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Cells of various organs and systems perform their functions and intercellular interactions not in an inert environment, but in the microenvironment of tissue fluids. Violations of the normal drainage of tissue fluids accompany lymphedema. An important mechanism of angiogenesis and vasculogenesis regulation in tissue fluids is the production and reception of vascular endothelial growth factors in combination with the regulation of matrix metalloproteinases. The aim of the work was to perform: a comparative analysis of some polymorphisms of vascular endothelial growth factor and their receptors and the genes encoding matrix metalloproteinases in two forms of lymphedema; an analysis of the relationship of these genes' polymorphisms with the levels of vascular endothelial growth factor and matrix metalloproteinases and their inhibitors in serum and affected tissues. Polymorphism of VEGF (rs699947, rs3025039), KDR (rs10020464, rs11133360), NRP2 (rs849530, rs849563, rs16837641), matrix metalloproteinases MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), Timp1 (rs6609533) and their combinations were analyzed by the Restriction Fragment Length Polymorphism method and TaqMan RT-PCR. The serum and tissue fluid levels were determined using the ELISA test system. Changes in the frequency distribution of MMP2 genotypes in primary and MMP3 in secondary lymphedema are shown. Significant frequency differences in NRP2 genotypes were revealed by comparing primary and secondary lymphedema. Features of the distribution of complex genotypes in primary and secondary lymphedema were revealed. The correlation analysis revealed the interdependence of the concentrations of the MMP, TIMP and VEGF products and differences in the structure of the correlation matrices of patients with both forms of lymphedema. It was shown that, in primary lymphedema, genotypes associated with low MMP2 and TIMP2 in serum and tissue fluid are detected, while in secondary lymphedema, other associations of the production levels with combined genetic traits are observed., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

Polymorphism of genes of transforming growth factor TGFB and its receptors (TGFBRI, TGFBRII, and TGFBRIIII) in patients with primary open-angle glaucoma was analyzed. The frequency of the TGFBRII CC genotype in patients is increased relative to the control group (OR=6.10, p=0.0028). Heterozygosity in this polymorphic position is reduced (OR=0.18, p=0.0052). As the effects of TGF-β is mediated through its receptors, we analyzed complex of polymorphic variants of the studied loci in the genome of patients. Two protective complexes consisting only of receptor genes were identified: TGFBRI TT:TGFBRII CG (OR=0.10, p=0.02) and TGFBRII CG:TGFBRIII CG (OR=0.09, p=0.01). The study showed an association of TGFBRII polymorphism with primary open-angle glaucoma and the need to study functionally related genes in the development of the disease, which should contribute to its early diagnosis and prevention., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study was to investigate the antimicrobial activity of citrate-stabilized sols of cerium oxide nanoparticles at different concentrations via different microbiological methods and to compare the effect with the peroxidase activity of nanoceria for the subsequent development of a regeneration-stimulating medical and/or veterinary wound-healing product providing new types of antimicrobial action. The object of this study was cerium oxide nanoparticles synthesized from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid (the size of the nanoparticles was 3-5 nm, and their aggregates were 60-130 nm). Nanoceria oxide sols with a wide range of concentrations (10 -1 -10 -6 M) as well as powder (the dry substance) were used. Both bacterial and fungal strains ( Bacillus subtilis , Bacillus cereus , Staphylococcus aureus , Pseudomonas aeruginosa , Escherichia coli , Proteus vulgaris , Candida albicans , Aspergillus brasielensis ) were used for the microbiological studies. The antimicrobial activity of nanoceria was investigated across a wide range of concentrations using three methods sequentially; the antimicrobial activity was studied by examining diffusion into agar, the serial dilution method was used to detect the minimum inhibitory and bactericidal concentrations, and, finally, gas chromatography with mass-selective detection was performed to study the inhibition of E. coli's growth. To study the redox activity of different concentrations of nanocerium, we studied the intensity of chemiluminescence in the oxidation reaction of luminol in the presence of hydrogen peroxide. As a result of this study's use of the agar diffusion and serial dilution methods followed by sowing, no significant evidence of antimicrobial activity was found. At the same time, in the current study of antimicrobial activity against E. coli strains using gas chromatography with mass spectrometry, the ability of nanoceria to significantly inhibit the growth and reproduction of microorganisms after 24 h and, in particular, after 48 h of incubation at a wide range of concentrations, 10 -2 -10 -5 M (48-95% reduction in the number of microbes with a significant dose-dependent effect) was determined as the optimum concentration. A reliable redox activity of nanoceria coated with citrate was established, increasing in proportion to the concentration, confirming the oxidative mechanism of the action of nanoceria. Thus, nanoceria have a dose-dependent bacteriostatic effect, which is most pronounced at concentrations of 10 -2 -10 -3 M. Unlike the effects of classical antiseptics, the effect was manifested from 2 days and increased during the observation. To study the antimicrobial activity of nanomaterials, it is advisable not to use classical qualitative and semi-quantitative methods; rather, the employment of more accurate quantitative methods is advised, in particular, gas chromatography-mass spectrometry, during several days of incubation.

