DYNAMICS OF ULTRASTRUCTURAL REARRANGEMENTS OF SKELETAL MUSCLE FIBROBLASTS AFTER SIMULATED GUNSHOT SHRAPNEL WOUNDS.

Purpose of the study the peculiarities of rearrangements of skeletal muscle fibroblasts surrounding the wound canal at various times after an experimentally modeled gunshot shrapnel wounds. Experimental modeling of gunshot shrapnel wounds of soft tissues has been carried out on 20 laboratory animals - breeding rabbits of the breed «Chinchilla¼. To laboratory animal was caused a gunshot wound in the sartorius area with the gun «Fort-12¼ caliber 9 mm. The initial velocity of the fragment was 305 m/s. Ultrathin muscle sections were examined using an EM-125 electron microscope at accelerating voltage of 75 kV, with a magnification of 20000 - 60000 arm. In an experiment it was revealed that on the thirtieth day most of the fibroblasts of the wound canal in the femoral muscle tissue had an ultrastructure characteristic of the course of compensatory-adaptive, synthetic, and reparative processes. Sixty days after a gunshot wound, the submicroscopic organization of fibroblasts from the wound canal area undergoes disorders associated with a decrease in the synthetic activity of fibroblasts.

NEUROCHEMICAL STATUS OF NITRIC OXIDE IN THE SETTINGS OF THE NORM, ISHEMIC EVENT OF CENTRAL NERVOUS SYSTEM, AND PHARMACOLOGICAL BN INTERVENTION.

The purpose of the given research is to study the efficiency of different inhibitors of NO-synthase in conditions of experimental cerebral ischemia by their capability to limit reactions of oxidative and nitrosative stress. In the given study a non-selective NOS inhibitor - N-nitro-L-arginine; a highly selective inhibitor of neuronal NOS - N-propyl-L-arginine and a highly selective competitive inhibitor of inducible NOS - (S)-methylurea were used. Cerebral circulation impairment was simulated by means of double-sided occlusion of common carotid arteries. It has been established that neurotoxic NO effect depends on definite enzyme of NO-synthase. Analysis of the obtained data shows a limited role of neuronal isoform in conditions of experimental impairment of blood circulation. The most relevant target for pharmacological regulation of NO-dependent mechanisms of neurodestruction is iNOS because of the fact that its activity begins to increase 12 hours after ischemia development and its action is implemented during several following days.

Fiber-dispersive Raman spectrometer with single-photon sensitivity.

The two major challenges in Raman spectroscopy are the low intensity of spontaneous Raman scattering and often accompanying luminescence. We overcome these two issues with a novel fiber-dispersive Raman spectrometer utilizing pulsed excitation and a superconducting nanowire single-photon detector (SNSPD). By exploiting chromatic dispersion in the fiber material, we stretched propagation times of Raman photons and performed correlated measurements in the time domain, where the two emission processes, Raman scattering and luminescence, can be effectively separated. The spectrometer greatly benefits from SNSPD metrics, i.e. broad spectral sensitivity (from UV to near-IR wavelength range) on a single-photon level and high timing resolution (small timing jitter), which outperform those of competing avalanche single-photon detectors. The spectral resolution achievable with a fiber-dispersive spectrometer for the optimized components is estimated to be as good as 3 - 10 cm-1 over the Stokes shifted range up to 4400 cm-1 with an excitation wavelength of 785 nm and below 5 cm-1 covering the same range with an excitation wavelength of 532 nm.

THE IMPACT OF THE CHEMICAL AGENTS OF DIFFERENT PHARMACOLOGICAL GROUPS ON THE KLOTHO PROTEIN CONCENTRATION IN THE CARDIOMYOCYTE AND NEUROCYTE SUSPENSION IN 120 MINUTE HYPOXIA IN VITRO.

