The study of the role of GABA-ergic system in realization of neurotropic effects of aza-15-crown-5 ether derivative

Показано, что механизм действия соединения С-3 связан с активацией эффектов ГАМК-ергической системы, о чем свидетельствует увеличение содержания ГАМК в гомогенате головного мозга крыс и уменьшение ферментативной активности ГАМК-Т. В концентрации 10-5 М макрогетероцикл способен на 50 % снижать связывание 3Н-ГАМК с мембранами фракции клеток головного мозга крыс. При сопоставлении противосудорожной активности соединения С-3 с эталонными препаратами оказалось, что ЕД50 макроцикла по методу «антагонизма с коразолом» ниже на порядок ЕД50 дифенилгидантоина и депакина.The aim of the work is the investigation of the GABA-ergic system role and antiseizure effects in macrogeterocycle C-3 neurotropic effects realization.The experiments were performed on 3-month Wistar rats weighting 160–180 g and mice weighting 18–20 g. The data obtained revealed that C-3 psychotropic activity characterizes by anticonvulsive activity wide spectrum appearance that is quite definite from compounds with nootropic activity. Macrogeterocycle C-3 has also expressed antiamnestic efficacy. It was shown that mode of action of compound C-3 is due to the activation of GABA-ergic system, that confirmed by the increase of GABA content and the decrease of enzymatic activity of GABA-T in rats brain gomogenate. The main effects of C-3 (antiamnesic, anticonvulsant) are diminished by bicuculline. Compoud C-3 in concentration of 10-5 M on 50% decreases the binding of 3H-GABA with membrane fraction of rats brain cells. Compound C-3 is more effective by its anticonvulsant activity than that of reference drugs of depakine and diphenylgidantoine. One could conclude that one of the possible mechanism of macrogeterocycle C-3 psychotropic effects realization is GABA molecule presence that could induce its direct interaction with brain GABA-ergic receptors

Система найма персонала в ОАО «ЕВРАЗ ЗСМК»

Объем ВКР – 90 с., источников – 40, схем – 1, таблиц – 1, приложений – 3 Ключевые слова: набор, отбор, найм персонала, система, методы. Объект работы: система набора, отбора и найма персонала в организации: ОАО «ЕВРАЗ ЗСМК». Предмет работы: методы отбора персонала. Цель работы: – исследовать систему набора, отбора и найма персонала в организации: ОАО «ЕВРАЗ ЗСМК». Методы: в ходе работы был произведен анализ необходимых теоретических источников, собраны эмпирические данные, систематизированы и синтезированы практические и теоретические материалы. В ходе работы был собран и систематизирован полученный материал по спектру вопросов, касающихся найма персонала.The volume of WRC - 90, sources -. 40, circuits - 1, tables - 1 application - 3 Keywords: recruitment, selection, hiring, system methods. The object of the work: a set of system selection and recruitment of personnel in the organization: JSC "EVRAZ ZSMK". The subject of work: staff selection methods. Objective: - to explore a set of system selection and recruitment of staff in the organization: JSC "EVRAZ ZSMK". Methods: During the work was carried out analysis of the necessary theoretical sources, the empirical data collected, systematized and synthesized practical and theoretical materials. The work has been collected and systematized the material obtained from the spectrum of issues relating to recruitment

Корреляционный анализ морфофункциональных и иммунологических параметров у пациентов с продвинутыми стадиями первичной открытоугольной глаукомы

