Effects of a Hydrolyzed Lignin Derivative on Bleomycin-Induced Pulmonary Fibrosis in Mice.

Female C57BL/J mice with pulmonary fibrosis induced by injections of bleomycin (20 mg/kg intraperitoneally, 8 times for 4 weeks) were treated with a lignin derivative-based composition BP-C3 (80 mg/kg, daily intragastric administrations for 4 weeks). Bleomycin treatment increased the severity of pulmonary fibrosis (Ashcroft score increased from 1.43±0.20 to 4.17±0.48) and the percentage of α-SMA+ tissue (from 15.22±1.01 to 33.12±2.30%) and DNA-synthetizing nuclei (from 1.05±0.14 to 3.38±0.375). After treatment with BP-C3, we observed a tendency to a decrease in Ashcroft score (to 3.40±0.51) and a significant decrease in the percentage of α-SMA+ tissue to 24.30±1.70%; the percentage of DNA-synthetizing nuclei decreased to a lesser extent (to 3.03±0.22%). These results suggest that BP-C3 has a moderate antifibrotic activity.

Measurement of the Pion Form Factor with CMD-3 Detector and Its Implication to the Hadronic Contribution to Muon (g-2).

The cross section of the process e^{+}e^{-}→π^{+}π^{-} has been measured in the center-of-mass energy range from 0.32 to 1.2 GeV with the CMD-3 detector at the electron-positron collider VEPP-2000. The measurement is based on an integrated luminosity of about 88 pb^{-1}, of which 62 pb^{-1} represent a complete dataset collected by CMD-3 at center-of-mass energies below 1 GeV. In the dominant region near the ρ resonance a systematic uncertainty of 0.7% was achieved. The implications of the presented results for the evaluation of the hadronic contribution to the anomalous magnetic moment of the muon are discussed.

Erythrocytes membrane fluidity changes induced by adenylyl cyclase cascade activation: study using fluorescence recovery after photobleaching.

In this study, fluorescence recovery after photobleaching (FRAP) experiments were performed on RBC labeled by lipophilic fluorescent dye CM-DiI to evaluate the role of adenylyl cyclase cascade activation in changes of lateral diffusion of erythrocytes membrane lipids. Stimulation of adrenergic receptors with epinephrine (adrenaline) or metaproterenol led to the significant acceleration of the FRAP recovery, thus indicating an elevated membrane fluidity. The effect of the stimulation of protein kinase A with membrane-permeable analog of cAMP followed the same trend but was less significant. The observed effects are assumed to be driven by increased mobility of phospholipids resulting from the weakened interaction between the intermembrane proteins and RBC cytoskeleton due to activation of adenylyl cyclase signaling cascade.

Adsorption of semiflexible wormlike polymers to a bar and their double-chain complex formation.

We theoretically study pairing (double-strand complexation) of semiflexible wormlike chains (WLC) due to their side-to-side attraction. Considering binding of two WLCs of high stiffness we start with the case of infinite stiffness of one chain which is replaced with a straight bar. A combination of the quantitative transfer matrix approach with scaling arguments in terms of trains, loops of different sizes, tails and supertrains allowed us to characterize all the regimes of semiflexible chain adsorption on a bar. In particular, we predict a self-similar monomer concentration profile c(r) ∝ r-10/3 near the bar (at distances r below the chain Kuhn length l) at the critical point for adsorption. Such localized critical profile leads to a sharp adsorption transition. Furthermore, we found that supertrains serve as the basic structural elements in WLC complexes leading to bridging, network formation and condensation of semiflexible polymers in dilute solutions. Polymer collapse (precipitation) and redissolution on increasing attraction strength are predicted in qualitative agreement with experiments on aqueous solutions of DNA and F-actin.

Effective elastic moduli of composites with a strongly disordered host material.

The local elastic properties of strongly disordered material are investigated using the theory of correlated random matrices. A significant increase in stiffness is shown in the interfacial region, the thickness of which depends on the strength of disorder. It is shown that this effect plays a crucial role in nanocomposites, in which interfacial regions are formed around each nanoparticle. The studied interfacial effect can significantly increase the influence of nanoparticles on the macroscopic stiffness of nanocomposites. The obtained thickness of the interfacial region is determined by the heterogeneity lengthscale and is of the same order as the lengthscale of the boson peak.

Transition between metastable equilibria: Applications to binary-choice games.

Transitions between metastable equilibria in the low-temperature phase of dynamical Ising game with activity spillover are studied in the infinite time limit. It is shown that exponential enhancement due to activity spillover, which takes place in finite-time transitions, is absent in the infinite time limit. In order to demonstrate that, the analytical description for infinite time trajectory is developed. An analytical approach to estimate the probability of transition between metastable equilibria in the infinite time limit is introduced and its results are compared with those of kinetic Monte Carlo simulation. Our study sheds light on the dynamics of the Ising game and has implications for the understanding of transitions between metastable states in complex systems.