Objective: Aim: The research is aimed to study certain aspects and experience of functioning of the Ukrainian Public Healthcare public management mechanisms during an outbreak of the acute respiratory disease COVID19., Patients and Methods: Materials and Methods: The studied materials include personal observations and accumulated practical material, as well as generalization of the collected data and their empirical treatment, conducted by the scientists, according to the present legislation requirements. The study was held using general scientific methods, including observation, description of results, specification and statistical data generalization., Conclusion: Conclusions: Generalization, arrangement and analysis of the Ukrainian experience of the Public Healthcare public management during the outbreak of the acute respiratory disease COVID19, provides exchange of experience between all subjects of the process. This helps to produce certain practical decisions, aimed at effective responding of the state healthcare system onto management of the COVID19 outbreak. Such activities are also directed at detection of flaws in the whole system, with their subsequent correction, and elimination or neutralization of possible negative outcomes. To adopt the priority activity directions within public relations, which make the subject of the study, the authors have studied a complex of activities against spread of the COVID19 in 2019-2020. These activities include issues, related to prompt responding onto the infection spread and approving quick professional decisions; fulfilling epidemiological supervision and introducing anti-epidemic activities; providing diagnostics, and accessibility of the safe and high-quality vaccine.

Determining outline, volume and effusion rate during an effusive volcanic eruption is crucial as it is a major controlling factor of the lava flow lengths, the prospective duration and hence the associated hazards. We present for the first time a multi-sensor thermal-and-topographic satellite data analysis for estimating lava effusion rates and volume. At the 2021 lava field of Cumbre Vieja, La Palma, we combine VIIRS + MODIS thermal data-based effusion rate estimates with DSMs analysis derived from optical tri-stereo Pléiades and TanDEM-X bi-static SAR-data. This multi-sensor-approach allows to overcome limitations of single-methodology-studies and to achieve both, high-frequent observation of the relative short-term effusion rate trends and precise total volume estimates. We find a final subaerial-lava volume of [Formula: see text] with a MOR of 28.8 ± 1.4 m 3 /s. We identify an initially sharp eruption-rate-peak, followed by a gradually decreasing trend, interrupted by two short-lived-peaks in mid/end November. High eruption rate accompanied by weak seismicity was observed during the early stages of the eruption, while during later stage the lava effusion trend coincides with seismicity. This article demonstrates the geophysical monitoring of eruption rate fluctuations, that allows to speculate about changes of an underlying pathway during the 2021 Cumbre Vieja eruption., (© 2023. The Author(s).)

The basalts of the 2021 Fagradalsfjall eruption were the first erupted on the Reykjanes Peninsula in 781 years and offer a unique opportunity to determine the composition of the mantle underlying Iceland, in particular its oxygen isotope composition (δ 18 O values). The basalts show compositional variations in Zr/Y, Nb/Zr and Nb/Y values that span roughly half of the previously described range for Icelandic basaltic magmas and signal involvement of Icelandic plume (OIB) and Enriched Mid-Ocean Ridge Basalt (EMORB) in magma genesis. Here we show that Fagradalsfjall δ 18 O values are invariable (mean δ 18 O = 5.4 ± 0.3‰ 2 SD, N = 47) and indistinguishable from "normal" upper mantle, in contrast to significantly lower δ 18 O values reported for erupted materials elsewhere in Iceland (e.g., the 2014-2015 eruption at Holuhraun, Central Iceland). Thus, despite differing trace element characteristics, the melts that supplied the Fagradalsfjall eruption show no evidence for 18 O-depleted mantle or interaction with low-δ 18 O crust and may therefore represent a useful mantle reference value in this part of the Icelandic plume system., (© 2022. The Author(s).)