Currently, central nervous and cardiovascular system disorders of hypoxia genesis are widely treated with drugs that restore blood flow, as well as drugs that affect cell metabolism, namely, individual units of adaptive molecular-biochemical reactions. Of particular interest are pharma-correction methods of affecting synthesis and expression of Klotho proteins, such as vitamin D and Necrostatin-1, estrogens. The purpose of the study was to identify the ability of vitamin D and tamoxifen estrogen receptor modulator to affect Klotho protein synthesis (under hypoxia in vitro modeling in brain and heart cells). The study was performed on sexually mature white non-linear rats - males weighing 190-230 g. Hypoxia in vitro was modeled by insertion of 0.6 µM concentration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridil (MPTP) into the suspension of respiratory tract tissue differentiator cardiomyocytes. By means of immunoenzyme analysis, concentration of Nitrotyrosin (Ntz) (ELISA Kit "Hycult biotechnology b.v.") and Klotho protein (Elabscience, USA) in cell suspensions was evaluated. Statistical processing of the results was carried out using the STATISTICA® for Windows 6.0 program (StatSoft Inc., No. AXXR712D833214FAN5). The reliability of the differences was carried out using the Student's t-criterion. The data analysis demonstrated that a 120-minute MPTP incubation of cardiomyocytes and neurocytes resulted in a significant deficiency of Klotho protein concentration compared to intact suspensions. Such a decrease, in our opinion, is related to the development of oxidative stress in cell suspension (increase of Ntz by 65% ​​and 69% in the cardiomyocyte and neurocyte suspensions, respectively), as well as hyperproduction of proinflammatory cytokines such as tumor necrosis factor (TNF) and interferon (INF). Vitamin D (10-7) addition to the incubation medium of cardiomyocytes and neurocytes resulted in the increase of Klotho protein content by 56% on average, with 36% and 42% reduction of Ntz concentration, respectively. The registered effects of vitamin D are explained with its direct stimulating of the expression and synthesis of Klotho protein and limiting FGF23 hyperproduction. The introduction of tamoxifen estrogen receptor modulator (10-7) into the cardio- and neurocyte incubation medium did not affect Klotho protein concentration (an increase in concentration of 34% and 28% respectively) in advanced cell suspensions as much as vitamin D, however, nitrotyrosine concentration decrease made a more expressed impact, on average by 52% and 60%. The effects of tamoxifen are implemented due to its impact on the HSP proteins system, which provides the structural and functional integrity of the Klotho protein.

ULTRASOUND DIAGNOSTICS OF CERVICAL CHANGES WITH DIFFERENT LOCALIZATION OF THE CERVICITIS IN WOMEN WITH THE ECTOPY OF THE VAGINAL PORTION OF THE CERVIX.

The aim of the study was to improve the diagnosis of structural changes in all parts of the cervix depending on the preferential localization of the inflammatory process - in the ectocervix, endocervix, and also in the stroma in women with ectopia (pseudoerosis) of the vaginal part of the cervix. The study included women of predominantly early and middle reproductive age, as these women have inflammatory processes more often than in menopause. To perform the work, a transvaginal imaging method was used, which allowed us to see the smallest structures (up to 0.5-1.0 mm) of the cervix. We have previously developed a technique for visualizing the external part of the cervix and obtained a patent of Ukraine. The results of the ultrasound were compared with laboratory data, colposcopy and cervicoscopy. Traditionally, the diagnosis of cervicitis was made on the basis of clinical symptoms, smear results to determine the presence and type of pathogen. Endoscopic methods allowed visualization of only the mucous membrane of the cervical canal and external part of the cervix. The deep layers of the ectocervix, endocervix and cervical stroma can only be visualized using high-frequency ultrasound in a transvaginal way. According to the results of the study, it was possible to determine the preferential localization of the inflammatory process, to determine the nature of changes in different layers of the cervix. These changes were expressed in the presence of calcifications and cystic cavities of various sizes (1-6 mm), an increase or decrease in echogenicity, the degree of heterogeneity of the structure of the ecto-, endocervix and stroma.

[A comparative analysis of intravesical sodium hyaluronate monotherapy and its combination with oral chondroitin sulfate in patietns with bladder pain syndrome/intersticial cystitis].

AIM: It is established that intravesical sodium hyaluronate and chondroitin sulfate has high efficacy in patients with bladder pain syndrome/interstitial cystitis (BPS/IC). Currently, an oral form of chondroitin sulfate is also available. The aim of study was to compare the efficacy of intravesical hyaluronic acid monotherapy and long-term oral chondroitin sulfate in combination with intravesical therapy in patients with BPS/IC. MATERIALS AND METHODS: A total of 59 patients with BPS/IC were randomized in two groups. In Group 1, 30 women (mean age 57.1 years) received viscoelastic solution of sodium hyaluronate 50 ml 1 time per week for 12 weeks as intravesical monotherapy. In Group 2 (n=29), patients were prescribed to complex therapy, which included the similar intravesical therapy combined with chondroitin sulfate in a dose 0.39 g, 2 capsules 3 times a day, also for 12 weeks. All patients completed visual analogue scale (VAS), interstitial cystitis symptom index (ISCI), interstitial cystitis problems index (ICPI) and voiding diary before and 1 week after the start of therapy. In all cases a cystoscopy and urodynamic study were performed in order to exclude other bladder pathologies. RESULTS: At baseline, a mean VAS score in both groups was 7 points, a mean ISCI score was 17 points in Group 1 and 18 points in Group 2 (p>0.1). The mean ICPI score in both groups was 15 points. A frequency of urination in Group 1 and 2 was 11.4 and 11.6 per day, respectively (p>0,1). A mean volume of urination was 138+/-24.6 and 131+/-18.6 , respectively. After 12 weeks of therapy there was significant improvement of VAS, ICSI and ICPI scores in both groups, as well as frequency and volume of urination, but in Group 2 an improvement in almost all parameters studied, except for the volume of urination, was more pronounced. CONCLUSION: The combined therapy of BPS/IC with intravesical hyaluronic acid and oral chondroitin sulfate provides significantly better results in comparison with intravesical hyaluronic acid as monotherapy.

