scholarly journals The Role of E-Cadherin in the Assessment of Esophageal Mucosal Damage in Patients with Gastroesophageal Reflux Disease Associated with Obstructive Sleep Apnea/Hypopnea Syndrome

Author(s):  
Y. Ya. Shaukovich

Aim. To evaluate the E-cadherin content in the blood plasma of individuals with suffering from both gastroesophageal reflux disease (GERD) and GERD combined with obstructive sleep apnea/hypopnea syndrome (OSAHS).Materials and methods. 120 patients with GERD and/or OSAHS were examined. All the patients underwent esophagogastroduodenoscopy with the biopsy of the lower third of the esophagus in order to perform GERD morphological verification. The diagnostics of respiratory disorders during sleeping was performed using computer pulse oximetry. Group 1 (n = 29) consisted of GERD patients, group 2 (n = 35) of patients with GERD in combination with OSAHS, group 3 (n = 30) of patients with OSAHS, group 4 (n = 26) was the comparison group. The concentration of E-cadherin in the blood plasma was determined using enzyme immunoassay. Results. There were no statistically significant differences in the plasma level of the N-terminal E-cadherin fragment between GERD patients and the comparison group (0.207 (0.128; 0.295) and 0.128 (0.067; 0.281) ng/ml, respectively, p = 0.082). However, the patients with erosive esophagitis were characterized by a higher content of E-cadherin in the blood plasma than those of the comparison group (0.284 (0.176; 0.858) and 0.128 (0.067; 0.281) ng/ml,  respectively, p = 0.03). In patients with GERD and OSAHS, statistically significantly higher plasma concentrations of E-cadherin were observed as compared to GERD patients (0.379 (0.277; 0.538) and 0.2007 (0.128; 0.295) ng/ml,  respectively, p = 0.017). A positive dependence of E-cadherin concentration in the blood plasma on the apnea/hypopnea index was found (r = 0.43, p <0.05).Conclusions. OSAHS negatively affects the state of histoarchitecture of the esophageal mucosa of GERD patients, as evidenced by an increase in N-terminal E-cadherin in the blood plasma and may indicate a loss of E-cadherin in the esophageal mucosa with the development of an impaired function of tight junctions. 

2019 ◽  
Vol 100 (5) ◽  
pp. 762-768 ◽  
Author(s):  
O A Karpovich ◽  
V I Shishko ◽  
V R Shulika

Aim. To evaluate the features of melatonin cyrcadian production in patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome. Methods. We examines 29 patients with gastroesophageal reflux disease were examined (group 1), 29 patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome (group 2), and 22 patients with obstructive sleep apnea/hypopnea syndrome (group 3). The comparison group included 21 people without gastroesophageal reflux disease and obstructive sleep apnea/hypopnea syndrome (group 4). The content of 6-sulfatoxymelatonin was determined in 24-hour urine and separately in its daytime and night portions by enzyme immune assay. The night/day index was calculated. The compared groups were comparable by gender but the patients with obstructive sleep apnea/hypopnea syndrome and gastroesophageal reflux disease associated with this syndrome differed from the patients from comparison group by older age, which is consistent with epidemiology of sleep apnea. The analysis of the data obtained was performed using the program Statistica 10.0. When comparing quantitative indicators between four independent samples, KruskelWallis test was used. In order to study the relationship between the phenomena, the Spearman rank correlation coefficient was calculated. Results. A significantly increased level of 6-sulfatoxymelatonin in 24-hour urine was determined in group 2 (p=0.0000), as well as in day (0.0000) and night portions (0.015) compared to group 1, in 24-hour urine (p=0.0007) and its day portion (p=0.0001) compared to group 3, in day portion of urine compared to group 4 (p=0.029). In group 2 compared to group 4 a significant shift in melatonin synthesis peak during daytime hours was observed, which is expressed in a statistically significant decrease in the night/day index (p=0.0003). Correlation analysis revealed statistically significant relations between the level of 6-sulfatoxymelatonin in urine and the severity of sleep apnea (in 24-hour urine: r=0.64, p=0.0000; in daytime portion: r=0.62, p=0.0000; in night portion: r=0.40, p=0.003), as well as respiratory monitoring indicators indicating sleep fragmentation due to apnea (the number of awakenings associated with respiratory events: r=0.58; p=0.00001; activation of the central nervous system associated with respiratory efforts: (r=0.50; p=0.0002). Conclusion. The patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome have an increased level of 6-sulfatoxymelatonin in urine associated with the shift of its peak synthesis to daytime hours; the identified changes correlate with apnea/hypopnea index reflecting the severity of apnea and sleep disturbance.


