Finding possible diagnostic markers for differentiating benign and malignant thyroid tumors on example investigate of rheological properties1.

BACKGROUND: The functioning of the thyroid gland is a multi-component process that in some conditions may undergo alterations. The thyroid gland is part of the endocrine system that produces the iodine-containing hormones thyroxine and triiodothyronine. Thyroid hormones, control metabolism and energy, growth processes, maturation of tissues and organs, regulation of blood flow, and, therefore, providing vital functions of the body. The role of thyroid hormones in the regulation of blood flow is determined by the intensity of their production and the quantity in the blood. Presumably, in case of oncological and non-oncological diseases of the thyroid gland, the fluidity of the blood, which depends on the rheological properties, will be different. OBJECTIVE: Our aim was investigating rheological characteristics for studying of changes of rheology in patients with thyrotoxicosis, with benign tumor pathology of the thyroid gland, with thyroid cancer and finding possible diagnostic markers for differentiating benign and malignant thyroid tumors. METHODS: In this regard, we examined, using modern methods accepted in clinical practice, a standard list of recommended diagnostic tests in the group of patients (thyrotoxicosis: n = 25; benign tumor: n = 47), thyroid cancer: n = 35) and control group (n = 15), and with new original methods, parameters that describe the rheological properties of the blood, such as blood rheological index, volume, thickness, surface area of erythrocytes, erythrocyte aggregation index, deformation index, plasma viscosity, hematocrits. RESULTS: Against the background of relative changes in the studied values, it is necessary to pay attention to the fact that erythrocyte aggregation in patients with a benign form and control, as well as in patients with a malignant form and control, differ significantly from each other, in addition, there is a significant difference between aggregation in the group of patients with benign and control aggregation. malignant forms of the disease. It is significant that aggregability differs in patients with thyrotoxicosis and in controls. This indicates that erythrocyte aggregation is particularly informative. The blood rheological index most clearly demonstrated the difference between benign and malignant forms of the disease. Significantly changed compared to control in various forms of thyroid diseases. CONCLUSION: Additional diagnostic markers for differentiating benign and malignant thyroid tumors may be consideredeerythrocyte aggregation index and blood rheological index.

Impact of different severity hyperglycemia on erythrocyte rheological properties1.

BACKGROUND: The triad "insulin resistance, prediabetes, diabetes" is three independent neologies with characteristic features and development. In addition, each are characterized by progression and the possibility of transition from one form to other. Due to the fact that diabetes is one of the common diseases associated with high rates of disability, it is necessary to improve diagnostic methods and educational regimens for successful prevention and treatment of the disease. OBJECTIVE: We investigated Band 3 protein (B3p) level, osmotic resistance of erythrocytes, the total antioxidant activity (TAA) of blood serum, level of HbA1 in group patients with insulin resistance (IR), prediabetes, and Type 2 Diabetes Mellitus (T2DM) and comparative with health control group. METHODS: We used original, accurate research methods that measure the essence of the studied quantities. RESULTS: Disruptions of glucose and insulin homeostasis ay lead to the initiation of oxidative stress (in our study demonstrated by a decrease of TAA of blood serum) increased redox-sensitive PTP activity and aberrant band 3 phosphorylation, potentially leading to reduced erythrocyte deformability. At the same time glycation of Hb during T2DM may affect its cross-link with membrane proteins, in particular with B3p, and although appears to limit its cross-linking and decrease its clusterization ability, induces alterations in the cytoskeletal matrix, and thereby decrease erythrocytes' osmotic resistance making them more susceptible to hemolysis. CONCLUSIONS: The osmotic resistance of the erythrocytes can be used as a sensitive marker for the detection of the early stages of hyperglycemia (prediabetes). This set of clinical trials will make it possible to identify diseases that make up the triad at an early stage. Early detection of disorders and continued research in this direction will help in the development of a diagnostic scheme for the prevention of such patients. Based on our data, research into anti-oxidation drugs is very important. With the help of the array of studies described in the article and antioxidant treatment, the likelihood of successful treatment will increase.

