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Aim To evaluate safety of using rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or transient, stable decline of glomerular filtration rate (GFR) to 15-29 ml /min / 1.73 m2 in the presence of atrial fibrillation (AF).Material and methods This multicenter prospective, randomized study included patients admitted to cardiology departments from 2017 through 2019. Of 10 224 admitted patients 109 (3 %) patients with AF and stage 4 CKD or a stable decline of GFR to 15-29 ml /min / 1.73 m2 were randomized at 2:1 ratio to the rivaroxaban 15 mg /day (n=73) treatment group or to the warfarin treatment group (n=36). The primary endpoint was development of BARC and ISTH major, minor, and clinically relevant minor bleeding. Mean follow-up duration was 18 months.Results Patients receiving warfarin had a significantly higher incidence of BARC (n=26 (72.2 %) vs. n=31 (42.4 %), р<0.01) and ISTH (n=22 (61.1 %) vs. n=27 (36.9 %), p<0.01) minor bleeding and all ISTH clinically relevant (minor clinically relevant and major bleedings) n=10 (27.7 %) vs. n=8 (10.9 %), р=0.03]. The number of repeated hospitalizations was 65 (43% of patients) in the rivaroxaban treatment group and 27 (48% of patients) in the warfarin treatment group (р=0.57), including 24 (36.9 %) and 11 (40.7 %) emergency admissions in the rivaroxaban and warfarin treatment groups, respectively (р=0.96). Significant improvement of changes in creatinine clearance and GFR (by CKD-EPI and Cockroft-Gault) was observed in the rivaroxaban treatment group.Conclusion The study provided evidence for a more beneficial safety profile of rivaroxaban compared to warfarin in patients with AF and advanced CKD.

Glucan linked to proteins is a natural mega-glycoconjugate (mGC) playing the central role as a structural component of a yeast cell wall (CW). Regulation of functioning of non-covalently bound glucanosyltransglycosylases (ncGTGs) that have to remodel mGC to provide CW extension is poorly understood. We demonstrate that the main ncGTGs Bgl2 and Scw4 have phosphorylated and glutathionylated residues and are represented in CW as different pools of molecules having various firmness of attachment. Identified pools contain Bgl2 molecules with unmodified peptides, but differ from each other in the presence and combination of modified ones, as well as in the presence or absence of other CW proteins. Correlation of Bgl2 distribution among pools and its N-glycosylation was not found. Glutathione affects Bgl2 conformation, probably resulting in the mode of its attachment and enzymatic activity. Bgl2 from the pool of unmodified and monophosphorylated molecules demonstrates the ability to fibrillate after isolation from CW. Revealing of Bgl2 microcompartments and their mosaic arrangement summarized with the results obtained give the evidence that the functioning of ncGTGs in CW can be controlled by reversible post-translational modifications and facilitated due to their compact localization. The hypothetical scheme of distribution of Bgl2 inside CW is represented.

Objective: To estimate the prevalence of chronic kidney disease (CKD) 3b - 5 stages and the newly diagnosed sustained reduction in glomerular filtration rate (GFR) <30 ml / min / 1.73 m2 in patients with atrial fibrillation (AF) in real clinical practice, as well as the features of their anticoagulant therapy., Materials and Methods:  Retrospectively, data of all discharge epicrisis from cardiological departments of five Moscow hospitals from June 1, 2016 to May 31, 2017 were analyzed. Patients over 18 years old with AF were enrolled. At the next stage, patients with CKD 3 b - 5 st and newly diagnosed sustained reduction in GFR <30 ml / min / 1.73 m2 (at least 2 measurements during hospitalization) were selected., Results: Data of 9725 patients were analyzed, AF was diagnosed in 2983 (31 %) cases, of which a decreased GFR <45 ml / min / 1.73 m2 was detected in 27 % (n = 794) cases. Among them, 349 (44 %) were diagnosed with CKD 3b st, 123 (15 %) with CKD 4 st, 44 (6 %) with CKD 5 st, 278 (35 %) had a newly diagnosed sustained reduction in GFR. In 63 % of patients with AF and GFR <45 ml / min / 1.73 m2, anemia was diagnosed, 39 % of them had moderate and severe one. 711 (89 %) patients were prescribed anticoagulants, 53 % were assigned direct oral anticoagulants (DOACs). Patients with CKD 3 b st. more often rivaroxaban 15 mg (29 %) was prescribed, with CKD 4 and CKD 5 - warfarin (48 % and 25 %, respectively), in patients with newly diagnosed sustained reduction in GFR <30 ml / min / 1.73 m2 - apixaban 10 mg / day (16.2 %)., Conclusion: A quarter of patients with AF revealed a decreased GFR <45 ml / min / 1.73 m2, half of them were recommended DOACs. 42 % of patients with GFR <30 ml / min / 1.72 m2 were prescribed DOACs, 27 % - warfarin. Patients with CKD 5 st DOACs were not assigned; in half of cases, none of the anticoagulants was recommended. Most often, the dose of the prescribed anticoagulant was not counted according to GFR in patients with newly diagnosed sustained reduction in GFR <30 ml / min / 1.73 m2.

