Репозиторий Университета

© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. AIM To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection. METHODS Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (doubleblind phase), and during 24 wk of DUAL in both arms combined. RESULTS I n total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistanceassociated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths. CONCLUSION DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

© 2017 Elsevier B.V. Two series of palladium(II) and platinum(II) complexes featuring esters of tetrazol-1-yl and tetrazol-5-ylacetic acids {trans-[PdCl2L2] and trans-[PtCl2L2], L = 5-methyl-1H-tetrazol-1-ylacetic acid and its ethyl, butyl, isobutyl esters (1–5); 2-R-2H-tetrazol-5-ylacetic acid and its ethyl esters, R = tBu, CH2CH2OH (6–10)} were synthesized and their binding to calf-thymus DNA (CT DNA) and bovine serum albumin (BSA) were studied by means of experimental (CD, UV, viscometry, fluorometric and electrophoretic techniques) and theoretical methods. According to the spectrophotometric data, the interaction of the metal complexes with CT DNA is observed. The significant increase of melting point of CT DNA in the presence of the metal complexes (ΔTm = 8–13 °C) indicates strong stabilization of the DNA helix. Electrophoretic studies demonstrate the ability of the metal complexes to interact with pBR322 plasmid DNA and to change its mobility. According to the data of the fluorescence quenching technique, binding with constants (Kbin) of Pd(II) complexes with BSA are in the range 0.83–4.12 × 105 L M−1. The molecular docking studies show the minor groove binding behavior of tetrazole-containing palladium(II) and platinum(II) complexes to DNA (ΔGbinding. −5.56 − −6.12 kcal/mol) and effective binding to BSA via the favored binding site Trp213 (ΔGbinding −7.2 − −7.56 kcal/mol). The complex trans-[PtCl2(2-tert-butyl-tetrazol-5-ylacetic acid)2] exhibited noticeable antiproliferative activity in two human cancer cell lines with IC50 values of 11.40 µM in HT-29 cells and 11.02 µM in MDA-MB-231 cell line.

© 2018 Elsevier B.V. Although recent Cannabis use is widely reported to be associated with drug-related traffic accidents, the evidence that Cannabis users show an increased risk of being involved in road crashes is still not unequivocally proved. The purpose of the present work is to provide an objective assessment of this hypothesis, by comparing the frequency of occurrence of positive urine analyses in drivers involved in traffic accidents (n = 1406) with that observed in a control population undergoing mandatory urine drug testing (n = 1953). Urine analyses for drugs of abuse were performed by screening immunometric techniques followed by confirmation with UHPLC-QQQ MS, adopting a cut-off concentration for THC-COOH of 15 ng/mL. A case was classified as “positive” when a driver admitted to hospital for road traffic injuries showed urine concentrations of THC-COOH higher than the cut-off. All samples showing positive results for any other controlled drug in urine or blood alcohol concentrations >0.5 mg/mL were excluded from the study. Subjects positive to THC-COOH, and negative to all the other tested substances were 116 in Group 1 (8.2%) and 16 in Group 2 (0.8%). Subjects resulting negative to any tested substances were 1290 in Group 1 and 1937 in Group 2. The frequency of THC-COOH detection in the two groups was compared by using the “chi square” test, which resulted = 119.57, i.e. highly significant (P <<< 0.01). The Odds Ratio of the two groups was =10.88, showing a high degree of association between the presence of THC-COOH in urine and the occurrence of traffic accidents (P < 0.0001). The presented data, proving a high degree of association between Cannabis use and the occurrence of traffic accidents with injuries of the driver, support the use of urine testing for Cannabis in the procedures for the issuing of the driving licence, particularly in the case of subjects formerly or presently using Cannabis. This finding looks even more relevant in the present times, because of the increasing success of the policies of legalization of Cannabis for medical and non-medical purposes.

