Daidzein ameliorates experimental acute reflux esophagitis in rats via regulation of cytokines.

Context: Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. Objective: The current work determines the preventive effect of daidzein against injury in the esophagus mucosa induced by esophageal reflux (RE) in an animal model. Methods: Adult male Wistar rats were classified into six groups: normal control, ER + different doses of daidzein and ER + omeprazole. RE was induced in all animals except controls and supplemented with daidzein and standard drugs orally for 6 hours. Serum and tissue were used for further biochemical parameters. Results: Daidzein as a flavonoid has antioxidant properties and shows in vitro antioxidant activity. The outcomes also reveal an elevation in lipid peroxidation and a decline in the levels of sulphhydryl groups and glutathione, along with the depletion in the activities of enzymatic antioxidants in the oxidative stress state. In a dose-dependent manner daidzein and omeprazole amended all macroscopic and biochemical variations and protected against the raised level of hydrogen peroxide (H2O2), calcium and free iron levels in esophageal tissue induced during RE. It also improved the expression and level of proinflammatory cytokines. Conclusion: The finding reports that daidzein has a potential to show a shielding effect against esophagus damage induced by RE in rats, at least in part via alteration of inflammatory cytokines.

The effect of Heweijiangni-decoction on esophageal morphology in a rat model of OVA-induced visceral hypersensitivity followed by acid exposure.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

Gastrointestinal symptoms in idiopathic pulmonary fibrosis patients treated with pirfenidone and herbal medicine.

Pirfenidone is an antifibrotic agent for patients with pulmonary fibrosis, but this drug has adverse gastrointestinal (GI) effects. The first aim of this study was to assess GI symptoms due to pirfenidone by using a new questionnaire for reflux symptoms and dismotility symptoms. Whether adding herbal medicine of rikkunshi-to improved GI symptoms due to pirfenidone therapy was also investigated. This was a randomized controlled trial performed on 17 IPF patients. The patients were assigned to two groups, and the study period was 8 weeks. The pirfenidone group received pirfenidone therapy for 8 weeks with add-on rikkunshi-to from 4 weeks, while the control group did not receive either of these agents. To assess the effects of RK, plasma levels of acyl-ghrelin and des-acyl-ghrelin, serum KL-6 and surfactant protein-D, and pulmonary function tests were monitored. GI symptoms were most severe during the initial 2 weeks of pirfenidone therapy at a dose of 600 mg/day. Both reflux symptoms and dismotility symptoms deteriorated. Rikkunshi-to improved GI symptoms to the level prior to pirfenidone therapy. Plasma levels of des-acyl-ghrelin and acyl-/des-acyl-ghrelin ratio changed significantly at 8 weeks compared to 2 weeks. GI adverse events due to PFD were most severe in the first 2 weeks of treatment at a dose of 600 mg/day, and both reflux and dismotility symptoms deteriorated, but the drug was well tolerated at 1200 mg/day. Rikkunshi-to contributed to improvement of GI symptoms, but plasma ghrelin levels did not reflect the improvement of GI symptoms.

Clinical effects of the new phosphorus binder, bixalomer in hemodialysis patients switched from sevelamer hydrochloride.

It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P=0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.

Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms.

Bixalomer (Bix) is an amine-functional polymer, non-calcium-containing phosphate (P) binder, and has been clinically available in Japan recently. Bix is expected to cause fewer gastrointestinal (GI) side-effects as compared with sevelamer hydrochloride (SH), because of less expansion of Bix in the GI tract. In this prospective observational study, we evaluated changes in GI symptoms by the Gastrointestinal Symptom Rating Scale (GSRS) score in long-term hemodialysis (HD) outpatients with SH-associated GI symptoms who switched to Bix from SH. A total of 114 patients (age 63.7±10.8 year (mean±SD), female 65.5%, HD vintage 11.2±8.6 years, diabetes mellitus 27.4%) were enrolled. The GSRS score was checked at 0 and 12 weeks after the start of Bix. Bix was started at the initial dose of 750 mg/day, and then was titrated. Serum albumin, P and corrected calcium levels did not significantly change during Bix treatment. However, serum low-density lipoprotein-cholesterol and bicarbonate levels significantly increased during Bix treatment (P<0.001). In GSRS scores, total and domain-specific scores, including constipation, diarrhea, reflux and abdominal pain were significantly reduced at 0, 4, 12 and 24 weeks as compared with those at 0 weeks (P<0.05). This study shows that Bix was well tolerated and managed hyperphosphatemia effectively after switching from SH in Japanese patients on long-term HD. In addition, Bix might be less often associated with GI symptoms as compared with SH.

