Репозиторий Университета

© 2018 Media Sfera. All rights reserved. Endocrine ophthalmopathy (EOP) is a severe chronic autoimmune disease associated with autoimmune thyroid pathology that leads to loss of sight, cosmetic defects and quality of life decrease. EOP is difficult to give prognosis for due to various factors affecting its course and outcome. Purpose - to develop a reliable and precise prognosis method for EOP activity and severity based on personalized combination of risk factors in specific patients by multidimensional linear regression modeling. Material and methods. A group of 139 patients (278 orbits) with newly diagnosed EOP associated with toxic diffuse goiter was observed during 1 year by an ophthalmologist and an endocrinologist; patient examination interval was 6 months. More than 250 indices were dynamically analyzed in the course of the study. Linear regression analysis was chosen as the research method; it allowed detection of linear dependencies between dependent and explanatory variables. Results. More than 600 various linear regression equations were derived that enabled prediction of EOP onset risk and development timeline, estimation of activity and/or severity of the disease, duration of active period in specific patients for the immediate and long-term outcome. From the derived models, the most reliable and safest for practical application were picked out. The present study introduces nine optimized models that can be used for patient follow-up since day one. Conclusion. The onset risk, progression and outcome of the disease can be determined by a combination of factors revealed in the study.

© 2018 Saint Petersburg Pasteur Institute.All Rights Reserved. Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The article is devoted to the study of attributive components of people diagnosed with Ischemic heart disease. Effort angina. The results of empirical studies of the attributive process are discussed in the article. Now more and more researchers, both domestic and foreign, are beginning to consider attribution as one of the principles of human existence. Attributive processes initially began to be developed in line with the cognitive orientation of social psychology. Currently, they are actively considered in the framework of the psychology of social cognition. Method: We conducted a study on 24 subjects with an average cholesterol level of 7.426 mmol / l (concomitant diseases-hypertension, diabetes, obesity, metabolic syndrome), who underwent treatment in the Central City Clinical Hospital in the rehabilitation department with the diagnosis of Ischemic Heart Disease. Effort Angina. Initially, we conducted the survey of subjects in order to identify their subjective judgment about the cause of the disease. They were asked a question: “In your opinion, what is the cause of your heart disease?” Results: The results of the survey conducted testify that only a small percentage of the subjects believe that they could exert any influence on their health and, for example, to reduce environmental or biological factors. One would assume that such results may be a specific demonstration of the fact that an individual gains experience that it is precisely human health that is difficult to correct and change and simply does not solve it due to the complexity of the problem. However, data obtained in the course of other experiments and studies [19] show that a person is inclined to explain what is happening by circumstances or situational causes, rather than personal ones. The results obtained with the help of T. Dembo’s cognitive self-assessment technique indicate that women believe that they actually have much less physical exertion and their daily routine is more correct than people who are close to them, in their opinion, think about it. We can assume that introjects are more often peculiar to women than men that are related to housekeeping, which sometimes requires considerable physical activity and time. When a woman has to, at the insistence of a doctor, reduce her physical activity and somehow comply with the daily regimen, she feels discomfort because of which she believes that she “does nothing at all”, although her relatives continue to persuade her to have a rest. Here it is appropriate, in our opinion, to raise the problem of accepting oneself and, as a sequence, to take adequate care of oneself. Significant differences in the self-attributive and reflexive components were also discovered in the emotional sphere of the female subjects. In their opinion, they experience low intensity of negative emotions, such as fear and anger, but at the same time they believe that their close relatives radically disagree. This situation can be explained either by the fact that they assume that they have negative emotions more strongly than they would like (and what they admit to this in the study), or they are judged by the words of relatives who can also make their judgments by interpreting the facts with varying degrees of adequacy. Conclusion: In conclusion, it should be noted that during the analysis we encountered at least two facts that require further empirical research. Firstly, we identified three types of explanations (attributions) in the subjects’ answers: adverbial, subjective and personal, and the latter type of causal attribution is not expressed clearly in the subjects of the study. This poses new questions: does a particular type of situation contribute to this perception, or are there any other factors (including personal ones) playing the role here. Secondly, the following questions arise: how exactly does a subject choose only one alternative from a variety of explanatory reasons. All these questions will be understood as a part of our further research.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The study of the features of the higher mental functions of the brain in patients suffering from addiction to psychoactive substances is very important for narcology. It is necessary not only to uncover the mechanisms of addiction, a complete understanding of the neurophysiological processes that determine the nature of the development and severity of the disease, but also to solve practical problems related to the development of treatment methods and the implementation of preventive measures. Method: In the study of patients, a specially designed map was used containing information on the hereditary and demographic characteristics, on the course of the disease, as well as on the socio-cultural status of patients. To determine the functional state of cortical activity in the process of perception of unconscious signals, a special technique was used. The obtained results were subjected to dispersive analysis and the significance of differences was calculated according to Student’s t-criterion. Results: An analysis of premorbid personality traits made it possible to establish the prevalence of instability, pathological conformity, and hysteroidal features in patients. It should be noted that a large percentage of the surveyed had a hereditary burden of alcoholism, mainly in the line of the father. Curiosity, passive submission, imitation of friends were among the motives of the first drug use. All patients in the process of addiction formed the following features: increased excitability, increasing effective disorders (depression, dysphoria), aggravated by exacerbation of craving for the drug, a decline in morals and ethics (egoism, deceit, indifference to one’s fate, hedonism, loss of sense of duty), disorders of the emotional-volitional sphere (emotional instability, hypersensitivity, vulnerability). Conclusion: The analysis of the duration of latent periods and magnitude of the amplitudes of the late positive R3OO wave in patients with heroin addiction revealed clear differences between the data obtained upon presentation of an unconscious neutral and motivationally significant word. Patients who use psychoactive substances, using the method of recording induced potentials of the brain, which is a sensitive indicator of the activity of brain structures in relation to the substance used, revealed a clear diffuse activation of the cerebral cortex in response to an unconscious verbal stimulus related to the motivation prevailing in patients, in particular to “heroin”. Such activation, as well as the difficult dying out of the developed reactions to an unconscious stimulus, indicate certain neurophysiological foundations of the mechanism underlying the changes in the motivational sphere and the stability of the pathological craving for the psychoactive substance.

