Репозиторий Университета

© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. We have performed the in vitro terahertz (THz) spectroscopy of human brain tumors. In order to fix tissues for the THz measurements, we have applied the gelatin embedding. It allows for preserving tissues from hydration/dehydration and sustaining their THz response similar to that of the freshly-excised tissues for a long time after resection. We have assembled an experimental setup for the reflection-mode measurements of human brain tissues based on the THz pulsed spectrometer. We have used this setup to study in vitro the refractive index and the amplitude absorption coefficient of 2 samples of malignant glioma (grade IV), 1 sample of meningioma (grade I), and samples of intact tissues. We have observed significant differences between the THz responses of normal and pathological tissues of the brain. The results of this paper highlight the potential of the THz technology in the intraoperative neurodiagnosis of tumors relying on the endogenous labels of tumorous tissues.

© 2018 Russian Association of Endocrinologists. All rights reserved. The presented paper is a third revision of the clinical recommendations for the treatment of morbid obesity in adults. Morbid obesity is a condition with body mass index (BMI) ≥40 kg / m2 or a BMI ≥35 kg / m2 in the presence of serious complications associated with obesity. The recommendations provide data on the prevalence of obesity, its etiology and pathogenesis, as well as on associated complications. The necessary methods for laboratory and instrumental diagnosis of obesity are described in detail. In this revision of the recommendations, the staging of prescribing conservative and surgical methods for the treatment of obesity are determined. For the first time, a group of patients with obesity and type 2 diabetes mellitus is selected, in whom metabolic surgery allows a long-term improvement in the control of glycemia or remission of diabetes mellitus.

© 2018 John Wiley  &  Sons Ltd. While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.

© 2018 Bentham Science Publishers. A number of biological and clinical characteristics typical of late life depression (LLD) have been suggested by recent research findings. The close association of LLD with cognitive impairment is now well documented and evidenced. However, it is still not clear whether it is depression that leads to cognitive decline, and in more severe cases, to dementia. The work presented in this review article suggests that depression and dementia frequently and strongly copresent, even if the causality remains largely opaque.

© 2018 Bentham Science Publishers. Background & Objective: Regulation of composition, volume and turnover of fluids surrounding the brain and damp cells is vital. These fluids transport all substances required for cells and remove the unwanted materials. This regulation tends to act as barrier to prevent free exchange of materials between the brain and blood. There are specific mechanisms concerned with fluid secretion of the controlled composition of the brain, and others responsible for reabsorption eventually to blood and the extracellular fluid whatever their composition is. The current view assumes that choroidal plexuses secrete the major part of Cerebrospinal Fluid (CSF), while the Blood-Brain Barrier (BBB) has a much less contribution to fluid production, generating Interstitial Fluid (ISF) that drains to CSF. The skull is a rigid box; thereby the sum of volumes occupied by the parenchyma with its ISF, related connective tissue, the vascula-ture, the meninges and the CSF must be relatively constant according to the Monroe-Kellie dogma. This constitutes a formidable challenge that normal organisms surpass daily. The ISF and CSF provide water and solutes influx and efflux from cells to these targeted fluids in a quite precise way. Microvessels within the parenchyma are sufficiently close to every cell where diffusion areas for solutes are tiny. Despite this, CSF and ISF exhibit very similar compositions, but differ significantly from blood plasma. Many hydro-philic substances are effectively prevented from the entry into the brain via blood, while others like neurotransmitters are extremely hindered from getting out of the brain. Anatomical principle of the barrier and routes of fluid transfer cannot explain the extraordinary accuracy of fluids and substances needed to enter or leave the brain firmly. There is one aspect that has not been deeply analyzed, despite being prevalent in all the above processes, it is considered a part of the CSF and ISF dynamics. This aspect is the energy necessary to propel them properly in time, form, space, quantity and temporality. Conclusion: The recent hypothesis based on glucose and ATP as sources of energy presents numerous contradictions and controversies. The discovery of the unsuspected intrinsic ability of melanin to dissociate and reform water molecules, similar to the role of chlorophyll in plants, was confirmed in the study of ISF and CSF biology.

© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved. Vaccination against pneumococcal infections by 13-va-lent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality. The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection. Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system. The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level. In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given. The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018. Results. Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided. Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively). In the 15-year-horizon noting the distribution of 65-year-olds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively. Conclusions. Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.

© 2018 Bentham Science Publishers. Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders. In this concern, the involvement of UT II in the pathophysiology of many processes determines the perspectives for the development of blockers of urotensin receptors for the treatment of the aforementioned diseases. It is important that even today this kind of perspective is feasible due to the synthesis of a series of GPR14 blockers. The objective of this review is to discuss current molecular mechanisms of biological activity, regulatory functions of UT II, its role in the pathogenesis of different nosologies, as well as analysis of the possible routes of exposure to GPR14 as potential therapeutic targets.

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is defined as the recurrence of wheals, angioedema, or both for >6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease-related biomarkers. To review available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroups allocation or response to treatment. We performed a Pubmed, Google Scholar and Web of Science search and identified and analysed 151 reports published prior to January 2016. We found strong evidence for significant differences between CSU patients and healthy controls in blood levels or values of D-dimer, C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), mean platelet volume (MPV), factor VIIa, prothrombin fragment 1+2 (F1+2), tumor necrosis factor, dehydroepiandrosterone sulfate and vitamin D. Also, there is strong evidence for a significant association between CSU activity and blood levels or values of D-dimer, F1+2, CRP, IL-6 and MPV. Strong evidence for reduced basophil count and high levels of IgG anti-FcεRI in the subgroup of CSU patients with positive autologous serum skin test was shown. In contrast, the evidence for all reported blood biomarkers for differentiating CSU from other diseases, or a role in prognosis, is weak, inconsistent or non-existent. We identified ten biomarkers which are supported by strong evidence for distinguishing CSU patients from healthy controls, or for measuring CSU activity. There is a need for further research to identify biomarkers which predict outcome or treatment response in CSU. This article is protected by copyright. All rights reserved.

Репликативный полипротеин 1а вируса желтухи свеклы (ВЖС) содержит консервативные домены лидерной папаин-подобной протеиназы (РСР), метилтрансферазы (MTR) и РНК хеликазы (HEL). Центральный район (central region, CR) между MTR и HEL ранее считали «вариабельным». Нами проведен компьютерный анализ CR, который позволил выявить новый консервативный домен между позициями 1287-1390 (здесь и далее приводится нумерация аминокислотных остатков белка 1а вируса желтухи свеклы, BYV), сохраняющийся у всех представителей рода Closterovirus. Этот домен содержит 4 предсказанных альфа-спиральных участка (альфа А – D) и три строго консервативные позиции – глютамат-1291, пролин-1380 и аргинин-1384. Кроме того, биоинформатический анализ позволил предсказать амфипатическую спираль в позициях 1368-1380 (входящую в состав участка альфа D). Гидрофобный домен CR-2 (позиции 1305-1494 белка 1а), вызывающий при экспрессии в растениях реструктуризацию эндоплазматического ретикулюма и образование подвижных глобул диаметром ~1 мкм, включает участки альфа В, С и D. Установлено, что экспрессия в растениях слитных белков CR-2:GFP и GFP:CR-2 вызывает сходный «глобулообразующий» фенотип, т.е. N-концевое или C-концевое положение маркера GFP в слитном белке не влияет на переформатирование мембран эндоплазматического ретикулюма. Проведен делеционный анализ CR-2 BYV. Показано, что делеционные варианты 1355-1494 и 1325-1484 сохраняют фенотип дикого типа (образование глобул и реструктуризация ЭР вокруг ядра клетки). Варианты 1375-1484, 1368-1484 и 1368-1432 индуцировали образование глобул, но утрачивали способность к реструктуризации ЭР. Внесение замен гидрофобных аминокислотных остатков на остатки серина и глицина в «минимальном» делеционном мутанте 1368-1432 блокировало образование глобул. Предложена рабочая гипотеза о влиянии консервативной амфипатической спирали 1368-1385 в белке 1а BYV на ремоделирование мембран ЭР растительной клетки и создание репликативных платформ при клостеровирусной инфекции.