CORRELATIVE ASSOCIATION OF OXYGENATION AND SEPSIS PANELS WITH THE USE OF ACE2 INHIBITORS AND WITHOUT IT IN THE CONDITIONS OF SEPTIC SHOCK IN COVID-19-INFECTED AND NON-INFECTED PATIENTS (COHORT STUDY).

Sepsis-associated hyperlactatemia (SAHL), Lactic acidosis, is a common problem in critically ill patients. The prevalence of Lactic acidosis is estimated to be approximately 1% of all hospitalized nonsurgical patients. The purpose of our study was to reveal possible associations between the level of Lactate with sepsis biomarkers: PCT, IL 6, and PO2 in the presence of ACE 2 inhibitors in Covid-19 infected and non-infected patients with Septic Shock. We conducted a cohort study, comparing outcomes of 212 critically ill patients with Septic shock, who were treated in the intensive care unit of First University Clinic of Tbilisi State Medical University during the 2020-2021 years. Inclusion criteria for the study were: Age>40ys; COVID-19 and other respiratory diseases associated with Septic shock, with respiration dysfunctions with prior exposure to ACE2 inhibitors o no history of treatment with the ACE2 inhibitors. Patients enrolled in the study were individuals who were diagnosed with COVID-19 infection and septic shock, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors; patients with septic shock who were not infected with COVID-19, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors. According to lactate level, the studied patients were divided into subgroups: lactate <3 mMol/l, and lactate > 3 mmol/l. In patients with septic shock who were not infected with COVID-19 the main Causative microorganisms were gram-negative bacteria. In patients' blood the Interleukin-6 (IL-6), lactate, procalcitonin (PCT), pO2, and pulmonary pressure were investigated. Results of the study show that the rise in lactate levels in COVID-19-infected and non-infected patients was accompanied by an increase in PCT content and a decrease in pO2 level in blood. Therefore, serum lactate levels can be used as a prognostic marker of the severity of septic shock in COVID-19-infected and noninfected patients. In COVID-19-infected patients together with the increased lactate level, increases the level of IL-6, which indicates the important link between the quality of immunological disorders, inflammation, and COVID-19 infection in patients with ARDS and sepsis. These alterations were not prevented by the prior use of the ACE2 inhibitors. In COVID-19-infected and noninfected patients who didn't use ACE2 inhibitors, high lactate levels were accompanied by decreased pulmonary pressure which was normalized in patients who prior used ACE2 inhibitors.

IMPACT OF THE ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS ON THE COURSE OF THE SEPTIC SHOCK DEVELOPED DURING COVID-19 AND OTHER SEVERE RESPIRATORY INFECTIONS IN PRESENCE OF HYPERFERRITINEMIA.

SARS-CoV-2 can cause sepsis regardless of the presence of secondary bacterial or fungal infections. The virus itself likely causes sepsis through a variety of possible mechanisms, including immune dysregulation, with respiratory dysfunction, which as a result of circulatory dysfunction leads to hypoxemia and metabolic acidosis. We conducted cohort study, comparing outcomes of 212 critically ill patients with Septic shock (134 men (63.3%) and 78 women (36.7%), with a mean age between 40-70 years) were evaluated, who were treated in the intensive care unit of First University Clinic during 2020-2021 years. All four groups had documented Hyperferritinemia (HF). Patients were divided according to ferritin concentrations: moderate HF (ferritin <1500ng/ml) and severe HF (ferritin >1500ng/ml). The study aimed to reveal the impact of the Angiotensin-Converting enzyme -2 (ACE2) inhibitors on the course of the Septic shock developed during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF). Study results show that severe HF in patients with Septic shock is associated with a high risk of mortality and can be considered an indicator of the severity of the disease. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock: ACE2 inhibitors reduce the levels of Ang II and C reactive protein (CRP) in the blood in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate and severe HF; regulate the activity of leukocytes and the blood pro-coagulation system in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate HF; reduce the expression of pro-inflammatory cytokines (IL-6), decrease the level of D dimer in СOVID-infected patients in conditions of moderate HF; Procalcitonin levels do not differ between COVID-19 infected and non-infected patients with Septic shock. Based on our study, we can assume that there is the important link between elevated Ang 2 and the quality of immunological disorders and inflammation. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock.

