Protection and regeneration of esophageal, pharyngeal, and laryngeal mucosa as a major element in therapy of patients with esophageal and extraesophageal reflux symptoms

Treatment of esophageal and extraesophageal reflux syndromes is mainly focused on inhibiting the secretion of hydrochloric acid. In spite of the high efficacy of proton pump inhibitors, approx. 30–60% of GERD patients experience daily symptoms. Beside acid reflux, other factors such as abnormal esophageal peristalsis, visceral hypersensitivity, ineffective esophageal clearance mechanisms, and impaired mucosal barrier also play an important role in generating GERD symptoms. An additional therapeutic proposition is a procedure aimed at improving the defense mechanisms of esophageal mucosa rather than inhibiting the damage-inducing factors. The preparation consisting of hyaluronic acid (HA), chondroitin sulfate (SC) and poloxamer 407 protects against harmful factors (hydrochloric acid, pepsin) and accelerates mucosal healing and regeneration, constituting a substantial element of monotherapy or add-on therapy in patients with gastroesophageal reflux disease.

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Bile-Induced Laryngitis: Is There a Basis in Evidence?

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940511400304 ◽

2005 ◽

Vol 114 (3) ◽

pp. 192-197 ◽

Cited By ~ 44

Author(s):

Clarence T. Sasaki ◽

James Marotta ◽

Jen Chow ◽

Jagdeep Hundal ◽

Richard N. Eisen

Keyword(s):

Chenodeoxycholic Acid ◽

Bile Reflux ◽

Acid Reflux ◽

Taurocholic Acid ◽

Alternative Methods ◽

Saline Control ◽

Healthy Population ◽

Esophageal Mucosa ◽

Laryngeal Injury ◽

Laryngeal Mucosa

Most agree that bile reflux occurs with regularity in an otherwise healthy population and that biliary and acid reflux may play a synergistic role in damaging esophageal mucosa. But to what extent is laryngeal mucosa at risk? We constructed a saline-controlled rat model (n = 40) in which active component solutions of bile — taurocholic acid and chenodeoxycholic acid — were applied to intact laryngeal mucosa at various pH levels. Histologic sampling of the laryngeal mucosa allowed inflammation scores to be generated by a pathologist blinded to the solutions used. Both taurocholic acid at acid pH and chenodeoxycholic acid at basic pH preferentially induced statistically greater inflammation scores than did the saline control, approaching or exceeding inflammation scores attributed to hydrochloric acid at pH 1.2. These observations may clarify reasons for failure to uniformly control laryngeal injury by adequate suppression of gastric acid alone and may further justify alternative methods of laryngeal protection in patients refractory to adequate acid control.

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Sex-Based Differences in pH Parameters and Esophageal Impedance of Patients With Gastroesophageal Reflux Disease

Frontiers in Medicine ◽

10.3389/fmed.2021.629302 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bixing Ye ◽

Yanjuan Wang ◽

Lin Lin ◽

Liuqin Jiang ◽

Meifeng Wang

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Ph Monitoring ◽

Acid Reflux ◽

Mucosal Barrier ◽

Esophageal Mucosa ◽

Reflux Symptom Index ◽

Symptom Index ◽

Esophageal Impedance

Background/Aims: The incidence of reflux esophagitis (RE) has a striking predominance in males. Conversely, non-erosive reflux disease (NERD) is more common in females. This imbalance of gastroesophageal reflux disease (GERD) implies sex-related differences in its pathogenesis. However, limited studies have analyzed the sex-based differences in pH parameters and esophageal impedance of GERD patients.Methods: This study evaluated sex-based pathogenesis differences by comparing reflux episodes, mean nocturnal baseline impedance (MNBI) values, and post-reflux swallow-induced peristaltic wave (PSPW) index values of males with GERD and females with GERD using 24-h multichannel intraluminal impedance and pH monitoring.Results: We analyzed 181 patients (102 males and 79 females) with GERD. Reflux symptom index (RSI) scores were higher in females than that in males (P < 0.05). Males had significantly longer acid exposure times, higher DeMeester scores, and more acid reflux episodes than females (P < 0.05). Females had more instances of weakly acidic reflux than males (P < 0.01). The PSPW index values of males and females were similar (P > 0.05). Compared with females, males had lower MNBI values for the mid and distal esophagus (P < 0.05). However, with increasing age, the MNBI values of females decreased more rapidly than those of males. MNBI values of elderly patients of both sexes older than 60 years were similar.Conclusions: Acid reflux is more likely to occur in males; however, females tend to have more instances of weakly acid reflux. The integrity of the esophageal mucosa is more fragile in males than in females; however, the esophageal mucosal barrier attenuates more rapidly with increasing age in females than in males.

