The review is devoted to the current assesment of the role of nitric oxide and inducible NO-synthase in physiological and pathological conditions. The inducible NO-synthase gene expression induction and post-transcriptional regulation of its activity are considered. Data on endogenous inducible NO-synthase inhibitors of are given. An analysis of the clinical trials aimed at studying the clinical efficacy of NO synthase inhibitors was carried out.

Hypertension remains the main risk factor of cardiovascular diseases despite the improvement of pharmacotherapy methods. This provides rationale for an in-depth study of pathogenetic mechanisms and development of new methods for the treatment of hypertension. There is increasingly more evidence for the essential role of immune-inflammatory disorders in the pathogenesis of hypertension. The article reviews the current state of knowledge on this problem. The authors provide a detailed analysis of the studies focusing on the role of abnormal factors of cellular immunity essentially associated with cell abilities to produce pro-inflammatory cytokines. Particular attention is paid to the effects of state-of-the-art methods of endovascular treatment on the changes in degree of severity of immune-inflammatory processes in patients with pharmacotherapy resistant form of hypertension. Possible mechanisms of the therapeutic action of renal denervation and the prospects for further clinical use of this method are discussed.

Despite the successes achieved, cardiovascular disease (CVD) remains the leading cause of death worldwide. With the help of traditional risk factors, it is not always possible to identify all patients with a high probability of developing cardiovascular events (CVЕ); therefore, the problem of finding new CVD biomarkers still remains relevant. Previous studies have shown the important role of excessive synthesis of ceramides in the development of obesity, insulin resistance (IR), type 2 diabetes mellitus (DM2), and liver steatosis. It is considered that ceramides are able to modulate signaling pathways involved in the regulation of glucose metabolism, triglyceride synthesis, development of apoptosis, fibrosis, and atherosclerosis. Given the wide range of metabolic effects, the study of ceramides is promising for identifying patients at high risk of CVD, as well as improving existing treatment and diagnostic strategies. This review article considers the role of ceramides in the development of atherosclerosis, the correlation with traditional risk factors, and the possibility of using them as new risk factors for early diagnosis of CVD.

Remote postconditioning of the heart (RPost) – performed several periods of short-term ischemia-reperfusion of an remote organ after a long period of ischemia immediately before the resumption or in the early reperfusion, which leads to a reduction in the size at the subsequently formed infarction – represents a great therapeutic potential for clinical practice. The mechanism of remote postconditioning includes a trigger that can be played by adenosine, opioids, cannabinoids, bradykinin, CGRP, and substance P. Protein kinase C, PI3 kinase, Akt kinase, and JAK play an important role in the signaling mechanism of remote postconditioning. Experimental studies found that genetically determined or diet-induced metabolic changes reduce the effectiveness of cardioprotection in RPost. As possible mechanisms of cardioprotection inefficiency, we can suggest a decrease in the release of humoral factors, dysfunction of the receptor and signaling link of RPost, the effect of metabolic disorders on the functioning of KATP channel, mPTP, and on the state of mitochondrial respiration. However, these assumptions need experimental substantiation. The results of clinical studies show both the antinecrotizing and infarct-limiting effect of RPost in AMI and cardiac surgery, and the lack of its effectiveness. The role of metabolic disorders in the absence of the effectiveness of RPost in patients requires substantiation.

Epicardial adipose tissue (EAT) is a visceral depot of the heart fat, which has high plasticity and directly contact with the myocardium and coronary arteries. Epicardial fat is a unique paracrine organ closely anatomically and physiologically related to the myocardium. Recent studies have repeatedly confirmed the role of epicardial fat in the progression of the cardiovascular diseases. The accumulation of EAT, measured by using new non-invasive imaging techniques, is prospectively associated with the onset and progression of coronary heart disease (CHD) and atrial fibrillation. This review focuses on modern in vivo methods for assessing epicardial fat.

Introduction. Platelet activation is the initial stage of thrombotic complications in pathological conditions, primarily in atherosclerotic cardiovascular diseases. Endogenous hydrogen sulfide (H₂S) is an antiplatelet agent, but the specific ways to realize its effects are not studied enough

Aim: To study the effect of H₂S on adenosine diphosphate (ADP)-induced platelet aggregation in patients with coronary heart disease (CHD) with blockers of Na⁺,K⁺,2Cl^- cotransporter (NKCC), an anion exchanger, and a phosphodiesterase (PDE) inhibitor of cyclic nucleotides.