Strain correlation functions in isotropic elastic bodies: large wavelength limit for two-dimensional systems.

Strain correlation functions in two-dimensional isotropic elastic bodies are shown both theoretically (using the general structure of isotropic tensor fields) and numerically (using a glass-forming model system) to depend on the coordinates of the field variable (position vector r in real space or wavevector q in reciprocal space) and thus on the direction of the field vector and the orientation of the coordinate system. Since the fluctuations of the longitudinal and transverse components of the strain field in reciprocal space are known in the long-wavelength limit from the equipartition theorem, all components of the correlation function tensor field are imposed and no additional physical assumptions are needed. An observed dependence on the field vector direction thus cannot be used as an indication for anisotropy or for a plastic rearrangement. This dependence is different for the associated strain response field containing also information on the localized stress perturbation.

Correlations of tensor field components in isotropic systems with an application to stress correlations in elastic bodies.

Correlation functions of components of second-order tensor fields in isotropic systems can be reduced to an isotropic fourth-order tensor field characterized by a few invariant correlation functions (ICFs). It is emphasized that components of this field depend in general on the coordinates of the field vector variable and thus on the orientation of the coordinate system. These angular dependencies are distinct from those of ordinary anisotropic systems. As a simple example of the procedure to obtain the ICFs we discuss correlations of time-averaged stresses in isotropic glasses where only one ICF in reciprocal space becomes a finite constant e for large sampling times and small wave vectors. It is shown that e is set by the typical size of the frozen-in stress components normal to the wave vectors, i.e., it is caused by the symmetry breaking of the stress for each independent configuration. Using the presented general mathematical formalism for isotropic tensor fields this finding explains in turn the observed long-range stress correlations in real space. Under additional but rather general assumptions e is shown to be given by a thermodynamic quantity, the equilibrium Young modulus E. We thus relate for certain isotropic amorphous bodies the existence of finite Young or shear moduli to the symmetry breaking of a stress component in reciprocal space.

Modified Estrogen-Progesterone Induction Method of Mammary Gland Hyperplasia in Rats.

In female Wistar rats, mammary gland hyperplasia (MGH) was modeled according to a modified protocol involving estrogen-progesterone induction and taking into account the duration of the estrous cycle of this animal species. MGH was induced over four 7-day cycles; each cycle included subcutaneous administration of 17ß-estradiol (0.5 mg/kg) for 4 days, injection of progesterone (5 mg/kg) on day 5, then 2 days without injections. In females with MGH, a significant increase in the height and diameter of the nipples of the mammary glands was recorded, two types of changes were observed in the gland tissue: tubuloalveolar and lobuloalveolar hyperplasia. The study confirmed the development of MGH in rats by a modified method.

[Metastatic risk factors in pheochromocytoma/paraganglioma].

Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic¼ and «non-metastatic¼. Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15-20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.

Effect of Polyphenolic Composition BP-C2 on Lung Carcinogenesis Induced by Urethane in Progeny of Irradiated Male BALB/c Mice.

We studied the effects of polyphenolic composition BP-C2, comprising molybdenum with lignin derivatives, on lung carcinogenesis induced by urethane in the progeny of F0 male BALB/c mice preconceptionally exposed to radiation in a dose of 1 Gy. The multiplicity of lung tumors in the progeny of irradiated mice was higher than in the progeny of non-irradiated male parents by 50% in females and 43% in males (p<0.05). In F1 mice (progeny of irradiated F0 male parents treated with BP-C2), the multiplicity of lung tumors was also higher, but this increase was less pronounced: 35% in females (p=0.3852) and 23% in males (p=0.0766). We have demonstrated that administration of BP-C2 to irradiated parents (F0) efficiently inhibits carcinogenesis in their F1 progeny. The use of BP-C2 in irradiated male parents and their progeny not only reduced the multiplicity of tumors, but also normalized body weights in the F1 progeny. Our study demonstrates potential of the polyphenolic composition BP-C2 for chemoprophylaxis of radiation-induced transgenerational carcinogenesis.

Method for hepatitis B virus DNA detecting in biological material at low viral load based on nested PCR with detection on three viral targets in real-time mode.