Volcanoes are traditionally considered isolated with an activity that is mostly independent of the surrounding, with few eruptions only (< 2%) associated with a tectonic earthquake trigger. Evidence is now increasing that volcanoes forming clusters of eruptive centers may simultaneously erupt, show unrest, or even shut-down activity. Using infrared satellite data, we detail 20 years of eruptive activity (2000-2020) at Klyuchevskoy, Bezymianny, and Tolbachik, the three active volcanoes of the Klyuchevskoy Volcanic Group (KVG), Kamchatka. We show that the neighboring volcanoes exhibit multiple and reciprocal interactions on different timescales that unravel the magmatic system's complexity below the KVG. Klyuchevskoy and Bezymianny volcanoes show correlated activity with time-predictable and quasiperiodic behaviors, respectively. This is consistent with magma accumulation and discharge dynamics at both volcanoes, typical of steady-state volcanism. However, Tolbachik volcano can interrupt this steady-state regime and modify the magma output rate of its neighbors for several years. We suggest that below the KVG the transfer of magma at crustal level is modulated by the presence of three distinct but hydraulically connected plumbing systems. Similar complex interactions may occur at other volcanic groups and must be considered to evaluate the hazard of grouped volcanoes.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy characterized by early loco-regional invasion. Portal vein resection (PVR) during pancreatoduodenectomy (PD) for PDAC is performed if tumor cell invasion to the venous wall (PVI) is suspected. The aim of this study is to evaluate radiological criteria for predicting PVR and PVI., Methods: Patients undergoing PD for PDAC were identified from a prospectively maintained database. On the basis of CT- and MRI-based imaging portal vein tumor contact (PV), stranding of the superior mesenteric artery (SMA) and any alterations of the superior mesenterico-portal vein (SMPV) were evaluated. The accuracy of PVI and PVR prediction based on the radiological parameters was calculated., Results: 143 patients were included in the study. 48 patients underwent PVR (34%), PVI was diagnosed in 23 patients (16%). Median overall survival was 22 months. Prediction of PVR (sensitivity 79%, negative predictive value 88%, p = 0.010) and PVI (sensitivity 95%, negative predictive value 99%, p = 0.002) was most accurate for any SMPV alterations as compared to the other radiological parameters. SMPV alterations qualified as an independent prognostic parameter (26.5 months vs. 33.5months, p = 0.034)., Conclusion: Radiological evaluation of any SMPV alterations is a simple preoperative method to accurately predict PVI. Assessing SMPV alterations may help to identify candidates for neoadjuvant therapy., Competing Interests: Declaration of competing interest None., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

An improved step-by-step colorimetric method for determination of halides has been developed. The method is based on successive selective oxidation of iodide, bromide and chloride into corresponding free halogens, their extraction by airflow and colorimetric detection with different paper test-strips. This procedure can be performed in a single analyzed solution and possesses high selectivity and good sensitivity due to the extraction step. Three types of paper test-strips were examined: paper modified with tetramethylammonium iodide and starch, paper modified with methyl orange and paper modified with silver triangular nanoplates. Limits of detection for iodide, bromide and chloride are 0.01, 0.02, and 0.04 mg L -1 respectively in case of the last mentioned paper. The method was applied to the analysis of samples having complex matrices, such as various seafood, preserves, bread, and natural waters, showing good accuracy of the analysis with recoveries of 95-105% and relative standard deviations not higher than 6%., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 μg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 μg/kg prevented the stress-induced changes in the composition of colon microbiota. The observed effects of Semax might be mediated by the central neurotropic effects as well as by binding to peripheral melanocortin receptors of the intestine.

