Contemporary investigations of mechanisms of resistance to platinides showed the key role of copper metabolism in cancer patients and proposed possible methods to attenuate the resistance by modulation of copper transporting mechanisms. In this vein, investigation of ceruloplasmin (Cp) levels -the main coppercontaining protein in blood, in experiments with tumor-containing animals upon cytostatics administration is topical and has great importance. the concentration of Cp was measured in the serum of tumor-bearing rats with ordinary (t8) and resistant to cisplatin (t8*) Guerin's carcinoma upon administration of cisplatin and quadruple bonding dirhenium(III) compound dichlorotetra-μ-isobutyratodirhenium(ІІІ) (I) in different medicamental forms. It was shown that development of tumor in t8 group led to increasing of concentration of Cp in 3.7 times and in T8* group -more than in 8 times in comparison to control, confirming the essential role of Cp in the formation of resistance phenomenon. administration of cisplatin together with I led to effective inhibition of tumor in groups with t8 and t8*, indicating decreased resistance in the group t8*. Greater reduction of Cp levels was observed in the groups with t8* upon administration of the rhenium-plati num antitumor system, than in groups with t8, that underlines the importance of further investigations of the dirhenium(III) compounds in the resistance to cytostatics cancer models. Some mechanisms concerning the regulation of copper homeostasis and properties of nano-composites are discussed. k e y w o r d s: ceruloplasmin, cluster rhenium(III) compound, Guerin's carcinoma, resistance to cisplatin.

Introduction: Genetic mechanisms among many other factors play a crucial role in the development and progression of nonalcoholic fatty liver disease (NAFLD). The farnesoid X-receptor (FXR) regulates the expression of target genes involved in metabolic and energy homeostasis, so it can be assumed that genetic variations within the NR1H4 gene, encoding FXR, can affect the development or progression of associated diseases, including NAFLD. The aim: To study the association of SNP rs11110390 NR1H4 gene with the probability of development and course of NAFLD in children. Materials and methods: 76 children aged 9–17 years and overweight were examined. According to controlled attenuated parameter (CAP) measurement (Fibroscan®502touch) children were divided into 2 groups: group 1 consisted of 40 patients with NAFLD, group 2 was composed by 36 patients without hepatic steatosis. According to genetic testing children were divided into 3 subgroups – children with CC-, CT-, TT-genotype SNP rs11110390 NR1H4 gene. Results: The frequency of TT-genotype SNP rs11110390 NR1H4 gene detection in children with NAFLD was 17.5% versus 2.8% in the control group (p < 0.05). In children with TT-genotype SNP rs11110390 NR1H4 gene the liver stiffness (p < 0.05) and CAP (p = 0.1) were higher than in patients with CC- and CT-genotypes. Patients with the TT-genotype differed from CC-genotype patients with lower levels of IL-10 (p < 0.05) and pro-inflammatory cytokine balance (p < 0.05). An increase in the concentration of taurine-conjugated bile acid fractions in the hepatic and gallbladder’s bile in children with TT-genotype SNP rs11110390 NR1H4 (p < 0.05) was demonstrated. Conclusions: SNP rs11110390 NR1H4 is associated with an increased probability of NAFLD development in children. An increase in the steatosis degree and liver stiffness in combination with increased taurine-conjugated bile acids fractions in the hepatic and gallbladder’s bile, shift in cytokine balance due to a decrease in IL-10 level in children with TT-genotype SNP rs11110390 NR1H4 were observed.

Background. Changes in the intestinal microbiome trigger the development and progression of nonalcoholic fatty liver disease (NAFLD). Adverse fluctuations in intestinal microbiota are associated with increased intestinal permeability, activation of mucosal and adaptive immunity, increase in production and intestinal absorption of short-chain fatty acids (SCFA). The ratio of acetic, propionic, butyric acid is an important indicator of the integrity of the microbial community of the intestine. Thus, the study of the gut microbiota composition and short-chain fatty acids production represents a very appealing approach to increasing our knowledge about the mechanisms leading to NAFLD in children. The purpose of the study was to determine the features of the fecal short-chain fatty acids (fSCFA) content and the colonic microbiota composition in children with NAFLD. Materials and methods. A comprehensive examination of 102 children was provided in the Department of Pediatric Gastroenterology of the Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine. According to the presence of obesity, transient elastography data and alanine aminotransferase levels the patients were divided into four groups: I group-children with simple hepatic steatosis (n = 24); II group-children with nonalcoholic steatohepatitis (NASH) (n = 14); III group-children with obesity without steatosis (n = 48), IV group-children with normal weight (n = 16). Chromatographic study of fSCFA was conducted using gas chromatograph Chromatec-Crystal 5000. The microorganisms were identified using a microbiological study of the colon content. Diagnosis of NAFLD was established with FibroScan 502 Touch (Echosens, France) with the determination of the controlled attenuation parameter. Results. Significant changes in the spectrum of fSCFA were observed in children of the III group with acetic acid content increased by 4.8 times (р < 0.05), propionic acid by 1.5 times (р < 0.001), and butyric acid by 1.7 times as compared to the control group, while in children with NASH, acetic content was 2.5-fold increased, propionic and butyric acid-1.4-fold in comparison with the control group (p = 0.1). Also, significant anaerobic index decrease was observed in NAFLD patients. The fecal content microbiological examination demonstrated the reduced level of Bifidobacteria strains in 11.8 % patients of group I and in 8.3 % of group III; decreased levels of Lactobacillus were found in 70.6 % children of group I, in all children with NASH, in 70.8 % patients of group III. Overgrowth of bacteria such as Klebsiella was identified in 23.5 % patients of group I and in 8.3 % people of group III. Pathogenic Staphylococcus was detected in 5.9 % patients of group I, in 8.3 % patients of group III. Overgrowth of Candida was detected in 23.5 % children of group I, in 14.3 % children of group II and in 20.8 % children of group III. Conclusions. Quantitative and qualitative deviation of intestinal microbiota such as a decrease in the number of major symbionts an...