EFFECTS OF IONIZING RADIATION ON COGNITIVE PARAMETERS IN WHITE MICE.

The aim of the study was to establish the dependence of memory processes and learning ability in gamma-irradiated white mice on the age and period after irradiation. The 3-month and 1-year-old male mice (Mus musculus) were used in the study. Mice whole-body irradiation was performed at a dose of 5 Gy with 137Cs by using a "Gamma-capsule-2". Spatial learning and formation of memory were estimated in the elevated-type multi-way maze and elevated plus-maze. Experiments were carried out 48 hours and 30 days after irradiation for seven days (five trials each day). The number of errors (deviations from optimal trajectory) and total time for crossing the maze were calculated. The results of the study indicate that ionizing irradiation with a total dose of 5 Gy results in a delayed spatial learning process, causes spatial memory and behavior changes in different age groups of animals - aged mice turned out to be more radio-resistant. Age-related radio-resistance plays an especially major role in the early stage of post-radiation recovery. Though, the late radiation aging effect is especially pronounced in young animals.

THE ROLE OF ANGIOTENSIN -2 IN THE PATHOGENESIS OF SEPTIC SHOCK DURING MULTIORGAN DYSFUNCTION SYNDROME (REVIEW).

Septic shock is an acute pathophysiological condition characterized by vasodilation, hypotension, decreased circulating blood volume, tissue hypoxia, organ failure, and high lethality. The causes of septic vasodilation, which can lead to vascular smooth muscle dysfunction or selective vasomotor imbalance, remain controversial. In septic vasodilation, optimal pharmacological intervention is needed. Expected vascular response to shock when various vasoconstrictors are used, requires further study of the therapeutic potential of these agents. Because of all the above, it is of great interest to study and compare the therapeutic effects of angiotensin-2 and already used catecholamine and non-catecholamine vasoconstrictors in the treatment of septic shock. Angiotensin 2, approved by the FDA in 2018, is the newest available vasopressor for the treatment of vasodilatory shock. In the setting of high-dose vasopressors, exogenously administered synthetic angiotensin 2 significantly improved mean arterial pressure, decreased background vasopressor dose, and lowered sequential organ failure assessment scores in patients with refractory septic shock, In the review, the role of angiotensin-2 and its correlation with markers of sepsis for adequate management of septic shock-induced multiorgan dysfunction and arterial hypotension with ACE inhibitors is evaluated.

[COMPARATIVE EVALUATION OF THE TREATMENT OF VASOMOTOR RHINITIS IN PATIENTS WITH AND WITHOUT COVID-19 INFECTION].

The aim of our study was to evaluate the effectiveness of treatment with the local antihistamine medicine Palada NS in patients with vasomotor rhinitis who have had COVID-19 infection (6 months after transfer) and have not. The diagnosis of vasomotor rhinitis was made on the basis of subjective (sneezing frequency, degree of difficulty in nasal breathing, nature, consistency, color of nasal discharge, as well as color of swelling of the nasal mucosa and turbinates, impaired olfactory function, general condition of the patient) and objective (anterior and posterior rhinoscopy, endoscopy, rhinomanometry) examination.Patients in both groups were treated with Palladium NS for 10 days (2 sprays, 2 times a day for 10 days). All studies were performed in patients before, 3-5 days after, and at the end of the treatment. The effectiveness of treatment was assessed according to patients' subjective complaints and objective indicators of instrumental examination. Symptoms before and after treatment were assessed on a 3-point scale. A positive result of treatment was revealed in the majority of patients. Which manifested itself in a decrease in the number of subjective and objective complaints. In patients who did not undergo COVID-19 infection, the subjective and objective indicators' improvement was revealed as early as on the 5th day of treatment, in patients with vasomotor rhinitis who underwent COVID-19 at least 6 months ago, the improvement was recorded only by the end of treatment. Based on the results of our studies, the proposed treatment regimen for vasomotor rhinitis with the local antihistamine medicine Palada NS can be recommended for patients with vasomotor rhinitis, both with and without COVID-19 infection.