Yeast cell wall GPI-anchored proteins lack the lipid part of the anchor and are covalently bound to the high-molecular-weight polysaccharides glucan and/or chitin through the mannose residues. They perform many functions, including participation in the cell wall molecular ensemble formation and providing cell resistance to stress. In this work, we identified a pool of GPI-modified proteins firmly bound to the cell wall by non-covalent interactions with the high-molecular-weight structural polysaccharides. We believe that the detected proteins are intermediate forms in the processing of the cell wall GPI-proteins, since they had already lost the lipid part of the GPI anchor and are absent in the lipoprotein fraction extracted according to Folch, but were not yet incorporated into the cell wall by the covalent binding to high-molecular-weight polysaccharides because they could be extracted into water by heating of delipidized cell walls. This group of previously unknown proteins might be present in the cell wall in a form of lipid-associated microcompartments represented by transport vesicles recently found in yeast. GPI-modified proteins non-covalently attached to the high-molecular-weight polysaccharides were found in the cell walls of both the parent strain and yeast devoid of glucanosyltransglycosylase Bgl2, which indicates that the pathway of their incorporation into the cell wall is independent on this enzyme.

Exhaled breath analysis is a novel tool for diagnostics of different diseases. Taking into account the secretory function of the lungs, the composition of exhaled breath is different in physiological and pathological conditions. In this review we consider of some substances which content vary in cardiovascular diseases - pentane, isoprene, carbon monoxide and trimethylamine. Modern technologies allow to move the analysis of exhaled breath from research laboratories into clinical practice. Thus, a new tool for real time of screening various cardiovascular diseases has appeared in the arsenal of physicians.

Nowadays an invasive evaluation of fractional flow reserve (FFR) is one of the main methods used for detecting lesions that cause ischemia. Invasively obtained FFR <0.75 has the specificity of 100 %, and FFR >0.80 has the sensitivity >90 %. Recent achievements in computational fluid dynamics and computer simulations allow noninvasive assessment of FFR using data obtained by CT angiography performed according to standard protocol at rest without additional radiation, modification of image acquisition protocols, or added medications for vasodilatation. The present review covers the results of the DISCOVER, the NXT, the DEFACTO and the PLATFORM randomized multicenter studies as well as the prospects of using a noninvasive method for measuring FFR developed by specialists of the Institute of Numerical Mathematics in collaboration with specialists of the I. M. Sechenov First Moscow State Medical University.

In this research, a novel IMAC sorbent with high specificity for chlorine-containing compounds was developed. Ni-functionalized monodisperse spherical mesoporous silica particles of 500±25nm diameter were synthesized and their metal affinity properties were studied with the use of diclofenac as the model substance. The particles were aggregatively stable in the pH range of 3-12. The sorbent demonstrated a high adsorption capacity (0.60±0.06μg of DCF per 1mg of the sorbent) and high adsorption/desorption rate (20 and 5min was enough for the sorbent saturation and desorption of DCF, correspondingly). A mixture of eluents with addition of PFOS providing the almost complete recovery (98%) of diclofenac was first proposed. The monodispersity and the high sedimentation and aggregative stability of the particles provide the formation of a stable hydrosol even under ultrasound treatment which makes the mSiO 2 /Ni particles suitable for batch chromatography., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Acute cerebrovascular accident (ACVA) and transient ischemic attack are among the leading causes of morbidity, disability, and mortality in the Russian Federation and the world. Ischemic strokes account for 70-80% of all ACVAs, with 20-30% of them being associated with stenotic atherosclerosis of the brachiocephalic arteries (BCA). The paper describes modern views on the problem of asymptomatic BCA atherosclerosis and considers the possibilities of identifying risk groups among the patients with asymptomatic atherosclerosis of the BCA.