© 2017 IEEE. The paper presents the study of the effect of radiation dose due to gamma background from construction materials in the Volgograd region on the exposure of the population and the identification of possible impacts. Methods to protect the population from the effects of natural radionuclides are suggested. Direct studies have established the absorbed dose rate of the Volgograd region inside wooden, brick and concrete buildings in Volgograd region. The analysis of the frequency distribution of the effective specific activity of natural radionuclides in building materials was conducted. It was found that the population of the Volgograd region is exposed to more radiation from building materials than in Russia on average. It is found that the dose received by the human body over a long period, results in a more serious injury than the same dose received in a short period.

© 2018 The Royal Society of Chemistry. A method for the generation of the CF3 radical from CF3-substituted borate complexes bearing a pyridine-N-oxide ligand is described. Cleavage of the C-B bond occurs via single electron reduction by a Cu(i) photocatalyst activated by visible light.

Despite a steady tendency of decreasing of indices of morbidity of tuberculosis of population of the Chechen Republic, the problems related to early diagnosis of tuberculosis and organization of specialized medical care of patients continue to be unresolved. The questionnaire survey of administrators of anti-tuberculosis medical organizations of the Chechen Republic was carried out with the purpose of establishing difficulties in medical care support of patients with tuberculosis and determining main directions of their overcoming. The results of study demonstrated that main problems are asocial behavior of patients, inadequate staffing of institutions with medical and paramedical personnel, absence of proper relationship with other medical organizations, inadequate level of financing. The administrators indicated as main directions of solving problems increasing of remuneration of labor of medical personnel of anti-tuberculosis medical organizations, development of social defense of patients, physicians and population, alteration of actual normative legal base according to modern social economic conditions, enhancement of preventive direction of work, optimization of manning table and standards of work load of physicians and also development of tactics of treatment and re-organization of dispensary observation of patients with tuberculosis.

Nowadays, the breast-feeding, despite the approved advantages, is not a standard in many communities. The multi-factorial determinants determining its prevalence need to be supported at various levels - from legal and legislative one to views and values of society, conditions of women's labor and also health care system that can develop a favorable environment for breast-feeding. The breast-feeding effects positively on health, economic development and ecology and therefor it is a benefit for children, women and whole society in short-term and long-term perspective. The defense, propaganda and support of breast-feeding need a political will, and financial investments to implement its advantages.

The article considers actual national and international publications concerning problems of organization and characteristics of stomatological care support of patients with particular types of somatic pathology. The new approaches are analyzed concerning organization of efficient stomatological care of patients with various diseases.

© 2018, Pediatria Ltd. All rights reserved. Clinical guidelines for the selection and use of antibiotics (AB) for common and most important community-acquired infections are aimed at increasing the treatment efficacy and overcoming growth of bacterial pathogens resistance to AB. They are based on the principle of positive ratio of «benefit/risk» of AB and selection of primary and alternative drugs. The article presents Russian and foreign data on pediatricians preferences in the choice of AB for ARI in children, on the level of Streptococcus pneumoniae resistance to penicillins and macrolides and other respiratory bacterial pathogens to macrolides in Russia (including the pediatric population) and abroad, which led to similar changes in grouping of AB in the Eurasian clinical recommendations and WHO recommendations. It demonstrates a significant coincidence of the AB choice for community-acquired pneumonia and acute bacterial rhinosinusitis in children in comparable recommendations with the recognition of amoxicillin as the first choice drug and the general tendency to restrict the use of macrolides. It also points on the need to control the AB use.

© 2018 Meditsina Publishers. All rights reserved. NLR family of receptors are important members of the innate immunity that respond to exogenous pathogens and endogenous danger signals. Activation of NLR leads to formation of a multimolecular complex called an inflammasome. This complex is used to drive the processing and release of pro-inflammatory cytokines IL-1β and IL-18. Defects in regulation of an inflammasome activation underlie the development of a series of autoinflammatory diseases such as cryopyrin-associated periodic syndromes, familial Mediterranean fever and others. In this review we discuss forms of pathology associated with mutations and gene polymorphism of inflammasomes NLRP3, NLRP1, NLRС2 and NLRP12.

