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BACKGROUND: Hereditary cancer is estimated to account for up to 10% of the worldwide cancer burden; 5% of all thyroid cancers are thought to be genetic. Inheritance of a deleterious mutation in genes associated with a high lifetime risk of developing cancer. Cancer-predisposing genes can promote the initiation and progression of thyroid cancer by enhancing the activation of major signaling pathways through oxidative stress mechanisms. AIM: Identification of the possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients. METHODS: Patients with thyroid cancer (with and without genetic predisposition) were investigated. Study participants were treated in Limited Liability Company (LLC) "Oncology Scientific Research Center" (Tbilisi, Georgia). The study group was collected between 2020 and 2021. In patients' blood, the thyroid hormones content (free Triiodothyronine (fFT3), free Thyroxine (fFT4), bound Triiodothyronine (FT3), bound Thyroxine (FT4), Thyroid-stimulating hormone (TSH)), and oxidative stress intensity (total activity of non-enzymatic antioxidant system (TAA) and the lipid peroxidation product, malondialdehyde (MDA), content) were investigated. RESULTS: The difference in free and bound forms of T3 and T4 levels in the blood serum between patients with thyroid cancer (Group 2 and Group 3) and the control group (Group 1) was not statistically significant (F1,2=0.5, p1,2=0.8, F1,3=2.31, p1,3=0.16). In patients with thyroid cancer the TSH level significantly increased compared to the control group (Group 1) (TSH (mean ± Std error): Group 1- 1.21 ± 0.12, Group 2-2.45 ± 0.11 (F1,2=107, p1,2<0.001), Group 3-2.47 ± 0.17 (F1,3=150, p1,3<0.001)) and the MDA levels increased by 4-5 fold. In patients with thyroid cancer from families with cancer aggregation(Group 2), the level of TAA statistically significantly decreased (F1 - 2=200; p1 - 2<0.001), in patients without genetic predisposition to cancer(Group 3), the level of TAA did not change compared to the control (F1 - 3= 2.13; p1 - 3=0.15), CONCLUSIONS: Oxidative stress plays a critical role in tumorigenesis, and antioxidant/oxidant imbalance may contribute to the malignant transformation of normal tissue. In patients with familial susceptibility to cancer mutations of several genes, which are involved in the regulation of oxidative metabolism, may contribute to the disruption of the redox balance, increase the level of oxidative stress, and contribute to the development of thyroid cancer.

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BACKGROUND: Modulation of endothelial function is a therapeutic option to reduce some of the significant complications of hypertension. However, the relationship between endothelial dysfunction reduced nitric oxide (NO) production, and the development of hypertension is not fully understood. To establish a potential pathogenetic link between impaired NO synthesis and hypertension, we investigated the results of competitive interaction of the substrate of NO synthase, L-arginine, and its analog, an non-selective inhibitor of NO synthase, N-nitro-methyl ether-L-arginine (L-NAME), in experimental rats. METHODS: Arterial hypertension was induced in male Wistar rats by intraperitoneal administration of L-NAME (Sigma-Aldrich) for 4 - 7 weeks. During the last 3 weeks, to a separate group of animals simultaneously with L-NAME, L-arginine (Sigma-Aldrich) was administered. In animals monitored for systolic and diastolic pressure, the level of NO in blood samples was determined spectrophotometrically using a Griess reagent. RESULTS: Administration of L-NAME for 4 - 7 weeks induced an irreversible decrease of NO content in blood, a reversible increase of systolic pressure (SP) and diastolic pressure (DP), and an irreversible increase in pulse pressure (PP). In rats against the background of 7 weeks of intraperitoneal administration of L-NAME, during the last 3 weeks, they were injected with L-arginine, the SP and DP indices returned to their initial values, PP decreased and the NO content in arterial blood increased. CONCLUSIONS: The results of the study indicate the presence of residual endothelial dysfunction (characterized by insufficient NO) after the correction of hypertension. Therefore, in developing the new therapeutic approaches for the treatment of hypertension, it is necessary to include drugs that, in addition to correcting blood pressure, will support normalization, and potentiation of endothelial function and endogenous NO synthesis.

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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.

