Pepsin in Nonacidic Refluxate Can Damage Hypopharyngeal Epithelial Cells

2009 ◽  
Vol 118 (9) ◽  
pp. 677-685 ◽  
Author(s):  
Nikki Johnston ◽  
Clive W. Wells ◽  
Tina L. Samuels ◽  
Joel H. Blumin
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Cell Damage ◽  
Ph Monitoring ◽  
Cytotoxicity Assay ◽  
Peptic Activity ◽  
Multichannel Intraluminal Impedance ◽  
Irreversible Inhibitors ◽  
Intraluminal Impedance ◽  
Fadu Cells

Objectives: Studies using combined multichannel intraluminal impedance with pH monitoring reveal a role for nonacidic reflux in laryngopharyngeal symptoms and injury. We have discovered that pepsin is taken up by laryngeal epithelial cells by receptor-mediated endocytosis. This finding reveals a novel mechanism by which pepsin could cause cell damage, potentially even in nonacidic refluxate. The objective of this study was to determine whether pepsin, at pH 7.4 and thus in nonacidic refluxate, causes cell damage. Methods: Cultured hypopharyngeal epithelial (FaDu) cells were exposed to human pepsin (0.1 mg/mL) at pH 7.4 for either 1 hour or 12 hours at 37°C and analyzed by electron microscopy, cytotoxicity assay, and SuperArray. Results: We report mitochondrial and Golgi complex damage in cells exposed to pepsin at neutral pH, observed by electron microscopy. We also report cell toxicity of pepsin at pH 7.4, measured by a cytotoxicity assay. Furthermore, using SuperArray, we found that pepsin at pH 7.4 significantly alters the expression levels of multiple genes implicated in stress and toxicity. Conclusions: These findings are perhaps the first to explain why many patients have symptoms and injury associated with nonacidic reflux, and could have important implications for the development of new therapies for reflux, such as pepsin receptor antagonists and/or irreversible inhibitors of peptic activity.

scholarly journals Effects of the cationic protein poly-L-arginine on airway epithelial cellsin vitro

2002 ◽  
Vol 11 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Shahida Shahana ◽  
Caroline Kampf ◽  
Godfried M. Roomans
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Cell Damage ◽  
Membrane Damage ◽  
Light And Electron Microscopy ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cationic Protein ◽  
Induced Apoptosis

Background: Allergic asthma is associated with an increased number of eosinophils in the airway wall. Eosinophils secrete cationic proteins, particularly major basic protein (MBP).Aim: To investigate the effect of synthetic cationic polypeptides such as poly-L-arginine, which can mimic the effect of MBP, on airway epithelial cells.Methods: Cultured airway epithelial cells were exposed to poly-L-arginine, and effects were determined by light and electron microscopy.Results: Poly-L-arginine induced apoptosis and necrosis. Transmission electron microscopy showed mitochondrial damage and changes in the nucleus. The tight junctions were damaged, as evidenced by penetration of lanthanum. Scanning electron microscopy showed a damaged cell membrane with many pores. Microanalysis showed a significant decrease in the cellular content of magnesium, phosphorus, sodium, potassium and chlorine, and an increase in calcium. Plakoglobin immunoreactivity in the cell membrane was decreased, indicating a decrease in the number of desmosomes.Conclusions: The results point to poly-L-arginine induced membrane damage, resulting in increased permeability, loss of cell-cell contacts and generalized cell damage.

Multichannel Intraluminal Impedance and pH Monitoring (pH-MII) in Infants and Children

2017 ◽  
pp. 89-110
Author(s):  
Maartje M. J. Singendonk ◽  
F. Jaime ◽  
S. Salvatore ◽  
M. M. Tabbers ◽  
M. A. Benninga ◽  
...  
Keyword(s):  
Ph Monitoring ◽  
Infants And Children ◽  
Multichannel Intraluminal Impedance ◽  
Intraluminal Impedance ◽  
In Infants And Children

Evaluation and Management of Laryngopharyngeal Reflux Disease: State of the Art Review

2019 ◽  
Vol 160 (5) ◽  
pp. 762-782 ◽  
Author(s):  
Jerome R. Lechien ◽  
Lee M. Akst ◽  
Abdul Latif Hamdan ◽  
Antonio Schindler ◽  
Petros D. Karkos ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Laryngopharyngeal Reflux ◽  
Ph Monitoring ◽  
Diagnosis And Treatment ◽  
Cochrane Library ◽  
Diagnostic Tools ◽  
Multichannel Intraluminal Impedance ◽  
Intraluminal Impedance ◽  
Number Of Patients ◽  
Multichannel Intraluminal Impedance Ph