STUDY OF BONE TISSUE REPARATION AFTER A FEMUR FRACTURE DEPENDING ON THE CORRECTION OF ARTERIAL HYPERTENSION IN MODEL OBJECT RATTUS NORVEGICUS (RAT GRAY).

The processes of bone remodeling and regulation of blood pressure are caused by common genetic determinants underlying the development of these diseases. To solve practical medical problems, it seems relevant to carry out the correction and treatment of syntropic diseases at the same time with the aim of achieving the maximum positive effect. The most serious complication of osteoporosis is bone fractures, especially fractures of the proximal femur, which are a serious medical and social problem. The aim of our work was to evaluate the repair of bone tissue after fractures of the proximal femur with subsequent intramedullary osteosynthesis on the background of arterial hypertension and its correction. A model object was used in the work - gray rats, lines Wistar and SHR, which were operated on. For the animals of one of the groups with genetically determined arterial hypertension, correction of the above-mentioned pathology in the form of enalapril monotherapy in the postoperative period was applied. In this group, the picture of the dynamics of blood pressure indices corresponded to the cumulative effect of enalapril - after three weeks of taking the drug, the rats' systolic blood pressure indices corresponded to those of normotensive animals, and the indicators of adhesion of the fracture zone were higher than in the group of rats with arterial hypertension, which was not corrected. Adequate correction of the level of blood pressure in the postoperative period favorably affects the reparative capabilities of the bone, while at the same time increasing the chances of positive results of surgical treatment of patients.

INTERACTIONS OF RANKL, OSTEOPROTEGERIN AND ADIPOKINES IN REGULATION OF BONE REMODELING IN EXPERIMENTAL CHRONIC KIDNEY FUNCTION DISORDER.

RANKL and osteoprotegerin are the key cytokines of the axis regulating not only bone remodeling but also bone-kidney interrelations. They are connected with adipokines in the regulatory actions. The aim of the article was to investigate the role of the main parts of RANK-RANKL-osteoprotegerin axis and cytokines of additional link of regulatory network - adiponectin and visfatin and the interrelationship of these cytokines in chronic kidney disorder model in rats. Chronic kidney disorder model was created in the rats 12 weeks after intramuscular 50 % glycerol injection-induced acute kidney injury. RANKL, osteoprotegerin, adiponectin and visfatin levels was measured using ELISA. Increase of all cytokines and changes of their interrelations has been revealed in rats with chronic kidney disorder model. Conclusion was made that effects of the cytokine axis where RANKL is a trigger in the regulation network of interconnections «bone - kidney¼ has inflammatory character, so as visfatin effect, and adiponectin has opposite preserving bone effect.

Nonlinear dynamics of contact interaction of a size-dependent plate supported by a size-dependent beam.

A mathematical model of complex vibrations exhibited by contact dynamics of size-dependent beam-plate constructions was derived by taking the account of constraints between these structural members. The governing equations were yielded by variational principles based on the moment theory of elasticity. The centre of the investigated plate was supported by a beam. The plate and the beam satisfied the Kirchhoff/Euler-Bernoulli hypotheses. The derived partial differential equations (PDEs) were reduced to the Cauchy problems by the Faedo-Galerkin method in higher approximations, whereas the Cauchy problem was solved using a few Runge-Kutta methods. Reliability of results was validated by comparing the solutions obtained by qualitatively different methods. Complex vibrations were investigated with the help of methods of nonlinear dynamics such as vibration signals, phase portraits, Fourier power spectra, wavelet analysis, and estimation of the largest Lyapunov exponents based on the Rosenstein, Kantz, and Wolf methods. The effect of size-dependent parameters of the beam and plate on their contact interaction was investigated. It was detected and illustrated that the first contact between the size-dependent structural members implies chaotic vibrations. In addition, problems of chaotic synchronization between a nanoplate and a nanobeam were addressed.

