THE EFFECT OF MELATONIN ON THE SERUM LEVEL OF INTERLEUKIN 31 IN HERPESVIRUS SKIN DISEASES ON THE BACKGROUND OF HIV.

The immune system of the skin is the first line of defense against various infections, on the other hand, its strategic location as a key barrier between external and internal environment makes the skin an important tool for maintaining homeostasis, so dermatological lesions are often a manifestation of various pathological conditions. Thus, herpesvirus skin diseases, which are the result of reactivation of a latent infection and occur against the background of human immunodeficiency, may be the first manifestation of HIV. Active study of melatonin in recent years in the dermatological field is associated with interest in its biological action, which extends to the skin due to the melatoninergic system, and promising prospects for the development of new treatments. The aim of this study was to investigate the effect of melatonin on the serum levels of interleukin 31 in herpesvirus skin diseases on the background of HIV. The current study selected 40 HIV patients who had an acute herpesvirus infection caused by HSV-1, HSV-2, VZV, EBV, and HHV-8 were selected. Patients were divided into two groups: group I consisted of patients receiving antiretroviral therapy, valaciclovir in standard therapeutic doses and melatonin as immunomodulatory therapy. Patients in the melatonin group received two melatonin tablet, 3 mg for 14 days, 6 mg daily (two doses of 3 mg). Group II included patients who received antiretroviral therapy in combination with valaciclovir. Serum levels of IL-31 were measured before and after 14 days of therapeutic intervention. The mean serum level of IL-31 was significantly lower in the melatonin group (p˂0.05). Also, in both groups, serum levels of IL-31 showed a significant increase compared to the indicator of the norm. The results of this study showed that melatonin administration could modify inflammatory cytokines secretion such as IL-31. Given the low toxicity of melatonin and its ability to reduce side effects and increase the efficiency of therapeutic agents, its use may be important and significant in combined therapy in combination with highly active antiretroviral therapy.

Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis.

In the modern world, cardiovascular diseases have a special place among the most common causes of death. Naturally, this widespread problem cannot escape the attention of scientists and researchers. One of the main conditions preceding the development of fatal cardiovascular diseases is atherosclerosis. Despite extensive research into its pathogenesis and possible prevention and treatment strategies, many gaps remain in our understanding of this disease. For example, the concept of multiple low-density lipoprotein modifications was recently stated, in which desialylation is of special importance. Apart from this, sialic acids are known to be important contributors to processes such as endothelial dysfunction and inflammation, which in turn are major components of atherogenesis. In this review, we have collected information on sialic acid metabolism, analyzed various aspects of its implication in atherosclerosis at different stages, and provided an overview of the role of particular groups of enzymes responsible for sialic acid metabolism in the context of atherosclerosis.

Development of a Method for Isolation of Mature Cardiomyocytes from Human Heart Biopsy Specimens.

To increase the yield of living cells and their survival, studies were carried out to optimize the method for isolating cardiomyocytes from biopsy specimens excised from the right atrial appendages. It was found that creatine, blebbistatin, and taurine are necessary components of the buffer solution during cardiomyocyte isolation, and that composition of the solutions is a more important factor than their oxygenation.

Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis

In the modern world, cardiovascular diseases have a special place among the most common causes of death. Naturally, this widespread problem cannot escape the attention of scientists and researchers. One of the main conditions preceding the development of fatal cardiovascular diseases is atherosclerosis. Despite extensive research into its pathogenesis and possible prevention and treatment strategies, many gaps remain in our understanding of this disease. For example, the concept of multiple low-density lipoprotein modifications was recently stated, in which desialylation is of special importance. Apart from this, sialic acids are known to be important contributors to processes such as endothelial dysfunction and inflammation, which in turn are major components of atherogenesis. In this review, we have collected information on sialic acid metabolism, analyzed various aspects of its implication in atherosclerosis at different stages, and provided an overview of the role of particular groups of enzymes responsible for sialic acid metabolism in the context of atherosclerosis.