Material and Methods. The study included 22 patients with CHD. The control group included 14 healthy volunteers. Platelet aggregation was determined by turbidimetric method. The degree of aggregation (%) and the size of aggregates (rel. units) were measured. ADP (2 μM) was an aggregation inductor. In some cases the incubation medium contained the hydrogen sulfide donor NaHS (1–100 μM) and aggregation modifier

Results. The H₂S donor at a concentration of 100 μM reduced the parameters of ADP-dependent platelet aggregation in healthy volunteers and increased it in patients with coronary artery disease. NKCC and anion exchanger blockers, as well as a PDE inhibitor, reduced ADP-dependent platelet aggregation in healthy volunteers. The combined action of these agents and NaHS enhanced the inhibitory effects of the applied modifiers. The results obtained for platelet aggregation in patients with coronary artery disease differed in different direction

Conclusion. The obtained data indicate that the antiaggregation effect of H₂S is realized through the effect on the NKCC and anion exchanger, as well as due to the effect on the links of the signaling system mediated by cyclic nucleotides.

The changes of epicardial adipose tissue’s (EAT) morphofunctional characteristics represent an important factor of cardiometabolic impairments development. However, factor data determining the severity of EAT adipocytes’ hypertrophy in patients with coronary atherosclerosis are absent in literature.

Aim: To compare the size of the EAT adipocyte and the percentage of hypertrophied adipocytes with the parameters of glucose/insulin metabolism, blood lipid transport function, adipokines’ profile and serum levels of high sensitive C-reactive protein (hsCRP) in patients with chronic coronary artery disease (CAD) undergoing coronary artery bypass grafting (CABG); to establish statistically significant determinants of a pronou ced degree of EAT adipocytes’ hypertrophy.

Material and Methods. The study included 42 patients (m/f 28/14) aged 53–72 y.o. with CAD, who underwent CABG. The material for the study was EAT adipocytes obtained by the enzymatic method from intraoperative explants. The basal blood levels of glycemia, insulinemia, C-peptide, blood lipid transport function, adipokines and hsCRP were determined. The median indicators of the size of EAT adipocytes and the proportion of EAT adipocytes over 100 μm were 87.32 μm and 14.64%, respectively. The total sample of patients was divided into two groups: gr. 1 with an average size of EAT adipocytes less than or equal to 87.32 μm and gr. 2 with an average size of EAT adipocytes more than 87.32 μm. Gr. 2 had higher body mass index, waist and hip circumferences, triglycerides, hsCRP, and lower adiponectin levels, while the median proportion of hypertrophied adipocytes was three times higher than in group 1. A model of multiple logistic regression was constructed, according to which statistically significant determinants of the pronounced EAT adipocytes’ hypertrophy are represented by the decreased level of adiponectin, and increased concentrations of hsCRP and C-peptide, which reflects the biosynthesis and secretion of insulin. The predictive accuracy of the model was 82%, sensitivity 85%, specificity 79%, AUC = 0.89.

Conclusion. Our results indicate a close correlation between the development of EAT adipocytes hypertrophy, impaired production of adiponectin, insulin, and inflammation processes. Concentrations of adiponectin, hsCRP, and basal C-peptide in the blood are biomarkers that accurately determine the presence of EAT adipocyte hypertrophy.

Aim: To study the nature of changes in oscillatory and nonlinear dynamic processes in the skin microcirculatory system by laser Doppler flowmetry in patients with obliterating atherosclerosis of the lower limbs arteries (OALLA) after limb revascularization.

Material and Methods. 27 male patients with OALLA before and after endovascular revascularization of the affected limb (median age 63.0 [60.0; 69.0] years) were studied. Microcirculation (MC) of the foot skin with assessment of nonlinear dynamic processes and spectral wavelet analysis of blood flow fluctuations was studied by laser Doppler flowmetry. The normalized amplitude indices of blood flow fluctuations were determined in frequency ranges reflecting: endothelial, neurogenic, myogenic, respiratory, pulse factors of hemocirculation. Bypass parameters and nutritive blood flow were assessed. An occlusion test was performed to determine capillary blood flow reserve. The study of nonlinear dynamic processes included assessment of fractal dimension, entropy determination and phase portrait analysis.

