In Vitro Hemocompatibility of Arabinogalactan, Betulin, and Betulin Derivatives.

The hemocompatibility of arabinogalactan, betulin and its derivatives was evaluated in vitro and samples suitable for creation of nanostructures or materials in contact with blood were selected. The prospects of arabinogalactan as a component of the construct (nanostructure) for drug delivery are due to the fact that it did not affect blood/plasma coagulation (at concentrations of 0.0033-3.333 mg/ml and 0.00465-4.65 mg/ml, respectively), platelet aggregation (0.00182-0.182 mg/ml), and demonstrated the degree of erythrocyte hemolysis less than 3%. Sodium salt of betulin monosulfate, diarginine salt of betulin disulfate (up to 0.465 mg/ml), and especially betulin and allobetulin formate with procoagulant properties (degree of hemolysis less than 2%) can be used to create a material, for example, sponge, gel, active against blood coagulation.

Hemocompatibility of Galactomannan and Galactoglucomannan Sulfates in In Vitro Experiments.

We identified compounds that do not independently provoke aggregation of human platelets and do not affect hemolysis of human erythrocytes in vitro: lacking anticoagulant activity sulfated galactoglucomannan (polydispersity 1.43; degree of sulfation 0.66) in concentrations ≤0.2 mg/ml; exhibiting anticoagulant activity (in concentrations up to 0.002 mg/ml) sulfated galactoglucomannan (polydispersity 1.5; degree of sulfation 1.81) and galactomannan obtained by sulfation with the sulfamic acid-urea complex (polydispersity 2.75; degree of sulfation 1.25) and galactomannans obtained by sulfation with chlorosulfonic acid in 1,4-dioxane (polydispersity 1.61/22.27; degree of sulfation 1.00/0.74).

Direct visualization and correlation of liver stereotactic body radiation therapy treatment delivery accuracy with interfractional motion.

This study used the visualization of hypo-intense regions on liver-specific MRI to directly quantify stereotactic body radiation therapy (SBRT) spatial delivery accuracy. Additionally, the interfractional motion of the liver region was determined and compared with the MRI-based evaluation of liver SBRT spatial treatment delivery accuracy. Primovist® -enhanced MRI scans were acquired from 17 patients, 8-12 weeks following the completion of liver SBRT treatment. Direct visualization of radiation-induced focal liver reaction in the form of hypo-intensity was determined. The auto-delineation approach was used to localize these regions, and center-of-mass (COM) discrepancy was quantified between the MRI hypo-intensity and the CT-based treatment plan. To assess the interfractional motion of the liver region, a planning CT was registered to a Cone Beam CT obtained before each treatment fraction. The interfractional motion assessed from this approach was then compared against the localized hypo-intense MRI regions. The mean ± SD COM discrepancy was 1.4 ± 1.3 mm in the left-right direction, 2.6 ± 1.8 mm in an anteroposterior direction, and 1.9 ± 2.6 mm in the craniocaudal direction. A high correlation was observed between interfractional motion of visualized hypo-intensity and interfractional motion of planning treatment volume (PTV); the quantified Pearson correlation coefficient was 0.96. The lack of correlation was observed between Primovist® MRI-based spatial accuracy and interfractional motion of the liver, where Pearson correlation coefficients ranged from -0.01 to -0.26. The highest random and systematic errors quantified from interfractional motion were in the craniocaudal direction. This work demonstrates a novel framework for the direct evaluation of liver SBRT spatial delivery accuracy.

Preparation of Type II Collagen Short Peptides: Temperature Conditions of Cartilage Homogenization and Collagen Hydrolysis.

Physicochemical properties of hyaline cartilage homogenates were studied by the method of microcalorimetry. Collagen hydrolysates were obtained after homogenization of hyaline cartilages under high pressure conditions at the temperatures that denaturate collagen. Thermodynamic parameters of thermal transition of collagen in cartilage suspension were determined. Enthalpy of thermal transition ΔН decreases in comparison with the control. Thermal transition half-width ΔТ varies with temperature. More denatured and homogeneous samples were obtained at homogenization temperature 80°C. According to spectral studies, particles in the samples obtained at the temperature of 80°C were smaller. The temperature of 80°C is preferred for homogenizing hyaline cartilages and obtaining collagen type II short peptides.

[Options for medical and psychological rehabilitation of combat veterans in the aftermath of combat stress and trauma]. / Varianty mediko-psikhologicheskoi reabilitatsii veteranov boevykh deistvii pri posledstviyakh boevogo stressa i travm.