Effects of heavy metals on sex inversion of the mussel Mytilus galloprovincialis Lam., 1819 in coastal zone of the Black Sea.

Sex inversion in the mussel Mytilus galloprovincialis under the influence of heavy metals as one of the reasons for the shift in the sex ratio in the mussel population on the Black Sea coastal zone of Crimea were considered in the work. The present study is the first to directly show that heavy metals can cause females of the mussel M. galloprovincialis to change into males during post-spawning development of gonads. The degree of impact of heavy metals on the sex change in mussel females was different and decreased in the following sequence: Cu2+ â†’ Cd2+ â†’ Hg2+ â†’ Pb2+ â†’ Zn2+. Copper ions had the greatest effect, which caused a sex inversion in 54 % of females. The heavy metals Hg2+ and Pb2+ were also quite toxic causing mortality in 13 % and 10 % of individuals, respectively. It is possible to use M. galloprovincialis as a model organism in the study of mechanism of environmental sex reversal in bivalves.

Interstitial Glucose Metabolism Monitoring as an Additional Method for Objective Assessment of Donor Liver, Prediction and Immediate Diagnosis of Early Graft Dysfunction.

The current clinical practice of assessing the quality and suitability of a donor liver for human transplantation does not exclude cases of primary graft dysfunction of the transplanted organ and, at the same time, leads to an unreasonable refusal to transplant a significant number of functionally suitable organs. In this regard, searching for new methods for additional objective assessment and monitoring of the state of donor organs in the peritransplant period is relevant. The aim of the study was to determine the clinical utility of monitoring interstitial concentrations of glucose and its metabolites to assess the viability and functional state of a donor liver before and after human transplantation. Materials and Methods: A retrospective observational single-center study included 32 cases of liver transplantation. Along with standard methods for assessing the initial function of grafts during the first week after surgery, interstitial (in the transplanted liver) concentrations of glucose and its metabolites were monitored. In 18 cases, the interstitial glucose metabolism was also studied during static cold storage (SCS). Results: With the development of early allograft dysfunction (EAD), compared with the uneventful post-transplant period, statistically significantly higher interstitial lactate concentrations were observed as early as 3 h after reperfusion: 12.3 [10.1; 15.6] mmol/L versus 7.2 [3.9; 9.9] mmol/L (p=0.003). A value above 8.8 mmol/L may be considered as a criterion for the immediate diagnosis of EAD (sensitivity - 89%, specificity - 65%).Interstitial lactate concentration at the end of SCS and the area under the "lactate concentration-SCS duration" curve were associated with the initial graft function. Values of these parameters greater than 15.4 mmol/L and 76.1 mmol/L·h, respectively, with a sensitivity of 100% in both cases and a specificity of 77 and 85%, may be used to assess the risk of primary EAD. Conclusion: Monitoring of interstitial concentrations of glucose and its metabolites, primarily, lactate, is an objective additional method for the assessment of the donor liver viability both during SCS and in the early postoperative period.

[Bilary anastomotic strictures after right lobe living donor liver transplantation: a single-center experience]. / Biliarnye anastomoticheskie striktury posle transplantatsii pravoi doli pecheni ot zhivogo rodstvennogo donora: opyt odnogo transplantatsionnogo tsentra.

