Charge carrier transport in PbS films doped with iodine.

The results of the measurements of electrical and Hall resistivities on polycrystalline PbS films doped with iodine obtained through hydrochemical deposition are presented. The analysis of the temperature dependence of resistivity points out the crossover from the hopping mechanism due to thermal delocalization in the impurity band to the variable range hopping mechanism. The increase in the iodine content in the films leads to an increase in the impurity ionization energy. It has been established that the temperature dependence of resistivity over a wide temperature range obeys the inverse Arrhenius law, which is characteristic of disordered polycrystalline films with different sizes and orientations of crystallites relative to the substrate, as confirmed by AFM topography, Raman spectra and X-ray diffraction measurements. We found that the type of charge carrier changes from electrons to holes with an increase in the iodine content. Additionally, for a wide range of iodine doping, the concentration of charge carriers is low, indicating the possible occurrence of a self-compensation mechanism due to the formation of impurity defects.

Monomeric form of C-reactive protein in the assessment of the residual inflammatory cardiovascular risk in patients with subclinical carotid atherosclerosis.

Aim      To study the relationship between monomeric C-reactive protein (mCRP) and the progression of asymptomatic carotid atherosclerosis in patients with a moderate risk for cardiovascular diseases (CVD) as assessed with the SCORE model.Material and methods  The study included 80 men and women aged 53.1±5.8 years assigned to the category of a moderate risk for CVDs by the SCORE model with a low-density lipoprotein cholesterol (LDL-C) level of 2.7-4.8 mmol/l and asymptomatic, hemodynamically insignificant (<50% luminal narrowing) carotid atherosclerosis according to ultrasonic data. All patients were prescribed atorvastatin to achieve a LDL-C level <2.6 mmol/l. After 7 years of follow-up, ultrasonic examination of carotid arteries was performed, and concentrations of high-sensitivity C-reactive protein (hsCRP) and mCRP were measured.Results A concentration of LDL-C <2.6 mmol/l was achieved in all patients. The progression of atherosclerosis as determined by an increased number of atherosclerotic plaques (ASPs), was observed in 45 (56 %) patients. At 7 months of follow-up, concentrations of cCRP were higher in the group of patients with progressive carotid atherosclerosis, while the levels of hsCRP did not differ between the groups. Increased mCRP concentrations were associated with changes in variables of the "atherosclerotic load", including the number of ASPs, total ASP height, and the intima-media thickness (IMT). In patients with a median mCRP concentration of 5.2 [3.3; 7.1] µg/l and more, the increases in mean ACP number and total ASP height were considerably higher than in patients with mCRP concentrations lower than the median (3.9 and 2.7 times, respectively), whereas the odds ratio for the progression of asymptomatic carotid atherosclerosis was 5.5 (95 % confidence interval, CI: 2.1-14.6; p=0.001). ROC analysis showed that the concentration of hsCRP had no predictive value for prognosis of asymptomatic carotid atherosclerosis (p=0.16), while the area under the ROC curve (AUC) for mCRP was 0.75±0.056 (95 % CI: 0.64-0.86; p=0.001).Conclusion      According to the results of 7-year follow-up, the plasma concentration of mCRP was significantly higher in patients with an increased number of ASPs than in patients without this increase. An increased level of mCRP may indicate a higher inflammatory risk of CVD.

[The prognostic value of high-sensitivity C-reactive protein blood level after coronary stenting for the development of stent restenosis].

Aim      To analyze the relationship between serum concentrations of high-sensitivity C-reactive protein (hsCRP) in dynamics and development of restenosis at 12 months following elective coronary stent placement (CSP).Material and methods  The key role in atherogenesis, neointimal proliferation and restenosis belongs to inflammation. This study included 91 patients (median age, 60 [56; 66] years) with stable exertional angina after an elective CSP using second-generation stents. Follow-up coronarography was performed for 60 patients at 12 months. Concentration of hsCRP was measured immediately prior to CSP and at 1, 3, 6, and 12 months after CSP. Restenosis of the stented segment (50% or more narrowing of the stented segment or a 5-mm vessel segment proximally or distally adjacent to the stented segment) was observed in 8 patients.Results According to results of the ROC analysis, the increase in hsCRP concentration >0.9 mg/l (>25%) at one month after CSP had the highest predictive significance with respect of restenosis (area under the ROC curve, 0.89 at 95 % confidence interval (CI) from 0.79 to 0.99; sensitivity, 87.5 %; specificity, 82.8 %; р=0.0005), which was superior to the absolute value of hsCRP concentration >3.0 mg/l (area under the ROC curve, 0.82 at 95 % CI from 0.68 to 0.96; р=0.0007).Conclusion      Increased concentration of hsCRP ≥0.9 mg /l (≥25 %) at a month after CSP was associated with restenosis of the coronary artery stented segment.