The problem of combatants' rehabilitation in the modern world is relevant for medicine in all countries. The forms of care are inpatient, sanatorium, outpatient and polyclinic. The choice of a specific program for a combatant is based on the compilation of a personalized target map with the measurement of the functional index measurements that allow assigning patients to relevant correction groups. Three variants of programs for the combatants' rehabilitation are proposed. Each one considers such components as a regimen and drug therapy. Psychotherapy plays an important role. The volume and tasks of psychotherapeutic influences are determined taking into account the mechanisms of the disease development and the psychological state of the patient. In the process of psychotherapy, various techniques and methods are used (psychodynamic, humanistic, cognitive-behavioral). Along with traditional psychotherapeutic techniques, psychophysiological trainings using the principle of biofeedback are used. An urgent component of the rehabilitation of veterans is carrying out correctional work with their family members. An important place is given to the rehabilitation of victims' family members - work with acute grief, life crisis, and catastrophic experiences. Preserving and restoring the health of war veterans is not only a medical but also a social problem.

Study of the Blood Compatibility of Sulfated Organosolv Lignins Derived from Abies sibirica and Larix sibirica Wood Pulp.

The effects of sulfated organosolv lignins derived from fir (Abies sibirica) and larch (Larix sibirica) (SLf and SLl; 4-3-7.5% sulfur, median-weight molecular mass 2960-4888 Da), on human blood/plasma clotting, platelet aggregation, and erythrocyte hemolysis were studied in vitro. Antithrombin activities of the samples were below 2 U/mg. Specimens of SLf (sulfur content 6.5, 6.6, and 7.5%, molecular weights 3503, 3487, and 3580 Da, respectively) and SLl (4.3 and 6.3%, 2960 and 3497 Da) in a concentration of 0.01 mg/ml did not prolong the blood clotting time, did not provoke human platelet aggregation, did not destroy erythrocyte membranes, and could be used for construction of drug delivery systems. The SLf sample (6.5%, sulfur, 3503 Da) in concentrations from 0.09 to 1.82 mg/ml did not stimulate platelet aggregation, reduced ADP-induced platelet aggregation, and 2-fold prolonged the blood/plasma clotting time 2-fold in comparison with control and could be used for creation of biomaterial with clot-resistant surface.

RNA (C5-cytosine) Methyltransferases.

The review summarizes the data on pro- and eukaryotic RNA (C5-cytosine) methyltransferases. The structure, intracellular location, RNA targets, and catalytic mechanisms of these enzymes, as well as the functional role of methylated cytosine residues in RNA are presented. The functions of RNA (C5-cytosine) methyltransferases unassociated with their methylation activity are discussed. Special attention is given to the similarities and differences in the structures and mechanisms of action of RNA and DNA methyltransferases. The data on the association of mutations in the RNA (C5-cytosine) methyltransferases genes and human diseases are presented.

Tumor Cell Behavior in Porous Hydrogels: Effect of Application Technique and Doxorubicin Treatment.

The effect of porosity on diffusion characteristics of scaffolds and invasive capacity of MCF-7 and PC-3 tumor cells was studied for gelatin hydrogels. According to MTS test results, the efficiency of population of a macroporous cryogel by cells applied by different techniques increased in the following order: migration from the monolayer

Results of program acute myeloid leukemia therapy use in National Medical Research Center for Hematology of the Ministry of Health of Russian Federation.

AIM: To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. MATERIALS AND METHODS: Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses "7+3" with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. RESULTS: The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 и 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. CONCLUSION: Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

Effect of Xylan Sulfates on Coagulation of Human Blood Plasma.

Sulfated derivatives of xylan (isolated from Bétula pubéscens wood) with average molecular weight ~34 kDa, sulfur content of 11.3-17.5%, a degree of substitution of 0.74-1.64 are anticoagulants of direct type of action. Antithrombin and antifactor Xa activities in three tested xylan samples did not differ and reached 30.8-31.8 and 13.5-14.3 U/mg, respectively.

Dose Dependence of the Anticoagulant Effect of Intravenously Administered Cellulose Sulfate.

Experiments on rabbits showed that increasing the dose of intravenously administered cellulose sulfate from wheat straw (dynamic viscosity 3.4 cP, sulfur content 14.1%) increased plasma clotting time in some coagulation tests and plasma anticoagulant activity. When cellulose sulfate was administered in the dose of 1 mg/kg, plasma clotting time in the presence of the anticoagulant (5 min after administration) was ~3-fold higher than after saline administration.

Antitumor effect of arabinogalactan and platinum complex.

The article presents the results of investigation of antitumor properties of platinum-arabinogalactan complex. We showed the ability of the complex to inhibit the growth of Ehrlich ascites tumor cells. It is found that the distribution of the platinum-arabinogalactan complex is not specific only for tumor cells in mice. The complex was found in all tissues and organs examined (ascites cells, embryonic cells, kidney, and liver). The mechanism of action of the arabinogalactan-platinum complex may be similar to cisplatin as the complex is able to accumulate in tumor cells.