PURPOSE. To study the correlations between the immunological data and the indicators of electroretinography (ERG) and optical coherence tomography (OCT) in patients with advanced stages of primary open-angle glaucoma (POAG).METHODS. Previously, we conducted a multimodal study of patients with advanced stages of glaucoma involving ERG, morphometric and immunological studies. In this new study we performed a correlation analysis of the immunological and morphofunctional data of patients with advanced stages of POAG. The study included 35 patients (35 eyes), among them 19 women and 16 men, who were divided into two groups: group 1 — stage II POAG (12 patients, 12 eyes), and group 2 — stage III POAG (23 patients, 23 eyes). The average age of the subjects was 64.2±6.5 years. Intraocular pressure was compensated in all study patients. The Pearson's correlation coefficient was used to calculate the linear relationship between continuous features.RESULTS. In the subgroup with stage II POAG significant correlations of moderate strength (according to the Chaddock scale) were found between the parameters of pattern ERG (PERG) and photopic negative response (PhNR) and the level of VEGF-A in the blood serum (BS), EGF in the tear fluid (TF) and aqueous humor (AH); strong correlations — for the concentrations of EGF and TGF-β2 in the AH. In group 2, moderate correlations between PERG and PhNR parameters and the level of IL-1RA in the TF were found, as well as moderate correlation of TGF-β2 expression in the AH with PnHR amplitude from the baseline. In patients with stage II glaucoma, the levels of MIP-1β/CCL4 in the TF, IL-1RA in the intraocular fluid correlated with the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (GCL), while the EGF in the TF and AH correlated with RNFL thickness. In the group with stage III POAG, correlations of moderate strength were found for the expression level of TNF-α, IL-8/CXCL8 in the TF and RNFL thickness, and strong correlations — for the level of IP-10/CXCL10, HGF/SF, TGF-β2 in AH and the thickness of RNFL and GCL.CONCLUSION. Comparison of ERG, OCT findings and the level of cytokines of various biological effects in the BS, TF and AH confirmed the high informativeness of PERG and PhNR indicators and immunological data as markers of advanced stages of POAG, and allow EGF to be considered as the most promising pathogenetically oriented immunological marker of II and III stages of glaucoma.ЦЕЛЬ. Изучить корреляционные взаимосвязи между данными иммунологических исследований и показателей электроретинографии (ЭРГ) и оптической когерентной томографии (ОКТ) у пациентов с продвинутыми стадиями первичной открытоугольной глаукомой (ПОУГ).МЕТОДЫ. Ранее нами было выполнено мультимодальное исследование пациентов с продвинутыми стадиями глаукомы, включающее электроретинографию, морфометрические и иммунологические исследования. В настоящей работе проведен корреляционный анализ данных иммунологических и морфофункциональных исследований у больных с продвинутыми стадиями ПОУГ. Проанализированы результаты исследований 35 пациентов (35 глаз), в том числе 19 женщин и 16 мужчин, в двух группах: 1 — с развитой (12 больных, 12 глаз), и 2 — далекозашедшей стадией ПОУГ (23 пациента, 23 глаза). Средний возраст исследуемых составил 64,2±6,5 лет. Внутриглазное давление было компенсировано у всех обследуемых. Для вычисления линейной зависимости между непрерывными признаками использовали коэффициент корреляции Пирсона.РЕЗУЛЬТАТЫ. В подгруппе с развитой глаукомой выявлены достоверные корреляции «заметной» силы (по шкале Чеддока) между параметрами паттерн-ЭРГ (ПЭРГ) и фотопического негативного ответа (ФНО) и уровнем VEGF-A в сыворотке крови (СК), EGF в слезной жидкости (СЖ) и внутриглазной жидкости (ВГЖ); и взаимосвязи «высокой» силы – для концентраций EGF и TGF-β2 в ВГЖ. В группе больных с далекозашедшей ПОУГ выявлены корреляции «умеренной» силы для параметров ПЭРГ и ФНО и содержания IL-1RA в СЖ, и «заметная» корреляция экспрессии TGF-β2 в ВГЖ с амплитудой ФНО от изолинии. У пациентов со развитой стадией глаукомы уровни содержания MIP-1β/CCL4 в СЖ, IL-1RA в ВГЖ коррелируют с толщиной слоя нервных волокон сетчатки (СНВС) и ганглиозных клеток сетчатки (ГКС), а концентрации EGF в СЖ и ВГЖ — с толщиной СНВС. В группе с далекозашедшей ПОУГ обнаружены корреляции «умеренной» силы для уровня экспрессии TNF-α, IL-8/CXCL8 в СЖ и толщины СНВС и «заметной» силы — для содержания  IP-10/CXCL10,  HGF/SF,  TGF-β2  в  ВГЖ  и  толщины СНВС и слоя ГКС.ЗАКЛЮЧЕНИЕ. Сопоставление результатов электроретинографии, ОКТ и уровня цитокинов разнообразного биологического действия в СК, СЖ и ВГЖ подтверждают клинически значимую информативность параметров ПЭРГ и ФНО и показателей иммунологических исследований как маркеров продвинутых стадий ПОУГ и позволяют выделить EGF в качестве наиболее перспективного патогенетически ориентированного иммунологического маркера II и III стадии глаукомы

Sedative-hypnotic and muscle relaxant activities of propoxazepam in animal models and investigation on possible mechanisms

Analgesic (for both neuropathic and nociceptive pain) and anticonvulsant action of 7-bromo-5-(o-chlorophenyl)-3- propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) make it perspective for further studying. Objectives: Propoxazepam was evaluated for sedative-hypnotic-like activity in mice and involved mechanisms in a battery of tests: acute oral toxicity, motor coordination and muscle relaxation studies. Materials and Methods: Acute toxicity (rats) and thiopental-induced sleeping (mice) were determined as motor coordination and muscle relaxation. Results: As relatively nontoxic substance (LD50>5000 mg/kg) propoxazepam belong to fifth category according to GHS toxicity classification. At high doses (700, 1100 and 1300 mg/kg, i.p.) a delay in the righting reflex was observed but not a total loss. The results indicated that substance induces hypnotic effects. Because propoxazepam produces any effect on rotarod test, seems that its effects on sleeping time and sleep latency are mediated by affecting motor movement. Conclusion: Based on previous results and present data, it should be presumed that GABAergic mechanisms may be involved in the potentiating effect of propoxazepam on thiopental-induced sleeping time and sleep latency in mice. Propoxazepam potentiates sleep induced by hypnotics like thiopental, but can not induce hypnosis by itself