Objective To review the current literature about the epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux (LPR). Data Sources PubMed, Cochrane Library, and Scopus. Methods A comprehensive review of the literature on LPR epidemiology, clinical presentation, diagnosis, and treatment was conducted. Using the PRISMA statement, 3 authors selected relevant publications to provide a critical analysis of the literature. Conclusions The important heterogeneity across studies in LPR diagnosis continues to make it difficult to summarize a single body of thought. Controversies persist concerning epidemiology, clinical presentation, diagnosis, and treatment. No recent epidemiologic study exists regarding prevalence and incidence with the use of objective diagnostic tools. There is no survey that evaluates the prevalence of symptoms and signs on a large number of patients with confirmed LPR. Regarding diagnosis, an increasing number of authors used multichannel intraluminal impedance–pH monitoring, although there is no consensus regarding standardization of the diagnostic criteria. The efficiency of proton pump inhibitor (PPI) therapy remains poorly demonstrated and misevaluated by incomplete clinical tools that do not take into consideration many symptoms and extralaryngeal findings. Despite the recent advances in knowledge about nonacid LPR, treatment protocols based on PPIs do not seem to have evolved. Implications for Practice The development of multichannel intraluminal impedance–pH monitoring and pepsin and bile salt detection should be considered for the establishment of a multiparameter diagnostic approach. LPR treatment should evolve to a more personalized regimen, including diet, PPIs, alginate, and magaldrate according to individual patient characteristics. Multicenter international studies with a standardized protocol could improve scientific knowledge about LPR.

scholarly journals COMBINED 24-HOURS ESOPHAGEAL PH MONITORING AND MULTICHANNEL INTRALUMINAL IMPEDANCE FOR COMPARISON OF GASTROESOPHAGEAL REFLUX IN CHILDREN WITH TYPICAL VERSUS ATYPICAL SYMPTOMS OF GASTROESOPHAGEAL REFLUX DISEASE

2016 ◽  
Vol 53 (3) ◽  
pp. 130-135 ◽  
Author(s):  
Seyed Mohsen DEHGHANI ◽  
Seyed Alireza TAGHAVI ◽  
Hazhir JAVAHERIZADEH ◽  
Maryam NASRI
Keyword(s):  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Reflux Disease ◽  
Ph Monitoring ◽  
P Value ◽  
Multichannel Intraluminal Impedance ◽  
Symptom Index ◽  
Atypical Symptoms ◽  
Intraluminal Impedance ◽  
The Mean

ABSTRACT Background - Gastroesophageal reflux disease is the most common esophageal disorder in pediatrics. Objective - The aim of this study was to compare reflux parameters of typical and atypical symptoms of gastroesophageal reflux disease using 24-hour esophageal pH monitoring and multichannel intraluminal impedance in pediatric population. Methods - In this prospective study, 43 patients aged less than 18 year with suspected gastroesophageal reflux disease were enrolled. The patients were divided into two groups based on the main presenting symptoms (typical versus atypical). Twenty four-hour pH monitoring and multichannel intraluminal impedance were performed in all the patients for comparing these two group regarding association of symptoms and reflux. Number of refluxes, pH related reflux, total reflux time, reflux more than 5 minutes, longest time of the reflux, lowest pH at reflux, reflux index were recorded and compared. Data comparison was done using SPSS. Results - The mean age of the patients was 5.7±3.4 years and 65.1% were male. Out of 43 patients 24 cases had typical symptoms and 19 had atypical symptoms. The mean reflux events detected by multichannel intraluminal impedance was more than mean reflux events detected by pH monitoring (308.4±115.8 vs 69.7±66.6) with P value of 0.037, which is statistically significant. The mean symptom index and symptom association probability were 35.01% ± 20.78% and 86.42% ± 25.79%, respectively in multichannel intraluminal impedance versus 12.73% ± 12.48% and 45.16% ± 42.29% in pH monitoring (P value <0.001). Number of acid reflux was 46.26±47.16 and 30.9±22.09 for atypical and typical symptoms respectively. The mean symptom index was 18.12% ± 13.101% and 8.30% ± 10.301% in atypical and typical symptoms respectively (P=0.034). Bolus clearance was longer in atypical symptoms compared typical symptoms(P<0.05). Conclusion - Symptom index was significantly higher in atypical symptoms compared to typical symptoms. Higher number of acid reflux was found in children with atypical symptoms of reflux. Longer duration of bolus clearance was found in group with atypical symptoms of reflux.

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