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Rare Etiology of Odynophagia in a Female Adolescent

Case Reports in Gastroenterology ◽

10.1159/000513801 ◽

2021 ◽

pp. 352-358

Author(s):

Anastasios Koutsoumourakis ◽

Asterios Gagalis ◽

Maria Fotoulaki ◽

Maria Stafylidou

Keyword(s):

Antiviral Treatment ◽

Healing Process ◽

Rare Condition ◽

Female Adolescent ◽

Mucosal Barrier ◽

Esophageal Mucosa ◽

Intact Immune System ◽

History Of ◽

Orolabial Herpes

Herpes esophagitis (HE) is a rare condition in immunocompetent adolescents. However, it commonly occurs as a primary infection in younger individuals. Herein, we report a 16-year-old female patient who had a history of fever for 5 days, odynophagia, and orolabial herpes infection for 7 days. Clusters of painful vesicles on an erythematous base on the lips, gingiva, and palate were observed on physical examination. Further, esophagogastroduodenoscopy revealed diffuse linear ulcerations in the distal esophagus. The patient then received the following treatment: intravenous (I.V.) acyclovir 5 mg/kg three times a day, I.V. omeprazole 40 mg two times a day, and acyclovir 5% cream four times a day. After 8 days of admission, the patient was discharged. A follow-up esophagogastroduodenoscopy was performed 7 weeks after discharge, and the results revealed that the esophageal mucosa had a normal appearance. The effect of antiviral treatment against HE remains unknown in these patients. Nevertheless, it is believed to accelerate the healing process in individuals with esophageal mucosal barrier damage. To the best of our knowledge, this case of a female adolescent with an intact immune system is the sixth case of herpes simplex esophagitis to be reported in the literature.

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Role of UropathogenicEscherichia coliVirulence Factors in Development of Urinary Tract Infection and Kidney Damage

International Journal of Nephrology ◽

10.1155/2012/681473 ◽

2012 ◽

Vol 2012 ◽

pp. 1-15 ◽

Cited By ~ 114

Author(s):

Justyna Bien ◽

Olga Sokolova ◽

Przemyslaw Bozko

Keyword(s):

Urinary Tract ◽

Signaling Pathways ◽

Virulence Factors ◽

Host Response ◽

Defense Mechanisms ◽

Inflammatory Responses ◽

Infectious Complications ◽

Mucosal Barrier ◽

Urological Complications ◽

Tract Infections

UropathogenicEscherichia coli(UPEC) is a causative agent in the vast majority of urinary tract infections (UTIs), including cystitis and pyelonephritis, and infectious complications, which may result in acute renal failure in healthy individuals as well as in renal transplant patients. UPEC expresses a multitude of virulence factors to break the inertia of the mucosal barrier. In response to the breach by UPEC into the normally sterile urinary tract, host inflammatory responses are triggered leading to cytokine production, neutrophil influx, and the exfoliation of infected bladder epithelial cells. Several signaling pathways activated during UPEC infection, including the pathways known to activate the innate immune response, interact with calcium-dependent signaling pathways. Some UPEC isolates, however, might possess strategies to delay or suppress the activation of components of the innate host response in the urinary tract. Studies published in the recent past provide new information regarding how virulence factors of uropathogenicE. coliare involved in activation of the innate host response. Despite numerous host defense mechanisms, UPEC can persist within the urinary tract and may serve as a reservoir for recurrent infections and serious complications. Presentation of the molecular details of these events is essential for development of successful strategies for prevention of human UTIs and urological complications associated with UTIs.

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Obesity and its effects on the esophageal mucosal barrier

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00199.2021 ◽

2021 ◽

Vol 321 (3) ◽

pp. G335-G343

Author(s):

Shere Paris ◽

Rebecca Ekeanyanwu ◽

Yuwei Jiang ◽

Daniel Davis ◽

Stuart Jon Spechler ◽

...

Keyword(s):

Adipose Tissue ◽

Gastroesophageal Reflux ◽

Visceral Adipose Tissue ◽

Esophagogastric Junction ◽

Mechanical Effect ◽

Mucosal Barrier ◽

Abdominal Pressure ◽

Esophageal Mucosa ◽

Barrier Integrity ◽

Visceral Adipose

Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.

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Current advances in the treatment of gastroesophageal reflux disease: a focus on esophageal protection

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.08.000387 ◽

2019 ◽

Vol 91 (8) ◽

pp. 4-11 ◽

Cited By ~ 2

Author(s):

I V Maev ◽

D N Andreev ◽

Yu A Kucheryavyy ◽

R I Shaburov

Keyword(s):

Molecular Weight ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Mucous Membrane ◽

