Clinical diagnosis of lipocalin 2 detection associated with neutrophil gelatinase (UNGAL) in urine in children with pyelonephritis debut
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01.09.2018 |
Yeremeyeva A.
Dlin V.
Korsunskiy A.
Zaykova N.
Bondarenko E.
Turina I.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018; Pediatria Ltd. All rights reserved. Search for biomarkers, reflecting the severity of inflammation and damage to kidney tissue in children with pyelonephritis is very important. Objective of the research - to study clinical significance of lipocalin 2 associated with neutrophil gelatinase (uNGAL) in urine as a marker of renal parenchymal lesion severity in children with pyelonephritis debut. Study materials and methods: 73 children with pyelonephritis debut hospitalized in the nephrologic department were examined. Children were divided into 2 groups: 1st group - 41 children with acute pyelonephritis (without USO abnormalities), 2nd group - 32 children with acute pyelonephritis combined with various abnormalities of urinary system organs. In all patients, the levels of urea, creatinine, cystatin C, procalcitonin, renal concentration capacity, uric excretion of lipocalin 2 associated with neutrophil gelatinase (uNGAL) were assessed. Results: the study revealed that the level of uNGAL/Cr excretionat the admission in children of both main groups did not differ significantly. A positive correlation was found between uNGAL/Cr value and cystatin C level in patients of the 2nd group. All children had a direct correlation between the duration of febrile fever from the onset of antibiotic therapy and the uNGAL/Cr excretion level. The study also revealed a correlation between uNGAL/Cr excretion level in the acute period of the disease and the degree of renal parenchymal lesion in children from the first and second groups confirmed by static DMCA nephroscintigraphy. Conclusion: a high urinary excretion of uNGAL/Cr in patients with acute pyelonephritis indicates a marked renal parenchyma lesion and requires static nephroscintigraphy with further observation, but not earlier than 6 months after the normalization of clinical-laboratory indicators.
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Drug Policy in the Russian Federation
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01.09.2018 |
Holownia-Voloskova M.
Vorobiev P.
Grinin M.
Davydovskaya M.
Ermolaeva T.
Kokushkin K.
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Value in Health Regional Issues |
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1 |
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© 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Objectives: To describe characteristics of the drug policy in Russia in terms of health technology assessment (HTA), registries of patients, pricing of drugs, cost-containment methods, and reimbursement of drugs. Methods: The legal and regulatory frameworks and the literature were reviewed to analyze several aspects of Russian healthcare: the scheme of cooperation between its structures, its levels, drug provision, issues related to HTA, the reimbursement system, pricing of medicines, and cost-containment methods. Results: The Russian drug policy has improved over the last few years: HTA has been developed, rules for the pricing of drugs and cost-containment methods have been established, and registries of patients have been created. The reimbursement system in Russia is different from the ones in Western Europe and consists of a few programs: reimbursement for specific categories of citizens, vital and essential drug list, list of 24 orphan diseases, list of 7 nosologies, and other programs, depending on region. Financing for drug provision in Russia is divided into 2 levels: federal and regional. There is still a lack of transparency and equality in healthcare as well as huge differences in access to healthcare, depending on region. Conclusions: The healthcare system in Russia is complicated and needs improvement. Nowadays, changes are being made; for example, there are attempts to implement HTA at federal and regional levels.
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Species specificity of rat and human α7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists
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01.09.2018 |
Yu J.
Zhu X.
Zhang L.
Kudryavtsev D.
Kasheverov I.
Lei Y.
Zhangsun D.
Tsetlin V.
Luo S.
