OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.
Chest Pain ; etiology ; Esophagus ; drug effects ; Gastroenterology ; methods ; Gastroesophageal Reflux ; diagnosis ; drug therapy ; Heartburn ; diagnosis ; drug therapy ; Humans ; Hydrogen-Ion Concentration ; Life Style ; Primary Health Care ; Proton Pump Inhibitors ; therapeutic use ; Surveys and Questionnaires

BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease, with eosinophilic infiltration limited to the esophagus. A minority of EoE patients respond well to proton pump inhibitor (PPI) therapy alone, and that condition is labelled PPI-responsive esophageal eosinophilia (PPI-REE). The prevalence of PPI-REE among EoE cases is unknown. We aimed to identify clinical manifestations of PPI-REE, and the proportion of PPI-REE among all EoE cases. METHODS: We reviewed pathology of the 4,075 patients who underwent esophageal biopsy at an institution from March 2003 to July 2015. EoE was diagnosed based on esophageal symptoms and eosinophilic infiltration limited to the esophagus, with ≥15 eosinophils per high-power field. We collected endoscopic and pathologic findings, and clinical features for these patients. RESULTS: Thirteen (0.3%) patients were diagnosed with EoE. Clinical manifestations were dysphagia (30.8%), foreign body sensation (23.1%), regurgitation (23.1%), cough (15.4%), heartburn (15.4%), nausea (7.7%), dyspepsia (7.7%). The endoscopic findings noted were polypoid lesion (23.1%), whitish plaque or exudate (23.1%), linear furrow (7.7%), concentric ring (7.7%), nodularity (7.7%), erosion (7.7%), and normal (30.8%). Of these patients, five had a favorable course with PPI as monotherapy. CONCLUSIONS: The proportion of EoE among all patients undergoing endoscopic biopsy was 0.3%. Of those, PPI-REE comprised 38%. Most of the endoscopic findings were atypical or normal when compared to the typical findings in EoE. In conclusion, patients who present with symptoms related to esophageal dysfunction need esophageal biopsy, regardless of the endoscopic findings. Moreover, patients diagnosed with EoE need to be treated first with PPI alone.
Adult ; Aged ; Endoscopy, Gastrointestinal ; Eosinophilic Esophagitis/*diagnosis/etiology ; Esophagus/pathology ; Female ; Gastroesophageal Reflux/drug therapy ; Hospitals, University ; Humans ; Male ; Middle Aged ; Proton Pump Inhibitors/*adverse effects/therapeutic use ; Retrospective Studies

OBJECTIVETo explore the effect of aluminum phosphate gel and Kangfuxin on esophageal pathology and expressions of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in rats with reflux esophagitis and explore the possible mechanisms.

METHODSSixty SD rats were randomized into aluminum phosphate gel group (n=10), Kangfuxin group (n=10), aluminum phosphate gel+Kangfuxin group (n=10), model group (n=20), and control group (n=10). Except for those in the control group, all the rats were subjected to infusion of diluted lysolecithin with hydrochloric acid in the esophagus for 14 days. Ten rats in the model group and those in the control group were sacrificed to examine the pathological changes and contents of IL-8 and PGE2 in the esophagus using optical and electron microscopes and radioimmunoassay. The next day the rest rats were given corresponding treatments (saline in model group) administered into the esophagus on a daily basis for 14 days, after which esophageal pathologies and IL-8 and PGE2 contents were examined.

RESULTSThe model rats showed obvious esophageal pathologies including inflammatory cell infiltration, vacuolar degeneration of the epithelial cells, esophageal erosion and even ulceration, with severe detachment of the epithelial cells. The rats in all the intervention groups showed lessened esophageal pathologies and lowered esophageal IL-8 and PGE2 contents compared with those in the model group. Esophageal mucosal injury index and IL-8 and PGE2 contents were all significantly lower in rats receiving combined treatment with aluminum phosphate and Kangfuxin than in those receiving either of the treatments (P<0.05).

CONCLUSIONSBoth Kangfuxin and aluminum phosphate gel are effective in the treatment for reflux esophagitis induced by lysolecithin and hydrochloric acid, and their therapeutic effects are achieved possibly by reducing IL-8 and PGE2 levels in the esophagus.

