RESUMEN
Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.
Asunto(s)
Endoscopía del Sistema Digestivo , Humanos , Endoscopía del Sistema Digestivo/métodos , Mucosa Gástrica/patología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/diagnóstico por imagen , Mucosa Intestinal/patología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/diagnóstico por imagen , Inhibidores de la Bomba de Protones/efectos adversos , Mucosa Esofágica/patología , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/diagnóstico por imagenRESUMEN
OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.
Asunto(s)
Mucosa Esofágica , Reflujo Gastroesofágico , Humanos , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/prevención & control , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/patología , Mucosa Esofágica/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Permeabilidad , Impedancia Eléctrica , Administración Tópica , Biopolímeros , Anciano , Fluoresceína/administración & dosificación , Esófago/efectos de los fármacos , Esófago/patología , Esófago/metabolismo , Pirosis/tratamiento farmacológico , Pirosis/prevención & control , Relevancia ClínicaRESUMEN
A device that can easily measure electrical impedance might be a helpful tool for investigating the pathophysiology of gastroesophageal reflux disease. The first aim of this study was to validate our newly developed bioelectrical admittance measurement (BAM) through in vitro experimentation. The second aim was to investigate whether evaluation of BAM by this measurement differed between patients with heartburn according to their response to proton pump inhibitor (PPI) therapy. Caco-2 cell monolayers and three-dimensional tissues were examined by BAM using a frequency response analyzer. BAM was also used to measure the impedance through cell layers. Subsequently, BAM was performed during endoscopy in 41 patients experiencing heartburn without esophageal mucosal breaks. After 2-wk administration of 20-mg rabeprazole twice daily, patient responses to PPI were classified as "good" or "poor" according to their clinical course. In each patient, histological alterations and gene expression levels of inflammation mediators and tight junction proteins were evaluated. Impedance profiles indicated that monolayer Caco-2 cells on top of eight-layered normal human dermal fibroblasts had the highest magnitude of impedance over the range of frequencies. In vivo results revealed that patients with good responses to PPI displayed significantly higher admittance. Severity of low-grade inflammation was significantly associated with esophageal wall admittance. Moreover, esophageal wall admittance may be more closely related to basal zone hyperplasia than dilatation of intercellular spaces. Thus, BAM may be able to detect abnormalities in the subepithelial layer of the esophagus.NEW & NOTEWORTHY Bioelectrical admittance measurement is a new method to evaluate esophageal mucosal permeability vertically during upper gastrointestinal endoscopy. Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing proton pump inhibitor responsiveness in patients with gastroesophageal reflux disease. As various gastrointestinal diseases are associated with changes in mucosal permeability, bioelectrical admittance measurement is expected to be clinically applied to therapeutic decision-making for these diseases in the future.
Asunto(s)
Conductividad Eléctrica , Reflujo Gastroesofágico/tratamiento farmacológico , Inflamación/metabolismo , Rabeprazol/farmacología , Animales , Células CACO-2/citología , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/fisiopatología , Monitorización del pH Esofágico/métodos , Femenino , Reflujo Gastroesofágico/fisiopatología , Humanos , Inflamación/clasificación , Inflamación/diagnóstico , Masculino , Ratones , Persona de Mediana Edad , Membrana Mucosa/fisiopatología , Estudios ProspectivosRESUMEN
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.
