Репозиторий Университета

© 2018 Elsevier B.V. Serotonin (5-HT) is involved in sleep in two different ways. First, when released during waking by the axonal nerve endings, it influences the synthesis of hypnogenic substances in specific brain targets. Such a synthesis might be in keeping with the waking qualitative aspects. As an example, the hypnogenic CLIP peptide (ACTH18-39) is synthesized when stressful events occur during wakefulness. Second, when released during sleep within the nucleus raphe dorsalis (nRD) by dendrites of 5-HT neurons, it contributes to 5-HT perikarya silencing through an auto-inhibitory process. Nitric oxide, co-synthesized with 5-HT, may act in synergy with this amine at both mentioned levels. Regarding the triggered hypnogenic substances, they induce sleep through acting on two components within the nRD: (1) the 5-HT component; its silencing is necessary to remove the gating effect exerted on phasic sleep events (ponto-geniculo-occipital, PGO, waves); (2) a substance P component; its silencing is necessary, at least, to alleviate the tonic influence exerted on somatic muscles. These two components may constitute the brain “sleep switch-on” mechanism allowing wake/sleep alternation. Pharmacological procedures influencing this switch may be determinant for treating insomniac patients. Serotonin appears thus to be involved in sleep preparation, triggering and maintenance.

© 2018, Allerton Press, Inc. The proportion of diploid cells in the G0/G1 cell cycle phases was estimated by flow cytometry in 60 samples of stage III serous ovarian cancer tissue. The tumor tissue shows considerable heterogeneity with regard to the content of this tissue fraction, which ranged from 27 to 95% with a median of 73%. Statistically significant differences in the size of this fraction were identified by comparing tumor subgroups sensitive and resistant to first-line platinum-taxane chemotherapy. Predictive significance of the G0/G1 fraction was concluded and quantitative evaluation of this fraction is recommended for clinical use.

© 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.

© 2018, Pleiades Publishing, Ltd. Abstract: In this paper, we present the results on immobilization of Photoditazine, the photosensitizer of the second generation, on vaterite (metastable modification of calcium carbonate) porous particles of two different sizes. The adsorption efficiency is found to be 3.0 and 3.2 wt % Photoditazine on vaterite particles with average diameters of 5 and 0.5 μm, respectively. The curves of Photoditazine desorption from vaterite particles are determined depending on the composition of the dispersion medium (water and bovine serum albumin solution). It is found that vaterite particles in water are subjected to recrystallization in accordance with the dissolution–precipitation mechanism. The presence of albumin molecules at a physiological concentration allows stabilizing metastable vaterite particles of micron and submicron size for at least 17 days.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The conceptual design for portable equipment for low-flow detoxification of the body by peritoneal dialysis is proposed. It uses dialysis−sorption or dialysis−electrochemical (with sorption aftertreatment) technologies of regeneration of the spent solution for peritoneal dialysis.

© 2018 Elsevier Masson SAS We performed a mesocosm experiment with rice paddy soils of three different soil types which were collected in the three major regions of rice production in Russia: Krasnodarsky Krai, the Republic of Kalmykia and Primorsky Krai. We used the earthworm species Eisenia fetida (Savigny 1826), introduced at different densities (0, 2, 4 and 6 individuals per mesocosm with an area of 69.4 cm2 and a soil column height of approximately 10 cm) to assess rice straw decomposition and carbon stabilization in the three soil types. After 20 days of the experiment, straw amendment consistently increased CO2 release from all three soil types. The effect was highest in the soil of Krasnodarsky Krai after a straw amendment was combined with 4 earthworms per mesocosm. The effect of earthworms on CH4 release remained soil type specific but did not demonstrate any synergy with the straw amendment. We also recorded the highest enrichment of soil with carbon from the rice straw when compared with the control mesocosms without straw amendment (the difference was 31.5 mg g−1 soil dwt) under the treatment with four earthworms, and this result was independent of soil type. We conclude that the practice of rice straw reincorporation with the amendment of a certain number of earthworms provides a potentially viable way to recycle crop residue.

