Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

Study on the Application of Refined Nursing Care in The Care for Elderly Patients with Reflux Esophagitis

Objective: To investigate the application effect of refined nursing care in the care for elderly patients with reflux esophagitis. Methods: Following the difference in nursing style, 84 cases of elderly patients with reflux esophagitis admitted to our hospital from May 2022 to May 2023 were randomly grouped into a control group and a research group, with 42 cases each. The control group was given conventional nursing care and the research group was given refined nursing care. The psychological state and treatment adherence of the two groups of patients after the nursing intervention were compared. Results: After the nursing intervention, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the research group were lower than those of the control group (P < 0.05). The treatment compliance of the research group was better than the control group (P < 0.05). Conclusion: The implementation of refined nursing care for elderly patients with reflux esophagitis exhibited a significant effect on improving the patient’s psychological state, treatment compliance, and rehabilitation.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

Clinical features of gastroesophageal reflux disease and erosive esophagitis:Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia

BACKGROUND Gastroesophageal reflux disease(GERD)is a common disease worldwide with varying clinical presentations and risk factors.Prevalence data for Africa is lacking,but an increasing trend is expected due to demographic and epidemiological transitions.Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis(EE),no studies in Ethiopia have investigated the clinical characteristics,risk factors,and severity of GERD using esophagogastroduodenoscopy(EGD).AIM To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE.METHODS We conducted a multicenter,retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022.Data were collected from electronic medical records and phone call interviews.We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value<0.05.RESULTS The mean±SD age of the patients was 44.8(±15.9)years,with a male-to-female ratio of 1.6:1.The most commonly reported symptom was epigastric pain(80.5%),followed by heartburn(43%).Los Angeles(LA)-A EE was diagnosed in 71.1%of patients,followed by LA-B(14.9%),LA-C(7.7%),and LA-D(5.9%).Multivariate analysis showed that age 50 or above,presence of bleeding,and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE(P<0.05).Stricture and Barrett’s esophagus were observed in 4.5%and 1.36%of patients with EE,respectively.CONCLUSION Most of the patients had milder EE with fewer complications.However,severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.

Huoxue Tongjiang decoction-resisted reflux esophagitis by activation stem cell factor/c-kit/interstitial cell of cajal pathway and regulating the T-helper 17/regulatory T-cells balance in rats

Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.

Double-tract reconstruction is superior to esophagogastrostomy in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy:Results from a prospective randomized controlled clinical trial in China

Objective:The aim of this study was to prospectively compare double-tract reconstruction(DTR)and esophagogastrostomy(EG)after proximal gastrectomy(PG)regarding the incidence of reflux esophagitis,quality of life(QOL),nutritional status and surgical safety.Methods:This study was a randomized controlled trial.Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group.The characteristics of patients,parameters for surgical safety,incidence of reflux esophagitis,nutrition status and QOL were collected and compared between the two groups.Univariate analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after PG.Results:Thirty-seven patients of the EG group and 36 patients of the DTR group were enrolled.The incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group(8.3%vs.32.4%,P=0.019).The DTR group demonstrated a more favorable QOL than the EG group after PG.The nutritional status was balanced within the EG group and the DTR group.The operation time was longer in the DTR group than in the EG group(191 min vs.221 min,P=0.001),while surgical safety was similar in the two groups.Conclusions:Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.

Clinical features of acute esophageal mucosal lesions and reflux esophagitis Los Angeles classification grade D: A retrospective study

BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different treatments.AIM To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML.METHODS We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral side.We examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each group.RESULTS Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,respectively.Multiple variables exhibited significantly different results,indicating that these two diseases are distinct.The clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML group.CONCLUSION AEML and RE-D were clearly distinct diseases with different clinical features.AEML may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.

A review of reflux esophagitis around the world

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Laryngopharyngeal reflux in patients with reflux esophagitis

AIM: To assess the prevalence of laryngopharyngeal reflux (LPR) in patients with reflux esophagitis and dis-close factors contributing to the development of LPR. METHODS: A total of 167 patients who proved to have reflux esophagitis by endoscopy were enrolled. They received laryngoscopy to grade the reflux find-ings for the diagnosis of LPR. We used validated ques-tionnaires to identify the presence of laryngopharyn-geal symptoms, and stringent criteria of inclusion to increase the specificity of laryngoscopic findings. The data of patients were analyzed statistically to find out factors related to LPR. RESULTS: The prevalence rate of LPR in studied sub-jects with reflux esophagitis was 23.9%. Age, hoarse- ness and hiatus hernia were factors significantly as-sociated with LPR. In 23 patients with a hiatus hernia, the group with LPR was found to have a lower trend of esophagitis grading. CONCLUSION: Laryngopharyngeal reflux is present in patients with reflux esophagitis, and three predicting factors were identified. However, the development of LPR might be different from that of reflux esophagi-tis. The importance of hiatus hernia deserves further study.