OBJECTIVE: To determine the incidence of AS after right lobe living donor liver transplantation with various biliary reconstructions and to identify the predictors of this complication. MATERIAL AND METHODS: A retrospective and prospective analysis included 245 RLLDLTs for the period 2011-2018 at the Burnazjan Federal Medical Biophysical Center. The results of transplantations in 207 patients aged 19-68 years (median 43 years) were assessed. There were 82 men and 125 women. Follow-up period ranged from 10 to 98 months (median 35 months). We analyzed the relationship between surgical characteristics (preoperative data of recipients and donors, graft parameters, technical features of biliary reconstruction and features of post-transplantation period) and incidence of anastomotic strictures. A total of 58 parameters were analyzed. RESULTS: AS occurred in 20 (9.7%) recipients. Median AS-free period was 5 months (range 1-44). In 17 (85%) patients, AC developed within a year after surgery. Cumulative 1-, 2- and 5-year incidence of AS was 8.3%, 8.9%, and 11%, respectively. Significant predictors of AS were impaired arterial blood supply to the graft (HR 7.8, 95% CI 2.3-26.0, p<0.001), biliary leakage ISGLS class B or C (HR 5.0, 95% CI 2.0-12.8, p<0.001), early allograft dysfunction (HR 4.2, 95% CI 1.5-11.6, p=0.006) and female recipient (HR 3.2, 95% CI 1.1-9.9, p=0.04). In our sample, variant biliary anatomy of the graft and recipient liver, as well as technical features of biliary reconstruction did not affect the risk of AS. CONCLUSION: Variant biliary anatomy of potential donor alone should not be considered as a contraindication for organ donation and right liver lobe transplantation. Precise surgical technique, high transplantation activity, as well as experience of reconstructive interventions on the bile ducts during other operations can significantly reduce the incidence of AS after RLLDLT up to 9.7%.

[Biological aspects of treatment resistance in psychiatry and pharmacodynamic approaches to its management]. / Biologicheskie predposylki formirovaniya lekarstvennoi rezistentnosti v psikhiatrii i farmakodinamicheskie podkhody k ee preodoleniyu.

Treatment resistance is a persistent neurochemical condition characterized by the presence of «hybrid¼ metabolism, which combines both pathological and drug-dependent metabolisms. The difficulties in management and prevention of treatment resistance are associated with a lack of understanding of neurochemical aspects of the development of higher mental functions. The authors suggest that the basic types of species-preserving behavior are associated with the activity of monoaminergic systems while the modulation of their activity is predetermined by local neuronal networks in the rostral parts of the brain, where a variety of co-transmitters play an important role. It is emphasized that the mechanisms of the development of resistance after previous treatment with agonists (antidepressants, anxiolytics) or antagonists (antipsychotics) are different. Depending on drug actions on synaptic transmission, methodological aspects of treatment resistance management by means of «polar therapy¼, «sensitization¼ and combination strategies are considered.

[Solitary fibrous tumor of pleura (symptoms, diagnosis, treatment)]. / Solitarnaya fibroznaya opukhol' plevry (klinika, diagnostika, lechenie).

OBJECTIVE: Optimization of diagnosis and treatment of patients with solitary fibrous tumor of pleura, analysis of overall survival and disease-free survival, predictors of recurrence. MATERIAL AND METHODS: There were 66 patients with solitary fibrous tumor of pleura (26 men and 40 women) aged 57.6 years (range 26-80 years). Asymptomatic course was found in 29 (44%) patients, various symptoms - in 37 (56%) patients. Thoracotomy was applied in 36 patients, thoracoscopy - in 30 patients. Immunohistochemical examination included analysis of definition of Stat6 expression. RESULTS: Benign variant of SFT was diagnosed in 50 (75.7%) patients, malignant variant - in 16 (24.3%) patients. STAT6 expression was observed in all cases. Postoperative morbidity was 9%, mortality - 1.6%. Recurrence was diagnosed in 2 (4%) patients with benign variant of disease and in 5 (31.2%) patients with malignant variant (2 of them died from progression of disease). Progression-free survival was 89.4%, overall survival - 95.4%. Predictors of recurrence are tumor dimension over 10 cm, necrosis and/or hemorrhagic component of tumor, mitotic count of at least four per 10 high-power fields. CONCLUSION. S: Olitary fibrous tumor of pleura is a rare mesenchymal fibroblastic neoplasm growing from submesothelial layer. Differential and preoperative morphological diagnosis of SFT is difficult and demands a special immunohistochemical examination with analysis of Stat 6 expression. Surgery is preferred for tumor de novo and recurrent neoplasm.