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The aim of the study was to establish the radioprotective activity of citrus polymetoxylated flavonoids extract (CPMFE) on the X-irradiated rats. The experiments were carried out on white Wistar rats. Animals were irradiated with X rays in doses of 5 Gy and 7 Gy. The control group consisted the sham-irradiated rats. Part of animals of each group were treated with intramusculary injections of CPMFE (dose 30 mg/kg) during 7 days; blood was taken from the tail vein (0.5 ml) for detection of lipoperoxides (LOO.) content. On the 3rd day after irradiation 3 animals from each group were sacrificed (under ether anesthesia) and blood samples were taken for the study of antioxidant status. The activity of antioxidant enzymes (catalase (CAT) and superoxidedismutase (SOD)) was determined by the spectrophotometric method; the content of LOO.in the blood was determined by electron paramagnetic resonance (EPR) mrthod. In group of irradiated rats a sharp dose-dependent inactivation of blood antioxidant enzymes (SOD, CAT) and intensification of the lipid peroxidation were detected. The direct and feedback mechanism in the regulation of CAT and SOD activity, ensuring the implementation of antioxidant protection in the body was revealed. Under irradiation with 7Gy rapid death of animals (on 3-d day after irradiation the mortality of animals was 70%, and on the 5th day all died) were detected. During irradiation with dose 5 Gy the survival of animals increased (on the 8-th day after irradiation - 50% survival rate). CPMFE in dose-dependent manner supported the reduce the intensity of lipid peroxidation processes - at relatively low doses of radiation (5Gy) during the first 3 days the content of LOO.in the blood decreased insignificantly compared with indices in untreated animals, whereas with an increase in the dose of irradiation (7Gy) a statistically significant antiradical effect of CPMFE (a statistically significant decrease in the LOO. content) was detected. Under the effect of CPMFE in the blood of rats irradiated with a dose of 5 Gy and 7 Gy, the activity of CAT and SOD, not statistically significant tends to increase (more significant with a dose of 7 Gy). CPMFE did not affect the cumulative survival of animals irradiated with a dose of 5 Gy, but reduced the mortality of rats by 20% (on the 3rd day of irradiation), and contributed to an increase in the life expectancy of animals by 2 times (up to 7 days) in the case of dose 7 Gr. Based on the analysis of the research results, it can be assumed that under conditions of radiation damage, exogenous antioxidants synergistically with a dose-dependently activated endogenous non-enzymatic antioxidant system of the body (especially at 7Gy) contribute to the effective suppression of chain reactions of peroxidation, reduction of mortality and increase in life expectancy of animals.

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The purpose of our study was to establish the laser effects on the epithelial tissue and immune metabolism. The research was conducted on human leukemic mature T cells (Jurkat cells) (DSMZ-Deutshe Sammulung von Mikroorganismen und Zellkulturen (Germany)) and MDCK cell line (Lugar Laboratory, Tbilisi, Georgia). Cells were radiated by Laser device "ОПТОДАН"- АЛСТ-01 (power 5 W) 3 -7 days (4 minutes per day). With the aim to model oxidative stress-induced apoptosis, 30% hydrogen peroxide (H2O2) (Sigma) is added to Jurkat cells, in doses 25 and 50µM [4, 5]; and MDCK cells, in doses 400 and 800 µM [19] added to incubation suspension with subsequent incubation for 24, 48 and 72 hrs. Control group is represented by intact Jurkat and MDCK cells. MTT test was used to assess the cells' proliferation activity (viability). Statistical analyses of the obtained results were performed by SPSS (version 10.0) program package. Our research results show that effects of laser therapy on proliferation of cell cultures depend on the type of cells and incubation conditions. Laser irradiation revealed equal efficacy in both types of the intact cells and increased their viability in time-dependent manner. Jurkat cells turned out to be more susceptible to oxidative stress. Laser therapy only slightly improved their viability at moderate intensity of oxidative stress and proved to be ineffective in strong oxidative stress conditions. The MDCK cells appeared to be more sustainable to oxidative stress; significant changes in these cells viability were observed only when high doses of hydrogen peroxide were added to their incubation medium. Thus, laser therapy was effective for these cells incubated in both regimens of oxidative stress. Our research results prove the efficacy of laser therapy use during periodontitis with the aim to recover epithelium in the oral cavity and to modulate immune metabolism in the patient's body.

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Content and metabolism of free NO in saliva, fluids of periodontal pockets and gingival tissue has been investigated by EPR (electron paramagnetic resonance) method with the use of nitric oxide spin-trap in patients suffering from periodontitis. It was found that increased generation of nitric oxide at early stages of periodontitis is of protective nature. However, at serious disorders of mitochondrial respiration and exaggerated formation of generators of reactive oxygen, nitric oxide converts into citotoxic peroxinitrite leading to destruction of parodontal tissue; part of free nitric oxide produces FeSNO, which in turn, supports and decreases content of free NO in gingival tissue. As a result, decreases local antimicrobial protection, hemocirculation, tissue nutrition, progresses inflammation. Periodontitis decreases local immunity due to NO deficiency in gingival tissue. Reduced content of NO in gingival tissue decreases regeneration ability of cells, which in turn, leads to deterioration on gingival tissue.

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