Relationship between ethanol-induced gastritis and gastric ulcer formation in rats

BACKGROUND/AIMS: Patients with peptic ulcer diseases have a high prevalence of coexisting chronic gastritis. The mechanism of how gastritis leads to gastric ulcer formation is yet to be determined. The purpose of this study was to clarify the relationship between gastritis and gastric ulcer in rats. METHODS: Ethanol (80% v/v, p.o.) was given repeatedly in rats to induce subchronic gastritis. Gastric ulcer was then induced by 60% acetic acid. RESULTS: Findings showed that subchronic gastritis potentiated gastric ulcer formation. It also produced more apoptotic cells, together with an overexpression of tumor necrosis factor-alpha (TNF alpha) in the gastric mucosa. Inhibition of the production/release of TNF alpha by pentoxifylline prevented the increase in apoptosis and the enhancement of susceptibility to ulcerative damage by subchronic gastritis. However, such subchronic gastritis did not further affect the rate of ulcer healing in these animals. CONCLUSION: The induction of gastritis resulted in an activation of TNF alpha expression followed by apoptosis in the gastric mucosa. This could lead to an increase in the severity of ulcerative damage in the stomach.     

Mechanisms of action of leptin in preventing gastric ulcer

AIM: To investigate the effects of leptin (1-20 ^g/kg) on acidified ethanol (AE)- and indomethacin (Indo)-induced gastric lesions in rats and compare it with ranitidine, lanso-prazole, and omeprazole and to determine its mechanisms of actions. METHODS: Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors (PPIs) lansoprazde and omeprazole, or H2-receptor antagonist ranitidine 30 min before AE or Indo was evaluated. A radioimmunoassay was used to determine the PGE2 concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content. RESULTS: Subcutaneous administration of leptin, two PPIs lansoprazole and omeprazole or H2-receptor antagonist ranitidine 30 min before AE or Indo produced a dose-dependent and reproducible inhibition of gastric ulcers (GUs). This inhibition was found to be more potent than other antagonists used. In NG-nitro L-arginine methyl ester (L-NAME)-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced, compared to rats without L-NAME pretreatment. However, the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE2 level in the gastric glandular tissues. Leptin also increased mucus secretion. CONCLUSION: The results of the present study show that leptin inhibits GU formation by AE or Indo in a dose-dependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.     

Enzyme Immunoassay of Gastric Luminal Prostaglandin E2 in Duodenal Ulcer Disease

A highly sensitive enzyme immunoassay was used to determine gastric juice prostaglandin E2 (PGE2) levels in control subjects with or without gastritis and in both active or inactive duodenal ulcer patients. Mean pentagastrin-stimulated PGE2 concentration was significantly lower in patients with duodenal ulcer than in control subjects considered as a whole group (with or without gastritis). However, no such difference was found between duodenal ulcer patients and controls showing histologically normal gastric mucosa. On the other hand, controls with chronic superficial gastritis had PGE2 levels significantly higher than those of histologically normal subjects and duodenal ulcer patients. Therefore, it seems unlikely that an absolute gastric PGE2 deficiency is involved in the pathogenesis of duodenal ulcer disease. However, the possibility that PGE2 synthesis could be deficient in relation to the prevailing level of mucosal inflammation cannot be excluded.     

Gastric mucosal prostaglandin E2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal disease, and in healthy subjects

Investigations were carried out as to whether a disturbance in the formation of cytoprotective prostaglandin (PG) E2 in gastric mucosa is implicated in chronic renal failure. PGE2-like immunoactivity in gastric mucosal specimens was measured in individuals with chronic renal failure (creatine clearance less than 10 ml/min), in individuals without any renal disease, presenting either gastric ulceration or not, as well as in healthy subjects. Regardless of the group of patients, compared to normal mucosa a significant decrease in PGE2-like immunoactivity (about 50-70%) was found in mucosa from atrophic gastritis but not from superficial gastritis. Whenever patients of the control group or patients with kidney disease suffered from ulcers, PGE2-like immunoactivity showed a decrease of about 60-70% in the non-ulcerated mucosa compared to that of non-ulcer subjects. Moreover, ulcer patients showed the same frequency of gastritis and similar mucosal PGE2-like immunoactivity in their non-ulcerated mucosa. Furthermore, compared to the tissue from the ulcer edge, independent of the presence of renal disease, a relative deficiency of PGE2-like immunoactivity of about 50-60% was detected in the non-ulcerated mucosa of ulcer patients. We therefore conclude that chronic renal failure probably has no impact on PGE2 formation in the gastric mucosa. All told, relative mucosal PGE2 deficiency in gastric ulcer disease seems not to be correlated with chronic renal failure.     