Results. Limb revascularization in patients with OALLA resulted in improvement of the clinical picture accompanied by statistically significant increase in nutritive blood flow (+9.7%) and reserved dilatation potential of microvessels (+43.2%), decrease in arteriolo-venular blood shunting (–5.0%) and venous plethora (–14.3%). The analysis of nonlinear dynamic processes of the MC showed that after angioplasty, along with the remaining deficit of oscillatory processes energy, there was a decrease in the fractal dimension index (–14.3%), indicating the limitation of lability of the functional system of the microvascular bed. At the same time, an increase in the chaotization of the regulatory mechanisms of the peripheral blood flow was established.

Conclusions. The results showed positive functional changes of the MC system associated with the improved clinical picture in patients with OALLA after limb revascularization. At the same time, changes in the nonlinear dynamics parameters indicate a compensatory increase in the chaotization of the system together with the remaining limitation of its functional lability and the energy deficit of oscillatory processes.

Introduction. Breast cancer is in the first place in the structure of morbidity among all malignant neoplasms in women. The prognosis of the disease depends on the tumor degree, including the presence of epithelial-mesenchymal transformation (EMT), the degree of invasion, the proliferative index, the preservation or absence of estrogen, progesterone, and epidermal growth factor receptors.

Aim: To study the immunohistochemical and morphological characteristics of the epithelial-mesenchymal transformation of breast cancer.

Material and Methods. Immunohistochemical study with antibodies to AE1/AE3, HMW, CK18, Snail, HER2/neu, E-cadherin, Vimentin, α-SMA, CD34, Ki-67 and p63 was performed in 60 patients of different age with breast cancer. Native preparations were stained with picrofuchsin according to van Gieson Alcian blue. Inflammatory infiltrate cells were examined for antibodies CD45, CD3, CD4, CD8, CD20, CD68.

Results. In ductal carcinoma, positive expression for estrogen and progesterone was found in 82.7% and 86.3%, respectively, the proliferation index ranged before 66,6%, and p-53 was positive in 97%. In lobular cancer, positive expression to estrogen and progesterone was observed in 83.4% and 66.6%, respectively, the index of proliferative activity at the level of 50%, and p-53 was positive in 66.6%. Positive moderate expression of HER-2/neu was determined in 47% of ductal and 50% of lobular cancers. Estrogen plays an important role in the development of invasive breast cancer, leads to tumor progression and contributes to EMT. EMT, in turn, leads to the expression of E-cadherin associated with a worse survival prognosis. EMT indirectly leads to the intensification of angiogenesis, and the presence of a large number of newly formed vessels increases the risk of metastasis. Histochemical methods were used to determine the growth of fibrous tissue around invasively growing cancer complexes. Cells located perifocally looked like fibrobla ts, immunohistochemically moderately expressed Vimentin and weakly expressed pancytokeratin, which proved the tumor nature of the cells and the acquisition of mesenchymal features by them. The inflammatory infiltrate along the periphery of the tumor growth consisted mainly of T- and B-lymphocytes, and around the cancer complexes - of B-lymphocytes and macrophages.

Conclusion.  The  study  of  the  immunohistochemical  tumor  phenotype  will  make  it  possible  to  prescribe  adequate polychemotherapy and determine the prognosis of the course of the disease.

The increase in cardiovascular diseases and metabolic disorders associated with longevity actualizes the study of the effect of high-calorie diets on heart aging.

Aim: the experimental study of the effect of a high-carbohydrate hig -fat diet on the myocardium in young and old age.

Material and Methods. A morphological study of the myocardium was carried out in four groups of male Wistar rats: group 1 - 150-day-old animals were kept on a standard diet; 2nd - 150 days, kept at a high-carbohydrate high-fat diet (HCHFD) for 90 days (from 60 days of age); 3rd - 540 days old, kept on a standard diet; 4th - 540 days old, kept at HCHFD for 90 days (from

450 days of age). ELISA method in blood serum was used to determine the concentration of fibronectin, transforming growth factor beta-1, connective tissue growth factor.