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Neuropharmacology |
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2 |
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© 2018 Peptide and protein neurotoxins, such as α-conotoxins from Cone snails and α-neurotoxins from snake venoms, are excellent tools to identify distinct nicotinic acetylcholine receptor (nAChR) subtypes. Here we compared the rat/human species specificity of α7 nAChR towards peptide and protein neurotoxins and found that α-conotoxin analogues [K11A]TxIB and [H5D]RegIIA are much more potent on the rat versus human α7 receptor expressed in Xenopus oocytes. In the hope to determine the key residue responsible for the difference in α-conotoxin analogues affinities, ten single mutants of rat α7 nAChR were obtained because there are 10 differences in the extracellular ligand-binding domains of these species, and only K185R mutation decreased the affinity for α-conotoxins [K11A]TxIB and [H5D]RegIIA, down to their low affinities for human α7 nAChR. On the other hand, the reverse mutation R185K in human α7 nAChR resulted in the greatest increase in the affinity for both conotoxins, while a double mutation hα7[S183N, R185K] made the potency of the receptor for them as high as that of rat α7 nAChR. The effects of mutations at position 185 were investigated also with some other α-conotoxins and cobra venom α-cobratoxin and found to have similar but much less pronounced effects on their species specificity. Molecular modeling provided possible explanation for the high species selectivity of [K11A]TxIB and [H5D]RegIIA towards α7 nAChR, opening the new way for design of their analogues with improved affinity to the human receptor.
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Photosensitizing Activity of Steroid Derivatives of Pyropheophorbide in the Oxidation of Tryptophan in the Aqueous Phase
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01.09.2018 |
Solov’eva A.
Kur’yanova A.
Savko M.
Aksenova N.
Afanas’evskaya E.
Zolottsev V.
Taratynova M.
Ponomarev G.
Timashev P.
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Russian Journal of Physical Chemistry A |
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0 |
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© 2018, Pleiades Publishing, Ltd. Solubilization with pluronic F-127 gave water-soluble forms of hydrophobic photosensitizers—steroid derivatives of pyropheophorbide a. Solubilization was performed by evaporating the chloroform co-solutions of photosensitizer and pluronic (triple block copolymer of ethylene and propylene oxide) and subsequently dissolving the resulting dry residue in water. The concentration ratios of modified pyropheophorbide–pluronic at which the photosensitizer completely passed into the aqueous phase were determined. Among the starting hydrophobic photosensitizers, pyropheophorbide–dihydrotestosterone possessed the highest activity in photosensitized oxidation of anthracene with singlet oxygen in chloroform, while after solubilization, pyropheophorbide–testosterone was most active in the test (for photodynamic therapy) oxidation of tryptophan in aqueous solutions.
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Rna viruses in Blechomonas (Trypanosomatidae) and evolution of Leishmaniavirus
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01.09.2018 |
Grybchuk D.
Kostygov A.
Macedo D.
Votýpka J.
Lukeš J.
Yurchenko V.
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mBio |
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1 |
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© 2018 Grybchuk et al. In this work, we analyzed viral prevalence in trypanosomatid parasites (Blechomonas spp.) infecting Siphonaptera and discovered nine species of viruses from three different groups (leishbunyaviruses, narnaviruses, and leishmaniaviruses). Most of the flagellate isolates bore two or three viral types (mixed infections). Although no new viral groups were documented in Blechomonas spp., our findings are important for the comprehension of viral evolution. The discovery of bunyaviruses in blechomonads was anticipated, since these viruses have envelopes facilitating their interspecific transmission and have already been found in various trypanosomatids and metatranscriptomes with trypanosomatid signatures. In this work, we also provided evidence that even representatives of the family Narnaviridae are capable of host switching and evidently have accomplished switches multiple times in the course of their evolution. The most unexpected finding was the presence of leishmaniaviruses, a group previously solely confined to the human pathogens Leishmania spp. From phylogenetic inferences and analyses of the life cycles of Leishmania and Blechomonas, we concluded that a common ancestor of leishmaniaviruses most likely infected Leishmania first and was acquired by Blechomonas by horizontal transfer. Our findings demonstrate that evolution of leishmaniaviruses is more complex than previously thought and includes occasional host switching. IMPORTANCE Flagellates belonging to the genus Leishmania are important human parasites. Some strains of different Leishmania species harbor viruses (leishmaniavi-ruses), which facilitate metastatic spread of the parasites, thus aggravating the disease. Up until now, these viruses were known to be hosted only by Leishmania. Here, we analyzed viral distribution in Blechomonas, a related group of flagellates parasitizing fleas, and revealed that they also bear leishmaniaviruses. Our findings shed light on the entangled evolution of these viruses. In addition, we documented that Blechomonas can be also infected by leishbunyaviruses and narnaviruses, viral groups known from other insects’ flagellates.