Simultaneous measurement of in vitro gastroduodenal prostaglandin E2 synthesis and degradation in peptic ulcer disease

The ability of mucosal specimens from the stomach and duodenum to synthesize and degrade prostaglandin E2 has been determined in normal subjects and peptic ulcer patients. Significant reduction in fundic PGE2 synthesis capacity was observed in gastric ulcer patients. There was also significant reduction in the PGE2 degradation capacity of antral, fundic, and duodenal mucosal specimens in gastric ulcer patients. Patients with gastritis showed significant elevation of both antral and fundic PGE2 synthesis capacity compared with normal but no alteration in PGE2 degradation. No differences were observed in PGE2 synthesis and degradation rates in patients with duodenal ulcer. The results argue in favour of an association between impairment of PGE2 metabolism in the mucosa of patients with gastric but not duodenal ulceration.     

“胃忧愈”治疗消化性溃疡临床及实验研究

本文对纤维胃镜证实的41例消化性溃疡患者进行了随机,对照研究。结果表明：“胃忧愈”治疗组8周病状消失率达80．0％,愈合率为75．0％,疗效与甲氰咪胍组相似（后者各为76．2％,66．7％）,但本药对幽门螺杆菌（Helicobacter pylori,HP)的清除率（45．0％）,合并的慢性胃窦炎好转率（50．0％）和慢性胃炎急性活动消失率（55．0％）显著高于对照组（分别为19．0％,14．3％,14．3％）。动物实验表明该方剂对无水乙醇所致胃粘膜损伤具有细胞保护作用。其机制与胃粘膜PGE2,胃酸无关,而与促进胃粘液分泌,加强粘液－碳酸氢盐屏障有关。     

The clinical significance of Campylobacter pylori

Campylobacter pylori has recently been isolated from gastric mucosal biopsy specimens. Campylobacter pylori has many attributes in common with other campylobacters but it may represent a new genus. It produces abundant quantities of urease, and this property has been used to develop a rapid diagnostic test. The organism is found predominantly beneath the gastric mucus layer that lines the surface epithelium of the stomach. Infection with C. pylori causes an acute histologic gastritis which may become chronic. The bacterium is the etiologic agent in type-B gastritis. Prevalence of the organism in asymptomatic persons appears to be age related. Campylobacter pylori is found commonly in patients with peptic ulcer disease, always in association with chronic gastritis. Eradication of the organism is associated with healing of the gastritis and a lower relapse rate in duodenal ulcer disease. A role for the organism in other upper gastrointestinal diseases is unproven.     

Effects of nitric oxide on gastric ulceration induced by nicotine and cold-restraint stress

AIM: Stress induces gastric ulceration in human and experimental animals. People tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine have opposing effects on gastric integrity. The present study examined the possible therapeutic benefit of NO in nicotine-treated rats with stress-induced gastric ulceration. METHODS: Rats drank a nicotine solution while control rats drank tap water for 20 days. The alkoloid was then replaced by water with or without supplementation of isosorbide dinitrate (NO donor) for an additional 10 days. Isosorbide dinitrate was given twice shortly before experiments (acute) or three times daily by oral gavages for 10 days after the rats stopped drinking nicotine solution. At the end of experiments, ulcer index, gastric adhesion mucus content and MPO activity were measured and analysed. RESULTS: Nicotine treatment decreased gastric mucus content and intensified stress-induced gastric ulcer. A higher ulcer index persisted even after the rats stopped drinking nicotine solution for 10 days. Acute NO donor showed no benefit on both mucus and ulcer index in nicotine treatment or/and stress condition. Chronic NO donor treatment reversed the worsening action of nicotine in stomach. Stress increased gastric mucosal myeloperoxidase (MPO) activity, which was antagonized by chronic NO treatment. However, nicotine was unlikely to change mucosal MPO activity. CONCLUSION: The intensifying action of nicotine on stress-induced gastric ulceration persists for 10 days after cessation. Nicotine treatment significantly decreases gastric mucus content that can be restored by chronic NO donor treatment. The present study suggests that NO antagonizes the ulcerogenic action of nicotine through a cytoprotective way.     