Asunto(s)
Antiinflamatorios/farmacología , Citocinas/efectos de los fármacos , Mucosa Esofágica/efectos de los fármacos , Reflujo Gastroesofágico/tratamiento farmacológico , Isoflavonas/farmacología , Animales , Antioxidantes/metabolismo , Supervivencia Celular/efectos de los fármacos , Claudina-4/metabolismo , Claudina-5/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mucosa Esofágica/lesiones , Esófago/efectos de los fármacos , Esófago/metabolismo , Reflujo Gastroesofágico/inducido químicamente , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Ratas , Ratas WistarRESUMEN
Hypergastrinemia has been associated with high-grade dysplasia and adenocarcinoma in patients with Barrett's esophagus, and experimental studies suggest proinflammatory and proneoplastic effects of gastrin on Barrett's esophagus. This is of potential concern, as patients with Barrett's esophagus are treated with medications that suppress gastric acid production, resulting in increased physiologic levels of gastrin. We aimed to determine whether treatment with the novel gastrin/CCK2 receptor antagonist netazepide reduces expression of markers associated with inflammation and neoplasia in Barrett's esophagus. This was a randomized, double-blind, placebo-controlled trial of netazepide in patients with Barrett's esophagus without dysplasia. Subjects were treated for 12 weeks, with endoscopic assessment at baseline and at end of treatment. The primary outcome was within-individual change in cellular proliferation as assessed by Ki67. Secondary analyses included changes in gene expression, assessed by RNA-sequencing, and safety and tolerability. A total of 20 subjects completed the study and were included in the analyses. There was no difference between arms in mean change in cellular proliferation (netazepide: +35.6 Ki67+ cells/mm2, SD 620.7; placebo: +307.8 Ki67+ cells/mm2, SD 640.3; P = 0.35). Netazepide treatment resulted in increased expression of genes related to gastric phenotype (TFF2, MUC5B) and certain cancer-associated markers (REG3A, PAX9, MUC1), and decreased expression of intestinal markers MUC2, FABP1, FABP2, and CDX1 No serious adverse events related to study drug occurred. The gastrin/CCK2 receptor antagonist netazepide did not reduce cellular proliferation in patients with nondysplastic Barrett's esophagus. Further research should focus on the biological effects of gastrin in Barrett's esophagus.Prevention Relevance: Treatment of patients with Barrett's esophagus with a gastrin/CCK2 receptor antagonist did not have obvious chemopreventive effects.
Asunto(s)
Adenocarcinoma/prevención & control , Esófago de Barrett/tratamiento farmacológico , Benzodiazepinonas/administración & dosificación , Neoplasias Esofágicas/prevención & control , Compuestos de Fenilurea/administración & dosificación , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Anciano , Esófago de Barrett/patología , Benzodiazepinonas/efectos adversos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Método Doble Ciego , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/patología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Esofagoscopía , Femenino , Gastrinas/antagonistas & inhibidores , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/efectos adversos , Receptor de Colecistoquinina B/antagonistas & inhibidoresRESUMEN
Acellular scaffolds from decellularized donor organs are showing promising clinical results in tissue and organ repair and regeneration. A successful decellularization process is determined by (a) its capability to decellularize complete organs of large animals, (b) retention of the extracellular matrix (ECM) structures and morphologies, and (c) minimal loss of ECM proteins. In this study, porcine esophagi were perfused in full thickness with 0.25% w/v sodium dodecyl sulfate at perfusion rates 0.1-0.2 ml/min for up to 5 days. Decellularized tissues were characterized for their residual DNA, histological staining for their matrix structures, immunohistochemical staining for collagen type IV and laminin, and scanning electron microscopy for structural integrity. Our results showed that full thickness esophageal tissues treated using the horizontal perfusion setup were decellularized with good structural and biochemical integrity in the ECM. Residual DNA content in decellularized tissues was found to be 36 ± 12 ng/mg of tissues (n = 6) which was significantly lower than that of native tissues (p = .00022). Our study showed that the organ must be decellularized in full thickness and perfusion pressure must be controlled to minimize radial expansion. These factors were found to be critical in preserving the folded mucosa in the decellularized tissues.
Asunto(s)
Materiales Biocompatibles/aislamiento & purificación , Mucosa Esofágica/ultraestructura , Perfusión/métodos , Animales , Diseño de Equipo , Mucosa Esofágica/citología , Mucosa Esofágica/efectos de los fármacos , Microscopía Electrónica , Perfusión/instrumentación , Dodecil Sulfato de Sodio/farmacología , Tensoactivos/farmacología , Porcinos , Andamios del TejidoRESUMEN
BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT), followed by surgery, is the current standard of care for patients with locally advanced esophageal squamous cell carcinoma. However, up to 30% of the patients do not respond to nCRT. Hence, a simple, cost-effective marker to predict response before initiation of nCRT is needed. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic marker in various cancers. However, its role as a predictive marker in patients with esophageal SCC planned for nCRT has not been prospectively analyzed. MATERIALS AND METHODS: All consecutive patients with locally advanced (T1N1 and T2-T4a with or without nodal involvement) SCC planned for nCRT (CROSS protocol) followed by esophagectomy with total two field lymphadenectomy between December 2013 and December 2019 were included in this prospective analytical cohort study. NLR was calculated 1 week before starting the nCRT and was correlated with the histopathological response [Mandard tumor regression grade (TRG)]. RESULTS: Of the 216 patients with esophageal cancer evaluated during the study period, 57 patients with SCC who fulfilled the inclusion criteria were included. A good pathologic response (TRG 1 and 2) to nCRT was seen in 28 (49.1%) patients. Using a ROC curve, the optimal cutoff value of pretherapy NLR for predicting good pathologic response was 2.33. With an NLR cutoff value of 2.33, 53.3% of patients had a good pathologic response to nCRT compared with 47.6% patients with NLR ≥ 2.33 (P = 0.77). CONCLUSION: In patients with locally advanced esophageal SCC, NLR is not a useful marker to predict pathologic response to nCRT.