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 μg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.

We analyzed cytokine profile in blood serum of patients with uterine myoma and revealed significantly reduced level of IFNγ and a tendency towards a decrease in the levels of IL-1β and TNFα; the levels of IL-6, IL-8, and IL-12p70 did not differ from those in healthy women. The drop in the concentrations of factors responsible for inflammation and angiogenesis in tissues are unfavorable for proliferation and differentiation of the uterine tissues.

Aim: To analyze treatment of victims with multiple trauma in multi-field hospital., Material and Methods: Retrospective analysis of 2139 medical records of patients with multiple trauma (NISS score over 17) was performed. In-hospital mortality, patient transfer time, dominant injury, hospital-stay, gender and age of victims were assessed., Results: New diagnostic and treatment options allowed achieving significant decrease of mortality from 39.7% (2004) to 10.8% (2016)., Conclusion: Improved mortality was achieved due to organized work of the 'regional traumatological systems'. Mortality rate was below 10.7% if victims were transferred to the hospital within 6 hours after trauma. The highest mortality was observed in patients who were transferred to the hospital within 6-12 hours after injury (20.3%).

The article describes a novel approach towards improving selectivity of volatile compounds detection using metal nanoparticles. It is based on combination of sensitive optical detection using convenient nanoparticle-modified paper test strips and dynamic gas extraction improving selectivity to volatile compounds. A simple and inexpensive setup allowing for realization of this combination is described. Analytical prospects of the approach are shown by the example of chlorine determination in highly salted aqueous solutions using silver triangular nanoplates and digital colorimetry. The limit of detection is equal to 0.03mgL -1 and the determination range is 0.1-2mgL -1 . This determination can be successfully carried out in solutions containing at least 2·10 5 greater molar amounts of Na + , K + , Zn 2+ , Cl - , SO 4 2- , and H 2 PO 4 - with no sample pretreatment. The approach seems to be compatible with different types of nanoparticles with respect to detection of various analytes, thus having good opportunities for further development., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: to study serum levels of vascular endothelium growth factor family peptides (VEGF-A, VEGF-C and VEGF-D) and functional gene polymorphisms of VEGFA gene (rs699947 and rs3025039) in patients with type 2 diabetes (T2D) depending on the presence of ischemic heart disease (IHD)., Materials and Methods: The study involved 196 Caucasian patients with T2D (age 43-70 years, 76 with IHD). The concentrations of VEGF-A, VEGF-C and VEGF-D in blood serum were determined by Multiplex assay. Twenty-four persons without diabetes and IHD served as controls. The genotyping of VEGFA polymorphism -2578A/C (rs699947) and +936C/ (rs3025039) was performed by TaqMan., Results: Concentrations of VEGF-A and VEGF-C in patients with T2D were significantly lower than those in controls (p=0.03 and p=0.006, respectively). The level of VEGF-D showed a tendency to decrease (p=0.14). Patients with IHD, as compared to other patients, had higher levels of VEGF-A (p=0.04) and a tendency to VEGF-D increase (p=0.06). The concentration of VEGF-C was not different between groups. No relationships were found between VEGF-A, VEGF-C and VEGF-D levels, HbA1c or glucose variability parameters. C-allele and CC-genotype at +936 position of VEGFA were more frequent among patients with IHD (odds ratio 2.14 and 2.41, respectively, p=0.02). The rs699947 polymorphism was not related to IHD and VEGF-A levels., Conclusion: Patients with T2D have decreased serum levels of angiogenic factors VEGF-A and VEGF-C. VEGFA rs3025039 polymorphism is associated with presence of IHD and levels of circulating VEGF-A in these patients.

Aim: To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA)., Subjects and Methods: The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis., Results: There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women., Conclusion: The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

The levels of spontaneous and concanavalin A-induced production of some key cytokines (TNF-α, IL-1β, IL-4, Il-6, and IL-10) were assessed in the cultures of mononuclear cells derived from healthy volunteers examined for polymorphism of the promotor sites of the respective genes. The presence of certain allelic variants in the promoter regions of human cytokine genes mostly determines the rates of induced and spontaneous cytokine production. Allelic variant -31C of IL-1β gene is associated with high production rate of the related cytokine. In addition, polymorphism of allelic variant C-590T of IL-4 gene significantly affects the production rates of IL-1β, TNF-α, IL-6, and IL-10.