A method has been developed for HBV DNA finding in biological material at low viral load based on nested PCR with real-time detection of three viral targets. When developing the method, blood plasma samples were used from 128 CHB patients living in the regions of the Russian Federation and countries of Central Asia and 173 hemodialysis center patients living in the North-West Federal District. Analytical sensitivity was tested using the stepwise dilution method. HBV was detected by nested PCR. According to the method developed by us, at the first stage, the HBV DNA is amplified using at the first stage oligonucleotides complementary to the greatest similarity regions of the various HBV isolates genomes flanking the entire virus genome. At the second stage, when using the amplification product of the first stage as a template, PCR was performed using three pairs of oligonucleotides and the corresponding oligonucleotide fluorescently labeled probes to three virus genome regions (Core gene, S gene and X gene), as well as one pair of primers and the corresponding probe complementary to a human HPRT gene region. The method sensitivity for DNA extraction from plasma with a 100 µl volume was 10 IU/ml. Obtaining a threshold Ct cycle for only one fluorophore may indicate the presence of HBV DNA in the sample at a load of less than 10 IU/ml, HBV detection in this case is possible with a repeated PCR study of the corresponding sample with HBV DNA extraction from an increased plasma volume (200-1000 µl). The developed method makes it possible to identify the disease in various HBV subgenotypes and can be used to diagnose CHB in the population and risk groups, including those with the HBsAg-negative form of the disease.

[Genetic diversity of the human immunodeficiency virus (HIV-1) in the Kaliningrad region].

INTRODUCTION: As is currently known, the epidemic process in the Kaliningrad Region was mainly associated with the spread of the recombinant form of HIV-1 (CRF03_AB); however, regular HIV importations from other countries and continents has created favorable conditions for emergence and spread of various recombinant forms of the virus.The most complete information on the diversity of recombinant forms in the region is also necessary to understand the structure of drug resistance (DR). The aim of the study was to explore the HIV-1 genetic diversity in the Kaliningrad Region. MATERIALS AND METHODS: We studied 162 blood plasma samples obtained from patients from the Kaliningrad Region, both with confirmed virological failure of antiretroviral therapy (ART) and with newly diagnosed HIV infection. For reverse transcription and amplification of HIV genome fragments, diagnostic «AmpliSense HIVResist-Seq¼. RESULTS AND DISCUSSION: The various recombinants between subtypes A and B (74%) were predominant in study group: recombinant was between CRF03_AB and subtype A (33.95%) and CRF03_AB-like (13.58%) were the most common. Among the "pure" subtypes of the virus, subtype A6 (16.67%). The circulation of subtypes B (3.70%) and G (1.23%) was also noted.Ninety-six patients (59.26%) were identified with at least one mutation associated with antiretroviral (ARV) drug resistance. CONCLUSION: The observed diversity of subtypes and recombinant forms of the virus implies that the new recombinants are actively emerging in the studied region, both between existing recombinant forms and "pure" subtypes, as well as between "pure" subtypes.

Different types of spatial correlation functions for non-ergodic stochastic processes of macroscopic systems.

Focusing on non-ergodic macroscopic systems, we reconsider the variances [Formula: see text] of time averages [Formula: see text] of time-series [Formula: see text]. The total variance [Formula: see text] (direct average over all time series) is known to be the sum of an internal variance [Formula: see text] (fluctuations within the meta-basins) and an external variance [Formula: see text] (fluctuations between meta-basins). It is shown that whenever [Formula: see text] can be expressed as a volume average of a local field [Formula: see text] the three variances can be written as volume averages of correlation functions [Formula: see text], [Formula: see text] and [Formula: see text] with [Formula: see text]. The dependences of the [Formula: see text] on the sampling time [Formula: see text] and the system volume V can thus be traced back to [Formula: see text] and [Formula: see text]. Various relations are illustrated using lattice spring models with spatially correlated spring constants. .

[Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. / Neimmunogennaya stafilokinaza ­ novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).

AIM OF THE STUDY: To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. MATERIAL AND METHODS: 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). RESULTS: At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98). CONCLUSION: The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

Complexes of ortho-Phthalic Acid in Spontaneous Animal Tumors.

The presence of diethyl-, dibutyl-, and 2-ethylhexyl phthalates in spontaneous animal tumors was determined for the first time. Small-cell breast cancer of the dog and Ehrlich ascites carcinoma with the cells are particularly rich of these compounds. It is assumed that the level of phthalates in these cells is due to the activity of expression of nuclear receptors for estrogens and progesterone, as well as the peculiarities of the metabolism of xenobiotics. The accumulation of these compounds in tumor cells can increase their malignancy. The data obtained can be used for development of new diagnostic and therapeutic technologies.

Theory of length-scale dependent relaxation moduli and stress fluctuations in glass-forming and viscoelastic liquids.