BAYESIAN MODELLING AND INFERENCE OF MIXTURES OF DISTRIBUTIONS OF MICRONUCLEAR BUCCAL CELLS IN THE POPULATION OF SACHKHERE DISTRICT'S VILLAGES.

Malignant tumors are one of the leading courses of mortality in the world, and it is believed that 19% of malignant tumors are associated with environmental risk factors. The aim of the study was to establish the spectrum of distributions of an informative biomarker of the unfavorable (genotoxic) effect of the external environment on the body by determining the level of micronuclei (LMN) in buccal epithelium cells in populations of villages of the Sachkhera region (Georgia). In the inhabitants of the Sachkhere district (both sexes, 50-65 years old) living in the villages of Sareki, Sairkhe, and Chorvila, LMN was determined in the cells of the buccal epithelium. The statistical significance of the difference in LML between the village population was assessed using the analysis of variance (ANOVA). Dixon's Q test was used to identify abnormal micronuclei. The χ2 criterion was used to assess the normality of LMN distributions among residents of the villages. The distribution of the population by LMN indicators in each individual village was described as the distribution of a two-component mixture. The statistical significance of the difference between the Gaussian means of the mixture components was assessed using the Z-test. To analyze the data and visualize the results, the SPSS and Open BUGS software packages were used. Differences in the LMN of the buccal epithelium in the studied populations were revealed, which may be due to the influence of external environmental factors: in Sareki, the effect of a certain (unidentified) clearly expressed genotoxic factor (both in terms of intensity and scale of exposure) was revealed, which is accompanied by a sharp increase in LMN, while in Chorvila and Sairkhe the presence of an inducing factor is not recorded and LMN remained practically within the norms. The identification of the causal relationship between the nature of the distributions of the used biomarkers and the specificity of the incidence of the population in the villages, as well as the possible contribution of unfavorable environmental factors, is the subject of further research.

ROLE OF Β-ADRENOCEPTORS IN REGULATION OF ERYTHROCYTES' RHEOLOGICAL FUNCTIONS (REVIEW).

In this review, we discuss the role of adrenoceptors in the regulation of the rheological functions of erythrocytes. ß-adrenoceptors play an important role in the regulation of erythrocytes functions and metabolism. They participate in the modification of transport membrane proteins (Na+/K+-ATPase, Ca+2-ATPase, Na+/K+/2Cl-cotransporter, Na+/H+-antiporter, CAT-1, Ca2+-dependent K+ channels (Gard channels), the activity of adenylate cyclase and cAMP, AMP-dependent activation of the L-arginine/NOS system and erythrocyte NOS) and by this way modulate the cells volume, rheological properties (deformability, aggregability), intensity of NO synthesis and ATP reliase. These properties of erythrocytes determine, that, in addition to the transport of gases, they play the oxygen sensors role and can participate in the mechanisms of vasorelaxation and maintenance of a normal level of microcirculation.

[EFFECT OF PROPRANOLOL ON CYTOKINE PROFILE IN AN EXPERIMENTAL MODEL OF HUMAN T LYMPHOCYTES (JURKAT CELLS) IN VITRO].