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Farming, slaving and enslavement: Histories of endosymbioses during kinetoplastid evolution
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01.09.2018 |
Harmer J.
Yurchenko V.
Nenarokova A.
Lukeš J.
Ginger M.
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Parasitology |
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4 |
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© 2018 Cambridge University Press. Parasitic trypanosomatids diverged from free-living kinetoplastid ancestors several hundred million years ago. These parasites are relatively well known, due in part to several unusual cell biological and molecular traits and in part to the significance of a few -pathogenic Leishmania and Trypanosoma species -as aetiological agents of serious neglected tropical diseases. However, the majority of trypanosomatid biodiversity is represented by osmotrophic monoxenous parasites of insects. In two lineages, novymonads and strigomonads, osmotrophic lifestyles are supported by cytoplasmic endosymbionts, providing hosts with macromolecular precursors and vitamins. Here we discuss the two independent origins of endosymbiosis within trypanosomatids and subsequently different evolutionary trajectories that see entrainment vs tolerance of symbiont cell divisions cycles within those of the host. With the potential to inform on the transition to obligate parasitism in the trypanosomatids, interest in the biology and ecology of free-living, phagotrophic kinetoplastids is beginning to enjoy a renaissance. Thus, we take the opportunity to additionally consider the wider relevance of endosymbiosis during kinetoplastid evolution, including the indulged lifestyle and reductive evolution of basal kinetoplastid Perkinsela.
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Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV)
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01.09.2018 |
Isakov V.
Paduta D.
Viani R.
Enejosa J.
Pasechnikov V.
Znoyko O.
Ogurtsov P.
Bogomolov P.
Maevskaya M.
Chen X.
Shulman N.
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European Journal of Gastroenterology and Hepatology |
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0 |
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© 2018 Wolters Kluwer Health, Inc. All rights reserved. Objective An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. Patients and methods In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. Results At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. Conclusion In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.
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Compartmental modeling of skin transport
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01.09.2018 |
Amarah A.
Petlin D.
Grice J.
Hadgraft J.
Roberts M.
Anissimov Y.
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European Journal of Pharmaceutics and Biopharmaceutics |
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1 |
Ссылка
© 2018 Elsevier B.V. The primary objective of this study is to introduce a simple and flexible mathematical approach which models transport processes in skin using compartments. The main feature of the presented approach is that the rate constants for exchange between compartments are derived from physiologically relevant diffusional transport parameters. This allows for better physical interpretation of the rate constants, and limits the number of parameters for the compartmental model. The resulting compartmental solution is in good agreement with previously published solutions for the diffusion model of skin when ten or more compartments are used. It was found that the new compartmental model with three compartments provided a better fit of the previously publish water penetration data than the diffusion model. Two special cases for which it is difficult to implement the diffusion model were considered using our compartmental approach. In both cases the compartmental model predictions agreed well with the diffusion model.
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What does the future hold for yellow fever virus? (II)
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01.09.2018 |
Klitting R.
Fischer C.
Drexler J.
Gould E.
Roiz D.
Paupy C.
de Lamballerie X.
