Ex vivo evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis.

AIM: To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an ex vivo model of gastro-oesophageal reflux. METHODS: An ex vivo evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000U/mL). RESULTS: The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (p<0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% vs. 18.9 (12.3)% for the control (p<0.05). In addition, after 30min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution. CONCLUSIONS: Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this ex vivo model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.

Development of a Mucoadhesive and an in Situ Gelling Formulation Based on κ-Carrageenan for Application on Oral Mucosa and Esophagus Walls. II. Loading of a Bioactive Hydroalcoholic Extract.

The aim of the present work was to load a Hibiscus sabdariffa (HS) hydroalcoholic extract into in situ gelling formulations for the treatment of oral mucositis and esophagitis. Such formulations, selected as the most promising options in a previous work of ours, were composed by κ-carrageenan (κ-CG), a sulfated marine polymer able to gelify in presence of saliva ions, hydroxypropyl cellulose (HPC), used as mucoadhesive agent, and CaCl2, salt able to enhance the interaction κ-CG/saliva ions. HS extract, which is rich in phytochemicals such as polyphenols, polysaccharides and organic acids, was selected due to its antioxidant and anti-inflammatory properties. For HS extraction, three different methodologies (maceration, Ultrasound Assisted Extraction (UAE) and Microwave Assisted Extraction (MAE)) were compared in terms of extraction yield and extract antioxidant activity, revealing that MAE was the best procedure. Rheological and mucoadhesive properties of HS-loaded formulations were investigated. Such formulations were characterized by a low viscosity at 25 °C, guaranteeing an easy administration, a proper in situ gelation behavior and marked elastic and mucoadhesive properties at 37 °C, functional to a protective action towards the damaged mucosa. Finally, the biocompatibility and the proliferative effect of HS-loaded formulations, as well as their antioxidant and anti-inflammatory properties, were proved in vitro on human dermal fibroblasts.

Effect of ethanolic extract of Quisqualis indica L. flower on experimental esophagitis in albino Wistar rats.

Quisqualis indica L., Syn. Combretum indicum (L.) DeFilipps., known as Rangoon creeper or Chinese Honeysuckle, is an abundant source of phenols and flavonoids thathave crucial role in free radical scavenging. Therefore, here we investigated whether extract of Q. indica flower has any role against esophagitis through scavenging of free radical oxygen species. In this study, we elucidated the effect of ethanolic flower extract of Q. indica on experimental esophagitis in albino Wister rats. The fasted animals divided into six groups and received carboxymethyl cellulose (CMC) (0.25%, 3 mL/kg, Sham control) or toxic control or pantoprazole (30 mg/kg) or flower extract of different doses (100, 200 and 300 mg/kg) were subjected to pylorus and fore stomach ligation. All the animals were sacrificed after 8 h and evaluated for various parameters such as total acidity, free acidity, gastric pH, volume of gastric juices and esophagitis index. Esophageal tissues were subjected to estimation of various oxidative stress parameters like malonaldehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and protein carbonyl (PC). In a separate experiment, in vitro antioxidant assays such as DPPH and H2O2 assays, total phenolic and flavonoid contents were also conducted. The results revealed that treatments with pantoprazole and flower extracts significantly inhibited the gastric secretion, total acidity and esophagitis index. Various oxidative stress parameters also restored to normal level in the treated groups. This action could be due to the presence of higher phenolic and flavonoid contents. All these findings collectively suggest that the flower extract of Q. indica possibly possess anti-esophagitis potential.

Effect of modified Zhuye Shigao Decoction and its components on preventing radiation esophagitis of rats.

OBJECTIVE: To investigate the effect of Modified Zhuye Shigao Decoction (MZSD) and its components on preventing radiation esophagitis of rats. METHODS: One 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 1ß (IL-1ß) 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. RESULTS: On 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-1ß 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-1ß and IL-8 compared with the radiation model group, ZSD group and added ingredients group (P <0.05 or P<0.01). CONCLUSION: MZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytokines TNF-α, IL-1ß and IL-8.

Endoscopic screening for precancerous lesions of the esophagus in a high risk area in Northern Iran.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD) in asymptomatic adults from Golestan Province, northern Iran, a high-risk area for ESCC, to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. METHODS: This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects were consented and then asked to fill in a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with Lugol's iodine staining was performed, biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. RESULTS: In total, 1906 GCS subjects were invited, of whom only 302 subjects (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). CONCLUSION: We observed a low rate for participation in endoscopic screening. Overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates.

Effect of Perilla frutescens fixed oil on experimental esophagitis in albino Wistar rats.

The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats (n = 6), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, n - 3) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis.

Beneficial effects of Ankaferd Blood Stopper on caustic esophageal injuries: an experimental model.

