44 research outputs found

    Operation modes of Sakmarskaya Solar Power Plant in Orenburg power system

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    One of the relevant directions in power industry development is the formation of renewable energy sources, especially solar power plants. In 2015 Sakmarskaya solar power plant was put into operation in the Orenburg region with total installed capacity of 25 MW. The studying of power system operation issues, become extremely interesting, it can be possible to evaluate the efficiency of their operation, to assess their technical and economic indexes and other factors.Одним из актуальных направлений развития электроэнергетики являются возобновляемые источниками энергии, прежде всего солнечные электростанции. Так, с 2015 г. В Оренбургской области России введена в работу Сакмарская СЭС установленной мощностью 25 МВт. Интересными являются исследования режимов работы станции, т.к. на их основе можно получить экспериментальные технико-экономические показатели

    Optical properties of melanin in the skin and skin-like phantoms

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    ABSTRACT Experimental study and computer modeling were used to investigate the optical properties of melanin in the skin and skinlike phantoms. To investigate light scattering by melanosomes in skin we made skin-like phantoms on the base of gelatin with different content of melanin particles. Spectra of total transmittance and diffuse reflectance of the phantoms were obtained in the wavelength range from 400 to 800 nm. Absorption and reduced scattering coefficients of melanin were calculated. Mie theory was used to estimate the optical properties ofmelanin particles. Wavelength dependence of refractive indices of eumelanin particles (isolated and purified from the ink of the cuttlefish Sepia officinalis) and synthetic melanin particles was estimated

    Nifedipin ublažava djelovanje kokaina na enzimsku aktivnost u mozgu i jetri te smanjuje njegovo izlučivanje putem mokraće

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    The aim of this study was to see how nifedipine counters the effects of cocaine on hepatic and brain enzymatic activity in rats and whether it affects urinary excretion of cocaine. Male Wistar rats were divided in four groups of six: control, nifedipine group (5 mg kg-1 i.p. a day for five days); cocaine group (15 mg kg-1 i.p. a day for five days), and the nifedipine+cocaine group. Twenty-four hours after the last administration, we measured neuronal nitric oxide synthase (nNOS) activity in the brain and cytochrome P450 quantity, ethylmorphine-N-demethylase, and anilinehydroxylase activity in the liver. Urine samples were collected 24 h after the last cocaine and cocaine+nifedipine administration. Urinary cocaine concentration was determined using the GC/MS method. Cocaine administration increased brain nNOS activity by 55 % (p<0.05) in respect to control, which indicates the development of tolerance and dependence. In the combination group, nifedipine decreased the nNOS activity in respect to the cocaine-only group. In the liver, cocaine significantly decreased and nifedipine significantly increased cytochrome P450, ethylmorphine-N-demethylase, and anilinehydroxylase in respect to control. In combination, nifedipine successfully countered cocaine effects on these enzymes. Urine cocaine excretion in the cocaine+nifedipine group significantly dropped (by 35 %) compared to the cocaine-only group. Our results have confirmed the effects of nifedipine against cocaine tolerance and development of dependence, most likely due to metabolic interactions between them.Cilj je ovoga istraživanja bio utvrditi kako nifedipin ublažava djelovanje kokaina na enzimsku aktivnost u mozgu i jetri Wistar štakora te utječe li na njegovo izlučivanje putem mokraće. Mužjaci su podijeljeni u četiri skupine po šest jedinki: kontrolnu skupinu, nifedipinsku skupinu koja je pet dana intraperitonealno primala nifedipin u dozi od 5 mg kg-1; skupinu koja je pet dana primala kokain u dozi od 15 mg kg-1 na dan te skupinu koja je zajedno primala nifedipin i kokain u odgovarajućim dozama. Dvadeset i četiri sata nakon posljednje doze izmjerena je enzimska aktivnost sintaze dušičnoga oksida (nNOS) u mozgu, razina citokroma P450 te aktivnosti enzima etilmorfi n-N-demetilaze i anilinhidroksilaze u jetri štakora. Uzorci mokraće prikupljeni su 24 sata nakon posljednje doze kokaina odnosno kombinacije nifedipina i kokaina. Koncentracija kokaina u mokraći izmjerena je s pomoću vezanog sustava plinske kromatografi je i spektrometrije masa. Kokain je povećao aktivnost nNOS-a u mozgu za 55 % (p<0,05) u odnosu na kontrolnu skupinu, što upućuje na stvaranje tolerancije i ovisnosti. U kombiniranoj skupini nifedipin je značajno smanjio aktivnost nNOS-a u odnosu na skupinu koja je primila samo kokain. Kokain je značajno snizio, a nifedipin značajno povisio razinu citokroma P450 u jetri te aktivnost etilmorfi n-N-demetilaze i anilinhidroksilaze u odnosu na kontrolnu skupinu. U kombiniranoj skupini nifedipin je uspješno ublažio djelovanje kokaina na aktivnost spomenutih enzima. Izlučivanje kokaina putem mokraće u kombiniranoj skupini bilo je značajno manje (35 %) nego u skupini koja je primala samo kokain. Ovi rezultati potvrđuju da nifedipin štiti od djelovanja kokaina i stvaranja ovisnosti, najvjerojatnije zbog interakcija u metabolizmu dvaju spojeva

