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Liver diseases represent one of the most common problems in gastroenterology. The liver, as the most important organ of metabolism, which plays a major role in anabolic and energy processes, takes part in the adaptive and compensatory reactions of the body under exogenous and endogenous adverse influences. Individual factors play a major role in the development of this disease, one of which is the duration of the effect of alcohol on the body. The duration of alcohol consumption affects the morpho-functional properties of the liver. When alcohol was given to the research animals, hypertrophic changes were seen in the linear dimensions of hepatocytes: in the 12th week of alcoholization, the nuclear area was 1.25 times larger, and the cytoplasmic area of hepatocytes was 1.16 times larger compared with the same indicators in the 6th week of alcoholization. Alcoholic hepatitis is characterized by protein-fatty degeneration, inflammatory lymphocytic infiltration, increase in the area of sinusoids and the size of hepatocytes, and, accordingly, the Vizotto coefficient (1.83 times in the 6th week and 2.10 times in the 12th week of the research). The alcohol consumption is accompanied by increase in the volume of the nucleus and cytoplasm of hepatocytes, decrease in the nuclear-cytoplasmic ratio with increase in pathohistological changes. With the lengthening of the terms of alcoholization, the number of binuclear hepatocytes decreased. Morphometric calculation of the number of fat cells per 100 hepatocytes showed that in the 12th week of the experiment, the number of fatty inclusions increased by 1.42 times, compared with 6 weeks of forced alcoholization. Fatty small- and large-droplet steatosis of hepatocytes was diffuse in nature. The duration of alcoholization also affects the liver vessels. The diameter of the central vein in the 6th week of the experiment was 1.52 times greater than in control rats, and 1.81 times in the 12th week of alcoholization. The bile ducts of rats of the experimental groups were also larger in diameter: by 37% after 6 weeks and 47% after 12 weeks of forced alcoholization. An increase in the area of the sinusoids and the diameter of the central vein indicates an impairment of the blood supply to the liver. The complexity of the structure of the liver and the diversity of its functions necessitate the use of a variety of diagnostic techniques and methodological approaches to assessing its activity in the normal condition, during a pathology. It will be promising to study the structure of the liver at the ultramicroscopic level of the effect of drugs on the treatment of alcoholic liver disease during different periods of alcoholization.

Aim. To determine the features of the intestinal microbiota in obese children with non-alcoholic fatty liver disease (NAFLD) depending on the functional state of the gallbladder. Materials and methods. A total of 73 children aged 10–17 years (mean age – 12.15 ± 2.51 years) were examined. According to body mass index, transient elastography (Fibroscan®), and ultrasound data, the patients were divided into 3 groups: group I – 35 obese children with NAFLD and gallbladder hypokinesia, group II – 30 obese children with NAFLD and gallbladder normokinesia, group III (control) – 8 healthy children with normal weight and gallbladder normokinesia. Contractile function of the gallbladder was assessed by ultrasound examination after physiological food loading. Small intestinal bacterial overgrowth (SIBO) and lactose absorption were assessed with the hydrogen breath test (HBT) with lactose loading using a Gastrolyzer (Bedfont Scientific Ltd, UK). Qualitative and quantitative intestinal microbiome composition were studied using bacterial culture method with ten-fold dilutions (10-1–10-9) on standard sets of selective and differential-diagnostic culture media for the isolation of aerobic and anaerobic microbes. Fecal short-chain fatty acid (SCFA) content was evaluated with gas chromatography (Chromatec-Crystal-5000). Results. Lactose-dependent SIBO was observed in almost half of NAFLD patients (42.9 %) without significant differences depending on functional activity of the gallbladder. Patients with decompensated dysbiosis predominated in group I children (37.1 % of patients). In group II children, the subcompensated dysbiosis was more common (36.7 % of patients). The concentration of Lactobacillus and Enterococcus in group I patients was significantly 1.9 times (P < 0.05) and 1.4 times (P < 0.05) lower, respectively, than that in group IІ patients. The level of fecal acetic acid and butyric acid in group I children was 6.9 and 2.0 times (P < 0.05) increased, respectively, compared to control group, assuming bile acids involvement in the regulation of microbiome composition. Conclusions. Impaired contractile function of the gallbladder in NAFLD children is associated with a sharp decrease in the number of major symbionts of the intestinal microbiota as well as increased production of acetic and butyric SCFA.

Non-alcoholic fatty liver disease is an important cause of global liver disease characterized by diffuse hepatocytes with hepatocellular ballooning, intrahepatic inflammation and progressive fibrosis. A relevant task is the study of the relationship between content of free fatty acids and serum cytokine profile in patients with chronic diffuse liver diseases. A total of 74 people with chronic diffuse liver diseases were examined, including 32 patients with non-alcoholic fatty liver disease, 22 patients with alcoholic liver disease, 20 patients with toxic hepatitis. Chromatographic examination of free fatty acids (FFA) in blood serum was carried out using a Chromatek-Crystal 5000 gas chromatography system. Patients with chronic diffuse liver diseases had a significant increase in the level of unsaturated free fatty acids (USFA) in cases of toxic hepatitis (by 2.92 times, P > 0.05) and a decrease in the level of saturated free fatty acids (SFA) in cases of non-alcoholic fatty liver disease (by 1.52 times, P > 0.05) compared with the control group; the balance between omega-6 and omega-3 PUFA significantly changed due to increase in linoleic acid in patients with alcoholic liver disease and toxic hepatitis (by 1.91 and 2.11 times, respectively) and arachidonic acid in patients with toxic hepatitis (by 1.78 times). The level of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α) were determined. In patients suffering chronic diffuse liver diseases there were multidirectional changes in the composition of free fatty acids of blood serum: a significant increase in the level of USFA, levels ІL-6 in toxic hepatitis; a decrease in the level of SFA, levels ІL-6 and TNF-α during non-alcoholic fatty liver disease; increased TNF-α production, ІL-6 during alcoholic liver disease compared with the control group. Significant change occurred in the balance between omega-6 and omega-3 PUFA due to increase in linoleic acid in cases of alcoholic liver disease and toxic hepatitis and arachidonic acid in cases of toxic hepatitis. The revealed correlations support the hypothesis that inflammation and lipotoxicity of FFA of blood serum contribute to the development and progression of structural changes in the liver. However, the pathomechanism of lipid metabolism and cytokine regulation with different etiological factors have their own characteristics, which should be taken into account when treating patients of these groups. Prospects for further research: these parameters may be used for serologic biomarkers of liver disease and development and implementation of the ratio between FFA and cytokines for the differential diagnosis of chronic diffuse liver disease in medical practice.

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 copper-containing 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-plati­num 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.