Great number of factors stimulating or inhibiting production of proteins in inflammatory process influence serum levels of markers of inflammation. A number of homozygous genotypes of inflammation, destruction, and angiogenesis genes have been found to be associated with basic clinical-laboratory indices of inflammation and atherosclerotic process. The revealed genetic markers can be used as complimentary markers of prognosis of the disease course.

Wastes and tailing ponds of Tyrnyauz tungsten and molybdenum factory are the main sources of heavy metal incoming into environment in Kabardino-Balkarian Republic. The factory was closed more than 10 years ago and the recultivation of it’s tailing ponds, where accumulated hundreds of millions tones of wastes, was completed. The aim of this investigation was an assessment of their possible influence on children residing in the vicinity of these tailing ponds (village Bylym). Village Verhny Baksan located about 30 km upstream of the valley of the Baksan River was chosen as reference (pure) locality. As a results of the performed investigations we revealed that in drinking water of Bylym and Verhny Baksan concentrations of molybdenum were 2.10±0.42 pg/l and 0.31±0.15 pg/l correspondingly, which is remarkably lower than maximum permitted concentrations. The concentrations of Mo, Cu and Pb in children’s hair in both villages were practically the same, which indicates to the absence of their accumulation in human organism. But the quantity of cells with cytogenetic disorders in buccal epithelial cells in children from Bylym was 4.1 times higher in comparison with the corresponding index of uncontaminated area. The obtained data demonstrate that genotoxic effect of remedied tailing ponds retains.

Aim: To study the promoter regions of the matrix metalloproteinase (MMP)2, MMP3, and MMP9 genes to assess their associations with the risk of rheumatoid arthritis (RA) and with the types of its clinical course in women., Subjects and Methods: 162 female patients with RA and 329 women without this condition were examined. Polymorphisms in the gene promoter region for MMP2 (-1306 С→Т), MMP3 (-1171 5A→6А), and MMP9 (-1562 С→Т) were studied. Genotyping was carried out using the restriction fragment length polymorphism method., Results: In the RA group, the -1306TT genotype of MMP2 was significantly more frequently encountered and the 6A6A genotype was less frequently seen. In the seropositive RA group, the frequency of the -1306ТТ genotype of MMP2 was significantly higher than that in the healthy individuals. The significant differences shown for the entire group of patients with RA were preserved when they were divided into groups according to the presence or absence of rheumatoid nodules. Furthermore, the frequency of the homozygous -1306 genotypes of MMP2 was higher in both groups than in the healthy individuals., Conclusion: The presence of the allelic variants of the MMP genes may be one of the genetic factors that predispose to RA in women.

Objective: To explore the correlations between plasma cholesterol and triglyceride levels and psychometric assessments in patients with psychosomatic illnesses and chronic cerebral ischemia (CCI)., Material and Methods: One hundred and ten patients (51% women, 49% men), aged from 46 to 76 years (mean 65.1 years) with CCI were examined. The study included cholesterol and triglyceride tests and a battery of tests for assessment of cognitive functions and neurotization level., Results: Cholesterol levels were higher in patients with post-infarct cardiosclerosis (PICS) compared to the comparison group but did not differ from those of patients with peptic ulcer disease (PUD). Triglyceride levels were high in both psychosomatic groups, with higher levels in the patients with PICS compared to the patients with PUD. Plasma cholesterol and triglyceride levels were not correlated with assessments of cognitive functions in patients of different age., Conclusion: Cognitive impairment and higher level of neurotization were characteristic of patients with psychosomatic illnesses. Regression analysis has demonstrated that plasma cholesterol and triglyceride levels may be a prognostic factor for cognitive impairment.