Asunto(s)
Quimioradioterapia Adyuvante/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Linfocitos , Terapia Neoadyuvante/métodos , Neutrófilos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Fraccionamiento de la Dosis de Radiación , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/patología , Mucosa Esofágica/efectos de la radiación , Mucosa Esofágica/cirugía , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/patología , Esofagectomía , Estudios de Factibilidad , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Estudios Prospectivos , Curva ROC , Valores de Referencia , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/epidemiología , Anciano , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Docetaxel/administración & dosificación , Esquema de Medicación , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/patología , Mucosa Esofágica/cirugía , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Esofagectomía , Esofagoscopía , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Pirimidinas , Estudios RetrospectivosRESUMEN
Gastroesophageal reflux disease (GERD) is a common digestive disorder that causes esophagitis and injuries to the esophageal mucosa. GERD symptoms are recurrent during pregnancy and their treatment is focused on lifestyle changes and nonprescription medicines. The aim of this study was to characterize the mechanism of action of a new patented medical device, an oral formulation containing hyaluronic acid, rice extract, and amino acids dispersed in a bioadhesive polymer matrix, by assessing its protective effects in in vitro and ex vivo models of esophageal mucosa damage. Acidic bile salts and pepsin cocktail (BSC) added to CP-A and COLO-680 N esophagus cells were used as an in vitro GERD model to evaluate the binding capacities, anti-inflammatory effects and reparative properties of the investigational product (IP) in comparison to a viscous control. Our results showed that the IP prevents cell permeability and tight junction dysfunction induced by BSC. Furthermore, the IP was also able to down-regulate IL-6 and IL-8 mRNA expression induced by BSC stimulation and to promote tissue repair and wound healing. The results were confirmed by ex vivo experiments in excised rat esophagi through the quantification of Evans Blue permeability assay. These experiments provided evidence that the IP is able to bind to the human esophagus cells, preventing the damage caused by gastroesophageal reflux, showing potential anti-irritative, soothing, and reparative properties.
Asunto(s)
Aminoácidos/administración & dosificación , Mucosa Esofágica/efectos de los fármacos , Reflujo Gastroesofágico/tratamiento farmacológico , Ácido Hialurónico/administración & dosificación , Oryza , Extractos Vegetales/administración & dosificación , Regeneración/efectos de los fármacos , Adhesividad , Aminoácidos/química , Línea Celular Tumoral , Equipos y Suministros , Mucosa Esofágica/fisiología , Humanos , Ácido Hialurónico/química , Permeabilidad , Extractos Vegetales/química , Regeneración/fisiologíaRESUMEN
The role of weak acids with pH values in the range of 4-7 has been implicated in the symptoms of gastroesophageal reflux disease (GERD). Prostaglandin E2 (PGE2) is associated with heartburn symptom in GERD patients; however, the precise productive mechanisms remain unclear. In this study, we revealed that exposure to weak acids increases PGE2 production with a peak at pH 4-5, slightly in human normal oesophageal cells (Het-1A), and robustly in oesophageal squamous carcinoma cells (KYSE-270). Release of PGE2 from the oesophageal mucosa was augmented by weak acid treatment in rat. Chenodeoxycholic acid (CDCA), a bile acid, upregulated cyclooxygenase-2 (COX-2) expression in Het-1A and KYSE-270 and induced PGE2 production in KYSE-270 cells. Weak acid-induced PGE2 production was significantly inhibited by cytosolic phospholipase A2 (cPLA2), ERK, and transient receptor potential cation channel subfamily V member 4 (TRPV4), a pH-sensing ion channel, inhibitors. Hangeshashinto, a potent inhibitor of COX-2, strongly decreased weak acid- and CDCA-induced PGE2 levels in KYSE-270. These results indicated that weak acids induce PGE2 production via TRPV4/ERK/cPLA2 in oesophageal epithelial cells, suggesting a role in GERD symptoms like heartburn. Interventions targeting pH values up to 5 may be necessary for the treatment of GERD.
