scholarly journals CASPASE-DEPENDENT ACTIVATION OF CASCADE CYTOKINES IN YOUNG PATIENTS WITH AUTOIMMUNE THYROIDITIS IN COMBINATION WITH GASTROESOPHAGEAL REFLUX DISEASE

2021 ◽  
pp. 58-63
Author(s):  
Tamara Pasiieshvili ◽  
Lyudmila Pasiieshvili ◽  
Natalia Zhelezniakova ◽  
Olga Kovalyova

The aim of the study: to assess the role of caspase-1 and IL-18 in the implementation of the inflammatory response in young patients with autoimmune thyroiditis (AIT) associated with gastroesophageal reflux disease (GERD). Materials and methods. The study was conducted in two groups of patients homogeneous by gender and age. The first group included 42 patients with an isolated AIT and the second group – 120 patients with a comorbid course of AIT and GERD. The contingent of the surveyed was students. Median age was from 18 to 25 years: 23.1±1.2 years in group with isolated AIT and 21.9±2.7 years in group with combined pathology. The activity of caspase-1 was determined using “Elabscience” kits, USA (China) by immunoassay method. The content of IL-18 was investigated using commercial kits “Bender MedSystems GmbH” (Austria) according to the proposed methods by immunoassay method. Statistical data processing was carried out using the local universal software package Statistica Basic Academic 13 for Windows En Local. Methods of non-parametric statistics were used: Kruskal-Wallis test, median test, Mann-Whitney test. Results. It has been found that caspase-1 is activated in patients both in the isolated course of AIT and in its combination with GERD. At the same time, a significant increasing in the synthesis of IL-18 was established, which has pro-inflammatory and autoimmune effects. Re-examination after 2 months of caspase-1 and IL-18 in examined persons determined decreasing their levels, but control results were not achieved. Conclusion. In young patients, the combination of GERD and AIT, as well as an isolated AIT is accompanied by an increasing the levels of caspase-1 and IL-18 in blood serum related to inflammatory process in the thyroid gland and esophageal mucosa with autoimmune component. These biomarkers may reflect the severity of clinical course of diseases and serve as prognostic indicator of outcome in case of comorbidity.

Author(s):  
Tamara Pasiieshvili ◽  
Natalia Zhelezniakova ◽  
Tetiana Bocharova ◽  
Lyudmila Pasiyeshvili

The aim of the work. To study the effect of concomitant autoimmune thyroiditis (AIT) on the pathomorphological features of lesions of the esophageal mucosa in young patients with gastroesophageal reflux disease (GERD). Material and research methods. The study included 165 individuals. The contingent of the surveyed was students of Kharkov higher educational institutions. The main group consisted of 120 patients with a combined course of GERD and AIT, the comparison group included 65 individuals with an isolated GERD. The morphological form of the GERD was revealed during esophagogastroduodenoscopy (“Fuginon” system). A histomorphological study of the obtained biopsy material from the mucous membrane of the esophagus was carried out. Samples were studied on an Olympus BX-41 microscope. Morphometric study of the esophageal mucosa was performed using the Olympus DP-Soft. Research results. Histological examination of biopsy specimens revealed that the main pathomorphological signs of GERD in both groups were hyperplasia of the basal zone, lengthening of epithelial papillae, leukocyte infiltration, intercellular edema, expansion of the intercellular space, dystrophic changes, submucous fibrosis, the presence of severe inflammatory infiltration in the submucosal layer. Presence of concomitant AIT was associated with a statistically higher frequency of occurrence of certain signs: hyperplasia of the basal layer of the epithelium, elongation of the papillae, epithelial edema, expansion of the intercellular space, dystrophic changes in the epithelium (p<0.05). Conclusions. The presence of concomitant AIT in young patients with GERD does not affect the incidence of erosive GERD, but is associated with a significant increase in the severity of erosive esophagitis. The comorbid course of GERD and AIT in the student population is accompanied by a significant increase in the incidence and statistically significant intensification of the severity of hyperplasia of the basal layer of the epithelium, elongation of connective tissue papillae and leukocyte infiltration compared with isolated GERD


Author(s):  
T.M. Pasiieshvili

The aim of this study is to establish the content of inflammation markers (tumour necrosis factor alpha and interleukin 18) and the index of total antioxidant activity in young patients with comorbidity between gastroesophageal reflux disease and autoimmune thyroiditis and to determine their dependence on morpho-histological changes in the oesophageal mucosa. Materials and methods. The study involved 182 students aged 18 to 25 years: 120 patients with comorbidity between gastroesophageal reflux disease and autoimmune thyroiditis, 42 those having an isolated course of autoimmune thyroiditis. The methodology included complex clinical, instrumental, immunological, statistical methods. Results. Determining the activity of proinflammatory cytokines has revealed their statistically significant increase. The level of these cytokines depends on morpho-histological changes in the mucous membrane and reaches the maximum during the erosive process. At the same time, the indicator of total antioxidant activity significantly decreases. In this case, the erosive form of the disease is accompanied by more expressive changes in this indicator. Conclusions. The inflammatory process in the oesophagus is accompanied by the activation of the pro-inflammatory segment of immunity against the background of the suppression of the antioxidant system, which is dependent on morphological changes in the oesophageal mucosa. These changes will contribute to the development of pathological apoptosis and the progression of nosologies.