Aluminum Compounds ; pharmacology ; Animals ; Dinoprostone ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Esophagitis, Peptic ; drug therapy ; metabolism ; Esophagus ; drug effects ; pathology ; Gels ; Interleukin-8 ; metabolism ; Phosphates ; pharmacology ; Rats ; Rats, Sprague-Dawley

Acute esophageal necrosis is uncommon in the literature. Its etiology is unknown, although cardiovascular disease, hemodynamic compromise, gastric outlet obstruction, alcohol ingestion, hypoxemia, hypercoagulable state, infection, and trauma have all been suggested as possible causes. A 67-year-old female underwent a coronary angiography (CAG) for evaluation of chest pain. CAG findings showed coronary three-vessel disease. We planned percutaneous coronary intervention (PCI). Coronary arterial dissection during the PCI led to sudden hypotension. Six hours after the index procedure, the patient experienced a large amount of hematemesis. Emergency gastrofibroscopy was performed and showed mucosal necrosis with a huge adherent blood clot in the esophagus. After conservative treatment for 3 months, the esophageal lesion was completely improved. She was diagnosed with acute esophageal necrosis. We report herein a case of acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention.
Acute Disease ; Aged ; Coronary Angiography ; Coronary Stenosis/diagnosis/physiopathology/*therapy ; Esophageal Diseases/diagnosis/drug therapy/*etiology ; Esophagoscopy ; Esophagus/drug effects/*pathology ; Female ; Hemodynamics ; Humans ; Necrosis ; Percutaneous Coronary Intervention/*adverse effects ; Predictive Value of Tests ; Proton Pump Inhibitors/therapeutic use ; Risk Factors ; Time Factors ; Treatment Outcome ; Ultrasonography, Interventional ; Wound Healing

OBJECTIVETo investigate the effect of Modified Zhuye Shigao Decoction (MZSD) and its components on preventing radiation esophagitis of rats.

METHODSOne hundred Wistar rats were randomly divided into 5 groups, including the control group, radiation model group, MZSD group, Zhuye Shigao Decoction (ZSD) group, and added ingredients group, 20 rats in each group. The model of radiation esophagitis of rat was established by once local radiation of 40 Gy (330 Mu/min) with a high energy linear accelerator. The administration of Chinese medicine was continued for 14 days from 7 days before radiation application in the three treatment groups. On the 7th and 14th day, the serum was isolated and the levels of inflammatory cytokines tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) and IL-8 were tested. The pathological slices of esophagus were obtained, and the pathological changes were observed. During the whole process, weight and food intake were recorded each day.

RESULTSOn the 7th day after radiation, the esophagus of rats in the MZSD group was almost intact, and the pathological injury score was significantly lower than that of the radiation model group, ZSD group and added ingredients group (P<0.01). Compared with the control group, the body weight and food intake of rats in the radiation model group were significantly decreased, and the levels of TNF-α, IL-1β and IL-8 were significantly increased (P<0.05 or P<0.01), while the MZSD group showed a significant increase in body weight and food intake, and a significant decrease in the levels of TNF-α, IL-1β and IL-8 compared with the radiation model group, ZSD group and added ingredients group (P <0.05 or P<0.01).

CONCLUSIONMZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytokines TNF-α, IL-1β and IL-8.

Animals ; Body Weight ; drug effects ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Esophagitis ; drug therapy ; pathology ; prevention & control ; Esophagus ; drug effects ; pathology ; Feeding Behavior ; drug effects ; Inflammation Mediators ; metabolism ; Male ; Neutrophil Infiltration ; drug effects ; Radiation Injuries ; drug therapy ; pathology ; prevention & control ; Rats, Wistar ; Time Factors

BACKGROUND/AIMS: This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 microg) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 +/- 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.
Administration, Oral ; Age Factors ; Aged ; Alendronate/administration & dosage/*adverse effects ; Bone Density Conservation Agents/administration & dosage/*adverse effects ; Calcitriol/administration & dosage/*adverse effects ; Drug Combinations ; *Endoscopy, Digestive System ; Esophagus/*drug effects/pathology ; Female ; Gastric Mucosa/*drug effects/pathology ; Humans ; Middle Aged ; *Postmenopause ; Predictive Value of Tests ; Republic of Korea ; Sex Factors ; Tablets, Enteric-Coated ; Time Factors ; Treatment Outcome ; Vitamins/administration & dosage/*adverse effects