© 2018, Silicea-Poligraf. All rights reserved. Aim. To evaluate the prevalence of myocarditis in adult patients with non-compaction myocardium (NCM) of the left ventricle (LV), and its influence on the disease course, results of treatment and outcomes. Material and methods. To the study, 103 adult patients included, with NCM, 61 males, mean age 45,6±14,9 y. o. (from 18 to 78). Mean end diastolic LV size was 6,0±0,8 сm, EF LV 38,8±14,5%. Diagnosis of NCM had been done by echocardiography, multispiral computed tomography (n=81) and magnetic resonance tomography (n=39). DNA-diagnostics was performed by NGS method with further Senger sequencing. Pathogenic mutations were found in 9% of patients in the genes MYH7, MyBPC3, LAMP2, DES, DSP, TTN. The investigation also included anticardiac antibodies, genome of cardiotropic viruses by PCR, coronary arteriography (n=26), scintigraphy (n=25). Morphological assessment of the myocardium was done in 19 patients (12 endomyocardial biopsies), 1 intraoperation biopsy, 3 explanted hearts, incl. 2 after biopsy, and 5 autopsies. Mean follow-up 12 [2; 32] months. Results. Myocarditis was found in 53,4%, incl. virus-positive in 32,7% of those, with morphology done for 19 patients (active myocarditis in 10, borderline in 6; with minimal signs of activeness in 3). Viral genome in myocardium found in 8 patients (42,1%). The prevalence of myocarditis 44,4% in an arrhythmic variant of NCM, 12,5% in chronic ischemic, 57,5% in dilation cardiomyopathy, 50,0% in NCM patients with other cardiomyopathies. Special cases were acute/subacute myocarditis in NCM (10,7% of all), acute necrosis (infarction) in 4,9%. Comorbidity with myocarditis in NCM led to significantly more severe LV dysfunction (CHF FC 2 [1; 3] v 1,75 [0; 2], p<0,01, EF 33,8±13,5 v 44,7±13,6%, p<0,001), more prevalent non-sustained ventricular tachycardia (67,3% v 29,3%, p<0,01), proper shocks (38,9% v 0, p<0,05), deaths (16,4 and 4,2%, OR 5,75, 95% CI 1,21-27,43, p<0,05) and transplantation (7,3% v 2,1%, p>0,05). Only in myocarditis patients, as a result of basis (antiviral, immune suppression) and cardiotropic therapy there was significant increase of EF (in acute myocarditis from 25,4±7,9 to 38,6±9,5%, p<0,01), decrease of LV size and pulmonary systolic pressure. Conclusion. Myocarditis is typical phenomenon developing in patients with the primary, i. e. genetically verified NCM. The nature of myocarditis in NCM varies (primary infectious-autoimmune, secondary as a response on genetic/ischemic damage of cardiomyocytes), however regardless of this, it leads to significant worsening of structural and functional parameters, increase of the life-threatening arrhythmias rate, and outcomes (death + transplantation, proper shocks), demanding for active basic therapy.