Asunto(s)
Ácidos/efectos adversos , Dinoprostona/biosíntesis , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/metabolismo , Reflujo Gastroesofágico/etiología , Reflujo Gastroesofágico/metabolismo , Animales , Células Cultivadas , Ácido Quenodesoxicólico/efectos adversos , Inhibidores de la Ciclooxigenasa 2/farmacología , Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Reflujo Gastroesofágico/tratamiento farmacológico , Pirosis/etiología , Pirosis/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Modelos Biológicos , Prostaglandina-Endoperóxido Sintasas/metabolismo , Ratas , Canales Catiónicos TRPV/metabolismoRESUMEN
The fabrication and characterization of ball-milling modified glutinous rice starch (MGRS):chitosan (CS) composite films were demonstrated. Effect of CS ratios (2:1, 1:1, 1:2 MGRS:CS) on the film properties was investigated. Lidocaine hydrochloride was used as a model hydrophilic drug. ATR-FTIR confirmed hydrogen bond formation between MGRS and CS. XRD indicated an amorphous state of all fabricated films. The uniform and comparable thickness, weight, and drug contents of all fabricated films were obtained. The presence of CS did not affect the mucoadhesiveness of MGRS films. The increase in tensile strength and decreases in elongation and folding endurance were observed with 1:2 MGRS:CS films. The film swelling and drug release decreased with the CS ratio. Drug permeation across porcine mucosa indicated the enhancement effect of CS, whereby the permeation flux of 1:2 MGRS:CS composite increased by 3 folds. In conclusion, the MGRS:CS composite could be useful for buccal delivery of hydrophilic drug.
Asunto(s)
Anestésicos Locales/farmacología , Quitosano/química , Portadores de Fármacos/química , Interacciones Hidrofóbicas e Hidrofílicas , Lidocaína/farmacología , Oryza/química , Almidón/química , Adhesividad , Administración Bucal , Animales , Liberación de Fármacos , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/metabolismo , Enlace de Hidrógeno , Permeabilidad/efectos de los fármacos , Porcinos , Resistencia a la TracciónRESUMEN
INTRODUCTION: With increasing advances in minimally invasive endoscopic therapies and endoscopic resection techniques for luminal disease, there is an increased risk of post-procedure bleeding. This can contribute to significant burden on patient's quality of life and health resources when reintervention is required. Hemospray (Cook Medical, North Carolina, USA) is a novel haemostatic powder licensed for gastrointestinal bleeding. The aim of this single-arm, prospective, non-randomised multicentre international study is to look at outcomes in patients with upper gastrointestinal bleeds following elective endoscopic therapy treated with Hemospray to achieve haemostasis. METHODS: Data was prospectively collected on the use of Hemospray from 16 centres (January 2016-November 2019). Hemospray was used during the presence of progressive intraprocedural bleeding post-endoscopic therapy as a monotherapy, dual therapy with standard haemostatic techniques or rescue therapy once standard methods had failed. Haemostasis was defined as the cessation of bleeding within 5 min of the application of Hemospray. Re-bleeding was defined as a sustained drop in haemoglobin (>2 g/l), haematemesis or melaena with haemodynamic instability after the index endoscopy. RESULTS: A total of 73 patients were analysed with bleeding post-endoscopic therapy. The median Blatchford score at baseline was five (interquartile range 0-9). The median Rockall score was six (interquartile range 5-7). Immediate haemostasis following the application of Hemospray was achieved in 73/73 (100%) of patients. Two out of 57 (4%) had a re-bleed post-Hemospray, one was following oesophageal endoscopic mucosal resection and the other post-duodenal endoscopic mucosal resection. Both patients had a repeat endoscopy and therapy within 24 h. Re-bleeding data was missing for 16 patients, and mortality data was missing for 14 patients. There were no adverse events recorded in association with the use of Hemospray. CONCLUSION: Hemospray is safe and effective in achieving immediate haemostasis following uncontrolled and progressive intraprocedural blood loss post-endoscopic therapy, with a low re-bleed rate.
Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Endoscopía Gastrointestinal/efectos adversos , Hemorragia Gastrointestinal/terapia , Hemostasis Endoscópica/métodos , Hemostáticos/administración & dosificación , Minerales/administración & dosificación , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Electivos/efectos adversos , Endoscopía Gastrointestinal/métodos , Mucosa Esofágica/irrigación sanguínea , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/cirugía , Femenino , Mucosa Gástrica/irrigación sanguínea , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/cirugía , Hemorragia Gastrointestinal/etiología , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
Exposure to acidic gastric content due to malfunction of lower esophageal sphincter leads to acute reflux esophagitis (RE) leading to disruption of esophageal epithelial cells. Carbon monoxide (CO) produced by heme oxygenase (HMOX) activity or released from its donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) was reported to protect gastric mucosa against acid-dependent non-steroidal anti-inflammatory drug-induced damage. Thus, we aimed to investigate if CO affects RE-induced esophageal epithelium lesions development. RE induced in Wistar rats by the ligation of a junction between pylorus and forestomach were pretreated i.g. with vehicle CORM-2; RuCl3; zinc protoporphyrin IX, or hemin. CORM-2 was combined with NG-nitro-L-arginine (L-NNA), indomethacin, capsazepine, or capsaicin-induced sensory nerve ablation. Esophageal lesion score (ELS), esophageal blood flow (EBF), and mucus production were determined by planimetry, laser flowmetry, histology. Esophageal Nrf-2, HMOXs, COXs, NOSs, TNF-α and its receptor, IL-1 family and IL-1 receptor antagonist (RA), NF-κB, HIF-1α, annexin-A1, suppressor of cytokine signaling (SOCS3), TRPV1, c-Jun, c-Fos mRNA/protein expressions, PGE2, 8-hydroxy-deoxyguanozine (8-OHdG) and serum COHb, TGF-ß1, TGF-ß2, IL-1ß, and IL-6 content were assessed by PCR, immunoblotting, immunohistochemistry, gas chromatography, ELISA or Luminex platform. Hemin or CORM-2 alone or combined with L-NNA or indomethacin decreased ELS. Capsazepine or capsaicin-induced denervation reversed CORM-2 effects. COHb blood content, esophageal HMOX-1, Nrf-2, TRPV1 protein, annexin-A1, HIF-1α, IL-1 family, NF-κB, c-Jun, c-Fos, SOCS3 mRNA expressions, and 8-OHdG levels were elevated while PGE2 concentration was decreased after RE. CO donor-maintained elevated mucosal TRPV1 protein, HIF-1 α, annexin-A1, IL-1RA, SOCS3 mRNA expression, or TGF-ß serum content, decreasing 8-OHdG level, and particular inflammatory markers expression/concentration. CORM-2 and Nrf-2/HMOX-1/CO pathway prevent esophageal mucosa against RE-induced lesions, DNA oxidation, and inflammatory response involving HIF-1α, annexin-A1, SOCS3, IL-1RA, TGF-ß-modulated pathways. Esophagoprotective and hyperemic CO effects are in part mediated by afferent sensory neurons and TRPV1 receptors activity with questionable COX/PGE2 or NO/NOS systems involvement.
Asunto(s)
Monóxido de Carbono/farmacología , Mucosa Esofágica/patología , Esofagitis/patología , Compuestos Organometálicos/farmacología , Sustancias Protectoras/farmacología , Enfermedad Aguda , Animales , Carboxihemoglobina/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/sangre , Mucosa Esofágica/efectos de los fármacos , Esofagitis/sangre , Esófago/irrigación sanguínea , Esófago/patología , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inflamación/patología , Moco/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico/metabolismo , Oxidación-Reducción , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Células Receptoras Sensoriales/efectos de los fármacos , Células Receptoras Sensoriales/metabolismo , Canales Catiónicos TRPV/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.