Energy Metabolism in Cellular Regenerative Processes: Focus on PPARα.

Reduced expression of the key regulator of cardiac metabolism, transcription factor PPARα, in surgical samples of the auricles from patients with coronary heart disease and heart failure was detected by real-time quantitative PCR. These changes indicate reduced activity of this factor and a shift of energy metabolism from oxidative phosphorylation to glycolysis typical of dedifferentiated cells. Electron microscopy revealed dedifferentiated cardiomyocytes with disassembled contractile apparatus and disorganized sarcomeres. In the examined specimens from patients with heart failure, severe myocardial fibrosis was revealed.

Multimarker Approach in Risk Stratification of Patients with Decompensated Heart Failure.

PURPOSE: to study prognostic value of various biomarkers and their combinations in patients who survived decompensation of chronic heart failure. MATERIALS AND METHODS: Patients (n=159) who were hospitalized with diagnosis of heart failure (HF) decompensation were included in a prospective single-center study. Examination on admission and the day of hospital discharge, included measurement of concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), copeptin, soluble suppression of tumorigenicity 2 (sST2), kopetin, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3. Te combined primary endpoint comprised cardiovascular (CV) death, frst hospitalization because of HF heart failure decompensation, episodes of HF deterioration which required additional i/v diuretics, and CV death with successful resuscitation. RESULTS: During one-year follow-up 56 pts (35.2%) reached the combined primary endpoint. Tere were 78 (49.1%) cardiovascular events. During hospitalization, patients with the decompensation of heart failure experienced a decrease of sST2, NT-proBNP, galectin-3, kopetin, hsTnT and an insignifcant increase of NGAL. ROC analysis identifed signifcant relation between concentrations of NT-proBNP, sST2, copeptin and, to a lesser degree, hsTnT, determined at hospital discharge, and risk of combined primary endpoint during 1-year follow-up: area under the curve (AUC) was 0.733 [95% CI 0.645-0.820], p<0.0001, 0.772 [95% CI 0.688-0.856], p<0.0001, 0.735 [95% CI 0.640-0.830], p<0.0001, and 0.659 [95% CI 0.553-0.764], p=0.005, respectively. Patients who during hospitalization did not achieve cut-off values of NT-proBNP ≤1696 rg/ml, sST2≤37.8 hg/ml, copeptin≤28.31 rmol/L and hsTnT≤28.37 rg/ml, had higher risk of reaching adverse events during 1 year; OR and 95% CI were 2.96 [1.61, 5.42] p<0.0001, 4.31 [2.34, 7.93] p<0.0001, 3.06 [1.59, 5.89] and 2.19 [2.12, 4.27]), respectively. According to Cox regression analysis, risk of the combined primary end point was the highest in patients with 3 or more elevated markers (OR = 6.6 [3.584, 12.158], p<0.0001), average in patients with 2 elevated markers (OR = 1.123 [0.51, 2.48]), p=0.7), and the lowest in patients with no markers increase or increase of only one marker (OR = 0.11 [0.049, 0.241], p<0.0001). In the Kaplan-Mayer survival analysis all three groups were statistically different. In order to identify the most prognostically strong model, a reclassifcation analysis was performed. According to this analysis, the combination of sST2 and NT-proBNP concentrations determined at hospital discharge, exceeded one NT-proBNP (reclassifcation = -8.1%). At the same time, predictive value of only sST2 just insignifcantly less than value of sST2 and NT-proBNP combination (reclassifcation = -1.9%). CONCLUSION: Patients with three and more elevated markers at hospital discharge have high risk of adverse events. Te biggest prognostic value has combination of sST2 and NT-proBNP concentrations. In order to determine the long-term prognosis of a patient with HF decompensation, it is sufcient to measure concentrations of sST2 and NT-proBNP at hospital discharge. Alternatively, it is possible to limit to sST2 only, which is just insignifcantly inferior to the sST2 and NT-proBNP combination. Patients with concentrations of sST2 ≥37.8 hg/ml and NT-proBNP ≥1696 rg/ml at hospital discharge have maximal 1year risk of death due to recurrent HF decompensation.