Human B-cell receptor-associated protein BAP31 (HsBAP31) is the endoplasmic reticulum-resident protein involved in protein sorting and transport as well as pro-apoptotic signaling. Plant orthologs of HsBAP31 termed 'plant BAP-like proteins' (PBL proteins) have thus far remained unstudied. Recently, the PBL protein from Nicotiana tabacum (NtPBL) was identified as an interactor of Nt-4/1, a plant protein known to interact with plant virus movement proteins and affect the long-distance transport of potato spindle tuber viroid (PSTVd) via the phloem. Here, we have compared the sequences of PBL proteins and studied the biochemical properties of NtPBL. Analysis of a number of fully sequenced plant genomes revealed that PBL-encoding genes represent a small multigene family with up to six members per genome. Two conserved motifs were identified in the C-terminal region of PBL proteins. The NtPBL C-terminal hydrophilic region (NtPBL-C) was expressed in bacterial cells, purified, and used for analysis of its RNA binding properties in vitro. In gel shift experiments, NtPBL-C was found to bind several tested RNAs, showing the most efficient binding to microRNA precursors (pre-miRNA) and less efficient interaction with PSTVd. Mutational analysis suggested that NtPBL-C has a composite RNA-binding site, with two conserved lysine residues in the most C-terminal protein region being involved in binding of pre-miRNA but not PSTVd RNA. Virus-mediated transient expression of NtPBL-C in plants resulted in stunting and leaf malformation, developmental abnormalities similar to those described previously for blockage of miRNA biogenesis/function. We hypothesize that the NtPBL protein represents a previously undiscovered component of the miRNA pathway.

Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC50 6.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology.

Autophagy is an evolutionary conserved intracellular catabolic process of vital importance to cell and tissue homeostasis. Autophagy is implicated in the pathogenesis of atherosclerosis but participating cells, molecular mechanisms and functional outcomes have not been fully elucidated. T-cadherin, an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily of adhesion molecules, is upregulated on smooth muscle cells (SMCs)¹ in atherosclerotic lesions. Here, using rat and murine aortic SMCs as experimental models, we surveyed the ability of T-cadherin to regulate autophagy in SMCs during serum-starvation stress. Ectopic upregulation of T-cadherin in SMCs resulted in augmented autophagy characterized by increased autophagic flux, LC3-II abundance and autophagosome formation. Analysis of signal transduction pathway effectors and use of specific pharmacological inhibitors demonstrated that T-cadherin-associated enhancement of the autophagic response to serum-deprivation was dependent on MEK1/2/Erk1/2 activation and independent of PI3K/Akt/mTORC1, reactive oxygen species or endoplasmic reticulum stress. T-cadherin upregulation on SMCs conferred a survival advantage during prolonged serum-starvation which was sensitive to inhibition of MEK1/2/Erk1/2 by PD98059 or UO126 and to blockade of autophagy by chloroquine. Loss of T-cadherin expression in SMCs diminished autophagy responsiveness and compromised survival under conditions of serum-starvation. Overall our findings have identified T-cadherin as a novel positive regulator of autophagy and survival in SMCs.