Results. In groups 2-4, leukostasis, focal lympho-monocytic infiltration of the myocardial stroma, an increase in the number of myocardial cells with karyopyknosis and edema of the perinuclear zone of the sarcoplasm, contracture disorders, and an increase in the specific volume of the connective tissue of the stroma were detected. The defeat of myocardial cells and fibrosis were most pronounced in group 4. HCHFD increased the concentration of fibronectin in animals in both age groups with predominance in group 4, caused a tendency to increase the content of transforming growth factor beta-1, connective tissue growth factor in blood serum. Thus, HCHFD accelerates and enhances age-related changes in the white rat myocardium.

Aim: To study the functional state of the components of the glutathione-dependent antioxidant system in the adipose tissue of rats with experimental metabolic syndrome (MetS).

Material and Methods. The MetS model was carried out on male Wistar rats using a high-fat, high-carbohydrate diet (HFHCD). Body and adipose tissue weight were measured. Blood serum levels of glucose, insulin, leptin, triacylglycerides and cholesterol were assessed. In epididymal adipose tissue the level of reactive oxygen species (ROS) was determined by fluorescent method. The concentration of reduced (GSH) and oxidized (GSSG) glutathione, activity of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase enzymes were assessed spectrophotometrically in epididymal adipose tissue.

Results. It was found that HFHCD led to an increase in body weight, obesity, hyperglycemia, insulin resistance, dyslipidemia, and leptinemia in the experimental group rats. An increase in adipose tissue mass had a positive correlation with an increase in the concentration of glucose, serum leptin, and ROS levels in the epididymal adipose tissue of rats with MetS. It was found that the level of total glutathione in the adipose tissue of the experimental group rats decreased mainly due to a decrease in the level of GSH. The rats receiving HFHCD also showed a decrease in the activity of glutathione peroxidase and glutathione-S-transferase, but the activity of glutathione reductase increased.

Conclusion. Obesity, as a key component of MetS, is a trigger of insulin resistance, chronic low-grade inflammation and oxidative stress. The study showed that the development of MetS and obesity in the experimental animal group is accompanied by a shift of adipocyte redox balance toward oxidative stress, which is expressed in a decrease of GSH/GSSG ratio and glutathione-dependent antiperoxide protection enzymes activity.

Introduction. The problems of studying the molecular mechanisms of pathogenesis, insulin resistance and finding new ways to correct them are still relevant.

Aim: To study the effect of electrical stimulation on the amount of pAkt in a cell culture of C2C12 mouse myoblasts cultivated under hyperglycemic conditions.

Material and Methods. We studied the effect of electrical stimulation on the amount of pAkt in a cell culture of C2C12 mouse myoblasts cultivated under hyperglycemic conditions. Cells were cultured in a medium containing 25 mM glucose and subjected to electrical impulse stimulation for 2, 6, and 24 hours.

Results. It has been shown that the cultivation of C2C12 myoblasts in a medium with excess glucose is accompanied by a decrease in the amount of pAkt in cells, while pulsed electrical stimulation from 2 to 6 hours increases the concentration of this enzyme and restores the sensitivity of its phosphorylation pathways to insulin.

Conclusions. The results obtained suggest that the contractile activity of muscle cells contributes to the restoration of cell sensitivity to insulin and the ability to absorb glucose, using the same regulatory and transport pathways that are affected i  the development of type 2 diabetes.

The age-dependent features of the inotropic response of isolated strips of rat papillary muscles in postinfarction cardiosclerosis were studied. The rhythmic-inotropic response of the myocardium to extrasystolic effects was assessed in sham-operated (SO) rats and rats with established post-infarction cardiosclerosis (PICS) in the age groups of 4, 12, and 24 months (mon). It was shown that the excitability of the sarcoplasmic membrane of cardiomyocytes increases in 12-mon-old SO animals, and decreases in 24-mon-old animals relative to the group of 4-mon-old SO animals. The ability of the sarcoplasmic reticulum (SPR) of cardiomyocytes to accumulate calcium ions (Ca2+) does not depend on age. Postinfarction myocardial remodeling is accompanied by a decrease in the excitability of the sarcolemma in 4-mon-old animals and an increase in 24-mon-old animals relative to the values in SO rats of the corresponding age. At the same time, the Ca2+-accumulating ability of the SBP decreases in 4- and 12-mon-old animals, remaining unchanged in 24-mon-old animals.