Reflux Disease ◽

Barrier Function ◽

Poloxamer 407 ◽

Low Molecular Weight ◽

Esophageal Mucosa ◽

Refractory Gerd

Gastroesophageal reflux disease (GERD) is characterized by high morbidity and a significant decrease in the quality of life of patients, and is a major risk factor for esophageal adenocarcinoma. Nowadays, antisecretory therapy with proton pump inhibitors (PPI) is the "gold standard" of conservative treatment of GERD, but in some cases this therapy is unsuccessful. According to various studies, the prevalence of refractory GERD can reach 30-40%. The latest scientific data in the field of genetics and pathophysiology of GERD demonstrate that a disruption of the barrier function of the esophageal mucosa and an increase of its permeability can be the leading causes of refractoriness. Thus, the optimal therapy for patients with GERD should not only suppress the secretion of hydrochloric acid, but also restore the barrier function of the mucous membrane, providing an esophagoprotective effect. To achieve these goals, Alfasoxx was developed, which consists of a mixture of low molecular weight hyaluronic acid and low molecular weight chondroitin sulfate dissolved in a bioadhesive carrier (poloxamer 407). The clinical efficacy of this product has been confirmed by three prospective, randomized, placebo - controlled trials. Alfasoxx has a healing and restorative effect towards the esophageal epithelium and due to high ability for bioadhesion provides long - term protection of the mucous membrane of the esophagus. Combination therapy for GERD with the use of PPI and an esophagoprotector offers new perspectives for the treatment of patients with GERD.

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Resistance of the Esophageal Mucosa in Patients with GERD: the Dialogue Between Clinician and Pathologist

Effective Pharmacotherapy ◽

10.33978/2307-3586-2021-17-4-34-39 ◽

2021 ◽

Vol 17 (4) ◽

pp. 34-39

Author(s):

I.V. Matoshina ◽

◽

M.M. Fedorin ◽

M.A. Livzan ◽

S.I. Mozgovoy

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Pathological Process ◽

Mucosal Barrier ◽

Esophageal Mucosa ◽

Mucosal Protection ◽

Natural Factor ◽

Immunological Mechanisms ◽

Functional Components

Gastroesophageal reflux disease (GERD) is the most common of all acid-related diseases, it is recognized as the leading cause of esophageal adenocarcinoma. The natural factor of protection against aggressive refluxate components is the integrity of the esophageal mucosa, which performs a barrier function with the participation of a number of mechanical, chemical and immunological mechanisms. Their damage under the regular influence of acidic or mixed reflux causes the development of the pathological process. The review was prepared to systematize knowledge of the main components of mucosal barrier of the esophagus providing resistance of mucosa under conditions of GERD. The literature was searched in Embase, PubMed, and Google Scholar using the keywords: gastroesophageal reflux disease, mucosal protection, esophageal mucosa epithelium, dense contact proteins, epithelial protection, esophagoprotection. The main structural and functional components of esophageal mucosal protection were emphasized

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Immunologic Response of the Laryngeal Mucosa to Extraesophageal Reflux

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940811701205 ◽

2008 ◽

Vol 117 (12) ◽

pp. 891-895 ◽

Cited By ~ 7

Author(s):

Martin A. Birchall ◽

Michael Bailey ◽

Danuta Gutowska-Owsiak ◽

Nikki Johnston ◽

Charlotte F. Inman ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Laryngopharyngeal Reflux ◽

Mucosal Immune Response ◽

Extraesophageal Reflux ◽

Major Histocompatibility ◽

Nkt Cell ◽

Histocompatibility Complex ◽

Laryngeal Mucosa ◽

A Prospective Study ◽

Antigen Presenting

Objectives: Extraesophageal reflux is common. The treatment costs are high, and there are associations with other diseases, including laryngeal cancer. Our studies of the mucosal immune response to this common inflammatory disease suggest an important role for the nonclassic antigen-presenting molecule CD1d in the response to inflammation. This study was performed to further explore the relationship between the CD1d–NKT cell–iGb3 axis and reflux. Methods: We carried out a prospective study of laryngeal biopsies from 12 patients with laryngopharyngeal reflux and 11 controls. Quantitative multiple-color immunofluorescence using antibodies for lymphocytes (CD3, CD161) and classic and nonclassic major histocompatibility complex (I, II, β2m, CD1d) was performed, and univariate and multivariate analysis and co-localization measurements were applied. Results: Epithelial major histocompatibility complex class I and II expression was unchanged by reflux, but expression of CD1d increased (p < 0.05; luminal layers) and confidence intervals diminished in the reflux group. Co-localization of NKT cells with CD1d increased in patients (p < 0.01); iGb3 exhibited strong expression throughout all layers of the laryngeal epithelium. Conclusions: These data indicate a role for the CD1d–NKT cell–iGb3 axis in response to extraesophageal reflux in humans. This represents a useful target for novel diagnostics and treatments for this common condition.

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Absorption of Protein and Protein Fragments in the Developing Intestine: Role in Immunologic/Allergic Reactions

PEDIATRICS ◽

10.1542/peds.75.1.167 ◽

1985 ◽

Vol 75 (1) ◽

pp. 167-171

Author(s):

W. Allan Walker

Keyword(s):

Human Milk ◽

Defense Mechanisms ◽

Bacterial Colonization ◽

Newborn Infants ◽

Mucosal Barrier ◽

Protein Fragments ◽

Susceptibility To Infection ◽

Impermeable Barrier ◽

Other Substances ◽

Life Threatening

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier the newborn infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms which act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. As a result of a delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, "nature" has provided a means for passively protectecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system, namely human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes but many other substances that can interfere with bacterial colonization and prevent antigen penetration.

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