In this paper, we consider the Universe at the late stage of its evolution and deep inside the cell of uniformity. At these scales, the Universe is filled with inhomogeneously distributed discrete structures (galaxies, groups and clusters of galaxies). Supposing that the Universe contains also the cosmological constant and a perfect fluid with a negative constant equation of state (EoS) parameter [Formula: see text] (e.g., quintessence, phantom or frustrated network of topological defects), we investigate scalar perturbations of the Friedmann-Robertson-Walker metrics due to inhomogeneities. Our analysis shows that, to be compatible with the theory of scalar perturbations, this perfect fluid, first, should be clustered and, second, should have the EoS parameter [Formula: see text]. In particular, this value corresponds to the frustrated network of cosmic strings. Therefore, the frustrated network of domain walls with [Formula: see text] is ruled out. A perfect fluid with [Formula: see text] neither accelerates nor decelerates the Universe. We also obtain the equation for the nonrelativistic gravitational potential created by a system of inhomogeneities. Due to the perfect fluid with [Formula: see text], the physically reasonable solutions take place for flat, open and closed Universes. This perfect fluid is concentrated around the inhomogeneities and results in screening of the gravitational potential.

Based on the pivotal trial showing no clinically relevant differences between pegylated interferon α-2b (Peg-α-2b) and α-2a (Peg-α-2a) combined with ribavirin for treatment of chronic hepatitis C virus (HCV) genotype 1 infection in Ukraine, a cost-minimization analysis was performed using a 1 year time horizon and both a health care and patients' perspective. A decision tree reflects treatment pathways. Drug costs were based on drug labeling and adjusted to the average body mass in Ukraine. Subgroup analysis was applied to deal with heterogeneity of patient's weight causing dose changes. A break-even price of Peg-α-2a and Peg-α-2b (based on the average dose) was calculated. Univariate sensitivity analyses and probabilistic sensitivity analysis were carried out to reflect decision uncertainty. For an average body weight, total medical costs per patient differ from US$9220 for Peg-α-2b to US$9513 for Peg-α-2a from a health care perspective, and from US$15,212 to US$15,696 from a patients' perspective. Sensitivity analyses show these results are robust. With average body weight, the break-even price of Peg-α-2b may be 7.3% higher than Peg-α-2a to have similar total costs.

Aim: To analyze the association of the promoter polymorphism of the genes of the matrix metalloproteinases (MMP) MMP2 (-1306), MMP3 (-1171), and MMP9 (-1562) and two vascular endothelial growth factor (VEGF) gene regulatory regions (-2578, +936) with the development of myocardial infarction (MI)., Materials and Methods: DNA was analyzed in 251 patients with a history of MI. Five polymorphic positions were genotyped by restrictase analysis of amplification products, by using specific primers., Results: In addition to the MMP3 5A5A monogenotype, there were 4 complex genotypes that were significantly different between two analyzed groups and positively associated with acute coronary syndrome. Among them, each of two genotypes included 2 polymorphic positions; two genotypes did 3 analyzed polymorphic positions. Four complex (two-locus (n = 1), three-locus (n = 2), four-locus (n = 1) genotypes that were negatively associated with MI were also identified., Conclusion: These findings are evidence in favor of our assumption that the increasing number of genotypes as part of the analyzed combined genetic complexes detectable in one patient considerably enhances the clinical significance of the results of immunogenetic analysis.

There were analyzed associating of functional polymorphism of the promoter regions of genes MMP2 C--1306T, MMP 9 C--1562 T, MMP3 5A--1171 6A in a group of healthy women and breast cancer patients in order to identify informative markers associated with the risk of developing the disease. The study included 395 DNA samples from women with breast cancer and 329 healthy women. Genotyping of polymorphisms was carried out by restriction analysis of amplification products (RFLP-analysis). Among female patients there was revealed significantly seldom a carrier of 6A6A MMP3-1117 and MMP 9-1562TT genotypes and also significantly increased the frequency of MMP3 5A6A genotype. The risk of lymph node metastasis reduced in patients with MMP9-1562CC genotype. Conversely heterozygosis at this position could be regarded as risk factor for metastasis. It was revealed associating of MMP3 5A6A genotype with the degree of malignancy.