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Genes |
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4 |
Ссылка
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. As revealed by the recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America, YFV control measures need urgent rethinking. Over the last decade, most reported outbreaks occurred in, or eventually reached, areas with low vaccination coverage but that are suitable for virus transmission, with an unprecedented risk of expansion to densely populated territories in Africa, South America and Asia. As reflected in the World Health Organization’s initiative launched in 2017, it is high time to strengthen epidemiological surveillance to monitor accurately viral dissemination, and redefine vaccination recommendation areas. Vector-control and immunisation measures need to be adapted and vaccine manufacturing must be reconciled with an increasing demand. We will have to face more yellow fever (YF) cases in the upcoming years. Hence, improving disease management through the development of efficient treatments will prove most beneficial. Undoubtedly, these developments will require in-depth descriptions of YFV biology at molecular, physiological and ecological levels. This second section of a two-part review describes the current state of knowledge and gaps regarding the molecular biology of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.
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Repair of damaged articular cartilage: Current approaches and future directions
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11.08.2018 |
Medvedeva E.
Grebenik E.
Gornostaeva S.
Telpuhov V.
Lychagin A.
Timashev P.
Chagin A.
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International Journal of Molecular Sciences |
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14 |
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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.
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QM/MM description of newly selected catalytic bioscavengers against organophosphorus compounds revealed reactivation stimulus mediated by histidine residue in the acyl-binding loop
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03.08.2018 |
Zlobin A.
Mokrushina Y.
Terekhov S.
Zalevsky A.
Bobik T.
Stepanova A.
Aliseychik M.
Kartseva O.
Panteleev S.
Golovin A.
Belogurov A.
Gabibov A.
Smirnov I.
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Frontiers in Pharmacology |
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3 |
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© 2018 Zlobin, Mokrushina, Terekhov, Zalevsky, Bobik, Stepanova, Aliseychik, Kartseva, Panteleev, Golovin, Belogurov, Gabibov and Smirnov. Butyrylcholinesterase (BChE) is considered as an efficient stoichiometric antidote against organophosphorus (OP) poisons. Recently we utilized combination of calculations and ultrahigh-throughput screening (uHTS) to select BChE variants capable of catalytic destruction of OP pesticide paraoxon. The purpose of this study was to elucidate the molecular mechanism underlying enzymatic hydrolysis of paraoxon by BChE variants using hybrid quantum mechanical/molecular mechanical (QM/MM) calculations. Detailed analysis of accomplished QM/MM runs revealed that histidine residues introduced into the acyl-binding loop are always located in close proximity with aspartate residue at position 70. Histidine residue acts as general base thus leading to attacking water molecule activation and subsequent SN2 inline hydrolysis resulting in BChE reactivation. This combination resembles canonical catalytic triad found in active centers of various proteases. Carboxyl group activates histidine residue by altering its pKa, which in turn promotes the activation of water molecule in terms of its nucleophilicity. Observed re-protonation of catalytic serine residue at position 198 from histidine residue at position 438 recovers initial configuration of the enzyme's active center, facilitating next catalytic cycle. We therefore suggest that utilization of uHTS platform in combination with deciphering of molecular mechanisms by QM/MM calculations may significantly improve our knowledge of enzyme function, propose new strategies for enzyme design and open new horizons in generation of catalytic bioscavengers against OP poisons.
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A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT
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01.08.2018 |
Porpiglia N.
De Palo E.
Savchuk S.
Appolonova S.
Bortolotti F.
Tagliaro F.
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Clinica Chimica Acta |
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3 |
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© 2018 Background and aim: The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Methods: Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. Results: PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Conclusions: Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology.
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Molecular-Genetic Characterization of Human Rotavirus A Strains Circulating in Moscow, Russia (2009–2014)
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01.08.2018 |
Kiseleva V.
Faizuloev E.
Meskina E.
Marova A.
Oksanich A.
Samartseva T.
Bakhtoyarov G.
Bochkareva N.
Filatov N.
Linok A.
Ammour Y.
Zverev V.