© 2018 The Author(s) Despite the fact that environmental pollution due to motorcycle exhaust gases reports a great increase, motorcycle production exhibits a great increase through the last years. Countries of Asia and Africa are reported to be the major regions where two-wheeled vehicles are a major transportation mode, with tens of millions of units sold per year. Motorcycle exhaust particles are considered to be the major contributor to environmental pollution due to their airborne dispersion, containing great amount of polycyclic aromatic hydrocarbons (PAHs). This study aims at reporting an objective analysis of the main sources of the ambient air pollution as also particle size distribution and chemical composition analysis of particulate matter originated from the exhausts of two-wheeled vehicles used in the territory of Vladivostok, Russia. Various types of two-wheeled vehicles were examined (motorcycles, ATVs, scooters and wet bikes) using different types of engine and fuel system. Experimental results showed that there was no clear relation to the particle size distribution with the engine displacement of motorcycle and the number of strokes and the fuel system. Instead, there were reported two clear assumptions. The first one is that regarding to the motorcycle brand, a few samples did not exhibit a great percentage of PM10 fraction. The second one is that more modern vehicles, that have a harmful gas afterburning system, are usually the source of an increased percentage of PM10 emitted particles. At last, it should be mentioned that the laser particle size analysis method is capable of determining the particle sizes after their agglomeration whereas the optical morphometry method allows to determine the real particle size of emissions. In conclusion, it can be pointed out that the agglomeration of particles can lead to the reduction in the toxicity of particles emissions originated from two wheeled-vehicles.

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose of the study. To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits. Materials and methods. From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m- 38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016. Results. We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the extraocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), increased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in patients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients. Conclusion. Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.

© 2018 Medical Education. All rights reserved. Mild asthma is characterized by infrequent and slight clinical manifestations and, therefore, is paid lack of attention both from patients and physicians. Physicians tend to underestimate risk of severe exacerbations including asthmatic status in patients with mild asthma. Patients with mild asthma are often poorly adherent to treatment. Also, certain difficulties are related to timely and correct diagnosis and the choice of the optimal treatment by primary care physicians who are first physicians encountering such patients. The paradoxus of asthma and use of short-acting β2-agonists (SABA) to treat chronic airway inflammation lead to excessive dependence on rescue inhalers and insufficient adherence to maintenance anti-inflammatory therapy. This could trigger acute exacerbations and even fatal outcomes in patients with mild asthma. Therefore, SABA monotherapy has to be limited. Easy-to-use questionnaires, algorithms and treatment protocols accessible for primary care physicians could improve detection of mild asthma. Favorable results of clinical trials on as-needed use of budesonide/formoterol Turbuhaler® could change the management paradigm for mild asthma regarding risk of exacerbations, control of asthma symptoms, airway inflammation, and cost-efficacy.

© 2017 Astro Ltd. A two-photon laser femtosecond crosslinking process at the wavelength of 525 nm was studied in a human donor cornea in the presence of riboflavin using two-photon optical microscopy and nanoindentation. It was shown that such an approach results in efficient crosslinking of the corneal collagen and a significant (three-fold) increase in the Young's modulus of the corneal structure. Application of a femtosecond laser with the wavelength of 525 nm allows a drastic enhancement of efficiency in the presence of riboflavin on human corneas and a 50-fold reduction of the laser treatment duration in comparison with the use of a femtosecond laser with the wavelength of 760 nm. We relate this effect to a significant growth in the coefficient of two-photon absorption due to the laser wavelength falling within the edge of the photoinitiator (riboflavin) absorption band. Our studies on a donor human cornea demonstrate the good potential for the clinical application of a femtosecond laser with the wavelength of 525 nm for increasing the cornea rigidity using the two-photon laser femtosecond crosslinking technique.

© 2017 Elsevier Inc. Rabies virus is endemic to Russia, among other countries. It is therefore critical to develop a high-quality and high-precision diagnostic procedure for the control and prevention of infection. The main objective of the research presented here was to develop a reliable RT-qPCR assay for rabies diagnostics. For this purpose, a RABV strains from various biological and geographical origins were used. In addition, rabies-positive and rabies-negative samples, as well as nucleic acids from other viruses and DNA extracted from the brain tissues of mice, dogs, cats, bats and humans, were studied using the developed assay. The analytical sensitivity of the assay, as assessed using armored recombinant positive control dilutions, was 103 copies/ml, and the sensitivity measured using characterized strains was between 0.1 LD50/ml and 1.0 LD50/ml. A broad range of RNA from RABV strains circulating in different regions of Russia, as well as RNA from RABV-positive primary brain samples from 81 animals and two humans, was detected using the developed assay. No false-positive or false-negative results were obtained. Given that high analytical and diagnostic sensitivities and a high specificity were verified for this assay, it has high potential as a screening test that may be suitable for the epizootiological monitoring of animals and for the fast postmortem diagnosis of rabies.

© 2018 by the MediaSphere. The materials of the National Consensus reflect the modern domestic and international experience on this issue. Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation. A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child's height is < –2.0 SDS, if the difference between the child's height SDS and child's midparental height SDS exceeds 1.5 SDS and/or a low growth velocity. The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation. The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day. With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum. GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphy-seal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient's desire and his parents / legal representatives satisfied with the achieved result of the final height. Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation. If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.