Aim: To study genotype distribution in the MMP and VEGF genes, angiogenesis regulators, and their combinations with genotypes in other cytokines genes with proangiogenic activity in female patients with rheumatoid arthritis (RA) and healthy individuals., Subjects and Methods: 509 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 135 female patients aged 27-66 years with RA, were examined. TNF-alpha gene promoter single nucleotide polymorphisms (SNP) -863 C --> A, TNFA -308 G --> A, TNFA -238 G --> A; IL 1beta-31 C --> T, IL4 -590 C --> T, IL6 -174 G --> C, IL10 -1082 G --> A and IL10 -592 A --> C; VEGF -2578 C --> A, VEGF +936 C --> T; MMP 2 -1306 C --> T, MMP 9 -1562 C --> T were investigated by the restriction analysis of amplification products., Results: The patients with RA show a preponderance of the combinations of genotypes in vascular endothelial growth factor (VEGF) synthesis inducers, which are related to the high-level production of this factor, and those of genotypes in the degradation of the extracellular matrix of MMP2 and MMP9, which characterize the low baseline elaboration of matrix metalloproteinases (MMP) with a high capability for their induced synthesis, which is specific to the dysregulated states of the angiogenesis control system. Along with MMP and VEGF genotypes, the combinations most commonly contain IL1beta, IL4, IL10, IL6, and TNF-alpha genotypes., Conclusion: The study of the pathogenesis of RA must comprehensively investigate the role of the genes of the factors involved in the regulation of angiogenesis and inflammation, with particular emphasis on molecular genetic mechanisms for monitoring the baseline level of production of these regulatory factors.

Objective: To study frequencies of occurrence of the combined genetic attributes including different variants of cytokines genotypes (TNFA, IL1B, IL4, IL6, IL10, VEGF), in different on sexual and age groups in population of Siberia Caucasoid., Material and Methods: Frequencies of distribution of variants of structure genes cytokines networks among 500 representatives of Siberia Caucasian population, men and women of two age groups--more younger than 35 years ("young") and 55 and more years ("elderly") are investigated. In structure of investigated genes cytokines net has come 10 variants of polymorphic sites of cytokines genes and vascular endothelial growth factor gene: TNFA-863 C --> A, TNFA-308 G --> A, TNFA-238 G --> A, IL1B-31 C --> T, IL4-590 C --> T, IL6-174 G --> C, IL10-1082 G --> A, IL10-592 A --> C, VEGF-2578 C --> A and VEGF+936 C --> T. Genotyping are carried out by restriction fragment length polymorphism method. Processing of results carried out on the basis of the original methodological approach including the complex connected computer analysis of genic circuits of various dimension., Results and Conclusions: It is shown, that the significant part of variants genes cytokines networks, which widely distributed among young people is completely absent in the "elderly" age group. Such variants disappearing with age separately for men and women are established. At the program mathematical analysis it is established, that parameters of the odds ratio achieve two-place sizes (OR = 27, p = 0,0004), that testifies to high specificity of complex genetic attributes. Presence in genome such variants of genes cytokines networks, found out in the childhood or young age, as supposed, is unfavorable personalized prognostic factors of life span of the individual.

Cytokines as regulators of activity of inflammation play significant role in mechanisms of formation of atherosclerotic plaques and in processes of their destabilization. One of leading genetic factors determining level of their production appears to be polymorphism of cytokine genes structure at their promoter loci. We have conducted an analysis of distribution in groups of healthy male and female survivors of myocardial infarction (MI) of combined genetic signs represented as a complex of genotypes of a number of studied cytokine genes : TNF-A863C; TNF-A308G; TNF-A238G; IL1B-C511T; IL1B-C-31T; IL4-C590T; IL6-C174G; IL10A-1082G IL10-A592C. Among these homozygous combinations of cytokine genotypes characterizing a group of men who have lived up to middle and old age without development of MI there are widely represented genotypes associated with high levels of production of both cytokines with pronounced proinflammatory (IL-1) and antiinflammatory (IL-4, IL-10) activity. Absence of such multidirectional combinations in genome of patients with myocardial infarction can be considered one of genetic factors of risk of development of acute distirbances of coronary circulation.