[Surgical repair of secondary tricuspid regurgitation]. / Khirurgicheskaia korrektsiia vtorichnoi nedostatochnosti trikuspidal'nogo klapana.

Optimal surgical strategy for secondary tricuspid regurgitation is still under discussion. First of all, this is due to rare organic disease of tricuspid valve and tricuspid regurgitation is almost always classified as secondary insufficiency. Fibrous annulus enlargement of tricuspid valve is the most common cause of tricuspid regurgitation. Annular dilatation may by the result of left ventricular failure due to myocardial or valvular diseases, right ventricular enlargement, pressure or volume overload. No surgical correction of tricuspid insufficiency during cardiac surgery for other leading disease aggravates short- and long-term results. Considering the wide interest and disputes around optimal surgical strategy for tricuspid regurgitation, this review is devoted to modern methods of surgical treatment of secondary tricuspid insufficiency.

[Procognitive effects of transcranial magnetic stimulation in the light of neurocognitive deficit in schizophrenia]. / Prokognitivnye éffekty transkranial'noi magnitnoi stimuliatsii v svete problemy neirokognitivnogo defitsita pri shizofrenii.

Transcranial magnetic stimulation (TMS) is a relatively new method of non-invasive therapy of mental and neurological diseases that has great potential of therapeutic and diagnostic application. In schizophrenia, TMS may exert a positive effect on cognitive deficit. However this issue remains open. The authors analyze recent studies focused on the dynamics of neurocognitive deficit in TMS therapy and consider clinical effects of TMS in schizophrenia. The analysis has shown that TMS is successfully implemented in treatment of auditory positive symptoms and studies on its effect on negative symptoms of schizophrenia are perspective. Procognitive effect was found in working memory domain, and partially in perception domain within the perception of faces and facial expressions. The data on regulative functions, attention, speech, and nondeclarative memory remains controversial. It has been concluded that further research is needed to clarify the place of TMS in schizophrenia therapy.

Relation between oxygen stoichiometry and thermodynamic properties and the electronic structure of nonstoichiometric perovskite La0.6Sr0.4CoO3-δ.

Continuous phase diagram 3 - δ - log pO2 - T of the nonstoichiometric perovskite La0.6Sr0.4CoO3-δ was obtained in a gas flow reactor by means of the quasi-equilibrium oxygen release technique. The thermodynamic properties of oxides were determined as a function of oxygen nonstoichiometry. Within the framework of the itinerant electron model, the dependence of the oxide nonstoichiometry on the oxygen activity was related to the density of electronic states near the Fermi level.

Relaxation damping in oscillating contacts.

If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect "relaxation damping". The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed.

Toward the Ultra-incompressible Carbon Materials. Computational Simulation and Experimental Observation.

The common opinion that diamond is the stiffest material is disproved by a number of experimental studies where the fabrication of carbon materials based on polymerized fullerenes with outstanding mechanical stiffness was reported. Here we investigated the nature of this unusual effect. We present a model constituted of compressed polymerized fullerite clusters implemented in a diamond matrix with bulk modulus B0 much higher than that of diamond. The calculated B0 value depends on the sizes of both fullerite grain and diamond environment and shows close correspondence with measured data. Additionally, we provide results of experimental study of atomic structure and mechanical properties of ultrahard carbon material supported the presented model.

[SPECIFICS OF INHALED ILOPROST PHARMACODYNAMICS IN PATIENTS WITH SEVERE LEFT VENTRICULAR SYSTOLIC DYSFUNCTION].

