scholarly journals Gene Expression Profiling of Inflammatory Cytokines in Esophageal Biopsies of Different Phenotypes of Gastroesophageal Reflux Disease: a cross-sectional study.

2020 ◽  
Author(s):  
Monica Zavala-Solares ◽  
Gabriela Fonseca-Camarillo ◽  
Miguel Valdovinos ◽  
Julio Granados ◽  
Guido Grajales-Figueroa ◽  
...  

Abstract Background: Patients clinical endoscopic phenotypes in gastroesophageal reflux disease (GERD) are classified as: Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD are subclassified in Abnormal acid exposure (AAE) and Normal acid exposure (NAE) according to pH monitoring study. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD.Methods: This is an observational and cross-sectional study. All patients with BE, EE, AAE, NAE and control group were subjected to a superior endoscopy (with biopsies of esophageal mucosa). The cytokine mRNA relative quantification of target genes was conducted by RT-PCR. Changes in gene expression were assessed of the genes associated with inflammation in each disease phenotype. Statistical analysis of differential gene expression was performed by using Dunn's Multiple Comparison non-parametric test. A p value < 0.05 was considered as significant. Results: A total of 82 patients were included and they were divided into the following groups: Group BE 16 (19.51%), Group EE 23 (28.04%), Group AAE 13 (15.86%), NAE (15.86%) and Control Group 17 (20.73%). When comparing with control group we found: patients with BE showed an increased expression of IL-8 (P<0.005) and higher levels of: IL-10 and MMP-3, MMP-9 as well; patients with EE had higher levels of IL-1B, IL-6 and IL-10 (P<0.005), patients with AAE showed an increased expression of Il-1B, Il-6, IFN-γ and TNF-α (P<0.005). AAE had a higher expression of Il-1B and TNF-α than NAE (P<0.005). Conclusions: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients in GERD endoscopic phenotypes. MMP3 could be implicated in damage to esophageal mucosa. IL-1B and TNF-α could be a differential diagnosis between AAE and NAE in the non-erosive phenotype from endoscopic biopsies.

2020 ◽  
Author(s):  
Monica Zavala-Solares ◽  
Gabriela Fonseca-Camarillo ◽  
Miguel Valdovinos ◽  
Julio Granados ◽  
Guido Grajales-Figueroa ◽  
...  

Abstract Background: Patients clinical endoscopic phenotypes in gastroesophageal reflux disease (GERD) are classified as: Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD are subclassified in Abnormal acid exposure (AAE) and Normal acid exposure (NAE) according to pH monitoring study. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD. Methods: This is an observational and cross-sectional study. All patients with BE, EE, AAE, NAE and control group were subjected to a superior endoscopy (with biopsies of esophageal mucosa). The cytokine mRNA relative quantification of target genes was conducted by RT-PCR. Changes in gene expression were assessed of the genes associated with inflammation in each disease phenotype. Statistical analysis of differential gene expression was performed by using Dunn's Multiple Comparison non-parametric test. A p value < 0.05 was considered as significant. Results: A total of 82 patients were included and they were divided into the following groups: Group BE 16 (19.51%), Group EE 23 (28.04%), Group AAE 13 (15.86%), NAE (15.86%) and Control Group 17 (20.73%). When comparing with control group we found: patients with BE showed an increased expression of IL-8 (P<0.005) and higher levels of: IL-10 and MMP-3, MMP-9 as well; patients with EE had higher levels of IL-1B, IL-6 and IL-10 (P<0.005), patients with AAE showed an increased expression of Il-1B, Il-6, IFN-γ and TNF-α (P<0.005). AAE had a higher expression of Il-1B and TNF-α than NAE (P<0.005). Conclusions: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients in GERD endoscopic phenotypes. MMP3 could be implicated in damage to esophageal mucosa. IL-1B and TNF-α could be a differential diagnosis between AAE and NAE in the non-erosive phenotype from endoscopic biopsies.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mónica R. Zavala-Solares ◽  
Gabriela Fonseca-Camarillo ◽  
Miguel Valdovinos ◽  
Julio Granados ◽  
Guido Grajales-Figueroa ◽  
...  