Background: Exhaled breath analysis is one of directions in the search for novel biomarkers of chronic heart failure (CHF). According.

The paper considers coronary flow in health and coronary flow autoregulation in health and disease. It gives basic methods used to estimate coronary flow reserve in patients with coronary atherosclerosis. The physiological bases for determining fractional flow reserve are presented. Clinical trials investigating the use of fractional flow reserve in patients with coronary heart disease are analyzed.

Modern medicine experiences deficit of inexpensive rapid screening technologies despite progress in the development of diagnostic methods for various diseases. A promising approach is the analysis of exhaled air known to contain thousands of volatile organic substances whose composition differs considerably in health and disease. We isolated certain compounds that may be used as biomarkers of cardiovascular pathology (nitric oxide, carbon monoxide, pentane, isoprene, acetone). There is a variety of methods for the detection of substances in the exhaled air; such as gas spectrography, mass spectrometry, etc. However, ion mobility spectrometry appears the most suitable technique for the purpose of screening studies due to its high speed and sensitivity, small size of the apparatus, and possibility to measure trace amounts of the substances of interest. Possibilities to diagnose lung cancer based on exhaled air composition are considered.

Non-contrast computed tomography (CT) of the major salivary glands was made in 127 patients, which revealed 95 space-occupying lesions (88 intraglandular and 7 extraglandular ones). Pleomorphic tumors of the parotid glands are solitary, round, high-density (29.6 +/- 4.2 HU) masses with well-defined, smooth margins. Salivary cysts were characterized by the presence of a dense capsule; the density of cyst contents was 8.0 +/- 2.0 HU. Salivary lipomas had a characteristic tomographic pattern due to the presence of adipose tissue; the lipoma density was -108.3 +/- 7.8 HU. Malignant parotid tumors were characterized by the presence of higher-density masses with irregular shapes and ill-defined, indistinct margins. Benign submandibular gland tumors had no well-defined margins that separated the tumor from the gland; the density of a tumor matched that of the parenchyma; the mean tumor size was 3.6 +/- 1.3 cm; there was an increase in the sizes of the gland as compared to those of the contralateral gland, as well as a displacement of the adjacent soft tissues. Malignant submandibular gland neoplasms tumors were characterized by the presence of inhomogenous lower-density masses with irregular shapes. Enlarged paraglandular lymph nodes were observed. The sensitivity, specificity, and accuracy of native CT in diagnosing space-occupying lesions of the salivary glands were 97.6, 96.4, and 97.6%, respectively.

The condition of mediatory systems, those of serotonin-, dopamin- and cholinergic, were studied in liquidators of the accident at the Chernobyl power station 15 year after the accident during the reaction of rosette-formation. The results showed an activated status of the studied serotonin- and cholinergic systems.

The outflow of viscous incompressible fluid from catheter holes into a small gap between the catheter and surrounding elastic tube is considered. Initially, the catheter is inserted into the tube lumen in such a manner that a considerable tube wall prestress exists. An additional longitudinally non-uniform external load is applied to the outer tube surface. The procedure of measuring the urethral "pressure profile" is discussed. It is shown that there is no easy way for extracting the external load (muscle forces in reality) from the measured pressure.

The functional-and-metabolic status of neutrophil granulocytes was studied in liquidators of consequences of the accident (LCA) at the Chernobyl nuclear power station (CNPS) by using the nitroblue tetrazolium test (NTT). Tests, involving the recovery of nitroblue tetrazolium in both spontaneous and stimulated variants, were made in LCAs and the obtained data were compared with the results of similar tests in the control groups. High NTT parameters were found in spontaneous tests. A lack of the activation in response to zymosan is a specific feature of LCA blood granulocytes. Profound disorders were detected in the phagocyte systems of LCAs, which is indicative of disrupted enzymatic processes in neutrophil granulocytes. On the whole, a sharp functional reduction of neutrophils inhibits their bactericidity. The obtained results were used to work out and to patient "The method of detecting a radioactive irradiation of the body."