Clinical significance of serial biomarkers activity determination after acute heart failure decompensation: sST2 NT-proBNP role during long-term follow-up.

AIM: Monitoring of concentrations of modern biomarkers to evaluate the efficacy of long­term treatment of patients after acute decompensated HF (ADHF). MATERIALS AND METHODS: The study included 100 patients with severe decompensated FC II-IV CHF and LV EF <40 % due to IHD, DCMP or AH. At discharge from the hospital, patients were divided into groups of low (NT­proBNP<1400 pg / ml) (control, n=30) and high (NT­proBNP≥1400 pg / ml) risk (n=70). Patients at high risk were randomized to two treatment groups, a group of NT­proBNP monitoring (NPM) (n=35) and a group of standard therapy (n=35). At the end of the study, noncompliant patients were isolated from these two groups into a separate group (n=10). The aim of the treatment was decreasing the NT­proBNP concentration to less than 1000 pg / ml and / or ≥50 % of the baseline level. In addition to the soluble suppression of tumorigenicity 2 (sST2) receptor, concentrations of copeptin, neutrophil gelatinase associated lipocalin (NCAL), galectin 3, and high­sensitivity troponin T were measured at discharge from the hospital (baseline) and at three and 6 months of treatment. RESULTS: The strongest correlations were found between changes in concentrations (Δ%) of NT­proBNP, copeptin, and sST2 and changes in CHF FC, 6­min walk distance, CCS, quality of life, LV EF, and Е / Е' (р<0.001). The incidence of cardiovascular events was directly related with the degree of decrease and / or increase in biomarker concentration. Patients of the NPM group had the lowest risk of adverse clinical outcome upon a decrease in NT­proBNP <988.5 pg / ml at 6 months of treatment or > 50 % of the baseline level at discharge from the hospital. For these patients, the mean Δ% was 60.7±8.5 % for NT­proBNP, 34.03±17.6 % for sST2, and 32.41±8.8 % for copeptin [OR at 95 % CI 0.08 (0.02-0.36), р <0.0001]. A significant increase in the risk for cardiovascular events was observed only at a considerable increase in NT­proBNP >50 % [OR at 95 % CI 3.8 (1.13-13.0), р=0.03], and the highest incidence of cardiovascular events was observed in the group of noncompliant patients (110 %). Besides NT­proBNP, to significantly decrease the risk of cardiovascular events, it was necessary to achieve a decrease in sST2 concentration to less than 30 ng / ml or by more than 24.9 % (Δ%) at the end of followup [ОR (95 % CI: 0.1 (0.02-0.5), р=0.004]. CONCLUSION: Among the modern biomarkers, changes in NT­proBNP, sST2, and copeptin concentrations most accurately reflect changes in the clinical and functional status, quality of life, and EchoCG parameters in HF patients during long­term monitoring. The lowest risk for adverse clinical outcomes was observed in post­decompensation patients with a decrease in NT­proBNP <988.5 pg / ml after 6 months of treatment or ≥50 % of baseline upon discharge from the hospital. The sST2 concentration has to be reduced by more than 24.9 % of baseline and less than 30 ng / ml in the course of long­term treatment after decompensated HF.

Bactericide, Immunomodulating, and Wound Healing Properties of Transgenic Kalanchoe pinnata Synergize with Antimicrobial Peptide Cecropin P1 In Vivo.