The clinical application of the results of the experimental radiotherapy on animals is currently not widely used. The research of radiation injuries after irradiation target in rat lungs using the image-guided platform SmART+ (Precision, North Branford, Conn., USA) is a pilot study for the establishment of an animal model of radiation-induced pulmonary toxicity.

Aim: To define the typical doses and target volumes in rat lung to o serve radiation pneumonitis.

Material and methods. Four groups of Wistar and Wag rats, distinguishing by age (10–16,5 months) and weight (350-850 g.), were studied. Dosimetric treatment plans were calculated prior to irradiation, using arc or static methods, doses (10–30 Gy), target lung volumes (0,045–1,24 cm³), localization (right or left, top or bottom). Dosimetric planning provides optimal radiation exposure to the target and controls organ at risk doses. Computer tomography (CT) scans were performed for 16 weeks to observe radiation pneumonitis

Results. To obtain the rat lung density in Hounsfield units (HU), healthy animals were scanned, CT images were processed, and the mean and standard deviation were calculated. Lung density values of rats (control values) are 519.6 ± 46.2 (HU). Comparison of experimental data on irradiated animals and control values was carried out. As a result, the relationship of the target volume, the delivered dose and the survival rate of animals after irradiation was established. It was shown that the “mean value of lung density” could be used for quantitative analysis of lung injuries after irradiation.

Conclusion. Typical doses and target volumes in rat lungs to observe radiation pneumonitis were obtained. Decreasing aeration of lung tissue was derived at delivered dose 16 Gy and irradiated target volume in lung at least 0.5 cm³ (8%).

The liver is a complex metabolic organ that, through the regulation of energy metabolism, maintains the homeostasis of the whole organism.

Aim: To establish the morphological changes in hepatocytes and the expression of endothelial vascular factor in a high-carbohydrate high-fat diet (HCHFD) depending on age.

Material and Methods. A histological study of the liver was carried out in four groups of male Wistar rats: 1^st group – 5-month-old animals on a standard diet; 2^nd  group – 5-month-old animals on HCHFD for 90 days (from 2 months of age); 3^rd  group – 18-month-old animals on a standard diet; 4^th  group – 18-month-old animals on HCHFD for 90 days (from 15 months of age). Using morphometric methods, the specific volumes (%) of unchanged and binuclear hepatocytes, sinusoidal capillaries, inflammatory infiltrates, and foci of fibrosis in the liver were determined. The expression of vascular endothelial growth factor (VEGF) in endothelial cells and hepatocytes was evaluated by immunohistochemical method. The concentration of cholesterol and triglycerides was determined by the enzymatic colorimetric method in the blood serum and in the liver.

Results. A morphological study revealed a significant expansion of sinusoidal capillaries in groups 2 and 4. A statistically significant increase in the specific volume of hepatocytes with vacuolar inclusions, binuclear hepatocytes, fibrous foci and small inflammatory infiltrates was detected in the 4^th  group. VEGF expression increased in hepatocytes of groups 2 and 4. Biochemical study found an increase in the concentration of triglycerides in the rats’ liver of the 4^th  group. Thus, HCHFD, despite the pronounced signs of regeneration, increased age-related changes in the liver of old rats.

Introduction. Chronic pain syndrome in the development of malignant neoplasms has a complex polyethological character. The study of the pathogenetic mechanisms of pain during the growth of the transplanted tumor in the experiment can open up broad perspectives for the creation of new domestic analgesic drugs for use in oncology.

Aim: To study the serotonin inactivation coefficient (SIC), the ratio of serotonin (S) and its main metabolite 5-hydroxyindolacetic acid (S-OH) in brain areas (cortex, hypothalamus) with simultaneous modeling of chronic neurogenic pain and malignant neoplasia.

Material and Methods. The study involved white mongrel rats (males). To create a model of chronic pain (CP), ligation of the sciatic nerve was performed according to the method of V.V. Kravtsova in modification. Rat sarcoma M-1 was used to simulate malignant neoplasia. At the main stage of the study, the animals were divided into 4 groups: control, two comparison groups (model of chronic pain, standard M-1 sarcoma grafting) and experimental (combined modeling of CP and oncological process). Animals of the second, third and fourth groups were euthanized sequentially at the 2nd and 3rd weeks of the development of the tumor process.