It is established that ethyl alcohol exhibits both immune and autoimmune effects. The blood of healthy people always contains a small amount of ethanol- and dopamine-sensitized lymphocytes and autoantibodies specific to these compounds. The ability of lymphocytes to interact with ethanol or dopamine bound to erythrocytes shows evidence that the corresponding receptors are available on the erythrocyte membrane. The action of ethanol upon these receptors leads to the development of immune response in vivo and ex vivo. The administration of ethanol is accompanied by an increase in the number of ethanol-sensitive lymphocytes which can be detected, thus indicating the presence of excess ethanol. The blood of patients with alcohol addiction contains of ethanol- and dopamine-sensitized lymphocytes and anti-ethanol antibodies. This is indicative of the permanent pathologic synthesis of autoantibodies specific to ethanol and dopamine. These data confirm the concept of the immune mechanism of chemical homeostasis, according to which the immune system participates in regulation of these biologically active agents and in maintenance of the chemical homeostasis in the organism. These conclusions extend our notions about the immune and autoimmune aspects of pathogenesis of the chronic alcohol intoxication and constitute a basis for further development of the laboratory diagnostic methods.

The method for laboratory diagnosis of multiple sclerosis (MS)--the loading serotonin test in vitro based on a specific type of interaction between MS patient's blood lymphocytes and serotonin--is suggested. An examination of 56 MS patients, 12 patients with vertebrale nervous system pathology, 33 patients with MS phenocopies and 19 healthy subjects revealed an initial low serotonin rosette-forming cell (RFC) content in MS patients, comparing to all the subjects studied. In contrast to healthy subjects and patients with other neurological disorders, serotonin receptor lymphocyte expression in MS patients does not change during serotonin stimulation in vitro and serotonin RFC number does not increase. The type of interaction is specific and selective, being confirmed in reaction of rosette-formation by serotonin excess and by the results of rosette-formation reaction with other biologically active components (histamine, nor adrenaline). A serotonin reception inhibition, specific for MS, can be determined already in the disease debut, regardless of patient's gender and age, clinical type, disease stage and duration, which proves to be of most importance. The loading serotonin test indexes are significant for differential diagnosis. The method patented in 1999 is realized in vitro, excludes a double blood collection that reduces allergy and infection danger for patients is easy to make and cost-effective.

The results of many experiments and clinical observations showed that each chemical agent and its metabolites introduced into or mobilized in the organism act, along with others, on the lymphoid cells obligatorily inducing a polyclonal immune response directed at restoration of the chemism of the internal medium. The specificity of the response is attested by the absence of intensification of the immune rosette formation phenomenon in administration of a chemical agent of a different structure into the animal, as well as when erythrocytes, sensibilized by some other chemical agent not introduced or freed in the organism is used in the reaction. That an excess of the agent saturates the receptors of cells only specific of its clone testifies to the monospecificity of each of the lymphocyte clones. Our data are in agreement in this respect with one of the main postulates of immunology on the narrow specialization and strict manner of clone formation of the lymphocyte B-pool. Our data may possibly set the way for understanding the phenomenon of the polyclonal character of the immune response to various antigens and effects. We studied intensified immune responses specific of endobiotics, in exposure of the lymphocytes of animal organs to the effect fo PGA, tuberculin, antiglobulin sera, foreign protein, genetically foreign cells (sheep erythrocytes), microbial antigens and toxins. This, possibly, underlies the well known phenomenon of synthesis of nonspecific immunoglobulins in the organism in response to the effect of an antigen, the mechanism of which is still not clear.

In a blood of 37 patients with different forms of myasthenia (M) there was found an increase of a number of rosette-forming lymphocytes specific to acetylcholine in a specific rosette-forming reaction with acetylcholine erythrocytes' diagnostic kit. A value of this index correlated with a duration of the disease, with a degree of its generalization, with a degree of its severity and with the type of myasthenic process' course. Meanwhile, it wasn't depended on the age of the patients. In a blood of both healthy individuals and the patients with some other neurologic diseases a number of rosette-forming lymphocytes specific to acetylcholine was considerably lower. A number of the lymphocytes specific to acetylcholine was increased even in the debut of M and remained altered during all the period of the disease. That may serve as an additional diagnostic marker of M in any age, at different character and severity of the disease, in any phase of this pathology.