Structural and Functional Disorders in Glaucoma: the Prospects for Preclinical Diagnosis. Part 1. Is the Search for what Comes First Relevant?

The review analyzes the capabilities of modern technologies of structural neuroimaging of the retina, standard perimetry, and studies of ocular blood flow in the early diagnosis and management of glaucoma. The relevance of the search for those structural and functional changes that are primary in the development of glaucomatous optical neuropathy (GON) and the diagnostic method that has the greatest clinical significance is discussed. Progress in understanding the pathogenesis of glaucoma and the expansion of scientific understanding of key risk factors for the development and progression of the disease, including genetic factors, can be crucially important to substantiate new strategies for preclinical diagnosis and the development of radically new approaches to personalized and preventive glaucoma therapy. However, the search for what arises most early with in primary open-angle glaucoma — changes in structure or function — will not have clinical relevance unless you take into account the capabilities of specific methods of structural and functional neuroimaging that represent information at various levels of organization of the visual system. The search for a single primary factor in the pathogenesis of GON can lead to an erroneous exaggeration of the close relationship between the variables being studied, which in reality either does not exist as a causal relationship or is significantly less than what is supposed — the phenomenon called “illusory correlation”. The reliable diagnosis of early changes that occur before the clinical manifestation of glaucoma is most likely to be based on a combination of structural, functional, and hemodynamic indicators, aimed not only to increase the sensitivity of diagnosis in detecting the earliest events in the development of GON, but rather to dramatically improve the understanding and quality of interpretation of those markers that we own

Blood Flow and Functional Changes in the Retina and the Optic Nerve Due to Blunt Eye Trauma

To assess the damaged regional blood flow and functional activity of the retina and the optic nerve, 96 patients (96 eyes) with a blunt eye trauma (BET) were observed, of which 62 patients (62 eyes) had mild BET (group I), and 34 patients (34 eyes) had moderate BET (group II). Using Ultrasound Doppler techniques, we revealed a statistically significant increase (p < 0.05) of the peak systolic velocity (Vsyst) in the ophthalmic artery (OA), and a decrease of Vsyst and the final diastolic velocity (Vdiast) in the central retinal artery (CRA) (p < 0.05) during the first three days after the trauma in both groups. The recorded photopic negative response (PhNR) in the cone ERG and visual evoked potentials (VEP) showed an inhibited electrical activity of the inner retinal neurons and the visual cortex and a delayed VEP latency. The degree of these changes depended on the severity of post-contusion effects. In patients of group II, a greater inhibition of VEP into small patterns, and a smaller PhNR amplitude in ERG in response to low and high stimulus intensities was observed. All patients displayed changes in the vascular and neuronal systems of the retina in the early post-contusion period, which almost fully disappeared after one month following a 1st degree trauma but remained in the 2nd degree trauma // Russian Ophthalmological Journal, 2016; 1: 32-38

Structural and Functional Disorders in Glaucoma: Prospects for Preclinical Diagnosis. Part 2. Electrophysiological Markers of Early Neuroplastic Events

Analysis of the literature on the problem of structural and functional relationships in the development and progression of glaucomatous optical neuropathy (GON) shows that the search for a single primary factor may lead to an erroneous exaggeration of its role in the pathogenesis of GON. A more promising approach may be to search for clinically significant combinations of current markers of changes in structure, function, and ocular blood flow, and to expand our fundamental understanding of the processes underlying these changes, designed to improve their interpretation radically. The discussed in this review data of recent studies showed that the earliest event in the development of GON is the weakening and loss of synapses, even with the preserved dendritic branching. We assume that the loss of synapses on dendrites and axon terminals, being a manifestation of synaptic plasticity, may occur simultaneously with the change in anterograde transport in axons of retinal ganglion cells (RGC), or, ahead of it. Early changes in the discharge timing of the RGCs associated with a decrease in the strength of synaptic contacts and the elimination of synapses on dendrites can be a target for neuroprotective therapy. The review analyzes the tests of modern electroretinography, which can serve as markers of early events in the development of GON, including plastic changes in the retina at the preclinical stage of glaucoma, and provides physiological rationales for their selective possibilities for clinical practice