Results. Chronic pain syndrome disrupts the process of serotonin metabolism: the decrease in SIC in the cerebral cortex of experimental animals was more significant by 48% (day 14) and 72% (day 21). The development of the oncological process in comparison groups (groups 3a and 3b) is accompanied by a decrease in the level of SIC, more significant at the 21th day of M-1 sarcoma development: by 37% in the hypothalamus, by 41% in the cerebral cortex. With simultaneous modeling of chronic neurogenic pain and malignant neoplasia, the lowest values of the studied indicator were noted, the decrease was 75% in the cerebral cortex (group 4a) and 87% (group 4b).

Discussion. Chronic neurogenic pain and M-1 sarcoma development in isolated modeling variants cause a significant decrease in SIC in hypothalamus and cerebral cortex due to disorders of serotonin formation. A more significant disruption of the serotonin mediator system was noted in cerebral cortex which leads to a decrease in the body’s adaptive capabilities to pain and a disruption of the regulatory mechanisms of metabolism.

Conclusion. Modification of serotonin metabolism can be considered as a potential therapeutic target for the treatment of chronic pain syndrome in oncology.

Fibrin  displays  promising  characteristics  for tissue  engineering.  However,  it has suboptimal  physical  and mechanical properties when used as a material for cardiovascular applications. Obtaining an interpenetrating polymer network (IPN) hydrogel based on fibrin and polyvinyl alcohol (PVA) can improve the physical and mechanical characteristics and shrink behavior of fibrin.

Aim: To perform sequential polymerization of fibrin and PVA to obtain IPN hydrogel and analyze its properties in comparison with monocomponent hydrogels.

Material and Methods. Fibrinogen was isolated from the peripheral blood of patients using ethanol precipitation, then polyvinyl alcohol dissolved in saline was added to it. First, fibrin polymerization was initiated by adding calcium chloride to the solution. Then, it was followed by polyvinyl alcohol undergoing freeze–thaw cycles. Thus, a hydrogel based on fibrin and PVA, samples from pure fibrin and pure polyvinyl alcohol were prepared. We studied the structure of hydrogels, their physical and mechanical properties, shrink behavior and biological activity. Statistical data processing was carried out using the GraphPad Prism 6 software.

Results. 3D structure of the hydrogel is presented by polyvinyl alcohol polygonal cavities with a network of thin fibrin fibers. The distribution of components was equal in the inside of the samples, while polyvinyl alcohol prevails on the surface. Elongation (247 (220.0; 293.2)%; p = 0.0005) and Young’s modulus (0.09 (0.11; 0.13) mPa; p = 0.0001) of the hydrogel were statistically significantly higher compared to fibrin values. The hydrogel did not shrink, unlike fibrin that shrunk (11-fold decrease in volume). The number of adherent endothelial cells on the hydrogel matrices was 8 times higher than on polyvinyl alcohol, but 10 times lower than on fibrin. There was no proliferative activity of cells on polyvinyl alcohol, but 13.6% of proliferating cells were noted on the IPN hydrogel, and 59.52% on fibrin

Conclusion. Using sequential polymerization to obtain the IPN hydrogel based on fibrin and polyvinyl alcohol provides an equal distribution of fibers in the thickness of the material, making it possible to obtain hydrogels with improved mechanical properties and shrink behavior. However, the components on the surface of the IPN hydrogel need to be redistributed - more polyvinyl alcohol should be added still maintaining a relatively low adhesiveness of the material. Therefore further research is necessary to create the most optimal conditions for cell activity.

Tissue-engineered vascular prostheses developed for prosthesis of small-diameter arteries have high biocompatibility and coverage of their patency after implantation into the vascular bed, and should also show a high probability of forming on their basis a newly formed tissue that is largely susceptible to native vascular tissue.

Aim: To evaluate the expected patency of biodegradable vascular prostheses with athrombogenic drug coating in large laboratory animal models.