Effects of carbon surface topography on the electrode/electrolyte interface structure and relevance to Li-air batteries.

This work is focused on the effect of the electrode/electrolyte interface restructuring under the variation of carbon surface topography, as one of the possible factors determining the electrochemical activity of different carbon materials in Li-air batteries. Molecular dynamics simulation was used to investigate an acetonitrile-based electrolyte in contact with the following carbon surfaces: graphene plane, single-layer graphene edge, and multi-layer graphene edge. It was shown that the surface topography strongly influences the electrolyte structure at the interface. Acetonitrile has a layered structure at the plane and the edge of graphene nanoribbons and a qualitatively different chessboard structure at the multi-layer graphene edge. It was found from the potentials of mean force that the variation of the surface topography induces the redistribution of the reactants Li+ and O2 near the surface and influences their adsorption rate. This should affect the kinetics of the oxygen reduction reaction and may explain massive deposition of discharge products on graphene edges in Li-air batteries.

[RELATIONSHIP BETWEEN INFLAMMATIONAND HEART DYSSYNCHRONY IN PATIENTS WITH CHRONIC HEART FAILURE AND DIABETES MELLITUS TYPE 2].

The study involved 100 patients with chronic heart failure of ischemic origin II-III functional class (NYNA) and diabetes mellitus type 2. The concentration of serum markers of inflammation was determined by enzyme immunoassay. Сardiac dyssynchrony was detected echocardiographic and electrocardiographic methods. The study showed that the presence of cardiac dyssynchrony is accompanied by significant increase concentrations of inflammatory markers (CRP (p=2•10-9), TNF-α (p=4•10-6), IL-1ß (p=0,01596), IL-6 (р=2•10-6) in patients. Аlso revealed statistically significant direct correlations between levels: Ts and CRP (r=0,604; p<0,001) and Ts-SD (r=0,611; p<0,001); TNF-α and Ts (r=0,585; p<0,001) and Ts-SD (r=0,561; p<0,001); IL-1ß with the QRS (r=0,257; p<0,05), Ts (r=0,365; p<0,001), Ts-SD (r=0,350; p<0,001) and IVMD (r=0,272; p<0,05); IL-6 and Ts (r=0,744, p<0,001) and Ts-SD (r=0,744; p<0,001), which implies that the amplification of inflammation contributes to the further progression of myocardial dyssynchrony in patients with chronic heart failure of ischemic origin and type 2 diabetes.

[A Detection of Allelic Variants at Microsatellite Markers by Using Capillary and Traditional Electrophoresis].

Microsatellite alleles are detected by PCR (polymerase chain reaction) that provides a manifold increase in the number of copies (amplification) of a given DNA fragment. The fragment visualization can be reached by two different methods. These are fragment analysis by capillary electrophoresis in denaturing gel and frag- ment separation in non-denaturing gel with subsequent gel staining. The first method is more accurate and automated, but expensive. The second method is much cheaper but less convenient. It requires manual pro- cessing and is presumably less accurate. In this study, we present the results of comparison of the allele typing at nine microsatellite loci using these two methods for one of the species of Pacific salmon, sockeye salmon Oncorhynchus nerka Walbaum. In most cases, both methods give identical fragment sizes or a constant differ- ence if the alleles are relatively small (not larger than 200-220 bp).

BONE REGULATORY MECHANISMS DESTRUCTION IN EXPERIMENTAL CHRONIC KIDNEY DISEASE.

The aim of our study was to investigate the role of intercellular mediators ­ interleukin-1 receptor antagonist (IL-1 RA), interleukin-17 (IL-17), receptor activator of nuclear factor kB ligand (RANKL) and osteoprotegerin in the mechanisms of metabolic regulation of renal and bone tissue on model of violations of bone remodeling in chronic kidney disease (CKD). It was found a significant increase in the content of cytokines IL-1 RA (4,207 ± 0,546 pg/ml), IL-17 (33,944 ± 0,938 pg/ ml), osteoprotegerin (28,338 ± 1,223 pg/ml) and RANKL (0,184 ± 0,018 pmol/l) in the serum of animals in violation of bone remodeling in CKD compared with the contents of the studied cytokines in animals in the control group (2,529 ± 0,132 pg/ml, 28,166 ± 0,526 pg/ml, 21,588 ± 0,763 pg/ml and 0,131 ± 0,006 pmol/l, respectively) (P<0.05). The obtained correlations reflect the relationship between regulation of bone remodeling and the development of inflammation in CKD. The imbalance between pro- and anti-inflammatory cytokine plays an important role both in the development of CKD and in processes of bone remodeling.