In this research, in order to establish the role of neuroendocrine mechanisms in the processes of immunomodulation, the effect of propranolol on the cytokine profile in an experimental model of human T lymphocytes (Jurkat cells) in vitro was investigated. Jurkat cells were incubated under standard conditions. Stimulation of the Jurkat cells was performed by incubation with Phytohemagglutinin (PHA) (50 µg/ml) in the presence of propanonol (10-4 M) and without it at 370 for 24 hours. The cytokine profile (IL-2, IL-10, IFN-γ) in intact and PHA-stimulated Jurkat cells, incubated with and without ß-adrenergic receptor antagonist propanonol, was examined by ELISA. The production of IL-2, IL-10 and IFN-γ in intact Jurkat cells was very low; in PHA-stimulated Jurkat cells, the production of IL-2, IL-10 and IFN-γ was markedly increased (p<0.05). Propranolol significantly reduced the production of IL-2, IL-10 and IFN-γ in PHA-stimulated Jurkat cells (p<0.05). Cytokine production (IL-2, IL-10, IFN-γ) did not change significantly after exposure to propranolol on intact Jurkat cells, which indicates that the inhibitory effect of propranolol on cytokine secretion in PHA-stimulated Jurkat cells is not due to the cytotoxic effect of propranolol on cells , but the result of its specific inhibitory activity. The results of the study allow us to conclude that in order to regulate the functional activity of lymphocytes during various diseases, it is necessary to take into account an autoregulatory mechanisms that ensure the interaction of immune cells with the mediators of the nervous and endocrine systems, maintaining the homeostasis of these systems and regulating the immune response.

THE PECULIARITY OF COVID- 19 GENOME AND THE CORONAVIRUS RNA TRANSLATION PROCESS AS APOTENTIAL TARGET FOR ETIOTROPIC MEDICATIONSWITH ADENINE AND OTHER NUCLEOTIDE ANALOGUES (REVIEW).

Despite the multifaceted effects of the medicines provided for COVID-19treatment, the number of the infected and mortality of patients increases which demonstrates the insufficient effectiveness of drugs used to fight coronavirus infections in medical practice, and clearly shows the need to develop new treatment tactics.In this review article are summarized and analyzed the literature data concerning specific features of COVID 19. Particular attention is given to genetic characteristic of this virus ,to mechanism of its invasion into the human organism, replication and interection with ACE-2 receptors ,as well as to the basic targets for the action of existing drugs with antiviral activity against COVID-19. Currently, the following medications are used to treat COVID-19: remdesivir, chloroquine, hydroxychloroquine (HCQ), ribavirin, lopinavir/ritonavir. According to a recent theory of coronavirus treatment, the starting point for the mechanism of action of a potential etiotropic drug is the inhibition of the coronavirus main protease (Mpro/3CLpro) and the papain-like protease (PLpro). Among the drugs listed above, lopinavir acts through this mechanism but is characterized by severe side effects.It is emphasized that remdesivir as adenosine analog provides inhibitory action on RNA dependent RNA-Polymerase,but there are controversial views about reduction in mortality during using of this drug against COVID-19. The present paper discusses the mechanism of action of a potential etiotropic drug against coronavirus, which implies the replacement of the nucleotides involved in the process of translation of the virus with their analogs with the aim to "inhibit" the ribosome and block the production of viral proteins.

[MORPHOLOGICAL ALTERATIONS IN THE INTERNAL ORGANS OF RATS WITH ALLOXAN DIABETES].

The aim of our study was to assess morphological changes in internal organs in a redox-induced model of alloxan diabetes in rats.According to the results of the study, the blood glucose level in rats began to increase 24 hours after the of alloxan administration, reached the maximum level on the 15th day of observation, and decreased on the 25-35 day, to the control level. In parallel with the increase in blood glucose level, an increase in the malondialdehyde (MDA) content in the blood serum was observed.Severe hyperemia, edema, and focal fibrotic changes were revealed morphologically in the kidneys, liver and myocardium. The degree of morphological changes was increased (lymphocytic-cell infiltration, degenerative changes (dystrophy), small necrotic areas) with an increase in the level of glucose and MDA in the blood. It can be assumed that the damage to the tissues of the kidneys, heart, liver and blood vessels in diabetes is largely due to the intensification of oxidative stress in the body.

NEW APPROACHES TO THE TREATMENT OF PERIIMPLANTITIS (REVIEW).