2019 ◽  
Vol 45 (4) ◽  
pp. 54-59
Author(s):  
T. M. Pasiieshvili

Cytokines are considered as “microendocrine system” due to the fact that they have a triple mechanism of action. First, they affect the cell-producer (autocrine effect); secondly, they influence neighboring (adjacent) cells (paracrine effect); thirdly, they affect the distant cells of organs and tissues (endocrine effect). Most cytokines have a wide range of biological activity, which is associated with their synthesis and secretion of various types of cells. Aim of study was to determine the role and prognostic values of tumor necrosis factor (TNF) α, interleukin (IL) 1β and IL-18 in young patients with autoimmune thyroiditis (AIT) and gastroesophageal reflux disease (GERD). Materials and methods. Study involved 83 patients (students) with GERD and AIT. The average age for the group was 22.1±2.11 years. The comparison group was represented by 30 patients of similar age with isolated GERD. The enzyme immunoassay was used to study the content of TNF-α, IL-1β and IL-18. Results. Upon evaluating the complaints of patients, it was found that the main manifestation of GERD was heartburn of varying severity, duration and frequency of occurrence. It has been shown that the course of GERD occurs against the background of the development of a systemic inflammatory reaction (increased synthesis of proinflammatory cytokines IL-1β and TNF-α), and also depends on the form of esophagitis: more pronounced in the erosive variant of the mucous membrane of the esophagus. At the same time, there was an increase in the synthesis of IL-18, which, with isolated GERD, is associated with a general inflammatory reaction, and with the addition of AIT, the inclusion of immune mechanisms. Relationship between the level of TNF-α in peripheral blood and the content of thyroid-stimulating hormone was studied. However, unlike the results of other scientists, the authors have not identified such a relationship.


Author(s):  
T.M. Pasiieshvili

Aim: to determine the state and role of autonomic reactivity and autonomic supply in patients with different manifestations of gastroesophageal reflux disease in combination with autoimmune thyroiditis through psychological testing by using a questionnaire of A.M. Vejn. Materials and methods. 87 patients with gastroesophageal reflux disease and autoimmune thyroiditis and 45 persons with an isolated gastroesophageal reflux disease were enrolled in the study. All the examined individuals were students. Results. It has been shown that the course of diseases is accompanied by a layering of clinical manifestations of autonomic dysfunction, which are more pronounced in cases of comorbidities. It has been found out that vegetative supply prevails in a number of indicators in the patients with an erosive form of gastroesophageal reflux disease. It has been proven that in almost all the cases of erosion (8 people - 72.7%), the individuals experienced some clinical manifestations of vegetative provision, such as general weakness, increased fatigue, lability of the pulse and blood pressure, and palpitation. At the same time, the “vegetative tail” was recorded only in a third (34.7%) of the studied without erosive lesions of the esophageal mucous membrane. The patients with an erosive form of the disease have a long period of experiencing some manifestations of autonomic dysfunction (up to 3 months) that considerably affects the quality of their life. Conclusions. Coupling of autoimmune thyroiditis and gastroesophageal reflux disease leads to the emergence of autonomic reactivity. Vegetative “supply” of the course of comorbidity between gastroesophageal reflux disease and autoimmune thyroiditis becomes more pronounced in the presence of an erosive process in the mucous membrane, which is also known as one of the factors of its possible manifestations.


Peptides ◽  
2009 ◽  
Vol 30 (6) ◽  
pp. 1082-1087 ◽  
Author(s):  
Thomas Wex ◽  
Klaus Mönkemüller ◽  
Doerthe Kuester ◽  
Lucia Fry ◽  
Arne Kandulski ◽  
...  

2021 ◽  
pp. 30-37
Author(s):  
D. N. Andreev ◽  
A. V. Zaborovsky ◽  
E. G. Lobanova

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.


2019 ◽  
Vol 91 (8) ◽  
pp. 4-11 ◽  
Author(s):  
I V Maev ◽  
D N Andreev ◽  
Yu A Kucheryavyy ◽  
R I Shaburov

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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