Relation between Helicobacter pylori and intractable gastric ulcer--PAS positive intramucosal mucus as an index]

Helicobacter pylori (Hp) is considered to be one of the causes of gastric mucosal injury. Using biopsy specimens from the gastric mucosa of patients with gastritis or gastric ulcer, the intramucosal mucus was quantified by computer image analysis to evaluate its relationship with Hp. In gastric mucosa positive for Hp, the mucus content within the gastric mucosa was significantly decreased. Ammonia was administered based on its assumed role in decreasing the mucus content of the gastric mucosa, and resulted in a decrease in rats to whom it was administered. Based on these results, cases of intractable gastric ulcer were studied. In these intractable cases, Hp was present significantly more often than in other cases and the intramucosal mucus content was significantly lower. These findings suggest that Hp may be a factor in the resistance of gastric ulcer to treatment.     

Gastric mucosal PGE2 levels in gastric nonulcer and ulcer patients with chronic renal failure or without renal diseases and in healthy subjects

PGE2-like immunoactivity in mucosal specimens from gastric corpus and antrum was measured in individuals with chronic uremia or without renal diseases in absence or presence of gastric ulcerations and in healthy subjects. Regardless the group of patients, compared to normal mucosa, a significant decrease in PGE2-like immunoactivity (50-70%) was found in mucosa from atrophic, but not from superficial gastritis. Whenever patients of the control group or patients with renal diseases suffered from ulcers, PGE2-like immunoactivity, compared to nonulcer subjects, revealed a decrease of about 60-70% in the nonulcerated mucosa. Compared to nonulcerated mucosa, the tissue of the ulcer rim in all patients with gastric ulcer showed a relative increase in PGE2-like immunoactivity, eg, PGE2-like immunoactivity was twice as high in tissue from the ulcer rim. The output of PGE2-like immunoactivity into the gastric juice of subjects without renal diseases was comparable to that found in patients with chronic uremia in both basal and pentagastrin-stimulated conditions. We therefore conclude that gastric mucosal formation is probably not influenced by chronic uremia.     

一氧化氮-氟比洛芬的胃肠毒性及其对胃粘膜前列腺素E_2的影响

目的　观察一氧化氮—氟比洛芬 (NO Flurbiprofen ,NO Flur)对大鼠胃肠的毒性以及对胃粘膜前列腺素E2 (PGE2 )的影响。方法　在解剖显微镜下分别观察大鼠胃内灌注NO Flur及氟比洛芬后 ,胃、小肠粘膜损伤指数及再进食胃窦溃疡模型溃疡面积 ,用EIA法检测胃粘膜PGE2 含量。结果　NO Flur的胃粘膜及小肠粘膜损害明显低于氟比洛芬 ,NO Flur组的胃窦溃疡面积稍低于氟比洛芬组 ,但无统计学意义。两药对胃粘膜PGE2 含量的抑制率无显著性差异。结论　NO Flur抑制胃PGE2 的程度与氟比洛芬相似 ,但胃肠毒性较轻     

Metabolism of oral trefoil factor 2 (TFF2) and the effect of oral and parenteral TFF2 on gastric and duodenal ulcer healing in the rat

BACKGROUND: Trefoil factors (TFFs) are peptides produced by mucus-secreting cells in the gastrointestinal tract. A functional association between these peptides and mucus, leading to stabilisation of the viscoelastic gel overlying the epithelia, has been suggested. Both oral and parenteral administration of the peptides increase the resistance of the gastric mucosa. AIM: To study the effect in rats of oral and parenteral porcine trefoil factor 2 (pTFF2) on the healing of gastric and duodenal ulcerations and to clarify the distribution and metabolism of orally administered pTFF2 in the gastrointestinal tract. METHODS: Gastric ulcers were induced in female Sprague-Dawley rats by indomethacin and duodenal ulcers by mercaptamine. The rats were treated for up to seven days with oral or subcutaneous pTFF2. Ulcer size after treatment was assessed by stereomicroscopy after whole mount staining with periodic acid-Schiff stain. (125)I-labelled pTFF2 was given orally to rats, and tissues were investigated by gamma counting of samples and by autoradiography of paraffin embedded sections. RESULTS: pTFF2 accelerated gastric ulcer healing after both oral and subcutaneous administration. Duodenal ulcers were aggravated by both treatments. After oral administration of (125)I-pTFF2, intact peptide was recovered from the superficial part of the mucus layer in the stomach; it passed through the small intestine but was degraded in the caecum. Only a minor part of the labelled pTFF2 entered the colon and was excreted in the faeces. Most of the label was excreted in the urine. CONCLUSIONS: Oral as well as parenteral pTFF2 accelerates the healing of gastric ulceration and aggravates duodenal ulcers. Oral pTFF2 binds to the mucus layer of the stomach and the small intestine but does not reach the colonic mucosa.     