Abstract Background The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD. Methods This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann–Whitney U non-parametric test. A p value < 0.05 was considered significant. Results A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05). Conclusion This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.


2020 ◽  
Author(s):  
Monica Zavala-Solares ◽  
Gabriela Fonseca-Camarillo ◽  
Miguel Valdovinos ◽  
Julio Granados ◽  
Guido Grajales-Figueroa ◽  
...  

Abstract Background: Patients clinical phenotypes in gastroesophageal reflux disease (GERD) are classified as: Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD.Methods: This is an observational and cross-sectional study. All patients with BE, EE, NERD and the control group were subjected to a superior endoscopy (with biopsies of esophageal mucosa). The cytokine mRNA relative quantification of target genes was conducted by RT-PCR. Changes in gene expression were assessed of the genes associated with inflammation in each disease phenotype. Statistical analysis of differential gene expression was performed by using Dunn's Test for Multiple Comparisons. A p value < 0.05 was considered as significant. Results: A Total of 98 patients were included and they were divided into the following groups: Group BE 16 (16.33%), Group EE 23 (23.47%), Group NERD 42 (42.86%) and Control Group 17 (17.35%). When comparing with control group we found: patients with BE showed an increased expression of IL-8 (P<0.005) and higher levels of: IL-1β, NF-κβ, IL-10 and MMP-3, MMP-9 as well; patients with EE had higher levels of IL-1B, IL-6, IL-8 and IL-10 (P<0.005) and patients with NERD showed a differential gene expression of cytokines Th1, particularly TNF-α and IL-1B (P<0.005) and decreased gene expression of Th2 cytokines such as IL-10, IL-8 and MMP9. Conclusions: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with the EE and BE phenotype.


2020 ◽  
Vol 50 (4) ◽  
Author(s):  
María Alejandra Mortarini ◽  
Daniela Neder ◽  
Ana Rocca

Motility disorders are frequent in children with cerebral palsy. The prevalence of gastroesophageal reflux disease varies from the 15% to 75% in patients with cerebral palsy. Nissen fundoplication is the most used antireflux technique not without complications in this population. Our objective was to determine the frequency and the characteristics of the long-term functional and motility complications in patients with Nissen fundoplication and cerebral palsy. A descriptive cross-sectional study was performed. Data collection was acquired retrospectively with neurologic compromise between 2012 and 2017 in patients between 0 to 18 years old, with neurological impairment and Nissen fundoplication. 35 patients were included. Median age was 55 months (2-190). Gastroesophageal reflux disease was diagnosed in the 48%, in the 52% of this the diagnosis was clinical. It was performed by laparoscopic technique in the 91.4% of the cases gastrostomy was done in the same surgical time in 86% of the patients because of neurological impairment and risk of aspiration. In 25.7% (n = 9) there were functional and motor complications, Dumping syndrome (5.5%) accommodation disorders (11.4%) and recurrence of reflux (11.4%). Redo Nissen was required in the 8.5% of the patients (n = 3). In 75% of the patients with complications, gastrostomy was performed in the same surgical time. It could not be demonstrated that gastrostomy at the time of antireflux surgery was associated with greater frequency of complications.


2014 ◽  
Vol 95 (1) ◽  
pp. 54-58
Author(s):  
N V Butorina ◽  
Ya M Vakhrushev ◽  
A M Zaprudnov