Ankaferd Blood Stopper (ABS) is an herbal extract that enhances mucosal healing. The aim of this study was to investigate the efficacy of ABS on the healing of the esophagus and prevention of stricture development after esophageal caustic injuries in rats. The study included 50 rats. Rats were divided into five groups: group 1 (no injury, sham surgery), group 2 (injury + no ABS + study after 2 weeks of injury), group 3 (injury + ABS + study after 2 weeks of injury), group 4 (injury + no ABS + study after 4 weeks of injury), and group 5 (injury + ABS + study after 4 weeks of injury). Standard esophageal burn injury was created by applying 50% NaOH solution to distal esophagus of about 1.5 cm. To rats in the sham group, isotonic solution was given instead of NaOH. ABS (2 mL/day) was given via oral route to group 3 and 5 rats. Fourteen days (group 2 and 3) and 28 days (group 4 and 5) later, all the live rats were killed. The distal esophageal segments of all rats were removed and divided into two equal parts for biochemical and histopathological examination. Mortality rate, weight changes, inflammation, stenosis index (SI), and biochemical measurements were evaluated. The SI was found as 0.31 ± 0.03 in group 1, 0.533 ± 0.240 in group 2, 0.568 ± 0.371 in group 3, 0.523 ± 0.164 in group 4, and 0.28 ± 0.03 in group 5. The SI and inflammation in ABS-treatment group 5 was significantly lower than that in non-treatment group 4 (P= 0.005). There were no significant differences between inflammation and SI among other groups. The mortality rate was 14.2% in group 1, 37.5% in untreated group 2, 14.2% in ABS-treated group 3, 80% in untreated group 4, and 33.3% in ABS-treated group 5. The mortality rate in group 4 was significantly higher than other groups (P= 0.025). Decrease rates in mean body weights of the groups were as follows: group 1, 1%; group 2, 15%; group 3, 14%; group 4, 46%; and group 5, 15%. Biochemical tests other than albumin and creatinine were comparable among the groups. Treatment with ABS prevents inflammation, scar formation, weight loss, and mortality in esophageal caustic injuries. Additional studies to evaluate the clinical benefits of ABS in esophageal caustic injury are recommended.

Early morbidity encountered in the dietary-related mouse model of Barrett's esophagus: a question of zinc?

Recently, a mouse model for Barrett's esophagus based on a zinc-deficient diet supplemented with deoxycholic bile acids has been published. The aim of this study was to attempt to reproduce these data and extend them by employing genetically modified mice and intraperitoneal iron supplementation. The study design encompassed six experimental groups (wild type, Apc-mutant and Smad4-mutant mice, with or without iron injections), with all animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids. All treatments were started at 3-5 weeks of age (the majority [78%] at 5 weeks). Animals were scheduled for euthanasia at two distinct time points, namely at 3 and 6 months of age. All mice showed signs of considerable distress already 4 weeks after the start of the modified diets, and had to be euthanized before the first evaluation time point (mean age 9.3 weeks, range 5-15 weeks). No differences were observed between wild type and genetically modified mice, or between animals with or without iron supplementation. On histological examination, we could not detect any lesions (Barrett's esophagus-like or tumors) other than esophagitis. In the currently presented experimental settings, we were not able to reproduce the mouse model according to which Barrett's-like lesions could be detected in animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids.

Correlation between eosinophilic oesophagitis and aeroallergens.

BACKGROUND: Aeroallergens have been implicated in the pathogenesis of eosinophilic oesophagitis. AIM: To determine whether a seasonal variation exists in the diagnoses of eosinophilic oesophagitis and whether there is a correlation with seasonal pollen count. METHODS: A retrospective review was performed from January 2006 to November 2008 to identify eosinophilic oesophagitis patients. Cases were classified by endoscopic date. Daily pollen counts for grass, trees and weeds were obtained from a certified counting station. Per cent of eosinophilic oesophagitis cases were collated seasonally and compared with mean pollen counts for grass, trees and weeds during the same time period. RESULTS: A total of 127 eosinophilic oesophagitis cases were identified (median age 41, range 19-92 years, 84% men). The highest percentage of cases (33.0%; Binomial P = 0.022) was diagnosed in the spring, while the least percentage (16%; Binomial P = 0.0.010) occurred in the winter. There was a significant association between per cent eosinophilic oesophagitis cases diagnosed seasonally and mean grass pollen count (r(s) = 1.000, P < 0.01), but not with trees (r(s) = 0.400, P = 0.600) or weeds (r(s) = 0.800, P = 0.200). CONCLUSIONS: A seasonal variation was seen in the diagnosis of eosinophilic oesophagitis which correlated with pollen counts. These findings have important implications regarding the pathogenesis of eosinophilic oesophagitis, suggesting a potential role for aeroallergens.

Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests.