© 2018 Frolov et al. Blastocrithidia papi is a unique trypanosomatid in that its life cycle is synchronized with that of its host, and includes an obligate stage of development in Malpighian tubules (MTs). This occurs in firebugs, which exited the winter diapause. In the short period, preceding the mating of overwintered insects, the flagellates penetrate MTs of the host, multiply attached to the epithelial surface with their flagella, and start forming cyst-like amastigotes (CLAs) in large agglomerates. By the moment of oviposition, a large number of CLAs are already available in the rectum. They are discharged on the eggs' surface with feces, used for transmission of bugs' symbiotic bacteria, which are compulsorily engulfed by the newly hatched nymphs along with the CLAs. The obligate development of B. papi in MTs is definitely linked to the life cycle synchronization. The absence of peristalsis allow the trypanosomatids to accumulate and form dense CLA-forming subpopulations, whereas the lack of peritrophic structures facilitates the extensive discharge of CLAs directly into the hindgut lumen. The massive release of CLAs associated with oviposition is indispensable for maximization of the infection efficiency at the most favorable time point.

© 2018 Wiley Periodicals, Inc. Vitiligo is a non-lethal, non-communicable, immune-mediated, and generally progressive skin disease, with poorly understood etiopathogenesis and weak evidence base. The aim of the study is to contribute to the scant research on the patient-reported outcomes in vitiligo, and to examine the presence of associations between various inputs for possible use in clinical practice. The study was designed as a web-based questionnaire with 40 inputs across seven dimensions. The questions include demographics, skin type, eye and natural hair color, age of respondent and age of onset, possible triggers, disease extent, localization, progression and activity, the efficacy of most common treatment modalities, medication side-effects, heredity and diseases among parents, and out-of-pocket expenses for treatments to date. The analysis presented with this work contributes to the discussion about the relation between therapies, socio-economic factors, and treatment outcomes in vitiligo. All physicians should adequately manage patient expectations in terms of overall treatment duration and expected out-of-pocket expenses, and actively evaluate patients at shorter intervals. A more aggressive therapeutic approach using telehealth devices should be considered to supplement therapy, monitor treatment progress, and protocol compliance.

© 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.

© 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.

© 2018 Cambridge University Press. Thanks to modern molecular biology methods, our understanding of the impact of (endo)symbiotic bacteria on parasitic protists and helminths is growing fast. In this issue, 9 papers have been brought together that describe various facets of the relationships between these microorganisms, reveal their range and high frequency, as well as their capacity to create novel biological complexity. Comparative analyses of these host-endosymbiont interactions indicate that there may be no discrete types of relationships but rather a continuum ranging from a dispensable endosymbiont minimally integrated within the host cell to organelles, such as mitochondria and plastids that evolved into an indispensable, deeply integrated components of the cell. We hope that this series of studies on parasites and (endo)symbiotic bacteria will increase awareness about these relationships and their representation in microbial ecology models.

The article considers the results of sociological survey of medical personnel of the Moscow oblast. The purpose of study is to analyze attitude of medical personnel to the system of mandatory medical insurance in modern conditions. The sociological survey carried out according standard methodology using originally developed questionnaire. The public opinion of medical personnel of medical municipal organizations of the Moscow oblast was investigated in 2013 (n = 632) and 2017 (n = 798). It was established that, 25 years later from the moment of organization of the system of mandatory medical insurance, not all medical personnel is oriented in it. The percentage of those who consider it as a false and over bureaucratized one increased. The number of respondents considering that medical insurance organizations protect interests of patients decreased and those who feel no impact of mandatory medical insurance foundations on activities of medical organizations increased up to 35%. The most of respondents consider functions of medical insurance organizations and mandatory medical insurance foundations exclusively as controlling ones. In both surveys less than 30% of respondents supported actual system of mandatory medical insurance. The general results of the sociological survey testify the necessity of changing policy of relationship between the system of mandatory medical insurance and medical personnel, including activization of activities concerning explanation of tasks, functions and authorities of mandatory medical insurance foundations and medical insurance organizations and also consensual consideration of opinions of all participants of the mandatory medical insurance system.