    Изучение влияния приёма пищи на биодоступность, безопасность и переносимость лекарственного препарата Атериксен®, таблетки, 100 мг у здоровых добровольцев

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    The aim. The primary objective of the study was to evaluate the effect of food on the bioavailability of Aterixen® 100 mg tablet after single oral dose under fasting or fed conditions. The secondary objective was to evaluate the pharmacokinetic parameters, safety, and tolerability of Aterixen® 100 mg tablet after single oral dose under fasting or fed conditions. Materials and methods. Healthy male and female volunteers aged 18 to 45 years were included in the study. Due to lack of data about intra-individual variability of the main pharmacokinetic parameters of the active substance in Aterixen® (XC221GI, 1-[2-(1-Methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione), an adaptive group sequential approach was used in the study. At Stage I, 24 volunteers were randomized into 2 groups (12 in each group): Group 1 (sequence AAB) received treatment A (administration of the drug under fasting conditions) during period I, treatment A during period II and treatment B (administration of the drug under fed conditions) during period III, Group 2 (sequence BBA) received therapy B during period I, therapy B during period II, and therapy A during period III. In each study period, serial blood samples were collected before and throughout 12 h after administration of the study drug. The quantification of the active substance XC221GI in plasma samples was performed using a validated high-performance liquid chromatography method with mass spectrometric detection. Safety evaluation was performed on the basis of frequency and severity of adverse events (AEs) and serious adverse events (SAEs), which were registered based on complaints, physical examination, laboratory tests, and electrocardiography (ECG). Drug tolerability was evaluated in terms of proportion of volunteers who prematurely discontinued participation in the study due to AE/SAE. Results. 24 randomized volunteers completed the study in compliance with the approved study protocol. The averaged pharmacokinetic curves profiles of XC221GI had similar shapes under fasting and fed conditions. Confidence intervals for the ratio of the geometric means for the primary parameters (AUC(0-t) and Cmax) of XC221GI and AUC(0-∞) were within the 80-125 % acceptance interval, while a small in absolute value, but statistically significant differences were noted in time until Cmax is reached. Throughout the study, 2 volunteers reported AEs (low RBC count, low hemoglobin concentration, and low hematocrit value) after receiving the study drug under fed conditions. All reported AEs were mild. The relationship between AEs and the study drug product was assessed by investigator as doubtful. Conclusion. The results of this study indicate that food does not affect the bioavailability of Aterixen® 100 mg, tablets, and the single oral dose of 100 mg was safe and well tolerated by healthy volunteers.Цель исследования. Первичной целью исследования являлась оценка влияния приёма пищи на биодоступность лекарственного препарата Атериксен®, таблетки, 100 мг после его однократного приёма натощак и после еды. Дополнительная цель заключалась в оценке фармакокинетических параметров, безопасности и переносимости препарата Атериксен® при его однократном приёме в дозе 100 мг натощак и после приёма пищи. Материал и методы. В исследование включали здоровых добровольцев мужского и женского пола в возрасте от 18 до 45 лет. В связи с отсутствием данных о внутрииндивидуальной вариабельности основных фармакокинетических параметров действующего вещества препарата Атериксен® (XC221GI, 1-[2-(1-Метилимидазол-4-ил)-этил]пергидроазин-2,6-дион) в исследовании применялся адаптивный последовательный