Corticotrophin-releasing factor (CRF) plays a major role in coordinating stress responses. We aimed to test whether blocking endogenous CRF activity can prevent the stress-induced dilation of intercellular spaces in esophageal mucosa. Eighteen adult male rats were divided into 3 groups: 1) a non-stressed group (the non-stressed group), 2) a saline-pretreated stressed group (the stressed group), 3) and an astressin-pretreated stressed group (the astressin group). Immediately after completing the experiments according to the protocol, distal esophageal segments were obtained. Intercellular space diameters of esophageal mucosa were measured by transmission electron microscopy. Blood was sampled for the measurement of plasma cortisol levels. Mucosal intercellular spaces were significantly greater in the stressed group than in the non-stressed group. Mucosal intercellular spaces of the astressin group were significantly smaller than those of the stressed group. Plasma cortisol levels in the stressed group were significantly higher than in the non-stressed group. Pretreatment with astressin tended to decrease plasma cortisol levels. Acute stress in rats enlarges esophageal intercellular spaces, and this stress-induced alteration appears to be mediated by CRF. Our results suggest that CRF may play a role in the pathophysiology of reflux-induced symptoms or mucosal damage.
Animals ; Corticotropin-Releasing Hormone/*antagonists & inhibitors/metabolism/pharmacology ; Esophagus/anatomy & histology/*drug effects ; Extracellular Space/*drug effects ; Hydrocortisone/blood ; Male ; Mucous Membrane/anatomy & histology/*drug effects ; Neuroprotective Agents/pharmacology ; Peptide Fragments/*pharmacology ; Rats ; Rats, Wistar ; *Stress, Psychological/blood/physiopathology

OBJECTIVETo study the influence of SGHWJN particles on inflammation and the mediators of inflammation in esophageal tissues of rat with reflux esophagitis.

METHODFifty SD rats were randomly divided into 5 groups, namely, a control group, a sham-operated group, a model group, a SGHWJN particles group and a PPI group. Reflux esophagitis was induced by adopting partial pyloric ligation plus cardiomyotomy. One week later, the rats were orally administered twice daily for 28 days. Pathological changes of esophagus mucous membrane were evaluated by using HE staining and Harry S. Cooper's method in every groups. MDA and SOD contents in esophageal tissues were measured by colorimetric method. Expression of TNF-alpha in esophageal tissues were examined by real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-FQ-PCR) with SYBR Green.

RESULTModel group, esophageal inflammation scores, expression of TNF-alpha in esophageal tissues and MDA contents compared with the normal group and sham operation group were significantly higher (P < 0.05). SOD contents in the esophageal tissues of the model group was significantly lower than that of control group and sham-operated group (P < 0.05). SGHWJN particles group and PPI group of esophageal tissue inflammation scores, expression of TNF-a in esophageal tissues and MDA levels than those in model group decreased significantly (P < 0.05). SOD content was significantly higher than that of model group (P < 0.05), SGHWJN particles group and PPI group showed no statistically significant difference between the above-mentioned indicators. The above-mentioned indicators showed no statistically significant difference between the normal group and sham-operated group. MDA content and expression of TNF-alpha in esophageal tissue was positively correlated with inflammatory scores of model group (r = 0.813). Model group esophageal tissue SOD content and inflammation scores were negatively correlated (r = -0.847). Esophageal tissue SOD levels were negatively correlated with MDA levels (r = -0.863).

CONCLUSIONSGHWJN particles can effectively inhibit inflammation in rat with reflux esophagitis through regulating TNF-alpha, SOD and MDA.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Esophagitis, Peptic ; drug therapy ; genetics ; immunology ; Esophagus ; drug effects ; immunology ; Female ; Gene Expression ; drug effects ; Humans ; Inflammation Mediators ; immunology ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; immunology

Animals ; Esophagus ; metabolism ; Glucagon-Like Peptide 2 ; pharmacology ; Intestinal Mucosa ; drug effects ; metabolism ; Intestine, Small ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Stomach ; metabolism