Asunto(s)
Cromolin Sódico/farmacología , Esofagitis Eosinofílica/inmunología , Estabilizadores de Mastocitos/farmacología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/inmunología , Médula Ósea/patología , Modelos Animales de Enfermedad , Esofagitis Eosinofílica/inducido químicamente , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/inmunología , Mucosa Esofágica/patología , Fibrosis/inmunología , Fibrosis/patología , Inmunidad/efectos de los fármacos , Inmunidad/inmunología , Tejido Linfoide/efectos de los fármacos , Tejido Linfoide/inmunología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/toxicidadRESUMEN
Salivary epidermal growth factor (EGF) plays an important role in the maintenance of the oral and gastro-esophageal mucosa. Sialoadenectomy delays healing of oral wounds and affects lingual papillae. In this work, we aimed to determine the effect of EGF deficiency induced by sialoadenectomy and evaluate the effect of exogenous EGF administration on the lingual papillae and taste buds in rats. Thirty male adult Wistar albino rats were equally divided into 3 groups; sham-operated control group, sialoadenectomy group and group of sialoadenectomyâ¯+â¯EGF. EGF was given 8 weeks after sialoadenectomy in a dose of 1⯵g /ml/day in drinking water for 2 weeks. The anterior two-thirds of the tongue was dissected and cut longitudinally into two halves; one half for light microscope and the other for electron microscope examinations. Saliva and blood were collected to determine salivary and plasma EGF. Our results revealed that sialoadenectomy significantly reduced plasma and saliva levels of EGF which resulted in severe disruption of the architecture of lingual papillae. These changes were effectively improved by the exogenous EGF administration. In conclusion, EGF supplementation reversed the effects of sialoadenectomy and restored almost normal architecture of lingual papillae and taste buds.
Asunto(s)
Factor de Crecimiento Epidérmico/metabolismo , Glándulas Salivales/metabolismo , Papilas Gustativas/metabolismo , Lengua/metabolismo , Animales , Factor de Crecimiento Epidérmico/deficiencia , Factor de Crecimiento Epidérmico/farmacología , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/metabolismo , Humanos , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/metabolismo , Ratas , Saliva/efectos de los fármacos , Saliva/metabolismo , Glándulas Salivales/efectos de los fármacos , Glándulas Salivales/cirugía , Papilas Gustativas/efectos de los fármacos , Papilas Gustativas/cirugía , Lengua/efectos de los fármacos , Lengua/patología , Lengua/cirugíaAsunto(s)
Diclofenaco/efectos adversos , Mucosa Esofágica/patología , Esofagitis/diagnóstico , Reflujo Gastroesofágico/etiología , Pirosis/etiología , Artritis/tratamiento farmacológico , Biopsia , Endoscopía del Sistema Digestivo , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/cirugía , Esofagitis/inducido químicamente , Esofagitis/complicaciones , Esofagitis/tratamiento farmacológico , Femenino , Fundoplicación , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Pirosis/diagnóstico , Pirosis/terapia , Humanos , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del TratamientoRESUMEN
Background: Drug-induced esophagitis is an uncommon diagnosis in the pediatric population. The following is a report of six adolescents with L-arginine-induced esophagitis. Case reports: All patients were under treatment with L-arginine for short stature. After using the prescribed medication for 1-3 months, all cases started with severe retrosternal pain, odynophagia, and dysphagia. The upper gastrointestinal endoscopies showed ulcers located in the mid esophageal mucosa. Conclusions: In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, drug-induced esophagitis should be considered as a possible diagnosis. Treatment includes liquid diet, pain control, sucralfate, omeprazole, and interruption of L-arginine. In addition, the physician should explain preventive measures focused on patient and family education on the drug side effects and precise instructions on how to take medications, as well as a careful balance of risk and benefits of any medication. At present, there are no clinical trials that support the use of L-arginine in treatment of short stature.