Material and Methods. Vascular prostheses Ø 4 mm were fabricated by electrospinning from a polymer composition of 5% polyhydrosibutyrate/valeriate (PHBV) and 10% polycaprolactone (PCL) and a complex of proangiogenic tissues (GFmix): vascular endothelial growth (VEGF), rare fibroblast growth (bFGF) and chemoattractant molecule (SDF-1α). To induce thromboresistant properties of grafts, an athrombogenic modification of the surface of parts of the fabricated prostheses with heparin and iloprost was carried out. Modified prostheses were implanted in the carotid artery for a period of 12 months. The group with autoarterial implantation acted as a control.

Results. In 12 months after implantation, the patency of auto-arterial grafts was 87.5%. The patency of PHBV/PCL/GFmix with heparin and iloprost reached 50% at the time of implantation. The biodegradable frame made of reinforced prostheses was almost completely resorbed with the formation of aneurysms throughout. In the modified prostheses, the main elements of the newly formed vascular tissue are present. There is no formation in the walls of the prostheses.

Conclusion. The results showed that biodegradable vascular prostheses PHBV/PCL/GFmixHep/Ilo  have a high final patency, which allows us to consider them suitable for the formation of newly formed vascular tissue on their basis. However, due to the aneurysm formation, a long-term execution of the bone tissue of the prosthesis and the thrombogenic properties of the inner surface are required.

Background. Due to the constant increase in the number of surgeries to restore blood flow in the affected vessels, the development of synthetic prostheses is relevant. One of the key success factors is an increase in the adhesive properties of the inner surface, since the rapid endothelialization of vascular prostheses is considered a factor necessary to prevent thrombosis and neointimal hypertrophy.

Aim: To determine the effect of surface modification of polymer matrices with fibrin, fibronectin, or type I collagen on the adhesion and viability of endothelial cells.

Material and Methods. Polymer matrices prepared by electrospinning from a mixture of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(ε-caprolactone) were studied. Matrix samples were coated with type I collagen or fibronectin or fibrin. Then, human umbilical vein endothelial cells (HUVEC) were colonized on the matrices and cultured for 3 days. Unmodified matrices and culture plate wells were used as controls. Cell viability was assessed by combined staining with Hoechst 33342 and ethidium bromide. The metabolic activity of the cells was studied using the MTT test. Cell adhesion was analyzed by staining for F-actin. Statistical analysis of the results was performed using the GraphPrism 7.0 program.

Results. It was found that the number of adherent cells and their metabolic activity of matrices with collagen did not differ from unmodified ones. Coating with fibronectin demonstrated higher rates of cell adhesion to the surface.  However, a rather high level of cell death in this group indicates that such a modification cannot fully ensure the normal functioning of cells. Finally, we observed the best results when using a fibrin coating, which was comparable to culture plastic in terms of adhesion and viability of endothelial cells.

Conclusion. Modification of the surface of polymer matrices with fibrin can significantly improve their adhesive properties and can be used in the development of polymer prostheses for small-diameter vessels.

Introduction. Organotin compounds are promising candidates for antitumor drugs. Identification of pathogenetic features of the general toxic effect of hybrid organotin compounds during the period of the greatest severity of the intoxication clinical picture will allow to estimate the risk of hepatotoxic and nephrotoxic complications with the administration of bis (3,5–di– tert–butyl–4–hydroxyphenylthiolate) dimethyltin (Me-3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyltin (M-e5) as chemotherapeutic agents.

Аim: To conduct a comparative analysis of morphological and biochemical changes with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated dose (MTD) on the 7th day of the toxic process development.

Material and Methods. Hybrid organotin compounds Me-3 and Me-5 were administered once intragastrically to Wistar rats (females) at a MTD of 2000 mg/kg and 750 mg/kg, respectively. Biochemical and morphological studies were carried out on the 7th day of the development of intoxication symptoms according to standard methods.

Results. With the introduction of Me-3 and Me-5 in the liver, signs of fatty dystrophy of varying severity were revealed, with a predominant lesion of centrolobular hepatocytes, an increase in the size of portal tracts due to edema and fibrosis, and scant lymphocytic infiltration. With the introduction of Me-5, morphological changes were more severe, with the involvement of the vascular bed of the organ in the process. When the tested compounds were administered in the kidneys, the same type of damage to the glomerular apparatus and renal tubules was recorded, characteristic of toxic nephropathy. Unidirectional changes in the blood of experimental animals were revealed in the group of nonspecific biochemical markers of cytolysis: a moderate decrease in transaminase activity and an increase in the activity of creatine kinase (CC), lactate dehydrogenase (LDH) and creatinine levels. The process of formation of urea and protein synthesis was functionally preserved.

