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. 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.

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.

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.

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 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.

The discovery and development of effective antihypoxic drugs is an important issue in modern experimental and clinical pharmacology. Complexes of zinc containing imidazole cycles as ligands are promising candidates for the design of novel drugs, including pharmacotherapeutic tools for patient’s protection under conditions of oxygen deficiency. Herein, we report antihypoxic activity of zinc complexes with N-alkenylimidazoles, and, specifically, a novel drug Acyzol, which can be used as efficient antidote after poisoning by carbon monoxide and other combustion products.

The present study investigates the hepatoprotective effect of a novel zinc-containing drug acyzol in comparison with silymarin, a medicinal extract of milk thistle (Silybum marianum). The hepatoprotective effect was studied in 40 albino nonlinear male rats in a model of toxic liver injury induced by intragastric administration of carbon tetrachloride. Both drugs were diluted in water and administered intragastrically at doses 10 mg/kg (acyzol) and 100 mg/kg (silymarin) for 10 days twice daily, after development of clinical toxic hepatitis. Biochemical and functional indicators of the liver parenchyma demonstrated that both drugs reduced mortality, normalized the body and relative liver weight, reduced intensity of cytolytic, cholestatic, and mesenchymal inflammatory syndromes, and restored liver function. The study demonstrates that acyzol and silymarin have comparable hepatoprotective effect, thus, providing a rationale for the use of acyzol in complex therapy of toxic hepatitis and hepatosis.

One the current challenges of modern hepatology is to find new approaches to stimulate liver regeneration and to find new methods for liver disease treatment. Cell therapies, which are based on using regional stem cells for disease treatment, are under active development. However, studies, devoted to their transplantation, are currently scarce. In recent years, hepatic stellate cells are considered to be hepatic stem cells. It is known that activated hepatic stellate cells can transdifferentiate into myofibroblasts and lead to liver fibrosis. The aim of our work was to study the influence of native and activated hepatic stellate cells in vivo by lead nitrate injection after transplantation into partial hepatectomized rats, which is considered to be a classical model to study liver regeneration. Injection of 2-acetylaminofluorene (AAF), which selectively eliminates hepatocyte proliferation, was used to understand the hepatic stellate cells role in liver regeneration process better. Our results suggest that transplanted native and activated hepatic stellate cells can differentiate into hepatocyte-like cells and positively influence liver regeneration without inducing liver fibrosis.

The TRPV1 receptor plays a significant role in many biological processes, such as perception of external temperature (above 43°C), inflammation development, and thermoregulation. Activation of TRPV1 leads to the pain occurrence and decrease in the body temperature, while inhibition of this receptor can lead to an increase in the temperature. The TRPV1 peptide modulators from sea anemone Heteractis crispa extract (APHC1 and APHC3) have been previously characterized as molecules, which generated a pronounced analgesic effect and a decrease in the body temperature in experimental animals. Using the combined APHC1 and APHC3 amino acid sequences, we have prepared a hybrid peptide molecule named A13 that contains all residues potentially important for the activity of the peptide precursors. Biological tests on animals have shown that the hybrid molecule not only combines the analgesic properties of both peptides but, unlike the peptide precursors, also raises the body temperature of experimental animals.

Изучено влияние лектинов растительного происхождения на цитотоксическую активность мононуклеаров периферической крови (МНПК) здоровых доноров. Установлено, что лектин гороха вызывает статистически значимый цитотоксический эффект МНПК по отношению к клеткам колоректального рака.

Бронхиальная астма - мультифакторное заболевание, в основе которого лежат генетическая предрасположенность и агрессивное воздействие различных аллергенов. Заболевание сопровождается такими симптомами, как кашель, дистанционные свистящие хрипы, одышка. Однако данные симптомы сопровождают и бронхообструктивный синдром (БОС), который наблюдается у детей в возрасте 5 лет и младше в связи с инфекциями верхних дыхательных путей, которые часто встречаются в этой возрастной группе. При оказании помощи ребенку с бронхиальной обструкцией необходимо оценить тяжесть БОС до лечения. В педиатрии для купирования остро возникающих нарушений бронхиальной проходимости используют ß2-агонисты, антихолинергические препараты и их комбинацию.

Цель работы — совершенствование диагностики и лечения односторонних параличей возвратных гортанных нервов с преходящим рефлекторным спазмом функционирующей голосовой складки. Проведено обследование и лечение 49 больных (46 женщин и 3 мужчин) в возрасте от 21 года до 75 лет с односторонним параличом возвратного гортанного нерва и преходящим рефлекторным спазмом функционирующей голосовой складки, возникшим вследствие операции на щитовидной железе. Для диагностики и объективизации результатов лечения проводились электромиографический тест на скрытую тетанию, исследование уровня ионизированного кальция крови и видеоларингостробоскопия. Лечение включало дыхательную гимнастику, рефлексотерапию (новокаиновые блокады зон Захарьина—Геда для гортани, аурикулотерапию), медикаментозную терапию (витаминно-кальциевая терапия, миорелаксанты и седативные препараты), фонопедию. У всех 49 больных был восстановлен достаточно громкий и звучный голос, а также нормализовано дыхание и прекращены или минимизированы приступы рефлекторного кашля и ларингоспазмы. Ни одному больному в дальнейшем не потребовалось проведение трахеотомии.