Using the data on increased level of opioids in the internal media of patients with multiple sclerosis it was found that blood lymphocytes from MS patients had elevated adhesive activity to opiates, including morphine, in the reaction of specific rosette formation. Immunopharmacologic method for MS diagnosis is proposed based on detection of considerably increased level of the rosette forming cells, specific to morphine (morphine test). This test is a reliable additional marker for all clinical forms of the disease and provides differential diagnosis of both MS and some other diseases with similar clinical symptomatology at any age, any duration and a character of a course of the disease.

The immune response to sheep erythrocytes (SE) is usually used as the indicator system in screening of immunotropic compounds. We had shown earlier that a rapid immune reaction develops in response to a chemical compound (drug). It is characterized by an increase in the number of antigen-recognizing and antigen-producing lymphocytes and their blast forms, titers of antibodies specific of the introduced compound and endobiotics mobilized under its effect.

Phosphacol drops applied to the eye of a mouse caused an immediate response of the blood lymphocytes. The number of phosphacol-immune rosette-forming and blast forms of lymphocytes increased. The response is specific since the formation of rosettes is blocked by the excess of phosphacol in vitro and does not occur when rausedyl-sensibilized erythrocytes are used. The formation of blast forms is intensified after small doses of phosphacol (10-9), but not rausedyl, are put into a suspension of blood cells. The technique proposed may be used for determination of phosphorus-containing compounds in the organism and the diagnosis of poisoning with them.

Experiments on rats and on human lymphocytes have indicated that a prompt immune response to low-molecular-weight biologically active agents is thymus-dependent, calls for cooperative interaction of T and B lymphocytes and macrophages, it is enhanced by T mitogens and implemented through the specific pharmacological receptors of T and B lymphocytes. The findings offer ample scope for controlling the immune mechanisms of habituation to drugs and poisons.

The ability of the blood sera from patients with disseminated sclerosis (DS) to lyse native sheep red cells but not any other red cells was revealed. A method for the diagnosis of DS was developed: sheep red cells hemolysis test (SRCHT). The test was positive in all DS patients (altogether 96 cases) and negative in the controls. The hemolysin titer correlated with the disease severity, SRCHT permitted the diagnosis of DS long before manifestation of clinical symptoms.

An early triggering of the immune mechanism of chemical homeostasis occurs in response to intravenous, intraperitoneal or intramuscular injection of drugs affecting the content of endogenous compounds of the mediator, enzymatic and hormonal type. This response is accompanied by morphological and functional changes in lymphoid cells of blood and organs as confirmed by immune rosette-formation and blast transformation, by variation of intercellular interactions that manifest in activation of immunocytoadhesion, in an increase in the titers of antibodies to the drug administered and in those of autoantibodies to the endogenous compounds that realize the drug effect. It has been shown that lymphocyte receptors specific for the endo- and exogenous compounds participate in the cell immune response to a chemical agent that might be pharmacologically monitored by means of the action of antagonists of the endogenous mediators on the receptor structure.

A high-sensitive "immune" proserine++ test was developed for the early detection of myasthenia, especially of its concealed and unclear forms. The results are derived from counting Ach-ROK immune to blood acetylcholine (Ach) before and 30 min after subcutaneous proserin administration. A high (over 10%) baseline Ach-ROK blood count which fell sharply after proserin injection was characteristic of myasthenia patients as compared to controls (under 10%). The reverse was found in healthy individuals and patients with other nervous diseases: an increase of ROK up to 24-39%.

In the study of obtained data on the part of immune mechanism in maintaining chemical homeostasis the authors found, by means of in vitro experiments, certain properties characterizing participation of the lymphatic apparatus of various rabbit and rat organs in the synthesis of antibodies against mediators, their metabolites, enzymes and hormons in comparison with effect of stimulators, [fytohemagglutinin, staphylococcal filtrate, xenogenic mixed lymphocytic cultures], active and passive immunization of potential cell preparations for the production of specific autoantibodies. Formation of the mechanism is shown on ontogenesis. It was ascertained that pathologic processes [adjuvant arthritis, rejection reaction, immobilization stress, sepsis] essentially act upon conditions of the immune mechanism of chemical homeostasis.