Implant therapy, a modern treatment option for completely and partially edentulous patients. However, numerous clinical studies indicate a sufficiently large number (9-20%) of the failure rate of implants. The achievement of osseointegration depends on many factors, such as a suitable host, alteration in bone metabolism, hormone balance, smoking habits, and local conditions (quantity and quality of bone, biocompatible materials, traumatic surgical technique, occlusal conditions, quality of dental implants, and corrosion of the metal of implants, thoroughness of surgery and healing time). As can be seen from the review data, achievements in the field of dental implantation are based on a deep understanding of the fundamental cellular processes of regeneration and restoration of periodontal tissues, maintaining optimal local conditions that contribute to accelerating the regeneration process. A thorough knowledge of the cellular mechanisms of wound healing and the clinical consequences of modern periodontal treatments should provide further improvement or the development of new treatment strategies for the restoration and regeneration of soft tissues and dental implants. Various immuno-inflammatory mediators and bone-related molecules can be considered potential biomarkers that will be used for monitoring peri-implant health and disease. Their timely detection and systematic maintenance therapy may have a crucial impact on decreasing the occurrence of peri-implant lesions. Importantly, individual genetic data might contribute to therapeutic planning and prognosis, make its coordination depending on observed genotype. Supplementary evidence concerning the molecular pathophysiology of peri-implantitis may, in the future, benefit the treatment of dental implants, development of preventive approaches to avoid peri-implant tissue breakdown.

[BAYESIAN SAMPLE SIZE DETERMINATION FOR CYTOGENETIC STUDIES IN A POPULATION].

Bayesian approach for the sample size determination (SSD) and a comparison with classical (Frequentist) approach are presented. Credible interval length estimation-type criterion was applied for the Bayesian SSD estimation in population studies of cytogenetic characteristics. The dependence of the sample size (n) on the length of the 95% Credible interval of the population mean has been estimated in the Gaussian approximation of the distribution functions with known variance and an unknown population mean. The Mean and Variance of the prior function in the Bayesian approach were estimated based on published data and the results of our previous studies. Mathematical analysis and graphical visualization of the results was carried out using the software STATISTICA-12, and WinBugs. It is shown that the Bayesian approach achieves an almost two-fold decrease in sample size and provides the possibility of flexible optimization of the planned procedures at the preliminary stage of the study. Further increase inaccuracy of the results is expected due to a more accurate approximation of asymmetric distributions using gamma functions.

RISK-FACTORS OF CORONARY ARTERY DISEASE (REVIEW).

The treatment of coronary arteries disease (CAD) and the prevention of their complications, intervention on the coronary arteries is usually recommended. In this review, with the aim of improving the treatment outcomes of patients with CAD, requiring percutaneous coronary intervention and/or coronary artery bypass grafting,risk factors of developing coronary syndrome are discussed. Understanding the causes of the disturbance of coronary artery conduction will provide a new perspective for improving patient treatment outcomes. Revascularization cannot protect against future acute thrombotic events; for the successful treatment of CAD combining optimal revascularization strategies with long-term measures of risk reduction in lifestyle, often in combination with pharmacological measures, is needed. Numerous primary and secondary prevention trials have shown that management of modifiable risk factors (reduction in LDL-cholesterol level, decrease in blood pressure, discontinuation of smoking) reduces death rates, myocardial infarction, stroke, and other cardiovascular events, including the need for revascularization. Refined guidelines for the primary and secondary prevention of atherosclerosis account for modifiable and nonmodifiable, and other emerging risk factors of CAD.

[SELECTIVE EFFICACY OF GEORGIAN LEGUME EXTRACTS ON JURKAT AND MDCK CELLS].

The goal of our study was to establish the anti- proapoptotic activity of the common in Georgia crops on the Jurkat and MDCK cells. Extracts of various varieties of beans (Tirkmela, Batumi meadow, Shulavera, Udelebi, as well as green peas, Lens Culinaris lentils, soy beans) were added to the intact or incubated under oxidative stress conditions Jurkat and MDCK cells. Cell viability (apoptosis intensity) was determined by a cell proliferative activity test (MTT test). Correlation and statistical analysis of ANOVA was performed using the package (SPSS version 11.0). In the presented study the selective effectiveness of extracts with different antioxidant activity on intact and incubated under oxidative stress Jurkat and MDCK cells was revealed, related with different sensitivity of cells to the oxidative stress. In normal MDCK epithelial cells, resistant to redox-active factors (H2O2), inverse relationship between the intensity of apoptosis and the antiradical potential of the extract was found; in leukemia transformated Jurkat cells, characterized by high sensitivity to oxidants (H2O2), a violation of the redox-dependent anti-apoptotic cell protection mechanisms was revealed, which is manifested by the absence of regularity of the cytoprotective / cytotoxic effects of the extracts on intact and incubated cells under oxidative stress conditions. These results can be used in the development of schemes of anti-tumor and anti-inflammatory therapy.

