Effects of Ecabet Sodium on Acute Mixed Reflux Esophagitis in Rats

Abstract

Objective. Ecabet sodium (ENa) is a drug that repairs epithelial cells in the digestive tract via selective adhesion to damaged tissue. While the principal cause of reflux esophagitis is gastroesophageal acid reflux, the involvement of duodenal juice has also been identified as an important factor. This study aimed to explore the effect of ENa in an acute mixed reflux esophagitis (AMRE) rat model. Material and methods. Eight-week-old male Wistar rats were used to prepare an AMRE model. There were four experimental groups: Group A (sham-operated rats), Group B (AMRE rats), Group C (AMRE rats dosed with ENa at 10 mg/kg), and Group D (AMRE rats dosed with ENa at 30 mg/kg). All rats were assessed for incidence of macroscopic esophageal lesions, esophagitis index, and pathological findings. Amylase activity, bile acid concentration in the digestive fluid retained in the esophagogastric lumen and ENa concentration in the esophageal mucosa were determined. Results. The incidence of esophagitis was 0% for Group A, 100% for Group B, 40% for Group C, and 20% for Group D. It was significantly lower for Groups C and D relative to Group B. The median esophagitis index was 0 for Group A, 58.2 for Group B, 0 for Group C, and 0 for Group D, and it was significantly lower for Groups C and D relative to Group B. The histological severity grade of esophagitis in Groups C and D was significantly less than that in Group B. Conclusion. Treatment with ENa inhibited the development of AMRE in rats.     

Protective Effect of Ammonia Against Reflux Esophagitis in Rats

Although several recent studies have reported that curing Helicobacter pylori (H. pylori) may result in the development of reflux esophagitis (RE), the mechanisms leading to this complication are unknown. One by product of H. pylori infection is ammonia, which serves as an acid neutralizer. The aim of this study was to clarify whether ammonia, which is produced during H. pylori infection, has a protective effect on the esophagus. Eight-week-old male Sprague-Dawley rats were fasted for 24 hrs. Under anesthesia, both the pylorus and limiting ridge were simultaneously ligated. One hour postligation, 0.3 ml of saline or ammonia at various concentrations was administered intragastrically by gastric intubation. Three hours after ligation, the animals were killed, the esophagus and stomach were removed, and the length of esophageal hemorrhagic erosions was measured. The incidence of RE was 100% (7/7) in the control group, 71% (5/7) in the low-ammonia group, 29% (2/7) in the middle-ammonia group, and 14% (1/7) in the high-ammonia group. The severity of lesions decreased in correspondence to increases in ammonia concentration. The development of RE was significantly inhibited by ammonia in a dose-dependent manner. This study indicates that ammonia protects against development of RE. A decreased amount of ammonia in the stomach might be related to the development of RE after H. pylori eradication therapy.     

Establishment of Surgically Induced Chronic Acid Reflux Esophagitis in Rats

Background: The purpose of the study was to establish an animal model of chronic acid reflux esophagitis which could be used for further investigations of the pathophysiology of reflux esophagitis. Methods: Esophagitis was produced by ligating the transitional region between the forestomach and the glandular portion with a 2-0 silk thread and covering the duodenum near the pylorus ring with a small piece of an 18Fr Né     

Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats

Background

Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE).

Aim

The aim of this study was to clarify the effect of LDA on chronic RE in rats.

Methods

Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2–0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells.

Results

Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p < 0.05). The grade of severity correlated with the depth of inflammation (r _s = 0.492, p < 0.001).