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Virologica Sinica |
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0 |
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© 2018, Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. Enteric viruses are the most common cause of acute gastroenteritis (AGE) in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are primarily associated with group A rotavirus (RVA) infection. In this retrospective study, the population structure of viruses linked to AGE etiology in young children hospitalized with AGE in Moscow was evaluated, and molecular characterization of RVA strains was performed. Fecal specimens were collected from children under 5 years old hospitalized with AGE between 2009 and 2014 in Moscow, Russia. Multiplex real-time reverse transcription PCR was used to detect enteric viruses and for G/[P]-genotyping of isolated RVAs. Sequencing of RVA VP7 and VP4 cDNA fragments was used to validate the data obtained by PCR-genotyping. The main causes for hospitalization of children with AGE were RVA (40.1%), followed by noroviruses (11.4%), while adenoviruses, astroviruses, sapoviruses, enteroviruses, and orthoreoviruses were detected in 4.7%, 1.9%, 1.4%, 1.2%, and 0.2% of samples tested, respectively. Nosocomial infections, predominantly associated with RVAs and noroviruses, were detected in 24.8% of cases and occurred significantly more frequently in younger infants. The predominant RVA genotype was G4P[8], detected in 38.7% of RVA-positive cases, whereas genotypes G1P[8], G9P[8], G3P[8], and G2P[4] were found in 11.8%, 6.6%, 4.2%, and 3.3% of cases, respectively. Together, the presence of circulating RVA strains with rare VP7 and VP4 gene variants (G6 and P[9]) highlights the need to conduct continuous epidemiological monitoring of RVA infection.
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Identification of surface epitopes associated with protection against highly immune-evasive VlsE-expressing Lyme disease spirochetes
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01.08.2018 |
Batool M.
Caoili S.
Dangott L.
Gerasimov E.
Ionov Y.
Piontkivska H.
Zelikovsky A.
Waghela S.
Rogovskyy A.
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Infection and Immunity |
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3 |
Ссылка
© 2018 American Society for Microbiology. The tick-borne pathogen Borrelia burgdorferi is responsible for approximately 300,000 Lyme disease (LD) cases per year in the United States. Recent increases in the number of LD cases, in addition to the spread of the tick vector and a lack of a vaccine, highlight an urgent need for designing and developing an efficacious LD vaccine. Identification of protective epitopes that could be used to develop a second-generation (subunit) vaccine is therefore imperative. Despite the antigenicity of several lipoproteins and integral outer membrane proteins (OMPs) on the B. burgdorferi surface, the spirochetes successfully evade antibodies primarily due to the VlsE-mediated antigenic variation. VlsE is thought to sterically block antibody access to protective epitopes of B. burgdorferi. However, it is highly unlikely that VlsE shields the entire surface epitome. Thus, identification of subdominant epitope targets that induce protection when they are made dominant is necessary to generate an efficacious vaccine. Toward the identification, we repeatedly immunized immunocompetent mice with live-attenuated VlsE-deleted B. burgdorferi and then challenged the animals with the VlsE-expressing (host-adapted) wild type. Passive immunization and Western blotting data suggested that the protection of 50% of repeatedly immunized animals against the highly immune-evasive B. burgdorferi was antibody mediated. Comparison of serum antibody repertoires identified in protected and nonprotected animals permitted the identification of several putative epitopes significantly associated with the protection. Most linear putative epitopes were conserved between the main pathogenic Borrelia genospecies and found within known subdominant regions of OMPs. Currently, we are performing immunization studies to test whether the identified protection-associated epitopes are protective for mice.
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Efficacy and safety of Subetta add-on therapy in type 1 diabetes mellitus: The results of a multicenter, double-blind, placebo-controlled, randomized clinical trial
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01.08.2018 |
Mkrtumyan A.
Romantsova T.
Vorobiev S.
Volkova A.
Vorokhobina N.
Tarasov S.
Putilovskiy M.
Andrianova E.
Epstein O.
