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Clinical and paraclinical features of gastroesophageal reflux disease in relation to the level of nitric oxide metabolites and genetic polymorphism of its synthases


Author: Scurtu Аlina
Degree:doctor of medicine
Speciality: 14.00.05 - Internal Diseases (with specification: Pulmonology, Gastroenterology, Hepatology, Nephrology, Functional Diagnostics and Endoscopy)
Year:2016
Scientific adviser: Valeriu Istrati
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific consultant: Vlada-Tatiana Dumbrava
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Institution: Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova

Status

The thesis was presented on the 16 March, 2016
Approved by NCAA on the 21 April, 2016

Abstract

Adobe PDF document1.55 Mb / in romanian

Thesis

CZU 616.329-002-008.9

Adobe PDF document 5.43 Mb / in romanian
153 pages


Keywords

gastroesophageal reflux disease, nitric oxide, metabolism, genetic polymorphism

Summary

Structure of the thesis: the thesis is exposed on 126 pages of printed text, consists of an introduction, 4 chapters, general conclusions, practical recommendations, summary in Romanian, Russian, English and bibliographic index with 198 references, and includes 30 figures, 36 tables, 5 formulas and 4 annexes. The obtained results were published in 16 scientific works, including 3 without co-authors and 13 in reviewed editions.

Field of study and objectives: the role of nitric oxide (NO) in regulating of gastrointestinal motility is determined by the presence of nitric oxide synthase n(NOS) in neurons that innervates the gastrointestinal tract. The most important physiological functions of NO in the digestive system are the vascular tone regulation, participation in the transmission of nerve impulses and providing of gastrointestinal motor functions.

It is assumed that one of the most important factors in the mechanism of development and evolution of gastroesophageal reflux disease (GERD), a condition with a complex multifactorial pathogenesis, is impaired NO metabolism. Spontaneous relaxations of the lower esophageal sphincter (LES) are determined by cholecystokinin, which stimulates the synthesis of NO, by disturbances of cholinergic action, or by increased inhibition of the NO neurotransmitter. Besides this, endogenous NO is involved, at least partially, in the physiological regulation of the motility of the distal portion of the esophagus and LES, it disturbs esophageal motility, reducing the frequency and amplitude of the primary peristalsis.

Estimation of metabolic peculiarities and role of NO in the emergence of the motor and neuroregulatory disorders in patients with GERD had found a statistically significant difference between the NO metabolism indicators and the severity of clinical and endoscopic manifestations of GERD.

The purpose of this research is to study the clinical, evolutive and diagnostic features of gastroesophageal reflux disease in relation to the level of nitric oxide metabolites and genetic polymorphism of its synthases.

Scientific novelty and originality: the role of nitric oxide in the development and progression of GERD was proved. For the first time the metabolism of NO and its role in the installing and evolution of the disease was studied. The obtained results can be used in the development of preventive measures and recommendations for the management of patients with gastroesophageal reflux disease. The important scientific problem solved in this research is examination of the clinical, evolutive and diagnostic features of gastroesophageal reflux disease in relation to the level of nitric oxide metabolites and genetic polymorphism of its synthases.

Theoretical value: the originality of the research consists in highlighting the clinical and evolutional peculiarities, endoscopic and morphological features of GERD depending on the degree of damage to the esophageal mucosa and the level of nitric oxide, and the study devoted to genetic polymorphism of NOS genes and its role in the installation and development of the disease. It allowed to identify an algorithm for diagnosis and treatment in this group of patients.

Applied value: the obtained results allow to predict and develop measures on prevention and treatment of gastroesophageal reflux disease.

Implementation of scientific results: The main results of the survey are applied in the teaching process at the Department of Semiology of Internal Medicine at Medical University "Nicolae Testemitanu" and implemented in therapeutic activity of the Gastroenterology Department at Railway Central Hospital in Chișinău, Central Hospital, Municipal Hospital N1.