[CHANGES IN THE AREA OF THE WOUND SURFACE ON EXPOSURE LOW­DOSE VACUUM].

Results of treatment of were analysed 30 patients over a long non­healing wounds and trophic ulcers, in which as a topical treatment, the method of vacuum therapy was applied. To study the activity of reparative regeneration in the wound using a dynamic method of determining the area of wounds using lqSquare computer program and immunohistochemical method for determining the Ki 67 positive cells in tissues of near wound area. It was found that low­dose exposure to vacuum at the wound contributed to increase the proliferative activity of tissues of near wound area and reduce the area of wound defect. Assessment of changes in the area of the wound surface is an important predictor of treatment efficacy, prevention of complications.

[Genetic diversity of charrs of the Commander Islands based on the analysis of mitochondrial DNA].

Nucleotide sequences of the mitochondrial DNA cytochrome b (CytB) gene fragment and the control region (D-loop) of Dolly Varden (Salvelinus malma) from the Commander Islands and the Kol River of the Kamchatka Peninsula were examined. A high level of genetic variability of island populations comparable to that of the mainland population of western Kamchatka was demonstrated. The belonging of the Commander Islands chars to the genetic lineage of northern Dolly Varden Salvelinus malma malma was confirmed.

[The Influence of Long-Term Meditation Practice on Early Emotional Processing in the Brain: an ERP Study].

The main aim was to study effects of long-term meditation practice on event-related brain potentials (ERPs) during affective picture viewing. The meditators' (N = 20), contrary to control (N = 20), did not demonstrate arousal-related increases in the mid-latency (200-400 ms) ERP positivity over the right hemisphere. We also found in the same time window stronger ERP negativity for meditators over central regions, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic detection of stimulus salience.

[Influence of the practice of meditation on the cardiovascular response in the perception and cognitive reassessment emotiogenic stimulus].

This study examines the effects of meditation on cardiovascular activity during affective image processing. 22 meditators and 20 controls were shown affective images and were asked either to attend to the images or to down-regulate negative affect (for negative images) or to up-regulate positive affect (for positive images) while continuous cardiovascular activity were recorded. During natural viewing meditators manifested identical pre-stimulus total peripheral resistance (TPR) for all images, whereas controls exhibited greatest,pre-stimulus TPR for negative images and reduced it only in the emotion regulation condition. No between-group differences were revealed for natural viewing of positive images, whereas up-regulation was associated with greater cardiac activation in meditators. The results provide a contribution to the understanding of the mechanisms responsible for the beneficial influence of meditation on cardiovascular risk factors.

[The regulation of negative and positive emotions during picture viewing: an ERP study].

The study examines the effects of cognitive reappraisal on the event-related potentials (ERPs) to affective stimuli. Participants (n = 53) were asked either to attend affective images, or to down-regulate negative affect, or to up-regulate positive affect. Reappraisal of negative images was associated with attenuation of the P300 and late positive potential (LPP) over parietal regions, whereas reappraisal of positive images had no significant effect on ERP components. The weak P300 reduction correlated with high personality scores of negative affectivity. We assume that only down-regulation of negative emotions is associated with the changes in primary appraisals, and so far reflected in ERP modulation.

[Role of functional state of neuronal mitochondria of cerebral cortex in mechanisms of nootropic activity of neuroprotectors in rats with alloxan hyperglycemia].

The influence of citicoline, phenylpiracetam, pentoxifylline and N-phenylacetyl-L-prolylglycine on cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats has been studied. The drug effects on cognitive processes were assessed using passive avoidance tests in the dark-light camera. Latent period and the number of animals with amnesia skill on 6th and 20th days of drug administration were recorded. Functional status of mitochondria was assessed by mitochondrial pore opening and mitochondrial transmembrane potential (Y) on 20th day. It has been established that course administration of phenylpiracetam, citicoline and to a lesser extent N-phenylacetyl-L-prolylglycine, but not pentoxifylline, improves the processes of learning and storing conditional skill. At the same time, the nootropic activity of studied drugs was comparable to their effect on the functional state of mitochondria in neocortical neurons in rats with chronic hyperglycemia. According to mitoprotective activity (prevention of opening of mitochondrial cyclosporin-A-sensitive pores and restoration of mitochondrial transmembrane potential), the maximum potential was observed for citicoline and phenylpiracetam, and the minimum--for pentoxifylline. The results point out the importance of mitoprotective properties in nootropic effects of studied drugs.