Introducción: La esofagitis inducida por medicamentos es un diagnóstico poco frecuente en pacientes pediátricos. A continuación, se describe una serie de seis casos de pacientes menores de 15 años con esofagitis inducida por L-arginina. Casos clínicos: Los seis casos se encontraban en tratamiento con L-arginina por talla baja e iniciaron con dolor retroesternal, odinofagia y disfagia de rápida instalación. Cuatro de ellos acudieron al servicio de urgencias por la intensidad de los síntomas. Los hallazgos en la endoscopia del tubo digestivo alto fueron úlceras en la mucosa del esófago a la altura del tercio medio, zona de estrechez natural por la compresión del bronquio izquierdo. Conclusiones: En presencia de odinofagia, disfagia, dolor retroesternal y el antecedente de la ingesta de L-arginina, la esofagitis inducida por fármacos debe considerarse como una posibilidad diagnóstica. El tratamiento está basado en el manejo del dolor, sucralfato, omeprazol, así como la suspensión del medicamento y medidas preventivas centradas en la educación del paciente y los familiares sobre los riesgos y beneficios de un medicamento y la forma correcta de administrarlo.
Asunto(s)
Arginina/efectos adversos , Mucosa Esofágica/efectos de los fármacos , Esofagitis/inducido químicamente , Adolescente , Arginina/administración & dosificación , Dolor en el Pecho/etiología , Niño , Trastornos de Deglución/etiología , Mucosa Esofágica/patología , Esofagitis/diagnóstico , Esofagitis/terapia , Femenino , Humanos , Masculino , Omeprazol/administración & dosificación , Sucralfato/administración & dosificación , Úlcera/etiologíaRESUMEN
Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue (P < 0.05). Evaluation of the interepithelial tight junctions showed well-defined membrane localization of occludin in lubiprostone-treated injured tissues. Pretreatment of tissues with the Na+-K+-2Cl- cotransporter inhibitor bumetanide blocked lubiprostone-induced increases in short-circuit current and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of ClC-2 with ZnCl2 blocked the effects of lubiprostone. We conclude that ClC-2 contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target.NEW & NOTEWORTHY This research is the first to describe the presence of anion channels ClC-2 and CFTR localized to the basal epithelia of porcine esophageal mucosa and the esophageal submucosal glands. In the setting of ex vivo acid exposure, the ClC-2 agonist lubiprostone reduced acid-related injury and enhanced recovery of the epithelial barrier. This work may ultimately provide an alternate mechanism for treating gastroesophageal reflux disease.
Asunto(s)
Mucosa Esofágica/efectos de los fármacos , Lubiprostona/farmacología , 16,16-Dimetilprostaglandina E2/farmacología , Animales , Bumetanida/farmacología , Agonistas de los Canales de Cloruro/farmacología , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Cloruros/farmacología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Ácido Clorhídrico/farmacología , Masculino , Ocludina/metabolismo , Porcinos , Factores de Tiempo , Compuestos de Zinc/farmacologíaRESUMEN
Keratinocytes take up serum-derived retinol (vitamin A) and metabolize it to all-trans-retinoic acid (atRA), which binds to the nuclear retinoic acid receptor (RAR). We previously reported that serum-affected keratinocyte differentiation and function; namely, it inhibited keratinization, decreased loricrin (LOR) and claudin (CLDN) 1 expression, increased keratin (K) 4 and CLDN4 levels, and reduced paracellular permeability in three-dimensional (3D) cultures of mouse keratinocytes (COCA). Contrarily, RAR inhibition reversed these changes. Here, we aimed to examine whether atRA exerted the same effects as serum, and whether it was involved in the differential oral mucosa keratinization among animal species. Porcine oral mucosal keratinocytes, which form non-keratinized epithelium in vivo, established keratinized epithelium in 3D cultures. Both mouse and porcine sera induced non-keratinized epithelium at 0.1% in COCA 3D cultures. Although atRA caused the same changes as serum, its effective concentration differed. atRA inhibited keratinization at 0.1 nM and 1 nM in porcine or human keratinocytes and COCA, respectively. Furthermore, atRA upregulated CLDN7 in the cytoplasm but not in cell-cell contacts. These atRA-induced changes were reverted by RAR inhibition. The results indicate that serum-induced changes are probably due to the effect of serum-derived atRA, and that mouse keratinocytes require higher atRA concentrations to suppress keratinization than porcine and human keratinocytes. We propose that the lower susceptibility of mouse keratinocytes to atRA, rather than a lower retinol concentration, is a possible reason for the keratinization of mouse oral mucosal epithelium.