Babych VL. Medication correction of functional disorders of gallbladder and Oddi's sphincter in children. - Qualified scientific work on the rights of the manuscript.
The dissertation for the scientific degree of Doctor of Philosophy in specialty 228 - "Pediatrics" (22 - Health Protection). – State Institution "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine", Dnipro, 2020.
Diagnosis and treatment functional disorders of gallbladder and Oddi's sphincter remains an urgent problem of modern pediatrics. Of particular relevance is the definition of risk factors and the activity of micro-RNA generation in the formation of functional disorders of gallbladder and Oddi's sphincter in children for further sound drug correction of these conditions.
Therefore, the aim of our study was to increase the effectiveness of drug treatment of functional disorders of gallbladder and Oddi's sphincter in children based on the study of risk factors for the disease and the activity of micro-RNA generation.
To achieve the goal and solve the set tasks, a comprehensive clinical and paraclinical examination of 90 children aged 4.0 to 14.0 years, of which 70 children with functional disorders of the gallbladder and Oddi's sphincter and 20 healthy children. The design of the study was chosen open, monocentric, cohort-prospective, randomized. The study was conducted clinically, controlled in parallel groups. By simple randomization, patients were divided into two groups. The main group consisted of 50 patients with functional disorders of gallbladder and Oddi's sphincter, who received therapy with ursodeoxycholic acid in accordance with the provisions, which was prescribed at a rate of 10-15 mg/kg/day. The comparison group was represented by 20 patients with functional disorders of gallbladder and Oddi's sphincter, who received therapy without ursodeoxycholic acid. The course of treatment was 4 weeks. To compare the results, the study included 20 healthy children of the same age who were included in the control group. The formed research groups were representative in terms of age and gender (p > 0.05).
Risk factors contributing to the development of functional disorders of gallbladder and Oddi's sphincter in children are the following clinical and anamnestic data: burdened heredity of functional disorders of gallbladder and Oddi's sphincter and housing and communal services (90.0 %), eating disorders (72.0 %), psycho-emotional load (50.0 %), hypodynamic lifestyle (30.0 %) and the presence of foci of chronic infection (14.0 %).
The development of functional disorders of gallbladder and Oddi's sphincter in children is accompanied by changes in the transcriptome of micro-RNA. There is a probable decrease in the expression level of micro-RNA-4714-3p (5.6 ± 1.5 SU in children with functional disorders of gallbladder and Oddi's sphincter compared with 42.7 ± 5.4 SU in almost healthy children) with a constant level of expression of micro- RNA-378f (2.0 ± 0.6 SU) and micro-RNA-4311 (1.5 ± 0.4 SU).
The level of micro-RNA expression is associated with clinical and paraclinical manifestations of the disease. The relatively low level of expression of micro-RNA-4714-3p (5.6 ± 1.5 SU) correlates with nausea (r = +0.30; p < 0.05), symptoms of astheno-vegetative syndrome (r = +0, 30; p < 0.05) and reduced contractility of the gallbladder (r = +0.36; p < 0.05); the expression level of micro-RNA-4311 is inversely correlated with abdominal pain on palpation (r = - 0.37; p < 0.05) and a positive Ortner's symptom (r = - 0.29; p < 0.05).
The main criteria for the diagnosis of functional disorders of gallbladder and Oddi's sphincter in children are: pain in the umbilical region of the abdomen (RR = 2.0), the duration of dyspeptic syndrome (RR = 1.57), astheno-autonomic syndrome (RR = 1.55) not less than 12 days, reduction of gallbladder contractility, cholesterol levels in the range of 4.3 - 5.2 mmol / l (RR = 1.83), AST – 45.0 - 59.0 n / l (RR = 3, 21) and ALT - 28.3 - 38.0 n / l (RR = 3.21) in blood serum.
The use of ursodeoxycholic acid in the treatment of functional disorders of gallbladder and Oddi's sphincter in children helps to regress the clinical symptoms of the disease, increase the reduced contractility of the gallbladder and normalize the altered biochemical markers. Against the background of treatment with ursodeoxycholic acid, the expression level of micro-RNA-378f (5.2 ± 0.7 SU) and the expression level of micro-RNA-4714-3p (1.9 ± 0.6 SU) probably increases.
The use of ursodeoxycholic acid causes hyperplasia of leiomyocytes and their intracellular ultrastructural changes, an increase in the nuclear activity of fibroblasts and an increase in the number of interstitial cells of the Kahal muscle of the gallbladder muscle in experimental animals. These morphological changes probably cause an increase in the contractile function of the gallbladder.