BACKGROUND: Eosinophilic esophagitis (EE) is a recently described disorder identified in patients with symptoms suggestive of gastroesophageal reflux disease (GERD) but unresponsive to conventional reflux therapies. Therapies have included corticosteroids, elemental diet, and diet restriction. We report our experience with skin prick and atopy patch testing and food elimination diets in patients diagnosed as having EE. OBJECTIVE: To identify food antigens that cause EE and the characteristics of patients who respond to food elimination vs those who are unresponsive. METHODS: Patients diagnosed as having EE had restricted diets based on skin prick and atopy patch testing results. Additional biopsies were performed after 4 to 8 weeks of restricted diet. Demographics, atopic tendencies, and food antigens were identified retrospectively in our food allergy database. RESULTS: A total of 146 patients diagnosed as having EE were evaluated with skin prick and atopy patch testing. Thirty-nine patients had unequivocal demonstration of food causing EE, with normalization of biopsy results on elimination and reoccurrence on reintroduction. An additional 73 patients, for a total 112 (77%) of 146 patients, had resolution of their EE as demonstrated by biopsy results. Fifteen (10%) of 146 patients were nonresponders manifested by no significant reduction in esophageal eosinophils despite restricted diet based on skin prick and atopy patch testing. Egg, milk, and soy were identified most frequently with skin prick testing, whereas corn, soy, and wheat were identified most frequently with atopy patch testing. CONCLUSION: In more than 75% of patients with EE, both symptoms and esophageal inflammation can be significantly improved with dietary elimination of foods. Skin prick and atopy patch testing can help identify foods in most patients.

Efficacy of a pectin-based anti-reflux agent on acid reflux and recurrence of symptoms and oesophagitis in gastro-oesophageal reflux disease.

OBJECTIVE: Gastro-oesophageal reflux disease may be treated with a drug forming a floating neutral raft in the stomach. The pectin-based raft-forming anti-reflux agent Aflurax (Idoflux) was examined, first regarding reduction of oesophageal acid exposure, and next as to its efficacy as maintenance treatment in patients with healed oesophagitis. DESIGN: Double-blind, placebo-controlled randomized clinical trials. SETTING: Open access endoscopy unit. PARTICIPANTS: Fourteen patients with erosive oesophagitis had measurement of acid exposure. Eighty-eight patients with healed erosive/ulcerative oesophagitis and relief of heartburn after pre-treatment with omeprazole received maintenance treatment. INTERVENTIONS: Crossover 12-h oesophageal pH monitoring during Aflurax/placebo treatment. Maintenance treatment for up to 6 months with two tablets of Aflurax 1200 mg or placebo four times daily. MAIN OUTCOME MEASURES: Percentage time pH less than 4 in 6 plus 6 h (upright + supine). Time to recurrence of moderate or severe heartburn (life table analysis). RESULTS: The median (interquartile range) acid exposure times in the upright position were: 3.1% (1.6-13.0%) on Aflurax versus 6.7% (2.5-14.9%) on placebo (P = 0.10). In the supine position no difference was found (Aflurax 13.7%, placebo 13.2%). The time to recurrence of heartburn with Aflurax treatment was prolonged significantly; after 6 months the life table estimates were 48% of patients in remission on Aflurax versus 8% on placebo (P = 0.01). Following treatment, erosive oesophagitis was found in 17/34 on Aflurax versus 28/38 on placebo (P < 0.05). CONCLUSION: Aflurax significantly delays recurrence of moderate or severe heartburn and erosive oesophagitis, when used as maintenance treatment. The acid exposure was not significantly reduced with pH monitoring.

High-dose famotidine in the maintenance treatment of refractory esophagitis: results of a "medium-term" open study.

Forty-four patients with esophagitis refractory to standard H2-blocker therapy, who had healed after a 4- to 16-wk course with either 20-40 mg omeprazole or ranitidine at doses of 300-600 mg daily in a randomized double-blind study, commenced a 3-month maintenance course of therapy with 40 mg bid famotidine. The aims of this investigation were to assess the effectiveness of this regimen in preventing recurrence of esophagitis lesions and symptoms in this subgroup of patients with therapy-resistant disease and to verify whether patients previously healed with omeprazole have a higher recurrence rate than those healed with ranitidine. The results of the study show that, despite the high dose of famotidine, 48% of patients relapsed within 3 months, a third of whom were asymptomatic. Moreover, previous omeprazole treatment is associated with a significantly higher risk of recurrence.

Beneficios de la restitución nutricional en patologías esofágicas / Benefit of the nutritional restitution in esophageals pathologies

Se evaluaron 46 pacientes con patología esofágica tratados en al Unidad de Soporte Nutricional del Hospital Universitario de Caracas entre 1985-87. La esofágitis ácido-cáustica y el cáncer constituyen los factores etiológicos principales (64 por ciento), consultándose usualmente en grados avanzados de desnutrición. Se utilizaron diferentes vías y métodos de nutrición a predominio enteral (47.8 por ciento), y albúmina como indicador bioquímico nutricional. A pesar de los inconvenientes de administración, control y accesibilidad a los productos, se logró mantener en condiciones óptimas a 2/3 (63 por ciento de los pacientes) tratados y cerrar 91 por ciento de las fístulas sin cirugía