© 2018 International Society for Cellular Therapy Background: Menstrual blood is only recently and still poorly studied, but it is an abundant and noninvasive source of highly proliferative mesenchymal stromal cells (MSCs). However, no appropriate isolation method has been reported due to its high viscosity and high content of clots and desquamated epithelium. Methods: We studied three different isolation approaches and their combinations: ammonium-containing lysing buffer, distilled water and gradient-density centrifugation. We tested the proliferative capacity, morphology, surface markers and pluripotency of the resulting cells. Results: Our isolation method yields up to four million nucleated cells per milliliter of initial blood, of which about 0.2–0.3% are colony-forming cells expressing standard mesenchymal markers CD90, CD105 and CD73, but not expressing CD45, CD34, CD117, CD133 or HLA-G. The cells have high proliferative potential (doubling in 26 h) and the ability to differentiate into adipocytes and osteocytes. Early endometrial MSCs (eMSCs) express epithelial marker cytokeratin 7 (CK7). CK7 is easily induced in later passages in a prohepatic environment. We show for the first time that a satisfactory and stable yield of eMSCs is observed throughout the whole menstrual period (5 consecutive days) of a healthy woman. Discussion: The new cost/yield adequate method allows isolation from menstrual blood a relatively homogenous pool of highly proliferative MSCs, which seem to be the best candidates for internal organ therapy due to their proepithelial background (early expression of CK7 and its easy induction in later passages) and for mass cryobanking due to their high yield and availability.

© 2018 The Author(s) Published by S. Karger AG, Basel. Background: The most common functional gastrointestinal disorders (FGID) are functional dyspepsia (FD) and irritable bowel syndrome (IBS), with a prevalence in the general population of 15-20% (FD) and 10% (IBS), respectively. The complexity of pathophysiologic mechanisms and limitations in therapeutic options make the management of FD and IBS patients a challenge in routine clinical practice. Summary: Syndromes classified as FGID frequently overlap, and coexist with gastroesophageal reflux disease (GERD). Patients with overlapping symptoms are more likely to seek medical care. The challenge for routine clinical practice is to find the best approach for treatment of multiple symptoms. STW 5, a combination of 9 herbal extracts, was shown to have multi-target effects: it normalizes the disturbed gastrointestinal motility, alleviates hypersensitivity, inhibits inflammation, suppresses gastric hypersecretion, and modulates the microbiota. Controlled randomized studies proved STW 5 to be efficacious both in FD and IBS, with control over the full spectrum of upper and lower gastrointestinal symptoms. STW 5 reduced concomitant heartburn in FD patients. STW 5 was well tolerated in the examined populations, independent of concomitant diseases and concomitant medication. Key Messages: The clinical use of the herbal preparation STW 5 in FD and IBS is evidence-based. STW 5 is an example for the concept of multi-target therapy. It offers treatment opportunities in routine clinical practice with high prevalence of overlap of FGID and concomitant GERD. Considering that FD and IBS are typically chronic and recurrent conditions, the clinically observed good tolerability and safety of STW 5 is an advantage.

© 2018, Pleiades Publishing, Ltd.  The uptake of NO 3 on a pyrene coating at [NO 3 ] = 2.5 × 10 12 –1.2 × 10 13 cm −3 is studied using a coated-insert flow tube reactor coupled to a mass spectrometer. It is established that, in this concentration range, the uptake occurs by the impact recombination mechanism, whereas the consumption of surface sites involves the unimolecular decomposition of stabilized surface complexes. Several hundreds of NO 3 radicals are consumed per surface site destroyed. The uptake coefficient depends on the exposure time, being described by the expression γ(t) = γ 0 exp(−t/τ), where γ 0 and τ are parameters dependent on the NO 3 concentration. Based on the Langmuir adsorption concept, the following elementary parameters determining the uptake process are estimated: the Langmuir coefficient, K L = 7.1 × 10 −13 cm 3 ; the desorption rate constant, k d = 44 s −1 ; and the rate constant for the unimolecular heterogeneous conversion of surface complexes, k r = 6.6 × 10 −2 s −1 . Gas chromatography–mass spectrometry measurements showed that the main products of the reaction are phthalates. The nitropyrene yield is found to be ~0.6%.