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Diabetes Research and Clinical Practice |
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2 |
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© 2018 Elsevier B.V. Background: To examine efficacy of Subetta as an add-on to insulin therapy in patients with type 1 diabetes mellitus (T1DM) a multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to insulin receptor β-subunit and endothelial NO synthase Subetta was previously proved to activate insulin signaling pathway. Methods: A total of 144 randomized patients with poor glycemic control in basal-bolus insulin regime were included in intention-to-treat analysis in Subetta add-on therapy or placebo (n = 72 in both groups). Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), basal and prandial insulin doses, number of hypoglycemia episodes confirmed by self-monitoring of blood glucose were recorded for 36 weeks. Results: The baseline characteristics of subjects did not differ between the two groups. HbA1c mean (±standard deviation) change was −0.59 ± 0.99% (95% CI −0.84 to −0.37) after 36 weeks in Subetta (vs. −0.20 ± 1.14%; 95% CI −0.44 to 0.11 in placebo; p = 0.028). The rate of overall hypoglycemia events was 7.9 per patient year (95% CI 7.1–8.6) in Subetta group and 7.6 (95% CI 6.9–8.4) in Placebo group (p = 0.63). The basal and total insulin doses did not change at the end of 36 weeks in both groups. Conclusions: Subetta add-on therapy boosting insulin activity and improving glycemic control in patients with T1DM is proved to be beneficial. Clinical trial registration: ClinicalTrials.gov identifier: NCT01868594.
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The Level of Toxic Elements in Edible Crops from Seleniferous Area (Punjab, India)
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01.08.2018 |
Skalnaya M.
Jaiswal S.
Prakash R.
Prakash N.
Grabeklis A.
Zhegalova I.
Zhang F.
Guo X.
Tinkov A.
Skalny A.
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Biological Trace Element Research |
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2 |
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© 2017, Springer Science+Business Media, LLC, part of Springer Nature. The primary objective of the present study was to assess the level of selenium and toxic trace elements in wheat, rice, maize, and mustard from seleniferous areas of Punjab, India. The content of selenium (Se) and toxic trace elements, including aluminum (Al), arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), lead (Pb), and tin (Sn), in crop samples was assessed using inductively coupled plasma mass-spectrometry after microwave digestion of the samples. The obtained data demonstrate that cultivation of crops on seleniferous soils significantly increased Se level in wheat, mustard, rice, and maize by a factor of more than 590, 111, 85, and 64, respectively. The study also showed that Se exposure affected toxic metal content in crops. In particular, Se-rich wheat was characterized by a significant decrease in Al, As, Ni, Pb, and Sn levels. The level of As, Cd, Ni, Pb, and Sn was significantly decreased in Se-rich rice, whereas As content was increased. In turn, the decrease in Al, As, Cd, Ni, Pb, and Sn levels in Se-rich maize was associated with a significant elevation of Hg content. Finally, Se-rich mustard was characterized by a significant increase in Al, As, and Hg levels, while the content of Ni, Pb, and Sn was significantly lower than the control levels. These findings should be taken into account while developing the nutritional strategies for correction of Se status. At the same time, the exact mechanisms underlying the observed differences are to be estimated.
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Paip2 is localized to active promoters and loaded onto nascent mRNA in Drosophila
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18.07.2018 |
Kachaev Z.
Lebedeva L.
Kozlov E.
Toropygin I.
Schedl P.
Shidlovskii Y.
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Cell Cycle |
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1 |
Ссылка
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Paip2 (Poly(A)-binding protein–interacting protein 2) is a conserved metazoan-specific protein that has been implicated in regulating the translation and stability of mRNAs. However, we have found that Paip2 is not restricted to the cytoplasm but is also found in the nucleus in Drosophila embryos, salivary glands, testes, and tissue culture cells. Nuclear Paip2 is associated with chromatin, and in chromatin immunoprecipitation experiments it maps to the promoter regions of active genes. However, this chromatin association is indirect, as it is RNA-dependent. Thus, Paip2 is one more item in the growing list of translation factors that are recruited to mRNAs co-transcriptionally.
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3′-O-Substituted 5-(perylen-3-ylethynyl)-2′-deoxyuridines as tick-borne encephalitis virus reproduction inhibitors
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15.07.2018 |
Proskurin G.
Orlov A.
Brylev V.