The spatiotemporal correlations of the local stress tensor in supercooled liquids are studied both theoretically and by molecular dynamics simulations of a two-dimensional (2D) polydisperse Lennard-Jones system. Asymptotically exact theoretical equations defining the dynamical structure factor and all components of the stress correlation tensor for low wave-vector q are presented in terms of the generalized (q-dependent) shear and longitudinal relaxation moduli, G(q, t) and K(q, t). We developed a rigorous approach (valid for low q) to calculate K(q, t) in terms of certain bulk correlation functions (for q = 0), the static structure factor S(q), and thermal conductivity κ. The proposed approach takes into account both the thermostatting effect and the effect of polydispersity. The theoretical results for the (q, t)-dependent stress correlation functions are compared with our simulation data, and an excellent agreement is found for qb̄≲0.5 (with b̄ being the mean particle diameter) both above and below the glass transition without any fitting parameters. Our data are consistent with recently predicted (both theoretically and by simulations) long-range correlations of the shear stress quenched in heterogeneous glassy structures.

[Prevalence of viral hepatitis B markers among blood donors in the Republic of Guinea].

INTRODUCTION: The problem of transfusion safety in relation to parenteral viral hepatitis still remains relevant. Viral hepatitis B (HB) remains the most common viral infection transmitted through transfusion procedures. One of the natural phases of chronic hepatitis B (CHB) is occult hepatitis B infection (OBI), characterized by an undetectable HBsAg (regardless of the other serological markers content) in the presence of hepatitis B virus (HBV) DNA in the liver tissue and an extremely low, up to undetectable, level of viral load in the blood. In the Republic of Guinea, as in most countries on the continent, the prevention of HBV transmission through transfusion is still based on HBsAg serological testing of donors only. In this connection, OBI remains as a potential threat to blood transfusion safety. Detection of HBV DNA is a reliable preventive measure against transmission of the virus from donors with HBsAg-negative HBV infection, especially in highly endemic regions. In this regard, the study was conducted to substantiate recommendations for improving blood safety against the background of significant HBV prevalence in the Republic of Guinea.The aim of the work was the evaluation of serological and molecular markers of HBV infection in blood donors in the Republic of Guinea. MATERIAL AND METHODS: We examined 250 blood samples obtained from donors living in Conakry, Republic of Guinea. Samples were tested for the presence of serological (surface antigen, HBsAg; antibodies (ABs) to surface (anti-HBs IgG) and core (anti-HBc IgG) antigens) and molecular (DNA) markers of HBV infection. RESULTS AND DISCUSSION: The overall detection rate of hepatitis B markers was 83.2%; HBsAg was detected in 16.4% of all individuals. The high incidence of HBsAg in men (19.55%) compared to women (8.45%) was shown, the relative risk of HBV infection with the formation of HBsAg-positive chronic hepatitis B in males was also significantly higher. The prevalence of the HBV DNA in the study group was 30.4%, the OBI cases accounted for 15.6%. The prevalence of this form of the disease was shown in donors aged 30-49 years (24.78%), in the group of people younger than 30 years, the incidence was lower (8.73%), and at the age of over 50 years, OBI was not detected. Based on the phylogenetic analysis of 76 virus isolates, it was shown that genotype E prevails in the examined group (85.53%).Cases of pathogen DNA detection occurred in HBsAg-negative blood donors in the presence of anti-HBs IgG (n = 4), as well as in the simultaneous presence of ABs anti-HBs IgG and anti-HBc IgG (n = 7). The viral load exceeded 200 IU/ml in OBI samples. Escape mutations were detected by sequencing in each OBI sample, contributing to the virus escaping from diagnostic based on screening for HBsAg. CONCLUSION: Assessment of the prevalence viral hepatitis B markers in blood donors, determination of genotypes and clinically significant mutations of virus variants are necessary to ensure safe medical manipulations, control and prevention of the spread of this infectious agent.

Algorithm for laboratory diagnostics of parvoviral infection in risk groups.

Parvovirus infection (PVI) is widespread, characterized by airborne, bloodborne and vertical transmission routes. Parvovirus B19 (PVB19) exhibits tropism to erythropoietic cells. According to the increased likelihood principle of PVB19 infection and the severity of the consequences, immunocompromised individuals, especially those with hematological manifestations of diseases, are in increased risk group. Based on the own research results and analysis of the published data, we have proposed specific algorithms for PVI laboratory testing in individual risk groups, taking into account the peculiarities of the development and infection manifestation in each group: in HIV-infected patients, in oncohematological patients with to whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been prescribed (blood and bone marrow recipients), as well as in patients with chronic anemia of parasitic etiology. For each group, the main clinical or laboratory marker, treatment procedure, or patient physiological parameters have been determined, based on which it was recommended to test for PVI. For HIV-infected patients, the main criterion for PVI testing is persistent anemia. For oncohematological patients, the basis for PVI testing is allo-HSCT procedure, which is planned or performed for this particular patient. For malaria patients, the patient's age was considered as major criterion, since in malaria and PVI coinfected young children can lead to a fatal outcome. The proposed PVI diagnostics algorithms usein risk groups can help to predict the severe course of underlying disease associated with PVB19 infection, and timely correct the therapy used.