© 2018, Pleiades Publishing, Ltd. A rapid method is developed for the quantitative determination of 5–35 g/L of isonicotinic hydrazide (INH, isoniazide) in aqueous media. The method is based on the formation of copper(I) oxide in the reaction of isonicotinic hydrazide with copper ions on the surface of indicator tablets and the subsequent recording of the analytical signal by reflectance spectrophotometry and colorimetry. Aluminum oxide is proposed as a solid-phase substrate for the production of indicator tablets. Isonicotinic hydrazide can be determined in the tablet form of the Isoniazid preparation.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A validated method for quantitative determination of flupirtine in human blood plasma using liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) was proposed. Biological samples were prepared by precipitating proteins using MeOH. The chromatographic separation used a Zorbax Eclipse Plus C18 column with gradient elution. A Shimadzu 8040 triple quadrupole mass spectrometer in multiple-reaction-monitoring mode (+MRM) with chemical ionization at atmospheric pressure (APCI) was used to determine the molecular ion of flupirtine with m/z 305.2. Acalibration curve for flupirtine was linear (R = 0.994) in the concentration range 25 – 2,500 ng/mL with a lower detection limit of 25 ng/mL. Validation of the method indicated that it was highly sensitive, specific, accurate, and precise and that the analyte was stable. The method was successfully applied to comparative pharmacokinetic studies of drugs containing flupirtine.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Studies of the effects of Trichoderma harzianum Rifai F-180 culture fluid concentrate containing L-lysine-α-oxidase antitumor enzyme produced by the fungus and the homogenous enzyme, on ultrahazardous bacterium Acidovorax citrulli demonstrated the antibacterial activity of the concentrate. Trichoderma harzianum Rifai F-180 producing L-lysine-α-oxidase was cultured in a technological device at G. K. Skryabin Institute of Biochemistry and. Physiology of Microorganisms, Russian Academy of Sciences. Activity of L-lysine-α-oxidase in the resulted culture fluid concentrate was 0.54 U/ml, activity of the homogenous enzyme was 50 U/mg.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The article describes special aspects of Good Manufacturing Practice (GMP) for biomedical cell products (BMCP) that imply high standards of aseptics throughout the entire productio process, strict requirements to donors and to the procedure of biomaterial isolation, guaranty of tracing BMCP products, defining processing procedures which allow to identify BMCP as minimally manipulated; continuous quality control and automation of the control process at all stages of manufacturing, which will ensure product release simultaneously with completion of technological operations.

© 2018 John Wiley  &  Sons A/S. Published by John Wiley  &  Sons Ltd This review presents evidence that the skin mast cell, in particular the MCTC subtype, is the primary effector cell in urticaria. Mast cells are located in the upper dermis, the ideal situation for wheal formation and sensory nerve stimulation. Increased numbers of mast cells are found in both lesional and non-lesional skin in CSU and inducible urticaria. Mast cell degranulation in the area of wheals has been demonstrated repeatedly by light and electron microscopy. Histamine, PGD2 and tryptase are found in the venous blood draining wheal formation. The last 2 are specific for mast cells rather than basophils. Mast cell reactivity is increased in active urticaria by local inflammatory cytokines and neuropeptides. Mast cell cytokines and neuropeptides, particularly nerve growth factor, induce a Th2 type inflammation that is particularly obvious at the sites of whealing. In conclusion, autoimmunity, either of Type 1 viz. IgE antibodies to local autoallergens, or Type 2b, viz. IgG autoantibodies to IgE or its receptor, are considered to be the most frequent causes of CSU. In both cases, the mast cell is likely to be the axial cell in producing the wheals.