[IMPACT OF LIPOSOMAL VITAMIN C AND VITAMIN E COMPLAX ON NORMAL AND TUMOR CELLS].

In order to assess the possibility of using liposomes to stabilize various antioxidant compounds, we investigated the effect of liposomes (1,2-palmitoyl-phosphatidic acid (DPPA) and dipalmitoylphosphatidylcholine (DPPC)) on the effectiveness of antioxidants, hydrophilic vitamin C and lipophilic vitamin E, in model systems of normal epithelial MDCK cells and tumor Jurkat T cells. The effect of vitamins C, E and (C + E) in combination with DPPC and DPPA liposomes on Jurkat and MDCK cells depends on the dissolution or integration of these liposomes with hydrophobic sections of the cellular membrane, as well as the subsequent release of vitamins from liposomes. Based on the results of the study, it can be concluded that the studied liposomes can modulate the effects of C and E vitamins on normal and tumor cells. These data can be used to study the possible selective regulation of the activity of various hydrophobic and hydrophilic antioxidants on normal and tumor cells, which is especially important for creating antitumor drugs, as well as effective radioprotectors that protect healthy tissues from radiation damage during radiotherapy.

[EVALUATION OF THE COMPARATIVE TOXICITY OF VARIOUS MATERIALS FOR DENTAL PROSTHETICS ON CELL CULTURE MODELS].

Difficulties in repairing the defects of the teeth are related with allergic-inflammatory, traumatic and dystrophic complications arising from the interaction of the foreign body with the mucous tissues of the oral cavity after the patient's prosthesis is established. The aim of our study was to establish the toxic pro-inflammatory activity of materials used for the manufacturing of bases of removable dentures - plastics based on polymethylmethacrylate prosthetic complexes Prothyl Hot, Ftorax and Perflex Flexi Nylon on the model of human leukemia transformed T cells (Jurkat cells) and MDCK cells. For the cells simulation Jurkat and MDCK cells was incubated with the components of prosthetic materials, Prothyl Hot, Ftorax and Perflex Flexi Nylon/ Prosthetic materials were added to the incubation medium at the doses used in practice (calculated at 106 cells); duration of incubation was 24 hours. A comparative assessment of the toxicity of prosthetic materials was determined by the MTT test (activity of mitochondrial dehydrogenases). Statistical analysis was carried out using the package (SPSS version 11.0). The statistical reliability of the difference between the indices was evaluated by the Student t test (the P <0.05 level was considered reliable). The results of the conducted studies testify to the absence of toxicity of the complexes Prothyl Hot, Ftorax and Perflex Flexi Nylon, used as a basis of circuit prostheses, on intact Jurkat and MDCK cells, as evidenced by the stability of their mitochondrial dehydrogenases. Based on the analysis of the conducted studies, it can be concluded, that as Jurkat and MDCK cells are used as models of immune and epithelial cells, the materials used for manufacturing of removable prostheses, the polymethylmethacrylate-based plastics (Prothyl Hot and Ftorax) and elastic thermoplastic polymer material Perflex Flexi Nylon, are not toxic. Studied materials, with the high probability, are not capable to cause massive death of immune cells, development of allergic or inflammatory damages, which in turn can stat cause the development of stomatitis and gingivitis, the destruction of the paradental tissue.

[A COMPARATIVE EVALUATION OF THE EFFECT OF DENTURES FROM VARIOUS MATERIALS ON THE ORAL CAVITY'S IMMUNOLOGICAL AND REDOX-DEPENDENT HOMEOSTASIS].