PURPOSE: To determine the specifics of inhaled iloprost effect on pulmonary and systemic hemodynamics in patients with pulmonary hypertension (PH) associated with left ventricular systolic dysfunction. MATERIALS AND METHODS: 47 vasore- activity tests (VRT) with 20 micrograms inhaled iloprost (Ventavis, Bayer) were performed in 39 candidates on heart transplantation. All patients had heart failure III-IV NYHA and PH with pulmonary vascular resistance (PVR) more than 2.5 Wood units. Hemodynamic parameters were evaluated at baseline and 15 minutes after inhalation of iloprost. RESULTS: Iloprost significant decreased PAPmean: from 36.8 ± 8.5 mm Hg to 29.9 ± 9.4 mm Hg (p < 0.001). There was a significant decrease in PVR:from 4.5 1.6 Wood units to 3 ± 1 Wood units (p < 0.001). PVR dropped more than 20% in 34 cases (72.3%). Iloprost inhalation caused significant changes in systemic hemodynamic. There were decrease in sys- temic vascular resistance (SVR)from 1820 ± 527 dynes·sec·cm(-5) to 1423 ± 427 dynes·sec·cm(-5) (p < 0.001), increase in stroke volume index (SVI) from 26.1 ± 8.7 ml/m2 to 30.5 ± 9.5 ml/m2 (p < 0.001) and decrease in PCWP from 20.6 ± 5.9 mm Hg to 18.4 ± 6.6 mm Hg. (p = 0.016). We found significant negative correlation between systemic effects of iloprost and initial cardiac index (r = -0.63). CONCLUSIONS: Inhaled iloprost caused significant changes in systemic hemodynamic when was used in patients with severe LV systolic dysfunction. Favorable changes in the left ventricle preload and after- load naturally increased its performance and decreased PCWP.

Friction between a viscoelastic body and a rigid surface with random self-affine roughness.

In this Letter, we study the friction between a one-dimensional elastomer and a one-dimensional rigid body having a randomly rough surface. The elastomer is modeled as a simple Kelvin body and the surface as self-affine fractal having a Hurst exponent H in the range from 0 to 1. The resulting frictional force as a function of velocity always shows a typical structure: it first increases linearly, achieves a plateau and finally drops to another constant level. The coefficient of friction on the plateau depends only weakly on the normal force. At lower velocities, the coefficient of friction depends on two dimensionless combinations of normal force, sliding velocity, shear modulus, viscosity, rms roughness, rms surface gradient, the linear size of the system, and the Hurst exponent. We discuss the physical nature of different regions of the law of friction and suggest an analytical relation describing the coefficient of friction in a wide range of loading conditions. An important implication of the analytical result is the extension of the well-known "master curve procedure" to the dependencies on the normal force and the size of the system.

[Finding an "invisible" binding site for low-molecular compounds on a protein molecule and predicting their inhibiting activity].

Current computational methods have not been able to discover an unknown binding site for low-molecular ligands on a protein receptor and predict parameters of their interaction when this binding site is not distinguished by energy of binding or structural features. Authors propose a method to find an unknown, structurally undefined site for binding low-molecular inhibitors with a protein, as well as to predict kinetic parameters for new compounds using x-ray structure of a protein receptor and experimental interaction constants of a training set of inhibitors. The developed method is applied to discover structural and kinetic parameters of binding C1q, a protein from the first component of complement system, to low-molecular ligands that inhibit its interactions with immune complexes. Authors have suggested that these ligands bind to a region of C1q globular head near residues Arg150 of chain B, and Lys160 and His67 of chain C, supposedly inhibiting the classical pathway of complement activation. Ligands that inhibit interaction of C1q with immune complexes can be used in the therapy of pathological conditions that are related to unwanted complement activation: allergic reactions, xenograft rejection, etc.

[Investigation of bacterial translocation regularities in diffuse peritonitis using labeled radionuclide colibacillus].

The investigation of the regularities of translocation of opportunistic pathogenic microflora from the small intestine lumen and abdominal cavity in diffuse peritonitis using labeled radionuclide colibacillus has shown that in normal condition the intestinal barrier is not permeable for bacteria. Under conditions of diffuse peritonitis the bacterial translocation and peritoneal resorption are developing since the first minutes of the disease. During the development of the pathological process the priority of the foci of bacterial toxemia is changed from peritoneal to intestinal. Relaparotomy with manipulations on the intestine in peritonitis induces sharp activation of bacteria translocation into the portal blood flow and systemic circulation.