Objective — to evaluate functional activity of the immune system, carbohydrate and lipid metabolism in children with biliary dysfunction against the background of overweight and obesity. Materials and methods. At the SI «Institute Gastroenterology of the National Academy of Medical Sciences of Ukraine» observations were performed on 108 children with the mean age 12.5 ± 2.51 years. Based on the results of investigation of motor and evacuator gallbladder (GB) function and body mass index, the pediatric patients were divided into three groups: group I included 52 overweight children with gallbladder hypofunction and obesity; group II consisted of 42 overweight children with normal gallbladder function and obesity; group III (comparison group) included 14 children with normal weight and biliary normokinesia. Investigations included anthropometric measurements and ultrasound imaging of the abdomen. ELISA was used to determine blood serum levels of insulin, interleukin‑6 (IL), IL‑10, tumour necrosis factor‑a (TNF‑a). Results. The following augmentation of the median levels was established when compared with group III: IL‑6 in 2.2 times (p < 0.05) and TNF‑a in 4.5 times (p < 0.05) in patients of group I, levels of IL‑6 in 2.3 times (p < 0.05) and TNF‑a in 4.3 times (p < 0.05) in patients of group II. The IL‑10 level in group I patients was lower in 2.5 times than in group II patients (p < 0.05), and in 4.4 times vs group III patients (p < 0.05). The serum insulin levels in children of groups I and II were in 2.2 times (p < 0.05) and 1.5 times (p < 0.05) lower, and HOMA‑IR index in 2.3 times (p < 0.05) and in 1.8 times (p < 0.05), respectively, in comparison with group III patients. The following blood serum levels vs group III were established: triglycerides (TG) increased in group I in 1.4 times (p < 0.001) and in group II in 1.5 times (p < 0.001); low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were increased both in I and II groups in 1.2 times, (p < 0.01) and 1.5 times, (p < 0.001), respectively. The atherogenic index (AI) raised in 1.6 times (p < 0.001) in group I patients and in 1.5 times (p < 0.05) in group II patients compared to group III, whereas high density lipoprotein (HDL) levels were decreased in the I and II groups in 1.2 times (p < 0.01) in comparison with group III patients. Conclusions. Regardless of the gallbladder functional state in overweight and obese pediatric patients, the abnormalities of the immune system indices have been established and, consequently, carbohydrate metabolism disorders (increased levels of insulin and index HOMA‑IR). The lipid metabolism disturbances have been established in the overweight and obese children with gallbladder hypofunction (significant increase in the levels of TG, LDL, VLDL, AI and decreased HDL levels). Correlation analysis in the groups of overweight and obese children with gallbladder hypofunction showed the presence of significant relationships between biliary sludge and IL‑6, TNF‑a levels, gallbladder volume and insulin and glucose levels, gallbladder hypofunction and levels of total cholesterol, HDL, LDL and as well as between the gallbladder dimensions and atherogenic index.

The article deals with the study on the content of fecal short-chain fatty acids (SCFA) and their association with insulin resistance in obese children. It was found that intestinal microflora in obese children is characterized by changes in the qualitative composition and increased metabolic activity of the intestinal microflora. A moderate increase of HOMA-IR is accompanied by elevated concentration of anti-inflammatory cytokines, the content of which correlates with that of acetic, propionic acid and a decrease in the metabolic activity of intestinal microflora. The progression of insulin resistance is accompanied by a further increase in the concentration of anti-inflammatory cytokines, the level of HOMA-IR correlates with the level of propionic SCFA. Thus, modulation of SCFA content may be a promising way of therapeutic influence to correct insulin resistance and obesity in children.