The goal of this study was to find genes that encode cytoskeletal proteins that are potential candidates for the role of triggers in cell mechanosensitivity in the fruit fly. Centrifugation was used to simulate the hypergravity effects (2g group); the constantly changing orientation of the larvae in the gravity field was performed in order to simulate the effects of microgravity (0g group) for 1.5, 6, 12 and 24 h. mRNA levels of different genes that encode the components of both tubulin and actin cytoskeleton were assessed by qRT-PCR. In the 0g group the mRNA levels of beta-tubulin and Msps were reduced after 1.5 h of the exposure and remained unchanged until 12 h, while they exceeded the control level after 24 h. The mRNA level of chaperonin containing T-complex 1 polypeptide subunits recovered earlier: after 6 and 12 h of the microgravity exposure. At the same time, the hypergravity effect led to more significant changes in the mRNA level of TCP1 complex components compared with those of tubulin and Msps. The mRNA level of beta-actin isoforms under micro- and hypergravity was decreased up to 12 h of the exposure, however, it remained reduced under microgravity conditions, while it recovered (Act87E) and even exceeded (Act57B) the reference level under hypergravity conditions. The mRNA level of supervillin was almost unchanged. Under microgravity conditions the mRNA level of fimbrin was decreased (it recovered by the 24 h time point), while the mRNA level of alpha-actinin was significantly increased by the 12 h time point of the exposure and after 24 h it was reduced to the control level. In contrast, under hypergravity conditions the mRNA level of fimbrin initially increased, and after 24 h it dropped below the control, while the mRNA level of alpha-actinin was significantly reduced, and after 24 h it was higher than the reference level. Similar results were obtained earlier in the experiments in rodents, but similar dynamics were observed for alpha-actinin isoforms 1 and 4, although no changes were observed for fimbrin. Since Drosophila melanogaster has no alpha-actinin isoform 4, it is hypothesized that its role in the cell is played by fimbrin.

Цель. Определить у детей в возрасте от 2 до 7 лет ультразвуковых параметров лимфатических узлов, подверженных наибольшей антигенной стимуляции (шейные, мезентериальные), и установить взаимосвязь этих параметров с относительными размерами селезенки. Пациенты и методы. Проведено открытое скрининговое поперечное одноцентровое исследование на базе ФНЦ медико-профилактических технологий управления рисками здоровью населения г. Перми. В исследование включено 133 ребенка (62 мальчика, 71 девочка) из дошкольных учреждений Пермского края в возрасте от 2 до 7 лет. В течение 2011-2013 гг. проведено анкетирование и интервьюирование родителей респондентов с последующим анализом историй их развития, а всем детям, включенным в исследование, выполнены стандартная клиническая гемограмма, а также ультразвуковое исследование (УЗИ) селезенки с вычислением коэффициента массы селезенки (КМС) по оригинальной формуле и шейных и мезентериальных лимфатических узлов (ЛУ). В зависимости от значения КМС дети были поделены на 2 группы: в основной (n = 46) КМС превышал 4 ед. В группе сравнения (n = 87) этот показатель варьировал от 2,0 до 4,0 ед. Результаты. Дети из основной группы в 2,5 раза чаще (p < 0,05) болели острыми респираторными вирусными инфекциями, которые протекали с осложнениями у 27 (58,7%) детей со спленомегалией; в группе сравнения их было 13 (15,3%, p < 0,01). У детей основной группы в 1,8 раз чаще диагностировали гипертрофию небных миндалин и/или аденоидов 2-3-й степени, они достоверно чаще болели пневмонией. Сравнительный анализ ультразвуковых характеристик глубоких латеральных яремных ЛУ показал статистически значимые различия (p < 0,05) по всем измеряемым параметрам (длина, индекс округлости, толщина коркового слоя), за исключением максимальной систолической скорости кровотока в артерии узлов. Характеристики мезентериальных ЛУ (кроме их длины) в обеих группах пациентов также имели статистически значимые различия. Обнаружено, что у 43 (93,5%) детей из основной группы преобладали цепочки или конгломераты (более 2 в ультразвуковом срезе) шейных ЛУ; в группе сравнения - у 71 (81,6%). Множественные мезентериальные ЛУ обнаружены в 39 (84,8%) и 64 (73,6%) случаях соответственно в группах. Корреляционный анализ выявил достоверную (p < 0,05) прямую связь между значениями КМС и толщиной коркового слоя у глубоких латеральных яремных ЛУ шеи (r = 0,44). Выводы. У практически здоровых детей дошкольного возраста с установленной при УЗИ относительной спленомегалией изменения параметров ЛУ 2-3-го порядка могут отражать процессы онтогенеза иммунной системы и свидетельствуют о повышенной антигенной нагрузке. За детьми, значение КМС у которых превышает 4 ед, рекомендуется динамическое наблюдение с обязательным исследованием параметров мезентериальных и средних глубоких латеральных яремных ЛУ шеи.