Conclusions

Maximal dose aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

     

Essential Role of Pepsin in Pathogenesis of Acid Reflux Esophagitis in Rats

Pepsin, a protease activated by gastric acid, is a component of the refluxate, yet the role of pepsin in the pathogenesis of reflux esophagitis has not been well studied. In the present study, we examined the effect of pepstatin, a specific inhibitor of pepsin, on acid reflux esophagitis. Acid reflux esophagitis was induced in rats by ligating both the pylorus and the forestomach for 3 or 4 hr. Pepstatin, ecabet Na (the anti-ulcer drug), and L-glutamine were administered intragastrically after the ligation. Pepstatin or ecabet Na, given intragastrically, significantly prevented esophageal lesions, even though they did not affect basal acid secretion in pylorus-ligated rats. Pepstatin significantly inhibited pepsin activity in vivo and in vitro, while ecabet Na inhibited this activity in vitro. By contrast, L-glutamine given intragastrically aggravated the lesions in a dose-dependent manner, but even in the presence of L-glutamine the development of esophageal lesions was totally prevented by coadministration of pepstatin or ecabet Na. L-Glutamine increased the pH of gastric contents to approximately 2.0, the optimal pH for the proteolytic activity of pepsin in vitro. In addition, intragastric administration of exogenous pepsin worsened the severity of esophageal damage. These results suggest that pepstatin is highly effective against acid reflux esophagitis, without influencing acid secretion, while L-glutamine aggravated these lesions by increasing the pepsin activity by shifting the intraluminal pH to the optimal pH range for proteolytic action. It is assumed that pepsin plays a major pathogenic role in the development of acid reflux esophagitis.     

环氧合酶-2在反流性食管炎大鼠食管组织中表达的实验研究

背景：环氧合酶（COX）-2在炎症、肿瘤等的发生、发展过程中发挥重要作用，但其在反流性食管炎（RE）中的作用尚未明确。目的：研究COX-2在混合性RE大鼠食管组织中的表达，探讨COX-2的表达与RE的关系。方法：采用贲门肌切开术加十二指肠半结扎术建立混合性RE大鼠模型。22只健康Sprague-Dawley大鼠随机分为RE模型组（n=12）和假手术组（n=10），于术前和术后1周测定食管下段和胃液pH值。处死大鼠，分别应用放射免疫测定和免疫组化方法检测食管组织中前列腺素（PG）E2的含量和COX-2的表达，光镜观察食管组织的形态学改变。结果：RE模型组术后食管下段pH值显著低于假手术组（P〈0．05），胃液pH值则显著高于假手术组（P〈0．05）；食管组织PGE2含量亦较假手术组显著增高（P〈0．001），COX-2表达均为阳性，假手术组食管组织中无COX-2表达。光镜观察显示RE模型组食管黏膜病理损害明显。结论：COX-2高表达和PGE2含量增高参与了混合性RE的发生、发展过程，COX-2可能通过升高PGE2含量而在RE的发病中起重要作用。     

Nonobstructive Dysphagia in Reflux Esophagitis

Dysphagia in the absence of organic esophageal stricture may occur in patients with reflux esophagitis. Although the exact mechanism of this "nonobstructive dysphagia" (NOD) is not known, it is believed to be related to transient segmental esophageal motor disorder. The goals of this study were to determine the frequency of NOD in patients with reflux esophagitis and correlate it with esophageal pH and motility changes. Sixty-three consecutive patients with symptoms of esophageal dysfunction were studied with endoscopy, infusion esophageal manometry, and 24-h ambulatory esophageal pH monitoring. Forty-seven had severe erosive esophagitis unresponsive to medical therapy; 16 with esophageal motility disorders were used as symptomatic controls. Twenty-eight of 63 patients studied experienced NOD during the 24-h pH study; 22 had esophagitis and six had esophageal dysmotility without esophagitis. NOD was noted with similar frequency in the two groups; 22/47 (46.8%) of patients with esophagitis and 6/16 (37.5%) with esophageal dysmotility experienced NOD during the period of study. NOD correlated with pH less than 4.0 in 88.6% of patients with esophagitis but in only 7% of patients with esophageal dysmotility (p less than 0.001). There was no difference in acid reflux patterns in esophagitis patients who experienced NOD (22/47), and in those who did not (25/47). There was no correlation between NOD and baseline esophageal motility abnormalities. In summary, 1) NOD is a common, intermittent symptom that occurred in up to 46.8% of esophagitis patients and 37.5% of symptomatic controls during the 24-h period of this study; 2) NOD correlates with esophageal pH less than 4.0 in patients with esophagitis and not in patients with esophageal dysmotility. These data strongly suggest that acid in the distal esophagus frequently triggers the sensation of dysphagia in esophagitis patients, but not in patients with esophageal motility disorders. Combined ambulatory intraesophageal motility and pH monitoring may further elucidate the mechanism of dysphagia in these patients.     