Update on the pathologic approach to the diagnosis of gastritis, gastric atrophy, and Helicobacter pylori and its sequelae

Biopsy sampling of the gastric mucosa at diagnostic endoscopy provides information that cannot be obtained otherwise. The most common indication for gastric biopsy is the need to know whether the patient is infected with Helicobacter pylori or not and whether the stomach is gastritic or not. Microscopic examination of gastric biopsy specimens gives, in addition to H. pylori status, information about the grade, extent, and topography of gastritis- and atrophy-related alterations in the gastric mucosa. This information provides further possibilities for the assessment of risk and likelihood of various gastric disorders. The presence of atrophy (loss of mucosal glands) results in failures in secretory functions of the corresponding mucosa and leads to errors in the homeostasis of normal gastric physiology. The grade of atrophy of the corpus mucosa linearly correlates with peak and maximal output of acid. The presence of advanced (moderate or severe) corpus atrophy indicates an extremely hypochlorhydric or achlorhydric stomach in which, for example, ordinary peptic ulcer is unlikely or impossible in spite of a possible H. pylori infection. Some well characterized and common topographic phenotypes of H. pylori gastritis and atrophic gastritis can be delineated as follows: Predominance or restriction of the H. pylori-related inflammation in antrum, in association with a nonatrophic corpus mucosa--of which phenotype is the most common--and with an increased risk of peptic ulcer disease, duodenal ulcer in particular ("duodenal ulcer phenotype" of gastritis); the presence of atrophic gastritis in corpus of the stomach ("corpus predominant gastritis"), which indicates a low risk of peptic ulcer and a reduction in the capacity of the patient to secrete acid; the occurrence of advanced atrophic gastritis and intestinal metaplasia multifocally in the stomach (advanced "multifocal atrophic gastritis"), which are features of a gastritis type and which also indicate a low acid secretion capacity and an increased risk of gastric neoplasias ("gastric cancer phenotype of gastritis"), suggesting a need for a careful exclusion of concomitant presence of small focal neoplastic or dysplastic lesions; and the presence of normal and healthy gastric mucosa, which indicates an extremely low risk of both peptic ulcer disease or gastric cancer and, therefore, is a finding of high clinical relevance. The presence of duodenal or gastric ulcer in conjunction with normal, healthy gastric mucosa suggests either aspirin or nonsteroidal antiinflammatory drugs to be the most likely cause of the ulcer.     

不同饮食对大鼠十二指肠溃疡愈合的影响及胃粘膜的保护作用

目的:观察小米。大米。面粉和全脂奶饮食对实验性十二指肠溃疡(DU愈合的影响及胃粘膜的保护作用,寻求DU患者更为合理的饮食种类。方法:应用5%半胱胺盐酸盐建立实验性大鼠DU模型,给予不同饮食后测定胃粘膜电位差(PD。前列腺素E2(PGE2)含量。计算溃疡指数(UI)及判定溃疡愈合程度。结果:小米组和大米组的UI分别为2.60±1.71和3.00±1.77,低于面粉组4.70±1.77(P<0.05);全脂奶组UI与以上三组相比无显著差异(P>0.05)。胃粘膜组织中PGE2含量亦以小米组和大米组为高,分别为1802.40 pg/mg±567.26pg/mg和1706.86pg/mg±429.08 pg/mg,与面粉组和全脂奶组相比差异显著(P<0.01,P<0.05)。胃粘膜PD检测:小米组为-22.32±10.59;面粉组为-11.76±8.08,两组相比差异显著(P<0.05)。结论:通过胃粘膜PD的检测,反映小米饮食可提高胃粘膜屏障的完整性;小米和大米饮食可增加胃粘膜组织中PGE2含量,对实验性大鼠DU愈合作用优于面粉饮食。     

Gastric ulcer and gastritis

The gastritis associated with chronic gastric ulcer has been studied by means of biopsy specimens taken under vision through a fibreoptic gastroscope from four standard sites in the stomach. Observations have been made in patients with untreated gastric ulcer and also in patients after medical or surgical treatment of the ulcer. The gastritis is usually widespread in chronic peptic ulcer of the body of the stomach, whereas it is commonly more localized in chronic prepyloric ulcer. Superficial or atrophic gastritis has been found to persist or even worsen after healing of the ulcer, whether the treatment was medical or surgical. This finding suggests that gastritis is the basic disease process and that gastric ulceration is a secondary phenomenon.     