В статье представлен аналитический обзор научных статей, опубликованных в электронных библиотеках Cochrane Library, MEDLINE, PubMed, E-library за последние 15-20 лет и посвященных изучению проблем микробиоценоза кишечника, начиная от общих понятий данного состояния до современных взглядов на терапию нарушений микробного состава тонкого и толстого кишечника. Авторы прослеживают эволюцию лечебных подходов от пробиотиков, пребиотиков, симбиотиков до метаболической терапии. В обзоре анализируются преимущества и недостатки пробиотической терапии, обсуждаются предлагаемые пути решения возникших проблем, таких как риск трансгенной передачи информации между бактериями и эндотелиальными клетками. В современной гастроэнтерологии разрабатываются новые подходы к лечению дисбиоза кишечника. Изучение метаболома эукариотов помогает синтезировать новые препараты - метаболики. Метабиотики, в качестве регуляторов физиологических функций, биохимических и поведенческих реакций, имеют ряд преимуществ по сравнению с пробиотиками и пребиотиками, в связи с благоприятным профилем безопасности и длительным сроком хранения, обладают лучшей абсорбцией, легко распределяются и выводятся из организма. Метабиотики являются эволюцией развития пробиотической концепции. Одним из представителей метаболических препаратов является Хилак форте. Эта свободная от бактерий жидкость содержит метаболиты бактерий Escherichia coli DSM 4087 (25 g), Streptococcus faecalis DSM 4086 (12.5 g), Lactobacillus acidophilus DSM 4149 (12.5 g), и L. helveticus DSM 4183 (50 g). Хилак форте имеет долгую историю применения и может быть применен на любом этапе коррекции дисбиотических нарушений широкой категории пациентов.

В области изучения нейробиологии униполярных депрессивных расстройств (УДР) перспективными считаются нейровизуализационные методы, особенно позитронно-эмиссионная томография (ПЭТ) и функциональная магнитно-резонансная томография (фМРТ). В статье приводится обзор современных нейровизуализационных данных, касающихся структурно-функциональных особенностей головного мозга у лиц, страдающих УДР. Результаты отдельных исследований представлены в зависимости от особенностей методов их проведения (состояние покоя, выполнение когнитивных и эмоциональных тестов) и соотнесены с основными нейробиологическими концепциями развития депрессивных расстройств. Отдельно рассмотрены возможности нейровизуализационных исследований для оценки и прогнозирования результатов антидепрессивной терапии.

Цель исследования. Изучение связи между генами иммунной системы и депрессией, а также ее эндофенотипами (невротизм и личностная тревожность) при ишемической болезни сердца (ИБС). Материал и методы. Исследование проведено в группе мужчин с ИБС с депрессией (78 человек) и без нее (91 человек), а также у здоровых добровольцев мужского пола (127 человек). Изучены полиморфизмы генов интерлейкина-4 (IL-4 –589C/T), интерлейкина-6 (IL-6 –174G/C), фактора некроза опухолей-α (TNF-α –308G/A) и С-реактивного белка (CRP –717A/G). Результаты. Обнаружена ассоциация полиморфизма IL-6 –174 G/C с депрессией, коморбидной ИБС (р=0,01; ОШ=2,3 ДИ 95% 1,2—4,3), которая выражалась в повышении частоты высокоэкспрессивного аллеля G в группе больных с депрессией. Полиморфизм IL-4 –589C/T был ассоциирован с ИБС: частота генотипа СС IL-4 –589C/T была выше в группе больных по сравнению с контрольной группой независимо от наличия депрессии (р=0,007; ОШ=2,1 ДИ 95% 1,2—3,4). Полиморфизмы TNF-α –308G/A и CRP –717A/G не были ассоциированы с депрессией при ИБС. Значимых различий в выраженности невротизма и личностной тревожности у носителей различных генотипов по локусам IL-4 –589 C/T, IL-6 –174 G/C, TNF-α –308 G/A, CRP –717A/G выявлено не было. Заключение. Ассоциация полиморфизма IL-6 –174G/C с депрессией, коморбидной ИБС, согласуется с данными литературы о роли IL-6 в развитии депрессии у кардиологических больных.