Author(s):  
A. A. Karpovich ◽  
V. I. Shyshko

The aim of the present research was to assess the expression of melatonin receptors (MTNR1B) in the esophageal mucosa in the gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome and to study the relationship between the detected changes and the sleep apnea severity. 84 patients aged 30–60 years, including those with gastroesophageal reflux disease (group 1, n  =  25), those with gastroesophageal reflux disease associated with sleep apnea/hypopnea (group 2, n = 23), those with obstructive sleep apnoe/ hypopnoe syndrome (group 3, n = 18), and almost healthy people (group 4, n = 18), were studied. Diagnoses were based on endoscopic imaging and respiratory monitoring. The MTNR1B expression in the esophageal mucosa was determined by the immunohistochemical method using specific antibodies. The MTNR1 B expression was evaluated quantitatively using the computer program Aperio ImageScope _v9.1.19.1567. The obtained material was analyzed statistically using the software Statistica 10.0. The group 2 patients were shown to have a higher MTNR1B expression compared to the group 1 patients (0.122 [0.064; 0.266] versus 0.620 [0.332; 0.983]; p =  0.00001) and the group 3 patients (0.620 [0.332; 0.983] versus 0.232 [0.120; 0.418]; р = 0.0098). The MTNR1 B expression increased with growing sleep apnea severity: it is 0.295 [0.198; 0.403] in patients with mild apnea versus 0.941 [0.345; 0.992] in patients with moderate and severe apnea (p = 0.0021). A direct correlation between the MTNR1B expression and the sleep apnea severity degree (r = 0.50; р = 0.0016) was revealed. Patients with gastroesophageal reflux disease combined with sleep apnea revealed an increase in the MTNR1 B expression associated with the apnea severity. The revealed features of the MTNR1 B expression secondary to esophageal mucosal damage indicate the MTNR1 B inactivation secondary to accompanying apnea of hypoxia.


2020 ◽  
Vol 4 (5) ◽  
pp. 268-273
Author(s):  
Yu.Ya. Shelkovich ◽  

Aim: to evaluate the effect of obstructive sleep apnea-hypopnea syndrome (OSAHS) on E-cadherin expression and epithelium histoarchitectonics of the lower third of the esophagus. Patients and Methods: 108 patients were included in a cross-sectional comparative study. According to the results of somnology, a mild severity of OSAHS was diagnosed in 49 patients (group 1), an average severity — in 29 (group 2). Group 3 included 30 people without OSAHS. All patients underwent esophagogastroduodenoscopy with a biopsy of the lower third of the esophagus. Morphometrics of epithelial thickness, height of connective tissue papillae, and internuclear distances in all epithelial layers was performed. To assess the E-cadherin expression, immunohistochemistry was performed using monoclonal antibodies to E-cadherin. Results: in contrast to the comparison group, patients with mild and moderate OSAHS were characterized by a higher epithelium thickness (273 (228; 372), 360 (312; 411), 186 (168; 192) μm, respectively, р1–3=0.000, р2–3=0.000), higher connective tissue papillae (108 (96; 120), 144 (120; 228), 72 (60; 84) μm, respectively, р1–3=0,001, р2–3=0,000), and larger internuclear distances in superficial layer (9 (7; 10), 8 (7; 9), 6 (5; 7) μm, respectively, р1–3=0.000, р2–3=0.002), spinous layer (8 (6; 9), 8 (7; 8), 6 (5; 7) μm, respectively, р1–3=0.000, р2–3=0.000), basal layer (4 (3; 5), 3 (3; 4), 2 (2; 3) μm, respectively, р1–3=0.000, р2–3=0,001) of epithelium. E-cadherin expression decreased in patients with both mild OSAHS (0.748 (0.623; 0.833) and 0.539 (0.263; 0.676), respectively, p=0.044) and moderate OSAHS (0.748 (0.623; 0.833) and 0.163 (0.026; 0.365), respectively, p=0.000) versus the comparison group. Correlations were found between respiratory monitoring indicators and E-cadherin expression in the esophageal epithelium. Conclusion: OSAHS negatively affects the lining condition of the lower third of the esophagus, contributes to the loss of E-cadherin, which creates conditions for disorganization of epithelial tissue and increases the risk of precancerous diseases and esophageal cancer. KEYWORDS: obstructive sleep apnea-hypopnea syndrome, E-cadherin, esophageal epithelium, histoarchitectonics, epithelial-mesenchymal transition, intermittent hypoxia, apnea-hypopnea index. FOR CITATION: Shelkovich Yu.Ya. Effect of obstructive sleep apnea-hypopnea syndrome on E-cadherin expression in esophageal epithelium. Russian Medical Inquiry. 2020;4(5):268–273. DOI: 10.32364/2587-6821-2020-4-5-268-273.


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