© 2018 Park-media, Ltd.  Common marmosets are small New World primates that have been increasingly used in biomedical research. This report presents efficient protocols for assessment of the parameters of adaptive cell-mediated immunity in common marmosets, including the major subpopulations of lymphocytes and main markers of T- and B-cell maturation and activation using flow cytometry with a multicolor panel of fluorescently labelled antibodies. Blood samples from eight common marmosets were stained with fluorescently labeled monoclonal antibodies against their population markers (CD45, CD3, CD20, CD4, CD8) and lymphocyte maturation and activation markers (CD69, CD62L, CD45RO, CD107a and CD27) and analyzed by flow cytometry. Within the CD45 + population, 22.7±5.5% cells were CD3 - CD20 + and 67.6±6.3% were CD3 + CD20 - . The CD3 + subpopulation included 55.7±5.5% CD3 + CD4 + CD8 - and 34.3±3.7% CD3 + CD4 - CD8 + cells. Activation and maturation markers were expressed in the following lymphocyte proportions: CD62L on 54.0±10.7% of CD3 + CD4 + cells and 74.4±12.1% of CD3 + CD8 + cells; CD69 on 2.7±1.2% of CD3 + CD4 + cells and 1.2±0.5% of CD3 + CD8 + cells; CD45RO on 1.6±0.6% of CD3 + CD4 + cells and 1.8±0.7% of CD3 + CD8 + cells; CD107a on 0.7±0.5% of CD3 + CD4 + cells and 0.5±0.3% of CD3 + CD8 + cells; CD27 on 94.6±2.1% of CD3 + cells and 8.9±3.9% CD20 + cells. Female and male subjects differed in the percentage of CD3 + CD4 + CD45RO + cells (1.9±0.5 in females vs 1.1±0.2 in males; p < 0.05). The percentage of CD20 + CD27 + cells was found to highly correlate with animals' age (r = 0.923, p < 0.005). The basal parameters of adaptive cell-mediated immunity in naïve healthy marmosets without markers of systemic immune activation were obtained. These parameters and the described procedures are crucial in documenting the changes induced in common marmosets by prophylactic and therapeutic immune interventions.

© 2018 Ima-Press Publishing House. All rights reservbed. The examination of a patient with acute low back pain (LBP) includes the clarification of complaints and history data, brief physical and neurological examinations, and an assessment of danger symptoms. The diagnosis of acute nonspecific (musculoskeletal) LBP is based on the exclusion of a specific cause of pain (a potentially dangerous disease), discogenic radiculopathy, and lumbar spinal stenosis. If there is typical musculoskeletal pain and no danger symptoms, radiography, X-ray computed tomography, and magnetic resonance imaging are not recommended in the first 4 weeks of disease. Whether it is expedient to perform these techniques is considered when LBP persists over this time period. A patient with acute nonspecific (musculoskeletal) LBP should be informed about the favorable outcome of the disease and the need to maintain physical and social activities, to avoid bed rest, and, if possible, to continue professional activities. The lowest effective dose of nonsteroidal anti-inflammatory drugs for short-term duration, as well as muscle relaxants (the medium level of evidence) can be used to relieve pain. It is recommended that one should use an educational program (to prevent over-exercising and prolonged standing or sitting in static and awkward positions; to lift weights properly; etc.) to prevent recurrent LBP, as well as therapeutic exercises during a non-exacerbation period.

© 2018 Altai State University. All rights reserved. The critical revision of Trollius L. (Ranunculaceae) in the Far East of Russia was made, in which nine species were recognized. The identifcation key and taxonomical synopsis of the genus have been provided. Synonymy, geographical distribution and coeno-ecological peculiarities of each species of these nine species are presented. For the frst time Trollius japonicus Miq. was found in the territory of Russia (the Kurile Islands: Iturup, Kunashir). Furthermore, we found that the information on the distribution of this species on Sakhalin Island is wrong owing to the incorrect identifcation. The information about the medical use of each of nine Trollius species is also provided.

© 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. 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.

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.

Objectives: Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia.

Methods: A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined. Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels, parameters of lipid and mineral metabolism were evaluated.

Results: In young women with central hypogonadism, the frequencies of psychoemotional, neurovegetative and urogenital complaints differed significantly from those in healthy young women and were similar to those in postmenopausal women. Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, parameters of lipid and mineral metabolism as well as quality of life in women with central hypogonadism were not typical of healthy young women but were similar to those of postmenopausal women of middle/old age.

Conclusions: Despite the young age of women with central hypogonadism, clinical, hormonal and biochemical abnormalities were similar in many aspects to those in postmenopausal women at middle/old age. These revealed features could be considered as signs of premature aging in young amenorrheic women with low gonadotropin levels.