Conclusion. On the 7th day of the development of intoxication with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated doses, biochemical and morphological changes in the body of animals could be attributed to a moderate degree of severity.

The greatest danger is the development of multiple antimicrobial resistance in microorganisms, including Klebsiella pneumoniae, which actualizes the necessity of development and synthesis of new antimicrobial compounds. Considering the versatile pharmacological activity, pyrimidine compounds became a subject of interest for scientists in the aspect of their use as a basis for new antimicrobial agents.

Aim: To assess the antimicrobial activity of the pyrimidine compound 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazoline-4(3H)-on against Kl. pneumoniae under in vivo conditions.

Material and Methods. The antimicrobial activity in vivo of the compound 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazolin-4(3H)-on against Kl. pneumoniae was performed simulating generalized infection by intraperitoneal injection of the pathogen at a dose of 3 × 10⁶. The experiment was conducted on CBA line mice (40 animals) divided into groups: control I – animals received intraperitoneal injection water; control II – infected animals received no treatment; experimental groups – mice with generalized infection treated with ceftriaxone at the dose 50 mg/kg intraperitoneally for 7 days, and the animals receiving the test compound at the dose 27 mg/kg against infection in the same mode. Antimicrobial activity was assessed by the following parameters: animal survival rate; internal organ and blood infestation index; total leukocyte count, C-reactive protein and procalcitonin.

Results. It was found that pyrimidine derivative 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazoline-4(3H)-on has a marked antimicrobial activity against Kl. pneumonia appeared in increase of animal survival in the conditions of generalized Klebsiella infection as well as in decrease of total leukocyte count, C-reactive protein and procalcitonin levels that confirms the reduction of the inflammatory reaction.

Conclusion. Thus, the pyrimidine derivative 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazoline-4(3H)-on exhibits antimicrobial activity, comparable with ceftriaxone, against Klebsiella pneumoniae in experimental generalized Klebsiella infection.

Introduction. This article discusses the problems of the quality of outpatient care for medical students. Most of the students prefer not to seek medical help from specialists even in difficult situations, and in most cases they self-medicate. This is caused by an insufficient degree of quality service by the outpatient polyclinic service of the attached contingent. The existing state system of medical care is imperfect: there is no unified approach to the organization of student polyclinics; medical organizations do not take into account the age and social specifics of students; low continuity in the rehabilitation and treatment of patients; there is insufficient preventive work among students.

Aim: To determine the level of satisfaction with the quality of medical services provided to medical students.

Material and Methods. The sociological method included a survey of medical students (1026 respondents) according to a specially designed questionnaire that contained questions about the scope, nature, quality of work and satisfaction with the conditions of the polyclinic institution. The logistic method consisted in the analysis of personnel, resource provision, as well as the activities of the medical institution.

Results. Most of the medical students encounter organizational obstacles (appointment, waiting lists at the registry, waiting lists at the day hospital, waiting lists at the reception, etc.). 38.0% of respondents noted that when health problems appear, it is easier for them to go to the medical office of the college than to the district doctor. Moreover, 64.3% of respondents do not have information about the district doctor. Satisfaction depends on a number of factors such as: waiting time for a doctor’s appointment at the office (p < 0.001), availability when making an appointment with a doctor at a polyclinic (p < 0.001), preference when contacting a doctor when health problems appear (p < 0.001), the presence of organizational difficulties to get an appointment or treatment in a polyclinic (p < 0.001), the location of the registry and specialist offices, the terminal for making an appointment (p < 0.001), as well as the conditions of stay in a medical facility (p < 0.001).

Conclusion. The necessity of introducing feedback into the practice of working with a contingent of medical students, using available screening technologies to actively identify the most significant factors and risk groups of the most common pathology, taking measures to reduce the impact of controlled factors, as well as annual preventive examinations and medical examinations has been identified.