Bacteria in ulcer pathogenesis

A great deal of information about the spiral bacteria of the stomach has accumulated in the past 5 years. These bacteria, currently named Campylobacter pylori but likely to be renamed as a new genus, have adapted to living beneath the mucus layer and above the gastric surface mucous cells. When metaplastic gastric mucous cells are also present in the duodenal bulb, C. pylori may also get a foothold in this latter location. Observations of the high prevalence of C. pylori in patients with gastritis and with duodenal ulcers, and the slightly lower prevalence in patients with gastric ulcer, have led to the hypothesis that the bacteria play an aetiological role in these three conditions. There is now fairly convincing evidence that the organisms can cause active chronic gastritis. The most persuasive of this comes from reports of the rapid development of gastritis and symptoms in two volunteers who swallowed the organism, plus two other series of accidental challenges. Other evidence is provided by the waning and waxing of gastritis, which has been correlated in several studies with clearance followed by recrudescence of the organisms. The role of the bacterium in peptic ulcer is less certain. The present data do not provide strong evidence for a causal role in gastric ulcer, although we cannot rule out that it may be important in some. The very high prevalence in patients with duodenal ulcer, including one series in children (who rarely harbour the organism), raises the distinct possibility that the bacteria play an aetiological role in this form of ulcer. Reports of ulcer healing with antibiotics and of lower recurrence rates in those cleared of the organism, increase the possibility, However, methodological flaws in some studies, plus the usual need for confirmation of key studies, indicate that we should await more definitive evidence before accepting that duodenal ulcer can be an infectious disease.     

替米沙坦对脑出血急性应激性胃黏膜病变大鼠胃黏膜细胞增殖和凋亡的影响

目的探讨血管紧张素Ⅱ受体拮抗剂替米沙坦对脑出血急性应激性胃黏膜病变大鼠胃黏膜细胞增殖和凋亡的影响。方法健康成年SD大鼠96只,随机分为假手术组、脑出血组、替米沙坦组,每组32只,各组再分为1、2、3和5d4个时间点,每个时间点8只大鼠。制作脑出血大鼠模型,大体观察胃黏膜病变并计算溃疡指数;HE染色光镜下观察胃黏膜组织形态学改变;免疫组织化学法检测胃黏膜增殖细胞核抗原(PCNA)蛋白的表达;TUNEL检测胃黏膜凋亡细胞。结果与假手术组比较,脑出血组大鼠1、2、3和5d胃黏膜溃疡指数明显增大、PCNA表达明显减少、TUNEL凋亡细胞明显增多(P<0.01)。与脑出血组比较,替米沙坦组大鼠1、2、3和5d胃黏膜溃疡指数明显减小、PCNA表达增多、TUNEL凋亡细胞减少(P<0.05)。结论替米沙坦能够减小脑出血急性应激性胃黏膜病变大鼠胃黏膜溃疡指数、增加PCNA表达、减少TUNEL凋亡细胞,减轻应激性胃黏膜病变。     

Gastroprotective and ulcer healing effects of solon, a synthetic flavonoid derivative of sophoradin

Solon, a synthetic isoprenyl flavonoid derived from sophoradin isolated from the root of an ancient Chinese plant, administered orally to rats, prevented, dose-dependently, the formation of acute gastric lesions produced by absolute ethanol given orally. Solon also enhanced the healing of chronic gastric and duodenal ulcerations induced by the serosal application of acetic acid. The gastroprotective action of Solon was probably mediated by increased mucosal content of prostaglandins (PG) due mainly to the inhibition of 15-OH-prostaglandin dehydrogenase. The ulcer-healing action of Solon was probably related to the stimulation of mucus-alkaline secretion, increased mucosal blood flow and the formation of a protective barrier on the ulcer base.