Procedure of manufacturing K. pinnata water extracts containing cecropin P1 (CecP1) from the formerly described transgenic plants is established. It included incubation of leaves at +4°C for 7 days, mechanical homogenization of leaves using water as extraction solvent, and heating at +70°C for inactivating plant enzymes. Yield of CecP1 (after heating and sterilizing filtration) was 0.3% of total protein in the extract. The water extract of K. pinnata + CecP1 exhibits favorable effect on healing of wounds infected with S. aureus (equal to Cefazolin) and with a combination of S. aureus with P. aeruginosa (better than Cefazolin). Wild-type K. pinnata extract exhibited evident microbicide activity against S. aureus with P. aeruginosa but it was substantially strengthened in K. pinnata + CecP1 extract. K. pinnata extracts (both wild-type and transgenic) did not exhibit general toxicity and accelerated wound recovery. Due to immunomodulating activity, wild-type K. pinnata extract accelerated granulation of the wound bed and marginal epithelialization even better than K. pinnata + CecP1 extract. Immunomodulating and microbicide activity of K. pinnata synergizes with microbicide activity of CecP1 accelerating elimination of bacteria.

[Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin Significance for Prognosis of Patients After Acute Heart Failure Decompensation].

PURPOSE: To assess the suppression of tumorogenicity 2 (ST2) and copeptin significance for risk stratification of patient (pts) with acute decompensated heart failure (ADHF) during long-term follow-up compared with traditional risk factors. METHODS: We included in a prospective study 159 pts with ADHF. Blood samples to determine copeptin, sST2, NT-proBNP and hsTnT concentration were collected at admission and at discharge from the hospital. Serial determination of biomarker concentration was performed at 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration requiring additional intravenous diuretics and CV death with successful resuscitation. RESULTS: During 1-year follow-up (295.3±113.2 days) 56 pts (35.2%) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (with CV events). Discharge copeptin and NT-proBNP values were comparable for pts risk stratification: AUC=0.727 (95% CI 0.637-0.816), р.

A new method of producing NS5A antigen of hepatitis C virus.

A task of creating a universal platform for engineering affordable recombinant producers of viral proteins conserving immunogenicity has not been solved yet. High toxicity of the viral proteins for the host cells, low yield and abnormal folding of the products often present severe obstacles to obtaining producers of the viral proteins. In this work, we report a new method of engineering and screening of deletion libraries from the viral antigen genes. This method allows selection of artificial derivatives of these genes adapted for expression in microbial producer cells. The method involves PCR amplification of the gene fragments using a system of randomized and adapter primers, which allows the spontaneous formation of duplexes from the random primers in the absence of the template DNA to be prevented. For selecting variants capable of in vivo expression, the obtained PCR products are cloned to a special vector of a direct phenotypical selection pQL30. It contains E. coli ß-galactosidase gene with an inserted polylinker producing a frame-shift mutation. Using this screening method, an artificial variant of hepatitis C (HCV) NS5a gene with optimal biotechnological properties was established. 27 clinical specimens of 1670 bp long HCV1b NS5a fragments were used as a source gene. A PCR bank of the deletion derivatives was produced. 40 LacZ-positive clones based on pQL30 vector with a 50-700 bp long insertion were selected. The LacZ activity of the cell lysates and the immunogenicity of the products were tested. As a result, a single clone encoding a soluble protein with Mr = 114 kDa was selected. Its yield reached 0.3% of the total cell protein. It was highly reactive with sera of HCV 1b infected patients but not with sera of the healthy donors.

[Detection of Autoantibodies Against the 1-Adrenergic Receptor in the Sera of Patients via the Competitive cell-Based Enzyme Linked Immunosorbent Assay].