Kozlovskaya L.
Chistov A.
Karganova G.
Palyulin V.
Osolodkin D.
Korshun V.
Aralov A.
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European Journal of Medicinal Chemistry |
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5 |
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© 2018 Elsevier Masson SAS A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C1–4-alkyl-1,2,3-triazol-1,4-diyl groups at 3′-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds (4, 6, 8a, 8b) showed EC50 ≤ 10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11.
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Turning Off the Tap: Using the FAST Approach to Stop the Spread of Drug-Resistant Tuberculosis in the Russian Federation
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13.07.2018 |
Miller A.
Livchits V.
Ahmad Khan F.
Atwood S.
Kornienko S.
Kononenko Y.
Vasilyeva I.
Keshavjee S.
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Journal of Infectious Diseases |
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5 |
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© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. Background We report the association of the FAST strategy (find cases actively, separate safely, and treat effectively) with reduction of hospital-based acquisition of multidrug-resistant tuberculosis in the Russian Federation. Methods We used preintervention and postintervention cohorts in 2 Russian hospitals to determine whether the FAST strategy was associated with a reduced odds of converting MDR tuberculosis within 12 months among patients with tuberculosis susceptible to isoniazid and rifampin at baseline. Results Sixty-three of 709 patients (8.9%) with isoniazid and rifampin-susceptible tuberculosis acquired MDR tuberculosis; 55 (12.2%) were in the early cohort, and 8 (3.1%) were in the FAST cohort. The FAST strategy was associated with a reduced odds (adjusted odds ratio, 0.16; 95% confidence interval,.07-.39) and 9.2% absolute reduction in the risk of MDR tuberculosis acquisition. Conclusion Use of the FAST strategy in 2 Russian hospitals was associated with significantly less MDR tuberculosis 12 months after implementation.
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Management of chronic spontaneous urticaria: A worldwide perspective
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04.07.2018 |
Kolkhir P.
Pogorelov D.
Darlenski R.
Caminati M.
Tanno L.
Le Pham D.
Gonzalez-Estrada A.
Antolín-Amérigo D.
Dimov V.
Weller K.
Sánchez-Borges M.
Ansotegui I.
Maurer M.
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World Allergy Organization Journal |
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2 |
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© 2018 The Author(s). Background: The approaches to the diagnosis and treatment of chronic spontaneous urticaria (CSU) differ in various parts of the world. We sought to determine the adherence to international and national urticaria guidelines as well as the motives to deviate from the guidelines among physicians worldwide. Methods: A web-based questionnaire was created and launched via e-mail by the World Allergy Organization (WAO) to representatives of all WAO Member Societies, the members of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the members of the WAO Junior Members Group (JMG), regardless of the specialty, affiliation, or nationality in March 2017. Results: We received 1140 completed surveys from participating physicians from 99 countries. Virtually all participants (96%) were aware of at least one urticaria guideline and reported that they follow a guideline. However, one in five physicians who follow a guideline (22%) reported to deviate from it. Reliance on own clinical experience is the most frequent reason for deviation from guidelines or not following them (44%). Young (< 40 years) and less experienced physicians more often follow a guideline and less often deviate than older and experienced ones. Physicians who follow a urticaria guideline showed higher rates of routinely ordering a complete blood count, the erythrocyte sedimentation rate, C-reactive protein, anti-thyroid antibodies, and thyroid-stimulating hormone and of performing the autologous serum skin test as compared to those who do not. Physicians who follow a urticaria guideline showed higher rates of using second generation antihistamines as their first-line treatment of CSU (p = 0.001) and more frequently observed higher efficacy of these drugs (or had more confidence that it would work, p < 0.019) as compared to those who do not follow the guidelines. Conclusions: Physicians' characteristics (e.g. age, clinical experience, and specialty) and country specifics and regional features (e.g. availability of drugs for CSU treatment) importantly influence adherence to urticaria guidelines and CSU patient care and should be addressed in more detail in future research.
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