Aim: To study the distribution of genotypes in the cytokine genes and their combinations with immunoregulatory activity in patients with type 2 diabetes mellitus (T2DM) and in healthy women., Subjects and Methods: 586 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 212 women aged 28-69 years with T2DM complicated and uncomplicated by osteoporosis, were examined. Seven polymorphisms located in the promoter regions of the interleukin (IL) gene: TNF-alpha at positions C-863A, G-308A, G-238A, IL1B T-31C, IL6 G-174C, IL10 C-592A, VEGFA C-2578A were investigated. Restriction analysis of amplification products was applied., Results: There were high associations of the predisposition and resistance to the development of T2DM with a number of polylocus cytokine genotype combinations having pro- and anti-inflammatory, angiogenic, and immunoregulatory activities. The association of the cytokine genes with T2DM was found to be mediated in nature through a relationship of the genotypes to the high or low production of regulatory cytokines and to different factors of regulation of lipid and carbohydrate metabolisms, inflammation, and bone remodeling., Conclusion: The high odds ratio and high specificity of the detected genetic combinations allow one to hope that they will be clinically used as predictors.

Analyzed the association of functional polymorphisms of VEGFA at positions -2578 of promoter region and at position +936 3' of untranslated region in a group of healthy women and breast cancer patients with the aim to detect informative markers associated with the risk of disease. The study included 395 DNA samples from women with breast cancer and 298 healthy women. Genotyping of polymorphisms of C-2578A and C +936 T VEGFA was performed by restrictase analysis of amplification products (RFLP-analysis). There was revealed the increase of the frequency-2578AA genotype in patients with breast cancer (OR 1.55, 95% CI 1,55-2,29), moreover, the frequency of this genotype increased in the group of patients with a common family history and with breast cancer in close relatives of relatively healthy women (OR = 2,03 95% CI 1,26-3,27 and OR = 2,22 95% CI 1,13-4,33, respectively). Genotype frequencies of -2578AA/+ 936 SS and -2578SS/+ 936 CT were significantly higher in the group of patients with a factor of family history as compared to the group of patients without it (OR = 1,84 95% CI 1,01-3,34 and OR = 2,91 95% CI 1,09-8,05 respectively).

Photochemical reaction of the electronically excited NO(2)* species with the water molecule is studied in terms of a new version of density functional theory by selecting the specific (2)A'' symmetry of the whole system, which is different from the ground-state pattern. The excited C(2)A(2) state of the NO(2) molecule is found to be distorted to the equilibrium structure O=N-O(.), which poses the (2)A'' symmetry in the C(s) point group. With the B3LYP functional it is shown that such an electronically excited NO(2)* molecule, generated by visible light (λ=420 nm), can react with water vapor to produce OH+HONO species, an important source of tropospheric hydroxyl radicals. This photochemical process can be considered as a possible mechanism of atmosphere self-cleaning.

The results of dynamic microbiological investigation, conducted in 37 patients, suffering diabetic foot syndrome (DFS) during 2008-2009 yrs period, were presented. There were 103 investigations made and 169 species of microorganisms revealed. The microflora structure of surgical infection in patients with DFS was presented by S. aureus (42.85%), P. aeruginosa (32.09%), E. coli (7.66%), S. pyogenes (7.16%), Enterobacteriaceae aerogenes (6.3%), E fecales (1.97%), E. cloacae (1.97%). S. aureus have shown resistance towards ceftriaxone (66.7%), lincomycine (75%), cyprofloxacine (58.3%); P. aeruginosa--towards cephoperazone (100%), amicacine (66.6%), vancomycine (89.9%), cyprofloxacine (87.8%), imipenem (87.8%). Enterobacteriaceae are resistant towards cefuroxym (60%) and amicacine (80%).

We studied polymorphism of three positions of promoter region of TNF alpha gene in patients with ischemic heart disease (IHD), development of unstable angina (UA) and acute myocardial infarction (MI). Analysis of frequencies of genotypes in position A308 showed that heterozygotness in patients with cardiovascular diseases significantly decreased. Lowering of risk of development of MI in carriers of heterozygous variant of the gene in position A308 was shown. In the group of patients with Q wave MI frequency of A308 AA genotype rose.