[DIAGNOSTIC AND THERAPEUTIC BRONCHOSCOPY IN PATIENTS UNDERGOING CARDIAC SURGERY IN INTRA- AND POSTOPERATIVE PERIODS].

The article presents research conducted to evaluate the use of diagnostic and therapeutic fiberoptic bronchoscopy in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis in patients in cardiac ICU. The paper presents the results of the study and comparison of invasive techniques for sampling from the respiratory tract for bacteriological analysis. We studied the bacterial profile of ICU, original content of the respiratory tract of cardiac patients in the intraoperative period and possible ways for prevention of VAP and tracheobronchitis in the postoperative period using bronchoscopy. In addition data on the effect of bronchoscopy on the respiratory and cardiovascular systems in cardiac surgical patients undergoing mechanical ventilation presented.

[Effect of Point Mutations in the Polymerase Genes of the Influenza A/PR/8/34 (H1N1) Virus on the Immune Response in a Mouse Model].

The vaccine strains for live attenuated influenza vaccines (LAIVs) have cold-adapted, temperature-sensitive, and attenuated phenotypes, which are guaranteed by the presence of specific mutations from the master donor virus in their internal genes. In this study, we used mutant viruses of the pathogenic A/Puerto Rico/8/34 (H1N1) that contained ts-mutations in PB1 (K265N, V591I), PB2 (V478L), and PA (L28P, V341L) genes along and/or in different combinations to evaluate the impact of these mutations in the immune responses. Sequential addition of tested mutations resulted in the stepwise decrease in virus-specific serum and, to a lesser extent, mucosal antibody levels. We demonstrated strong positive correlation between virus attenuation (virus titer in lung) and antibody titers. The ts-mutations in PB1, PB2, and PA genes are mostly involved in the modulation of the humoral immunity, but also have a moderate effect on the cellular adaptive immune response.

[THE ROLE OF MICROBIOLOGICAL MONITORING AND DRUG HISTORY IN THE EFFECTIVENESS OF ANTIBIOTIC PROPHYLAXIS AND ANTIBIOTIC TREATMENT OF INFECTIOUS COMPLICATIONS AFTER RECONSTRUCTIVE SURGERIES].

MATERIAL AND METHODS: We analyzed the results of the local microbiological monitoring carried out in 2010-2013. The monitoring included the study of biological material of patients with clinical signs of infectious and inflammatory complications after reconstructive surgery. We studied the dynamics of the isolation of major pathogens (Staphylococcus spp., Enterococcus spp., representatives of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida spp.) and their sensitivity to major antibiotics. RESULTS: We demonstrated the role of local monitoring and knowledge of the "drug history" in achieving of effective starting empirical antibiotic therapy.

[Palivizumab: four seasons in Russia].

In 2010, the Russian Federation (RF) registered palivizumab--innovative drug, based on monoclonal antibodies for passive immunization of seasonal respiratory syncytial virus (RSV) infection in children of disease severe progress risk group, which include primarily premature infants, children with bronchopulmonary dysplasia and hemodynamically significant congenital heart disease. Currently, palivizumab is included in the list of recommended medicines and medical care standards of different countries, including Russia. In the review the results of Russian research on the progress of RSV infection, its epidemiology and immunization experience gained over the 2010-2014 period are summarized in relation to the foreign data. During the four epidemic seasons palivizumab immunization covered more than 3,200 children of severe RSV infection risk group with a progressive annual increase in the number of patients who received the drug. Geography of palivizumab immunization is also greatly expanded in our country during this time. If during the first two seasons measures of immunization were taken mainly in Moscow and St. Petersburg, at the present time, thirty one territorial entities of the Russian Federation have the experience in the drug application. Analysis of the results of RSV infection immunization (made in several regions) confirms the high clinical efficacy and palivizumab safety already demonstrated in international studies. In addition, the analysis presents the potential to improve the efficiency of the integrated RSV infection immunization programs, realizing in the establishment of high-risk child group register, adequate counseling for parents, as well as the development of the routing of patients and coordination of interaction between different health institutions during the immunization.

[Clinical and bacteriological characteristic of infectious purulent complications in patients after related renal transplantation].

We investigated the frequency and characteristics of infectious purulent and non-infectious complications in living related renal transplant recipients in early postoperative period. It was identified the prevalent microorganisms in urinary tract infections and its antibiotic sensitivity: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Staphylococcus epidermidis, Enterococcus faecalis, Candida albicans. 182 strains of bacteria and Candida were isolated from urine of renal graft patients in early postoperative period (from 2 days to 3 months). The prevention and treatment schemes, antimicrobial drugs dosing regimen were developed. It leads to decrease the infectious complications rate.