The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study

Background/AimsTo investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis.MethodsA total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score.ResultsThe mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009).ConclusionsOver a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.     

GERD; Reflux Esophagitis

The incidence of GERD in Asian countries is relatively different compare to Western world. In Japan, heartburn affects approximately 2% of the population, and in another population based study, about 20% of the age group over the age of 40 years are reported to have heartburn on the daily bases eventhogh only in mild form. Recent data from USA showed the prevalence of weekly heartburn being 18% and prevalence of any heartburn within the last year being 42%. It seems that the prevalence increase with age and a wide geographic variation with the highest orevalence in Western countries.     

Gastric Accommodation Studied by Ultrasonography in Patients with Reflux Esophagitis

The aim of this study was to investigate gastric accommodation to a meal in patients with reflux esophagitis using ultrasonography. Twenty consecutive patients with reflux esophagitis of grade I (14) or II (6) and 20 healthy subjects underwent ultrasonographic measurements of the stomach before and after ingestion of a 500 ml soup meal. Reflux esophagitis patients revealed a significantly larger sagittal area of the proximal stomach at 5 min (P = 0.002) and 15 min (P = 0.007) postprandially and experienced more epigastric fullness after the meal (P = 0.0006). Postprandial fullness and sagittal area of the proximal stomach correlated significantly (r = 0.69; P = 0.0007). We conclude that patients with mild or moderate reflux esophagitis have a larger sagittal area of the proximal stomach and more postprandial fullness in response to a soup meal than healthy subjects. Postprandial distension of the proximal stomach may be a pathogenetic factor in reflux esophagitis.     

Helicobacter pylori Protection Against Reflux Esophagitis

Background and Aim

Negative association has been reported between presence of Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its complications. The aim of this study was to determine whether H. pylori (HP) can be protective against GERD in an African American (AA) population.

Methods

From 2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both esophagitis and gastritis (363) and a normal control group (41). We collected their pathology and endoscopy unit reports. HP status was determined based on staining of gastric biopsy.

Results

HP data was available for 79 % (1,611) of the cases. The frequency of HP positivity in gastritis patients was 40 % (506), in esophagitis patients 4 % and in normal controls 34 % (11), while HP was positive in 34 % of the patients with both esophagitis and gastritis. After adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01–0.59; P value = 0.01) for the esophagitis group versus the normal group.

Conclusions

Our results show H. pylori has a significant negative association with esophagitis in AAs which may point to a protective role of H. pylori in the pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low GERD complications in AAs.     

Gastric Emptying in Patients with Severe Reflux Esophagitis

The pathogenesis of gastroesophageal reflux (GER) is not fully understood. There have been reports that delayed gastric emptying is a contributing factor in some patients. To determine whether delayed gastric emptying plays a role in the genesis of GER, we correlated gastric-emptying measures obtained by scintigraphic techniques with the degree of acid reflux assessed by esophageal pH monitoring. Ten patients, all of whom had evidence of esophageal mucosal disease and severe acid reflux, were studied. Four of the 10 patients with reflux had prolongation in the lag phase of gastric solid emptying, and one of the four showed prolonged gastric-emptying t1/2. There was no significant difference, however, in the mean gastric-emptying t1/2 between a control group and the patient group. Furthermore, there was no correlation between gastric-emptying measures and degree of acid reflux. We conclude that in this group of 10 patients with severe GER, delayed gastric emptying does not play an important role in the development of gastroesophageal reflux.     