Risk factors for gastroesophageal reflux disease,reflux esophagitis and non-erosive reflux disease among Chinese patients undergoing upper gastrointestinal endoscopic examination

AIM: To analyze the spectrum and risk factors of gastroesophageal reflux disease (GERD) based on presenting symptoms and endoscopic f indings. METHODS: A cross-sectional survey in a cluster random sample was conducted from November 2004 to June 2005 using a validated Chinese version Reflux Disease Questionnaire (RDQ) and other items recording the demographic characteristics and potential risk factors for GERD. Subjects were def ined as having GERD symptoms according to the RDQ score (> 12). All subjects were endoscopied and the def inition and severity of erosive esophagitis were evaluated by Los Angeles classif ication. The statistical analysis was performed with SPSS13.0 programs. RESULTS: Of 2231 recruited participants, 701 (31.40%) patients were diagnosed as having GERD while 464 (20.80%) patients had objective findings of reflux esophagitis (RE). Of those 464 patients, only 291 (13.00%) were reported as subjects with GERD symptoms. A total of 528 (23.70%) patients were found to have GERD symptoms, including 19.50% patients with grade A or B reflux esophagitis, 0.90% with grade C and 0.40% with grade D. On multivariate analysis, old age, male, moderate working burden, divorced/widowed and strong tea drinking remained as signif icant independent risk factors for erosive esophagitis. Meanwhile, routine usage of greasy food and constipation were considered as significant independent risk factors for non-erosive reflux disease (NERD). CONCLUSION: GERD is one of the common GI diseaseswith a high occurrence rate in China and its main associated factors include sex, anthropometrical variables and sociopsychological characteristics.

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.

H pylori infection and reflux oesophagitis: A case-control study

AIM： To examine the relationship between Hpylori and gastro-oesophageal reflux disease （GORD） in Iran. METHODS： In this study 51 GORD patients （referred to endoscopy at Taleghani hospital） were compared with 49 age-sex matched controls. Diagnosis of H pylori was made by gastric mucosal biopsy and rapid urease test （positive if the result of one or both diagnostic methods was positive）. Updated Sydney system was used to report histopathological changes. RESULTS： The frequency of H pylori infection based on rapid urease test and histology was 88.2% （45） in patients and 77.6% （38） in controls, which showed no significant difference. The frequency of H pylori infection was significantly higher in the antrum than in the corpus and cardia. The mean activity, inflammation, and gastritis scores were also higher in the antrum of patients than in the antrum of controls. The mean scores were significantly higher in the corpus of controls than in the corpus of patients. Diffuse active gastritis was observed in a significantly larger number of controls, while the frequency of diffuse chronic gastritis was higher in patients. There in the frequency of other patients and controls. was no significant difference histological findings between.CONCLUSION： H pylori infection cannot prevent GORD in this region.

Beneficial effect of probiotics supplements in reflux esophagitis treated with esomeprazole: A randomized controlled trial

BACKGROUND Reflux esophagitis(RE) is a common digestive disorder, and its frequent recurrences cause significant physical pain and are financially burdensome to patients. However, studies on the natural history of treated RE are few. Although proton pump inhibitors(PPIs) as the first-line treatment provide notable symptomatic relief, disordered gut microbiota has been observed among PPI users. Probiotics are commonly administered to patients to regulate the disordered intestinal flora.AIM To evaluate the therapeutic effects in RE patients treated with a combination of esomeprazole and probiotics [Bacillus subtilis(B. subtilis) and Enterococcus faecium(E. faecium)].METHODS One hundred and thirty-four RE patients were randomized into two groups of 67 subjects each. The probiotics group was administered with esomeprazole 20 mg b.i.d. and live combined B. subtilis and E. faecium enteric-coated capsules 500 mg t.i.d. for eight weeks; the placebo group was administered with esomeprazole 20 mg b.i.d. and placebo for eight weeks. Subsequently, 12-wk follow-up was carried out on patients who achieved both endoscopic and clinical cure. Endoscopy,reflux diagnostic questionnaire(RDQ), gastrointestinal symptom rating scale(GSRS), and lactulose hydrogen breath test were performed to evaluate the therapeutic effects. A difference of P < 0.05 was considered statistically significant.RESULTSSixty-six patients in the probiotics group and 64 patients in the placebo group completed the 8-wk treatment. The healing rate and RDQ score had no significant difference between the two groups(P > 0.05). However, the GSRS diarrhea syndrome score was decreased significantly in the probiotics group(P = 0.002),and the small intestinal bacterial overgrowth negative rate in the probiotics group was significantly higher than that in the placebo group(P = 0.002). Of 114 endoscopically and clinically cured patients, 96 completed the follow-up. The logrank test showed that the time to relapse was shorter in the placebo group than in the probiotics group(P = 0.041). Furthermore, the therapy had a significant influence on relapse time, and the risk of relapse in the probiotics group was lower than that in the placebo group at any time point during the 12-wk followup(hazard ratio = 0.52, P = 0.033).CONCLUSION Esomeprazole combined with probiotics(B. subtilis and E. faecium) have a beneficial effect on RE treatment and patient management.