It has been shown that rausedyl administration is followed by enhanced synthesis of autoantibodies to serotonine and adrenaline. Meanwhile bucarban enhances the synthesis of autoantibodies to endogenous insulin and ACTH to hydrocortisone and testosterone. Activation of the autoimmune system of regulating the balance of endogenous compounds was shown by an increased number of specific antibody-producing cells in the organs and tissues and by the growth of the titer of circulating antibodies in the blood.

In blood of patients with diabetes mellitus receiving bucarban or adebit antibodies to these drugs were discovered. Patients medicated with bucarban demonstrated an elevated content of antibodies to insulin. The appearance of specific antibodies occurred in rabbits and rats following introduction of bucarban, glucophage or adebit per se or when mixed with adjuvants. An increased production of antibodies to endogenous insulin was observed in all animals reveiving bucarban. Introduction to rats of inactivated (at 56 degrees C for 30 minutes) serum of patients with diabetes mellitus that contained antibodies to bucarban or adebit as well as immune rabbit sera greatly mitigated the hypoglycemic effect of the latter. Introduction to rats of the blood serum taken in patients reveiving bucarban allso attenuated the effect of exogenous insulin. These findings suggest that, possessing neutralizing properties, these antibodies to bucarban, adebit and glucophage cause habituation to these substances. Accumulation in the blood of autoantibodies to insulin following introduction of bacarban reduces the sensitivity to the exogenous hormone and manifests the existence of an immune mechanism securing the preservation of chemical homeostasis in the organism.

Experiments on animals were made to study the diabetogenous effect of repeated administrations of bucarban. The drug-induced immunization and insulin release were accompanied by the increased immune response of the humoral and cellular types specific for bucarban and insulin as well. The changes in the animals' immune status were accompanied by disorders of carbohydrate and lipid metabolism, characteristic for diabetes mellitus and by a lowering of the hypoglycemic effect of the antidiabetic drug in question. It was shown for the first time that the changes in carbohydrate, lipid and lipoprotein blood indicators seen in the animals given sulfanilamide antidiabetics occur in the presence of intense autoimmune response to the body own insulin and are undoubtedly related to this response.

Experiments conducted on rabbits demonstrated formation of antiserotonin antibodies in response to introduction to the animals of a serotonin-proteinic conjugate. The effect of antibodies on the development of a serotonin- and dextran-induced inflammation in rats and on the serotonin level in cells of slices of their organs, as well as in the blood thrombocytes was studied. The antibodies were found to produce an antiphlogistic effect in regard to exogenous (serotonin-induced) and endogenous (dextran-induced inflammation) serotonin. Histochemical investigations showed the antibodies to exert a neutralizing action on intracellular serotonin.

Specific autoantibodies of neutralizing character to histamine, serotonin, kallikrein, bradykuinine, acetylcholine, adrenalin, noradrenalin, insulin, and to the serotonin metabolite--5-hydroxyindolacetic acid, were found in donor serum (47.2%) and in intact rabbits, guinea pigs, rats, and mice (24.4%). Anti0odies to histamine, serotonin, kallikrein were found in a number of samples of commercial gamma-globulin. They were relatively often observed during the morning and day-time hours, in summer and in winter, in luteal phase of menstrual cycle, early in pregnancy (6-8 weeks), after surgical treatment, burns, inflammation, administration of foreign albumin, in the course of immunization by different antigens. The results of fractional analysis of serum showed that antibodies belonged to immunoglobulins with the constant of sedimantation 7S and 19S. The data obtained suggest the existence of an immune mechanism for the content regulation of different substances of endogenous origination in any organism.

Experiments with rabbits showed the formation of antibodies in response to introduction of histamine-, serotonin-, kalllikrein-, bradykinin-proteinic conjugates. The influence of antibodies on the exudative reaction following introduction of histamine, serotonin, kallikrein, bradykinin, dextran and agar to rats was studied. The ability of antibodies to block both the introduced from outside specific mediators of inflammation and their natural analogues is demonstrated. This bears proof to the possibility of utilizing the specific antibodies in the study of the mediating structure common to various types of inflammation and for the regulation of the inflammatory process.