反流性食管炎几种诊断方法的研究

本文对41例有典型反流性食管炎症状者,进行了内镜检查、粘膜活检、食管X线检查和核素闪烁显像综合检查.23例无反流症状者作对照.41例有反流症状组的内镜检查.均见食管粘膜有轻或中度炎症改变.病理活检的阳性率为76%,其中87%为中期食管炎.内镜检查用于观察有无食管炎症及其程度.41例均行核素闪烁显像检测,显示有反流者81%.本组病例中有31例行X线钡餐检查,显示有反流者53%.核素显像和X线钡餐用于确定有无胃食管反流,前者较后者敏感.     

Gastric Secretion, Gastroesophageal Reflux and Esophagitis

Neither gastroesophageal reflux nor esophagitis were found to have a clear-cut relationship with gastric secretory output. Patients with esophagitis had significantly longer periods of reflux than those without esophagitis. It is concluded that the important factor in the genesis of esophagitis is the duration of contact between the esophageal mucosa with gastric contents rather than gastric secretory output.     

Multiple Esophagogastric Fistulas Resulting from Reflux Esophagitis

A case of multiple esophagogastric fistulas is reported along with the endoscopic and radiological findings. The literature is reviewed. There is only one other case report of multiple, isolated esophagogastric fistulas described by Mullen, et al (1975). In that individual the etiologic factor was previous esophageal surgery for stricture. In the patient reported here, the long history of reflux symptoms and endoscopic and biopsy findings strongly suggest a causal relationship. Fistula formation may be an additional complication of prolonged gastroesophageal reflux.     

Barrett食管、反流性食管炎和非糜烂性胃食管反流病的反流物特点

目的应用食管24 h pH-阻抗(MII-pH)等检查方法,分析具有胃食管反流病(GERD)典型症状、并且食管MII-pH检查结果异常的GERD患者,比较分析其各亚型,即Barrett食管(BE)、反流性食管炎(RE)和非糜烂性胃食管反流病(NERD)患者的胃食管反流特点。 方法入选具有典型胃食管反流症状(烧心/反流),并且食管24 h MII-pH检查结果异常的GERD患者,根据内镜检查结果分为BE、RE、NERD三组,收集患者24 h的食管pH-阻抗信息,应用SPSS16.0统计软件进行组间Mann Whitney检验、多因素方差分析,P< 0.05认为具有统计学差异。 结果共入组103例具有典型反流症状且MII-pH监测阳性的GERD患者,其中有15例BE患者、32例RE患者、56例NERD患者。三组患者的平均年龄、性别构成、以及BMI无显著差异性。将三组患者的各项胃食管反流指标数值进行Mann-Whitney检验,显示RE、BE患者的DeMeester评分、pH<4反流时间百分比、长反流周期数显著高于NERD患者,具有显著性差异。BE患者的反流周期数显著多于RE和NERD患者,具有显著性差异。阻抗相关指标在三组患者之间均没有统计学差异。 结论与NERD相比,酸反流对于RE和BE具有更重要的致病意义。     

The Effect of Gastric Acid on Reflux Esophagitis

In recent years, many parameters associated with GERD are studied sum as number of reflux lasting more than five minutes (NRs), number of reflux and the longest time of reflux in 24 hours continuous introesophageal pH monitoring. It is considered that NR is the best one. Thus, both the effect of NR and the relationship with acid secretion level are deserved attention. 20 patients with reflux esophagitis and 10 healthy subject (HS group) have been studied for the changs of NRs and the longest time of reflux using 24 h continuous introesophageal pH monitoring.     

胃大部切除术后硷性反流性食管炎机理研究

本文以30例胃大部切除术后患者及30例正常人为研究对象,采用腔内单根导管微型传感器测定食管下端括约肌压力(LESP),内镜、病理活检观察食管下端粘膜变化,放免方法测量空腹血清胃泌素浓度。结果:胃大部切除术组与正常对照组食管下端括约肌压力,血清胃泌素浓度分别为15.4±3.3mmHg,22.6±4.5mmHg;44.9±14.9pg/ml,68.4±20.3pg/ml,P<0.01。胃镜及病理检查发现胃大部切除术组有6例有反流性食管炎改变,与临床表现相符.本研究提示:胃大部切除术后LESP降低,并发反流性食管炎,应引起重视。