Effect of Lonicerae Flos extracts on reflux esophagitis with antioxidant activity

AIM： To observe the effects of traditional antiinflammatory medicine Lonicerae FIos （LF） on rat reflux esophagitis （RE） induced by pylorus and forestomach ligation compared with the well-known proton antioxidant, α-tocopherol. METHODS： Rats were pretreated with three different dosages of LF （500, 250 and 125 mg/kg） orally, once a day for 14 d before pylorus and forestomach ligation. Nine hours after pylorus and forestomach ligation, changes to the stomach and esophagus lesion areas, gastric volumes, acid and pepsin outputs, antioxidant effects, esophageal lipid peroxidation, superoxide dismutase （SOD）, catalase （CAT）, malondialdehyde （MDA）, myeloperoxidase and glutathione （GSH） levels, and collagen contents （marker of flexibility） were observed on the esophageal and fundic histopathology. The results were compared with an α-tocopherol （once orally, 1 h before operation, 30 mg/kg） treated group in which the effects on RE were already confirmed.RESULTS： Pylorus and forestomach ligations caused marked increases of gross esophageal and gastric mucosa lesion areas, which corresponded with histopathological changes. In addition, increases of esophageal lipid peroxidation, decreases of SOD, CAT, and GSH-free radical scavengers, increases of collagen were observed. However, these pylorus and forestomach ligation induced RE were dose-dependently inhibited by treatment of 500, 250 and 125 mg/kg of LF extract, mediated by antioxidant effects. RE at 250 mg/kg showed similar effects α-tocopherol. CONCLUSION： The results suggest that antioxidant effects of LF could attenuate the severity of RE and prevent the esophageal mucosal damage, and validate its therapeutic use in esophageal reflux disease.

Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

AIM: To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs). METHODS: Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale (0: none; 1: mild; 2: mild-moderate; 3: moderate; 4: moderate-severe; 5: severe). RESULTS: The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. CONCLUSION: Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.

Interleukin-6, desmosome and tight junction protein expression levels in reflux esophagitis-affected mucosa

AIM： To investigate the correlation between the expression levels of interleukin （IL）-6 and proteins in tight junctions （TJs） in the esophageal mucosa of rats modeling different types of reflux esophagitis （RE）, and the ability of aluminum phosphate to protect against RE-induced mucosal damage via these proteins. METHODS： Male SPF Wistar rats aged 56 d were divided randomly into acid RE, alkaline RE, mixed RE, and control groups. Various surgical procedures were performed to establish rat models of acid RE. At 14 d after the procedure, some of the rats started aluminum phosphate treatment. Transmission electron microscopy （TEM） was used to observe the morphological features of TJs and desmosomes in the esophageal epithelium. Immunohistochemical methods and Western blotting were used to measure expression of claudin 1, occludin, ZO-1, JAM-l, DSG-1 and IL-6; reverse transcription polymerase chain reaction （RT- PCR） was used to measure expression of mRNA of claudin 1, occludin, ZO-1, JAM-1, DSG-1 and IL-6. RESULTS： At day 14 alter the procedures, an RE model was established in all subsequently sacrificed rats of groups A, B and C. By both gross and microscopic observation, the mucosa was damaged and thickened as the disease progressed. With TEM observation, a widened intercellular space was noticed, with significantly fewer desmosomes. Immunohistochemistry showed significantly higher levels of all proteins in all RE models compared to control rats at 3 d after operation （65.5% ± 25.6% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. At 14 d after operation, along with continuing hyperplasia in the basal layer, the expression of TJ proteins in individual cells gradually decreased （12.4% ± 2.1% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. Western blottings and RT-PCR showed a directly proportional increase in IL-6 levels in relation to TJ proteins, as compared to controls （0.878 ± 0.024 vs 0.205 ± 0.021 and 0.898±0.022 vs 0.205 ± 0.021, P 〈 0.05, respectively）. Upon treatment with aluminum phosphate, however, these protein levels were restored to normal gradually over 30-60 d in rats with acid RE （30.4% ± 2.1% vs 20.5% ± 2.1%, P 〉 0.05, treated vs untreated, respectively）. These levels increased in the rat with alkaline RE, and this increase was accompanied by continued hyperplasia in comparison with controls （85.5% ± 25.6% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. Furthermore, the expression of TJ proteins was not correlated significantly with that of IL-6 in this group. CONCLUSION： These findings indicate that TJ proteins are highly expressed as an early molecular event involved in RE development, and that IL-6 is an inflammatory factor in this process,

Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis

To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model. METHODSA surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting. Changes in esophageal pathology were analyzed by gross and histological examinations. RESULTSThe CARE exposure modeled rats showed increased levels of the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment completely resolved these CARE-related increases. The CARE rats also showed markers of cytokine stress, including elevated levels of TNF-α and reactive oxygen species as well as of the consequent increase in JNK activation, and subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic effect, as evidenced by altered expression of the apoptosis-related genes for bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly ameliorated the CARE-related esophageal mucosal ulcerations. CONCLUSIONIn the rat model of CARE, BHSST can suppress development of esophageal mucosal ulceration via regulation of reactive oxygen species-dependent apoptosis.

Rabeprazole is effective for bile reflux oesophagitis after total gastrectomy in a rat model

AIM:To elucidate the effect of a proton pump inhibitor(PPI,rabeparazole)on oesophageal bile reflux in oesophagitis after total gastrectomy.METHODS:Twenty-one 8-week-old male Wistar rats were studied.They were performed oesophagoduodenostomy of total gastrectomy to induce oesophageal reflux of biliary and pancreatic juice.Five rats were performed the sham operation(Sham).On post-operative day 7,they were treated with saline(Control)(n=8)or PPI(rabeprazole,30 mg/kg per day,ip)(n=8)for 2 wk.On post-operative 21,all rats were sacrificed and each oesophagus was evaluated histologically.Oesophageal injury was evaluated by macroscopic and microscopic findings as well as the expression of cyclooxygenase-2(COX2).We measured bile acid in the oesophageal lumen and the common bile duct.RESULTS:At 3 wk after surgery,a histological study analysis revealed an increase in the thickness of the epithelium,elongation of the lamina propria and basal cell hyperplasia in the oesophageal mucosa.The macroscopic ulcer score and microscopic ulcer length of the control group were significantly higher compared to those of the rabeprazole-treated group.The expression of COX2 was significantly increased according to the immunostaining in the control group compared to rabeprazole-treated group.Although there was no difference between the control and PPI groups in the total bile acid in the common bile duct,the bileacid activity in the oesophageal lumen was significantly decreased in the rabeprazole-treated group due to augmentation of the duodenal motor complex.CONCLUSION:With this model,rabeprazole is good effect for reflux esophagitis after total gastrectomy from bile reflux.Bile acid is an important factor in the mucosal lesion induced by duodenal reflux.

Expression of CXC receptor 1 and 2 in esophageal mucosa of patients with reflux esophagitis

AIM: Interleukin 8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about the two distinct receptors, CXC receptor (CXCR)-1 and -2.The purpose of this study was to determine CXCR-1 and -2 messenger RNA expression levels in RE.METHODS: We studied 26 patients with RE and 15asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of CXCR-1 and -2 mRNA levels by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and another was formalin-fixed for histopathological evaluation.We also examined the association of the expression levels of CXCR-1 and -2 mRNA with histopathological hallmarks of RE.RESULTS: The relative CXCR-1 and -2 mRNA expression levels were rather decreased in esophageal mucosa of patients with RE, compared to those in normal esophagus of controls. There were no significant difference in the relative mRNA expression levels of CXCR-1 and -2 among endoscopic grades of RE based on the Los Angeles classification. Each histopathological hallmark of GERD was not associated with the expression levels of CXCR-1 and -2 mRNA.CONCLUSION: Apart from overexpression of IL-8, the relative expression levels of CXCR-1 and -2 mRNA were rather lower than expected in the affected esophageal mucosa of patients with RE.