OBJECTIVE: This study aimed to assess the level of anti-1-adrenergic receptor autoantibodies in patients with ventricular arrhythmias with no signs of organic heart disease and with presence of cardiovascular pathology in comparison with a group of healthy volunteers. MATERIAL AND METHODS: The study included 44 patients with ventricular arrhythmias with no signs of organic heart disease ("idiopathic"), 34 patients with diagnosed dilated cardiomyopathy (DCM) of inflammatory origin, 35 patients with coronary heart disease and ventricular arrhythmias, 12patients with coronary heart disease with no ventricular arrhythmias, and 19 healthy volunteers (control group). The level of autoantibodies against the 1-adrenergic receptor was determined by the developed competitive cell-based enzyme-linked immunosorbent assay (ELISA) and by the standard ELISA using peptides corresponding to the second extracellular loop of the 1-adrenergic receptor. RESULTS: Elevated level of autoantibodies detected by a competitive cell-based ELISA was observed in 62% of patients with DCM compared to 21% of healthy volunteers (p=0.0006). In patients with "idiopathic" ventricular arrhythmias, the level of 1-adrenergic receptor autoantibodies was lower than in healthy subjects (p=0.003). Coronary heart disease patients with or without ventricular arrhythmias exhibited no differences from the control group. The number of significantly positive signals in peptide-based ELISA did not exceed 10% in any of the groups. No correlation between the data from competitive cell-based ELISA and peptide-based ELISA was found. CONCLUSIONS: This study demonstrated that competitive cell-based ELISA technique can be applied for detection of 1-adrenergic receptor autoantibodies. The results in DCM patients generally correspond to the expected. Decreased level of autoantibodies in patients with "idiopathic" ventricular arrhythmias indicates that this disease is related to changes in the immune system. Such relation is not observed in the case of coronary heart disease patients.

[Mexidol in the rehabilitation of patients in the acute ischemic stroke]. / Meksidol v reabilitatsii bol'nykh v ostrom periode ishemicheskogo insul'ta.

UNLABELLED: Research objective - studying of results of a comprehensive neuro-rehabilitation patients in the acute ischemic stroke (according to the Samara regional vascular centre). MATERIAL AND METHODS: A review of the work of RVC on the main indicators for 2014, detailed analysis of 20 patients in the acute period of ischemic stroke, in which treatment was used the drug mexidol with the dynamics on standardized assessment scales (NIHSS, Rankin, Rivermead, MoCA, HADS). RESULTS AND DISCUSSION: The use of «Mexidol¼ in the treatment of stroke leads to a significant statistically and clinically significant improvement in cognitive, motor, sensory functions, reduction of fatigue, anxiety, improved adaptation to physical loads.

[Estimation of immune response parameters in patients with frequent premature ventricular contractions without signs of organic pathology of the cardiovascular system].

AIM: To study the specific features of an immune response and the role of infectious pathogens in the occurrence, development, and maintenance of ventricular ectopic activity in patients without signs of organic disease of the cardiovascular system (CVS). SUBJECTS AND METHODS: The investigation enrolled 91 patients (27 men and 64 women with a mean age of 36.5 +/- 11.5 years) with premature ventricular contractions (PVC) without signs of organic CVS pathology. A control group comprised 31 healthy volunteers. In addition to standard physical examination, a study of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cellular and humoral immune parameters was performed and the serological and molecular genetic markers of infections were determined in all the patients. RESULTS: The persons with PVC, as compared to the control group, were recorded to have a higher NT-proBNP level (49.2 pg/ml versus 25.4 pg/ml; p = 0.001) accompanied by an increase in both the total number of PVC and the number of coupled PVC and the episodes of ventricular tachycardia. They were also found to have elevated CD3(+)HLA-DR+ (2.4% versus 1.56%) and CD3(+)CD95+ (27.6% versus 18.8%) counts (p = 0.001). In patients with a C-reactive protein level of more than 2 mg/l, the total number of PVC was larger than that in the other patients (p = 0.065). The patients with PVC did not show a statistically significant difference from the controls in the levels of antiviral and antibacterial antibodies. The people with PVC displayed a number of relationships between the infectious pathogen antibody titers and the ECG Holter monitoring and echocardiography readings. CONCLUSION: In the patients with PVC without signs of organic CVS pathology, the parameters of an immune response were not different from those obtained in the control group, which was likely to be associated with the involvement of the immune system in the development and maintenance of ventricular arrhythmias.

[A change of the medium salinity as a functional load for evaluation of physiological state of the crayfish Astacus leptodactylus].

