that in the corresponding area of a peptic ulcer, which is prone to relapse. Moreover, the blood flow ratio (blood flow at the ulcer margin/blood flow in the surrounding mucosa) at the S1 stage in artificial ulcers was significantly higher than that in peptic ulcers (p<0.05). These results suggest that blood flow in the SI stage is an important aspect of ulcer healing and relapse.     

乙酸性胃溃疡大鼠一氧化氮、内皮素及表皮生长因子受体相互关系研究

目的 :探讨一氧化氮 (NO)、内皮素 (ET- 1)、表皮生长因子受体 (EGFR)在乙酸性慢性胃溃疡大鼠中的作用及相互关系。方法 :采用乙酸性慢性胃溃疡疾病模型 ,游标卡尺测定溃疡指数 ,硝酸还原酶法测定 NO含量 ,放射免疫法检测血浆 ET- 1含量 ,SABC免疫组织化学方法及图像分析观察 EGFR在溃疡周围粘膜的表达。结果 :左旋精氨酸 (L - Arg)组溃疡指数与模型组及亚硝基左旋精氨酸 (L - NNA )组比较显差有显著性意义 (P <0 .0 5 ,<0 .0 1) ;L- Arg组血清 NO及血浆 ET- 1含量与对照组、模型组及 L- NNA组比较差异有显著性意义 (P <0 .0 5 ,<0 .0 1) ;L - NNA组血清 NO及血浆 ET- 1含量与模型组及对照组比较差异均有非常显著性意义 (均 P <0 .0 1) ;L -Arg组 EGFR表达较模型组、L- NNA组及对照组显著增加 (积分光密度值及阳性细胞占总面积百分比均 P <0 .0 5 ) ;L- NNA组 EGFR显著弱于模型组 (P<0 .0 1)。结论 :NO前体 L- Arg可以诱导、促进 NO合成 ,反馈性地抑制 ET- 1的释放 ,从而维持 NO和 ET的动态平衡及胃粘膜 EGFR正常水平表达 ,促进溃疡愈合。     

Gastric Mucosal Cell Cycle Regulation with Ulcer Healing by Sulglycotide

Background: The progression of the events associated with gastric mucosal repair is controlled in an orderly manner by a plethora of the extracellular cues exerting their effect on the cell cycle regulatory proteins, cyclins, and cyclin-dependent kinases, the expression of which varies through the cycle stages. The purpose of this study was to evaluate the expression of cyclin-dependent kinase (Cdk2) and proliferating cell nuclear antigen (PCNA) during chronic ulcer healing with sulglycotide. Methods: Rats with experimentally induced gastric ulcers were treated twice daily for 14 days either with sulglycotide at 200 mg/kg or vehicle, and at different stages of the treatment their stomachs were used for macroscopic damage assessment and quantitation of gastric mucosal Cdk2 and PCNA expression. Results: The assays showed that the ulcer healing was accompanied by an increase in mucosal expression of Cdk2 and PCNA. The maximum increase in Cdk2 (2.3-fold) occurred by the 4th day of healing, whereas the expression of PCNA reached a maximum increase (4.7-fold) on the 2nd day of healing. An accelerated ulcer healing (10 days) with sulglycotide treatment was reflected in a marked enhancement in Cdk2 and PCNA. In comparison with the controls, sulglycotide caused a 2.2-fold enhancement in PCNA expression by the 2nd day of treatment and a 2.5-fold enhancement by the 6th day, whereas the Cdk2 expression attained a maximum 2.1-fold increase by the 6th day of treatment and remained substantially increased for up to 10 days. Conclusions: The findings show a complex interplay between the extracellular cues and cell cycle regulatory proteins, an orderly progression that drives the mucosal repair process. We also show that the gastroprotective agent sulglycotide is capable of affecting the expression of the cell cycle regulatory proteins that control cell cycle progression through Gl and into S phase.     

心室间隔缺损患儿血清表皮生长因子测定及其意义

目的：了解先天性心脏病患儿心室间隔缺损（室缺）自然愈合与血清表皮生长因子水平的关系。方法：将７２例室缺患儿分为自愈组（３５例）、大型未愈组（１７例）、小型未愈组（２０例）、正常对照组（４０例），并对其中的部分病例作了１年以上的随访。结果：各组的血清表皮生长因子自愈组为３．７２±１．２８μｇ／Ｌ，大型未愈组为２．０６±０．５６μｇ／Ｌ，小型未愈组为２．１３±０．７８μｇ／Ｌ，正常对照组为３．４０±１．０３μｇ／Ｌ；室缺患儿的体肺循环流量比值与血清表皮生长因子无显著的相关性；随访者中血清表皮生长因子持续较高者，室缺自然愈合的变化较明显。结论：室缺的存在和不愈可能与血清表皮生长因子水平较低有关，正常水平的血清表皮生长因子可能有助于室缺的自然愈合。     

Changes in Gastric Function During Healing of Gastric Ulcers

Abstract: To determine changes in pathophysiology during the healing process of gastric ulcers, gastric acid secretion, gastric emptying, fasting gastrin levels (FGL) and the integrated gastrin response (IGR) were studied in normal volunteers and in each stage of gastric ulcers. In a study of patients with gastric ulcers in the lesser curvature of the ventricular angulus including 20 in the active stage, 49 in the healing stage and 11 in the healed (scar) stage, gastric acid secretion (BAO and MAO) and FGL gradually decreased as the patients progressed from the active stage through the healing and healed stages. IGR values did not change, but gastric emptying showed marked prolongation in the active and healing stages although this was alleviated in the healed stage. In 11 of the same gastric ulcer patients who were followed up, gastric acid secretion, especially BAO, was lower in the healed stage than in the active stage. No fixed tendency was seen for gastric emptying and IGR, but FGL showed higher values in the active stage than in the healing stage. These findings indicated that changes in the pathophysiology of the stomach occur during the healing of gastric ulcers, and it was assumed that these changes are closely related to the stage of the ulcer.