[Problem of treatment for pyo-inflammatory complications caused by Acinetobacter].

The article deals with analysis of a detection frequency and antibacterial treatment resistance of Acinetobacter spp.of different species affiliation. Strains of bacteria detected in patients with pyo-inflammatory complications after surgeries (period from 2010 to 2012) were involved in the study 137 strains of Acinetobacter spp. were detected and studied Fraction of Acinetobacter spp. in 2010, 2011 and 2012 was 2.3, 3 and 3.4% respectively. Fraction of P. aeruginosain all non-fermentative Gram-negative bacteria (NFGNB) decreased by 120% and fraction of Acinetobacter spp. increased by 200-250%. Acinetobacter spp. detection frequency was not significantly changed in the period from 2006 to 2012. However the fraction of Acinetobacter spp. in NFGNB increased by 150% and was 29% in 2012. Detection frequency of A. baumanii sharply increased in 2012. A study of antibacterial treatment resistance of Acinetobacter spp. (10 antibacterial medicines) showed that Polymyxin B and E (Colistin) was the most effective medicine for A. baumanii and A. calcoaceticus infection. 85-95% of Acinetobacter spp.strains kept sensitivity to this antibacterial medicine. 66-88.9% of A. baumanii strains, 66.7-81.8% of A. alcoaceticus and 66.6% of other Acinetobacter spp. were sensitive to Tigecycline. Dioxidine effectiveness was close to Tigecycline in 66.7-80% of A. baumanii strains. 85-100% of A. calcoaceticus strains were sensitive to Dioxidine. There is a trend of decreasing of A. baumanii sensitivity to Carbapenems by 200%. Fraction of strains sensitive to Meropenem and Imipenem in 2012 was 21.4% and 16.7% respectively. All studied strains of A. lwoffi and A. haemolyticus kept sensitivity to Carbapenems. In 2012 23.8% of A. baumanii and 50% of A. calcoaceticus strains were sensitivity to Amikacin, meanwhile A. lwoffi and A. haemolyticus were not sensitive to this medicine. 31.3% of A. baumanii and 50% of A. calcoaceticus strains were sensitive to Ceftazidime/Sulbactam. 5.3% of A. baumanii and 15.8% of A. calcoaceticus strains were sensitive to Piperacillin/Sulbactam. Gentamicin effectiveness was fixed in 12.5% of A. baumanii and 45.5% of unidentified Acinetobacter-strains. Gentamicin was not effective against A. lwoffii and A. haemolyticus. Thus Polymyxins (in monotherapy or in combination with glycopeptides), Dioxidine and Tigecycline in combination with Carbapenems or Cefiazidime/Sulbactam are to be drugs of choice in treatment for pyo-inflammatory complications caused by Acinetobacter spp.

[Comparative analysis of associations of polymorphic genes F2, F5, GP1BA and ACE with the risk of stroke development in Russian and Ukrainian populations].

The comparative analysis of the associations between G20210A polymorphism of F2 gene, G1691A polymorphism of F5 gene, -5T/C polymorphism of gene GP1BA, I/D polymorphism of gene ACE and the risk of development of the stroke in two ethnical samplings--Russian and Ukrainian populations--was conducted. It was shown that the patients of the Russian population with genotype DD have a higher level of the risk of ischemic stroke development (OR = 1.4, 95% CI [1.05; 1.78], p = 0.02), whereas genotypes I/I and I/D are associated with the lower level of risk of ischemic stroke (OR = 0.7, 95% CI [0.56; 0.95], p = 0.02). In the Ukrainian ethnical sampling, differences in distribution of genotypes and alleles frequencies between patients with stroke and healthy persons upon given polymorphic locus are not significant, and I/D polymorphism of gene ACE is not associated with the risk of development of the stroke (OR = 0.8, 95% CI [0.48; 1.32], p = 0.45). The G20210A polymorphism of gene F2, G1691A polymorphism of gene F5, -5T/C polymorphism of gene GP1BA are not associated with the risk of stroke in two ethnical samplings.

[Study of membranotropic and antioxidant activity of flavonoids and their complexes with ferric iron].

We studied the interaction with liposomes and the antioxidant activity of flavonoid (quercetin, catechin, taxifolin) complexes with iron (III). It was found that the lipophilicity of complexes depends on an iron:flavonoid ratio and grows at a ratio of 1 to 1, while complexes in a 2:1 ratio were the most effective to slow down the lipid peroxidation and restore radical 2,2-diphenyl-1-pic: rylhydrazyl. Thus, the stoichiometry of complexes formed in aqueous solution, may differ from the stoichiometry of complexes that most effectively protect membranes from.peroxidation.