The necessity of developing criteria for evaluation of the functional state of benthic invertebrates for toxicological studies or for their use as biosensors in systems of the water quality biomonitoring is emphasized. It is proposed to evaluate the organism state with aid of standard test actions dosed by strength and duration. For freshwater crayfish, such action--the functional load--can be the medium salinity change by 1%o, which can be achieved by addition of sodium chloride. Peculiarities of the response reaction of the crayfish cardiac system to such action have been shown by non-invasive method of recording of cardiac activity.

Alterations of cytological and karyological profile of human mesenchymal stem cells during in vitro culturing.

Transplantation of human bone marrow mesenchymal stem cells is considered as a promising therapeutic approach to the therapy of many diseases. However, the problem of possible alterations of the properties of mesenchymal stem cells during their expansion in in vitro cultures before transplantation is not solved. In our study, one of two hundred examined cultures of mesenchymal stem cell cultures derived from donors without bone marrow pathologies and developed under standard culturing conditions demonstrated spontaneous disturbances in morphology, proliferation, and karyotype at early passages. The cells of this abnormal culture retained immunophenotype characteristic of normal mesenchymal stem cells, but some of them (15-25%) had numerous numerical and structural chromosome aberrations.

[Evaluation of functional state of crayfish Pontastacus leptodactylus in normal and toxic environment by characteristics of their cardiac activity and hemolymph biochemical parameters].

The work deals with study of basic characteristics of cardiac activity (HR and stress-index) and hemolymph protein parameters in the crayfish Pontastacus leptodactylus. The main criteria of the crayfish selection are developed for formation of the animal reference groups available for subsequent toxicologic experiments. The action of a model toxicant, hydroquinone (often present in waste water), at a concentration of 1 g/l on parameters of the crayfish cardiac activity at various exposition time, its effect on circadian cardiac activity and on the hemolymph total protein were studied. At its short-term exposure, hydroquinone produced a temporary increase of HR and stress-index, but had no marked effect on the total protein parameters in hemolymph. At long action (for one day), hydroquinone led to a considerable tachycardia, disturbance of the circadian cardioactivity and to a decrease by 40% of the hemolymph total protein. In 50% of cases the toxicant caused death of the animals either in the course of its action or at period of washout from the toxicant. Mechanisms of the toxic action of hydroquinone at various levels of organization are discussed.

[External proprioceptors of locust locomotor organs and their changes during early larval ontogenesis].

This work studies topography and structure of such important insect external proprioceptors as campaniform sensillae (CS). These mechanoreceptors are essential components of insect posture and locomotion regulation and participate in control of various forms of insect motor behavior (walking, jump, flight). There are traced their quantitative changes as well as differences in distribution of groups of these leg receptors at consecutive stages (from the 1st to the 4th) of ontogenetic development of larva of the locust Locusta migratoria L. The presence of groups of CS in proximal parts of extremities has been noted as early as in the 1st instar larvae. The CS groups in the wing pads were revealed only in the 4th instar larvae. The presented data allow connecting changes in structure and distribution of these proprioceptors on central generators of the locomotion rhythms.

[Characteristics of autoimmune reactions in chronic cardiac failure of different etiology].

AIM: To characterize autoimmune reactions in patients with chronic cardiac failure (CCF) of different etiology. MATERIAL AND METHODS: Basic markers of immune activation were measured in 43 patients with coronary heart disease stage I-IIB (NYHA FC I-IV) and 44 patients with dilated cardiomyopathy (DCMP) stage I-IIB (NYHA FC I-IV). Antibodies to myocardial tissue were studied with indirect immunofluorescence. Echocardiography was made by standard recommendations with evaluation of systolic and diastolic left ventricular function. Concentrations of C-reactive protein, IgG, IgA, IgM were estimated nephelometrically. Enzyme immunoassay studied serum levels of IL-8, IL-2R, IL-6, IL-18, IL-10, IFN-gamma, endothelin. RESULTS: Patients with DCMP had higher titers of antimyocardial autoantibodies than in coronary heart disease (CHD) reflecting more severe autoimmune inflammation. In CHD endothelial, systolic and diastolic dysfunctions severity correlated with severity of inflammation. CONCLUSION: Some characteristics of autoimmune reactions in CCF determine severity of the disease course.