Epidemiological study on the incidence of gastroesophageal reflux disease symptoms in patients in acute treatment with NSAIDs.

Gastroesophageal reflux disease (GERD) is one of the most common disorders in medical practice. The prevalence of GERD in Spain has been reported to be 15%. GERD is associated with esophageal and extra-esophageal complications and with a negative impact on the patients' related quality of life. Several risk factors have been related with the development of GERD, including smoking, coffee intake, alcohol consumption and use of medication, such as NSAIDs. If untreated, GERD symptoms can lead to a decrease of patients' related quality of life and to treatment discontinuation. From this study, it was confirmed that the relationship between GERD and some behavioral risk factors, such as alcohol intake, smoking and coffee consumption, and concomitant treatment with NSAID drugs. Among the protective factors for GERD, antisecretory agents and antacids have shown to be essential for the control of GERD, the use of proton pump inhibitors being the predominant protective factor.

Barrett's esophagus and medications that relax the lower esophageal sphincter.

OBJECTIVES: Medications that may increase gastroesophageal reflux could be risk factors for esophageal adenocarcinoma; however, epidemiologic studies present conflicting results. We evaluated patients with a high-risk condition, Barrett's esophagus, to identify risk factors that may act early in the carcinogenic process. METHODS: We conducted a nested case-control study within a large integrated health-services organization. Electronic databases were used to identify incident diagnoses of Barrett's esophagus (cases); two controls were matched to each case. Electronic databases provided information on the use of medications that may induce reflux (nitrates, calcium channel blockers, xanthines, benzodiazepines, and beta agonists) and potential confounders. A supplemental mailed questionnaire evaluated additional potential confounders. RESULTS: We identified 421 cases and selected 842 controls. The association between any medication use and a Barrett's esophagus diagnosis was modified by age; an increased risk was observed only among subjects <70 yr of age (adjusted odds ratio [OR] = 2.6; 95% confidence interval [CI] 1.5-4.6). A Barrett's esophagus diagnosis was associated with asthma medication use (OR 5.8; 95% CI 2.2, 14.9), but not with the other medications studied. Subgroup analyses suggested that medication use was not independently associated with reflux symptoms and that adjustment for asthma symptoms substantially reduced the association between medication use and a Barrett's esophagus diagnosis. CONCLUSION: The use of medications that may induce reflux was associated with a Barrett's esophagus diagnosis among younger persons. This association was only observed with asthma medications; the analyses suggested the possibility of confounding by indication, whereby reflux may cause both asthma and Barrett's esophagus.

Bioadhesive oesophageal bandages: protection against acid and pepsin injury.

The rate of acid and pepsin diffusion through solutions of sodium alginate was measured using in vitro techniques. Previous work has demonstrated that solutions of alginate may adhere to the oesophagus for up to 60 min; this work measured their ability to protect the oesophageal epithelial surface from damage caused by refluxed acid and pepsin. Franz diffusion cells were used to measure the rate of acid and pepsin diffusion through an alginate layer. The effect of the type of alginate, alginate concentration and depth of alginate applied were investigated. The rate of both acid and pepsin diffusion was significantly reduced (ANOVA analysis; P<0.05) in the presence of an alginate solution compared to the control. A 2% (w/v) alginate solution with a high guluronic acid component, in a layer of 0.44 mm depth, demonstrated the greatest reduction in acid diffusion with a permeation coefficient 14% than that of a control value. All three alginates demonstrated significant reductions in acid diffusion with both increasing depth and increasing concentration, as expected. Pepsin diffusion was also significantly reduced as the depth and concentration of applied alginate increased. This study demonstrates that an adhesive layer of alginate present within the oesophagus will limit the contact of refluxed acid and pepsin with the epithelial surface.

The effect of decaffeination of coffee on gastro-oesophageal reflux in patients with reflux disease.

BACKGROUND: Patients with reflux disease often complain of heartburn after ingestion of coffee. Induction of gastro-oesophageal reflux has been demonstrated by pH-metry following the intake of coffee in healthy volunteers. The reflux was reduced when the coffee had undergone a decaffeination process. The aim of this study was to investigate the effect of decaffeination of coffee on reflux in patients with reflux disease. METHODS: Seventeen reflux patients underwent two osesophageal 3-h pH measurements. The patients received, in a double-blind study design in a randomized order, 300 mL of either regular or decaffeinated coffee together with a standardized breakfast. The fraction time oesophageal pH < 4 was calculated during the three postprandial hours. RESULTS: For regular coffee the fraction time was calculated to a median of 17.9% with a range of 0.7-56.6%. The fraction time was significantly reduced to 3.1% (0-49.9%) after ingestion of decaffeinated coffee. CONCLUSION: The amount of gastro-oesophageal reflux induced by the intake of regular coffee in patients with reflux disease can be reduce by the decaffeination of coffee.