© 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.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature.  Introduction: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E 2 (PGE 2 ) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e., asthma and obstructive bronchitis). Objectives: To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo. Methods: Experimental in vivo study randomly assigning the target drug (treatment group) or a saline solution without the drug (vehicle control group) to 12 rabbits (n = 6 in each group). Untargeted (5880 initial features; 1869 negative–4011 positive ion peaks; UPLC–IT–TOF/MS) and 84 targeted moieties (Nitroproston® related metabolites, prostaglandins, steroids, purines, pyrimidines and amino acids; HPLC–QQQ–MS/MS) were measured from plasma at 0, 2, 4, 6, 8, 12, 18, 24, 32 and 60 min after administration. Results: PGE 2 , 13,14-dihydro-15-keto-PGE 2 , PGB 2 , 1,3-GDN and 15-keto-PGE 2 increased in the treatment group. Steroids (i.e., cortisone, progesterone), organic acids, 3-oxododecanoic acid, nicotinate d-ribonucleoside, thymidine, the amino acids serine and aspartate, and derivatives pyridinoline, aminoadipic acid and uric acid increased (p < 0.05 AUCROC curve > 0.75) after treatment. Purines (i.e., xanthine, guanine, guanosine), bile acids, acylcarnitines and the amino acids l-tryptophan and l-phenylalanine were decreased. Nitroproston® impacted steroidogenesis, purine metabolism and ammonia recycling pathways, among others. Conclusion: Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites (i.e., guanine, adenine, cortisol, cortisone and aspartate) involved in purine metabolism, urea and ammonia biological cycles, steroidogenesis, among other pathways. Suggested mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented.

© 2018 Royal Pharmaceutical Society Objectives: Anxiolytic drug zolpidem was incorporated into the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in polymer film modelling nasal mucosa was investigated. The anxiolytic effect of zolpidem upon intranasal administration of microcontainers and free medicine was determined by in vivo experiments on mice. Methods: The structures of all compounds during zolpidem synthesis were established using nuclear magnetic resonance spectroscopy. The loading efficacy and release kinetics of zolpidem were analysed by spectrophotometry. Surface morphology of formulation was investigated by scanning electron microscopy. To determine the effect of zolpidem-loaded containers administration by the intranasal route in vivo experiments was carried out applying the open field test. Key findings: Nasal administration of zolpidem in the form of the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell has a pronounced anxiolytic effect on the behaviour of the animals in the open field test. Conclusions: The polyelectrolyte shell deposited together with zolpidem enhances the loading efficacy of the microcontainers. In vivo experiments on mice demonstrate increase in anxiolytic effect of zolpidem in microcontainers compared with upon intranasal administration of free medicine.

© 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.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Colostrum is produced in the first days postpartum. It is a known source of immune mediators for a newborn within the first week of life. Although it is still unclear if colostrum composition varies between populations, recent data suggest differences. Hepatocyte growth factor (HGF); transforming growth factor-β (TGF-β) 1, 2, and 3; and immunoglobulin A (IgA) are key immunological components of colostrum that stimulate neonatal gastrointestinal and immune system development. We aimed to investigate the differences in the concentration between immune markers in the colostrum of mothers living in Burundi and Italy, and to identify the factors associated with differences. In this cross-sectional birth cohort study, a total of 99 colostrum samples from Burundian (n = 23) and Italian (n = 76) women were collected at 0 to 6 days postpartum. A clinical chemistry analyser was used for IgA quantification and electro-chemiluminescence, for HGF and TGFβ1-3 assessment. A univariate analysis and multivariate linear regression model were used for statistical testing. The concentrations of TGF-β2 (p = 0.01) and IgA (p < 0.01) were significantly higher in the colostrum from the women residing in Burundi than in Italy, both in a univariate analysis and upon the adjustment for confounding factors. A similar trend is seen for HGF, reaching statistical significance upon a multivariate analysis. We found a moderate to strong positive correlation between the TGF-β isoforms and IgA concentration in both countries (p < 0.01), with stronger concentration in the colostrum from Burundi. The results of this study are in support of previous data, suggesting that concentration of the immune active molecules is higher in the human milk of women residing in developing countries. However, with a small sample size, caution must be applied, as the findings require further confirmation. Future work should also be focused on other factors (e.g., lipid and microbial composition), as well as the investigation into colostrum and between populations comparison, adjusting for potential confounders.

© 2018 Society of Photo-Optical Instrumentation Engineers (SPIE). We present the nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography (OCT). It employs an experimental training algorithm based on imaging of a test-object, made of the colloidal suspension of the monodisperse nanoparticles and contains the microscale inclusions. The geometry and the scattering properties of the test-object are known a priori allowing us to set the criteria for the training algorithm. Using a wide set of the wavelet kernels and the wavelet-domain filtration approaches, the appropriate filter is constructed based on the test-object imaging. We apply the proposed approach and chose an efficient wavelet denoising procedure by considering the combinations of the decomposition basis from five wavelet families with eight types of the filtration threshold. We demonstrate applicability of the wavelet-filtering for the in vitro OCT image of human brain meningioma. The observed results prove high efficiency of the proposed OCT image denoising technique.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The original version of this article unfortunately contained mistakes in author group section.

© 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.