Aim. To study the collagen metabolism and secretion of hormones, and estimate their association in gastroesophageal reflux disease (GERD). Methods. 62 children with gastroesophageal reflux disease were examined. Control group included 32 children. Insulin and cortisol blood levels were determined by electro-chemiluminescence immunoassay (ECLIA), gastrin and somatostatin blood levels were determined by ELISA. Hydroxyproline and sialic acids levels were measured in gastric juice. Results. Esophageal mucosa lesions of different stages were diagnosed in all children with GERD: 36 (58%) children had I stage of esophagitis, 24 (38.7 %) children - II stage, 2 (3.2%) children - III stage. It was revealed that children with GERD demonstrated increased collagen breakdown level in esophageal and gastric mucosa, confirmed by high free hydroxyproline levels (29.6±3.2 μmol/L; p 0,05) and peptin-associated hydroxyproline (25.5±2.1 μmol /L; p 0.01). This collagen breakdown might be possible due to high cortisol level (389±15.5 nmol/L versus 204.4±12.1 nmol/L in control group, р 0.05). Increased insulin level (28.5±3.2 μU/ml vs 9.3±2.5 μU/ml; р 0,05) in patients with GERD might be a compensatory reaction to catabolic processes. Increased level of somatostatin (0.457±0.14 nmol/L; р 0.001) associated with low levels of gastrin (7.2±1.4 nmol/L) was discovered in children with GERD aged 9-12 years. On the contrary, children older than 12 years demonstrated high gastrin levels (18.72±3.2 nmol/L) associated with low levels of somatostatin (0.129±0.09 nmol/L). Conclusion. Influence of cortisol increased blood level on mucosa results in disbalance between aggressive and protective gastroduodenal factors in children with GERD, resulting in collagen breakdown. Increased insulin level signs the stimulation of the protective and adaptation mechanisms in children with GERD.


2021 ◽  
Vol 6 (1) ◽  
pp. 125-131
Author(s):  
Reva T. V. ◽  
◽  
V. B. Reva ◽  
I. V. Trefanenko ◽  
G. І. Shumko ◽  
...  

The article identifies the features of the pathology of the gastrointestinal tract in patients with gastroesophageal reflux disease on the background of hypothyroidism. The frequency of gastroesophageal reflux disease and the severity of this disease increase with age and the presence of comorbid pathology. In the elderly, the frequency of the typical esophageal manifestations decreases, and the erosive esophagitis with atypical symptoms is more common. The growing number of cases of combined thyroid dysfunction with gastropathology requires in-depth study of the reasons for the relationship between these processes. Pathological changes in the gastrointestinal tract in these patients make their condition severer, contributing to the development and progression of metabolic disorders. An important aggravating effect on the regulatory mechanisms of esophageal kinetics has a pathological functioning of the thyroid gland on the background of iodine deficiency. Results and discussion. In patients with gastroesophageal reflux disease with hypothyroidism, all changes in gastric and duodenal function are associated with a decrease in the acid-forming function of the gastric mucosa, due to its atrophy, decreased tone and contractility of the stomach. This in turn leads to a slowing of gastric and duodenal evacuation, dysfunction of the closing capacity of the cardia and, as a consequence, the development of duodenogastroesophageal reflux. The esophageal contents are not so pronounced, so patients with non-erosive forms of esophagitis predominate (46.2%) against 16% of patients in the second group (patients with gastroesophageal reflux disease). At the same time, erosive forms predominate among patients in the control group with predominant acid reflux. It should be noted that there is a clear relationship between the frequency of erosive changes in the esophageal mucosa and the duration of the disease. Thus, among patients of the main group with a 5-year history of the disease, the number of erosive forms of gastroesophageal reflux disease was minimal. The number of erosive changes in the esophageal mucosa increased sharply in patients with a 10-year history and reached its maximum after 15 years from the onset of the disease. Conclusion. The delay in gastric evacuation is more pronounced in patients with gastroesophageal reflux disease on the background of hypothyroidism. It can be explained by a decrease in gastric motility and the presence of duodenostasis. The slowing of gastric evacuation was more pronounced in patients with gastroesophageal reflux disease on the background of reduced thyroid function. In patients with gastroesophageal reflux disease on the background of hypothyroidism there is an alkaline duodenogastroesophageal reflux as a consequence of reduced acid-forming function of the gastric mucosa and reduced contractility of the stomach and duodenum


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