Effect of different coffees on esophageal acid contact time and symptoms in coffee-sensitive subjects.

The purpose of this study was to correlate the effects of different coffees on esophageal acid contact, heartburn, and regurgitation in patients with coffee-sensitivity. Twenty volunteers with coffee-sensitivity were studied in a double-blind, 3 period, crossover study examining the effect of three regular (caffeinated) coffees (a coffee from the USA--"A"; a "treated" coffee from Europe--"B"; and an "untreated" coffee from Europe--"C") before and after a high-fat test meal. The median acid contact times for coffees A, B, and C were 6.5%, 9%, and 10.5%, respectively (A vs. C, p = 0.005). Significantly fewer patients reported any symptoms with coffee A compared with coffee C (p < 0.05). Symptoms were usually more frequent and severe after the test meal. There was a trend toward fewer and less severe symptoms with the treated coffee (B) compared with its untreated counterpart (C). Our conclusions are as follows: (a) Different coffees induce variations in gastroesophageal reflux in coffee-sensitive individuals. (b) Coffee can be treated in a manner which decreases heartburn symptoms by 75% while decreasing acid contact by only 14%. (c) Gastroesophageal reflux and symptoms of coffee sensitivity increase with the concomitant ingestion of food. (d) Symptoms of dyspepsia appear to be influenced by variations in both the coffee itself and characteristics of susceptible individuals. (e) Although gastroesophageal reflux is important in the genesis of coffee-sensitivity, there must be other factors which act in concert with reflux to produce symptoms of coffee-sensitivity.

"Oesophageal angina" in patients with angina pectoris: a possible side effect of chronic therapy with nitroderivates and Ca-antagonists.

The study was carried out on 18 patients with angina pectoris in whom the usual treatment with nitroderivatives and/or Ca-antagonists did not improve or prevent the angina-like chest pain in the absence of unstable angina. The patients underwent the following oesophageal examinations: X-ray, endoscopy-biopsy, manometry, acid perfusion test and 24-hour oesophageal pH ambulatory monitoring, the latter two being made in association with dynamic ECG. The presence of coronary insufficiency had been previously determined by means of ECG and scintigraphic stress tests and, when necessary, coronary arteriography was performed. In 10/18 patients severe oesophageal motor disorders were observed, the most frequent being diffuse oesophageal spasm. In the entire group the lower oesophageal sphincter basal tone was significantly lower than normal. In 14/18 patients a pathologic gastroesophageal reflux was detected: in 2 of these patients a temporal correlation between pain attacks and episodes of gastroesophageal reflux were observed in the absence of ECG modifications. Acid perfusion test induced the angina-like chest pain in another 2 patients without ECG modifications. In conclusion, the angina-like chest pain of these patients is not due to a failure of the antianginal therapy in relieving the coronary insufficiency, but is most probably related to gastroesophageal reflux. This oesophageal disorder may be considered a side effect caused by prolonged therapy with nitroderivatives and Ca-antagonists. In fact, these drugs decrease the lower oesophageal sphincter tone which is the main barrier against the reflux of gastric contents into the oesophagus so favoring gastroesophageal reflux and related disorders, including oesophageal pain.

Anaesthesia induction and lower oesophageal sphincter pressure.

The effects of some drugs generally used in premedication for and induction of anaesthesia on the lower oesophageal sphincter (LOS) pressure were investigated in 30 dogs, using the modern oesophageal manometric technique. In thiopental-induced anaesthesia, a distinct pressure gradient was noted between the LOS and gastric pressure. Atropine eliminated this pressure gradient almost completely. Metoclopramide increased the LOS pressure significantly, and subsequent atropine administration was unable to bring it down. Metoclopramide administered after atropine was unable to elevate the LOS pressure reduced by atropine. Succinylcholine had no observable lasting effect on the LOS pressure. The present findings seem to indicate that of the drugs generally used in premedication for and induction of anaesthesia, atropine significantly reduces the LOS competence, thereby creating favourable conditions for gastro-oesophageal reflux (GOR) and consequent postoperative pulmonary complications. Use of metoclopramide in premedication for or induction of anaesthesia to eliminate the depressant effect of atropine on the LOS pressure appears to be indicated.