Objective. To assess antioxidant therapy (ascorbic acid (AA), Cytoflavin) prescribed as part of the standard treatment scheme based on clinical and morphological data in cerebral infarct. Materials and methods. The study was performed from 2010 to 2014 in eight vascular centers in the Russian Federation. A total of 373 patients with acute ischemic stroke in the carotid basin were studied. Group 1 consisted of 132 patients who received 5% AA solution at a daily dose of 20 ml; group 2 consisted of 113 patients receiving the antioxidant Cytoflavin at a daily dose of 20 ml for 10 days; group 3 consisted of 108 patients receiving Cytoflavin for 20 days, the dose being decreased to 10 ml from day 11 to day 20. Patients’ status was evaluated using a set of clinical, laboratory, and instrumented methods. Results and conclusions. Analysis of CT scan results obtained on treatment days 1 and 21 showed that Cytoflavin led to significant regression of the volume of cerebral ischemia, by an average factor of 1.5–1.7. No significant morphological changes were seen in the AA-treated group; among Cytoflavin-treated patients there was a two-fold reduction in the proportion of patients in which the volume of cerebral ischemia increased during the period 1–21 days. In patients with initial assessments of at least 14 points on the NIH scale, Cytoflavin treatment for 20 days promoted more marked improvements in neurological, functional, and cognitive status than seen in patients given infusions for 10 days.

Background: The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions.

Conclusion: In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.

Background Urethral reconstruction is one of the great surgical challenges for urologists. A cell-based tissue-engineered urethra may be an alternative for patients who have complicated long strictures and need urethral reconstruction. Here, we demonstrated the feasibility of using autologous urine-derived stem cells (USCs) seeded on small intestinal submucosa (SIS) to repair a urethral defect in a rabbit model. Methods Autologous USCs were obtained and characterized, and their capacity to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs) was tested. Then, USCs were labeled with PKH67, seeded on SIS, and transplanted to repair a urethral defect. The urethral defect model was surgically established in New Zealand white male rabbits. A ventral urethral gap was created, and the urethral mucosa was completely removed, with a mean rabbit penile urethra length of 2 cm. The urethral mucosal defect was repaired with a SIS scaffold (control group: SIS with no USCs; experimental group: autologous USC-seeded SIS; n = 12 for each group). A series of tests, including a retrograde urethrogram, histological analysis, and immunofluorescence, was undertaken 2, 3, 4, and 12 weeks after the operation to evaluate the effect of the autologous USCs on urethral reconstruction. ResultsAutologous USCs could be easily collected and induced to differentiate into UCs and SMCs. In addition, the urethral caliber, speed of urothelial regeneration, content of smooth muscle, and vessel density were significantly improved in the group with autologous USC-seeded SIS. Moreover, inflammatory cell infiltration and fibrosis were found in the control group with only SIS, but not in the experimental autologous USC-seeded SIS group. Furthermore, immunofluorescence staining demonstrated that the transplanted USCs differentiated into UCs and SMCs in vivo. Conclusions Autologous USCs can be used as an alternative cell source for cell-based tissue engineering for urethral reconstruction.