The purpose of our study was a comparative analysis of the effect of dentures from various materials on the immunological and redox-dependent homeostasis of the oral cavity. We studied 60 patients with removable dentures made based on plastics Prothyl Hot, Vertex BasiQ 20 (differing by polymerization regime) and elastic thermoplastic polymer Perflex Flexi Nylon. The control group consisted of 15 volunteers with a practically healthy oral cavity, who did not use dentures. Saliva collected on an empty stomach in a glass tube without the use of a stimulator before the establishment of a denture and 3 days and 1 month after. The content of the protein P-53 in saliva determined by immunoenzymatic assay with use of "Cusabio" reagent. The cytokines (IL1ß, IL10) content in saliva was determined immunoenzymatic assay. To determine the redox balance in the saliva of patients, the lipoperoxydradicals content (LOO.) content (by EPR method, using the spin-labeled α-phenyl-tertbutylnitron (PBN) (SIGMA)) and the activity of antioxidant enzymes (catalase and SOD) (by spectrophotometry) studied. Statistical processing of the results was carried out using the software package SPSS (version 10.0). Results of analysis show that defects associated with a lack of teeth do not affect the immune and oxidative balance of the oral cavity, but contribute to the development of destructive changes in the oral cavity's soft tissues, which manifested by an increase in the content of the proapoptotic protein P-53 in the saliva. After establishment of a denture, the intensity of apoptosis in the oral cavity tissues reduced. Establishment of a denture induced development of an inflammatory reaction during the first days, the intensity of which gradually decreased and completely disappeared at the end of the first month of the observation (manifested by the normalization of the parameters of the immune balance and antioxidant system). Minimal traumatic effects observed during establishment of a denture made based on Perflex Flexi Nylon.

[STUDY OF TOTAL ANTIOOCIDANT STATUS OF THE ORGANISM AS A POSSIBLE BIOMARKER OF DOSE AND EFFECT OF RADIATION EXPOSURE].

In presented article, by means of a comparative analysis of the relationship between the dose-dependent alterations in the organism's redox status, measured by the innovative method developed by us and the standard methods used for assessing catalase and superoxide dismutase activity, and an end radiobiological effect, was attempted the preliminary assessment of the possibility to apply the parameter of blood plasma total antioxidant activity (TAA) as marker of dose and effect of radiation exposure. The experiments were carried out on white mice randomly divided into groups of irradiated and sham irradiated animals. The mice were exposed to a whole body gamma irradiation by source Cesium-137 (137Cs) at doses of 5 and 7 Gr, a dose rate of 1.1 Gr / min. After 5 days of beginning of observation in animals' blood measurements of the activity of antioxidant enzymes (superoxide dismutase - SOD and catalase - CAT) and total antioxidant activity by spectrophotometric method were evaluated. Parallel monitoring of animal survival was conducted. At the given stage of the study, applicability of OAA as a marker of dose-dependent alterations in antioxidant status was assessed by the criteria of sensitivity and linearity, and as a marker of the effect the strength of the relation between the antioxidant status indicators and the final radiobiological effect, measured by animal life span in post- radiation period (time-effect) For comparative analysis of the effects of radiation on the levels of antioxidant status indicators (SOD, catalase, OAA), ANOVA methods were used, the nature of the causal relationship between levels of antioxidant status and the life span of laboratory animals was analyzed on the basis of the Cox proportional intensity model with time covariates, preliminary processing of data, basic calculations and visualization of the results were carried out using a mathematical package that " STATISTIC 12". The received results testify to the significantly high sensitivity of the total redox-status indicator (OAA) to the dose of irradiation, which makes it possible with full justification to consider it as a promising candidate of the biological exposure dose marker. In addition, the indicator of the total antioxidant status (OAA) of the body allows predicting the dose dependence of the survival of laboratory mice more accurately than the indices of the activity of individual antioxidant enzymes (catalase and SOD), which makes it possible to consider it as a promising candidate for the biomarker of the dose and the effect of radiation exposure.