подход. На Этапе I было рандомизировано 24 добровольца (по 12 в каждой группе): группа 1 (последовательность ААВ) принимала терапию А (приём препарата натощак) в периоде I, терапию А в периоде II и терапию В (приём препарата после еды) в периоде III, группа 2 (последовательность ВВА) принимала терапию В в периоде I, терапию В в периоде II и терапию А в периоде III. В каждом периоде исследования у добровольцев отбирали образцы крови до и в течение 12 ч после приёма препарата исследования. Количественное определение действующего вещества XC221GI в образцах плазмы крови проводилось валидированным методом высокоэффективной жидкостной хроматографии с масс-спектрометрическим детектированием. Безопасность препарата оценивали по количеству и степени тяжести нежелательных явлений (НЯ) и серьёзных нежелательных явлений (СНЯ), зарегистрированных на основании жалоб, данных физикального осмотра, а также по изменениям лабораторных показателей и электрокардиографического исследования (ЭКГ). Переносимость исследуемого препарата оценивали по доле добровольцев, досрочно прекративших участие в исследовании из-за возникновения НЯ/СНЯ. Результаты исследования. 24 рандомизированных добровольца завершили исследование полностью в соответствии с одобренным протоколом исследования. Усреднённые профили фармакокинетических кривых XC221GI при приёме исследуемого препарата натощак и после приёма пищи имели близкие формы. Доверительные интервалы для отношений средних геометрических значений первичных показателей (AUC(0-t) и Cmax) XC221GI, а также AUC(0-∞) соответствовали пределам эквивалентности 80,00–125,00 %, при этом было отмечено небольшое по абсолютной величине, но статистически значимое различие по времени достижения максимальной концентрации исследуемого вещества. На протяжении исследования у 2 добровольцев при приёме препарата после приёма пищи отмечались НЯ в виде снижения количества эритроцитов, концентрации гемоглобина и значения гематокрита. Все зарегистрированные НЯ имели лёгкую степень тяжести. Связь НЯ с исследуемым препаратом по оценке врача-исследователя была расценена как сомнительная. Заключение. Результаты исследования показали отсутствие влияния фактора приёма пищи на биодоступность лекарственного препарата Атериксен®, таблетки, 100 мг, а также его безопасность и хорошую переносимость при однократном приёме здоровыми добровольцами в дозе 100 мг

    Protection by the NDI1 Gene against Neurodegeneration in a Rotenone Rat Model of Parkinson's Disease

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    It is widely recognized that mitochondrial dysfunction, most notably defects in the NADH-quinone oxidoreductase (complex I), is closely related to the etiology of sporadic Parkinson's disease (PD). In fact, rotenone, a complex I inhibitor, has been used for establishing PD models both in vitro and in vivo. A rat model with chronic rotenone exposure seems to reproduce pathophysiological conditions of PD more closely than acute mouse models as manifested by neuronal cell death in the substantia nigra and Lewy body-like cytosolic aggregations. Using the rotenone rat model, we investigated the protective effects of alternative NADH dehydrogenase (Ndi1) which we previously demonstrated to act as a replacement for complex I both in vitro and in vivo. A single, unilateral injection of recombinant adeno-associated virus carrying the NDI1 gene into the vicinity of the substantia nigra resulted in expression of the Ndi1 protein in the entire substantia nigra of that side. It was clear that the introduction of the Ndi1 protein in the substantia nigra rendered resistance to the deleterious effects caused by rotenone exposure as assessed by the levels of tyrosine hydroxylase and dopamine. The presence of the Ndi1 protein also prevented cell death and oxidative damage to DNA in dopaminergic neurons observed in rotenone-treated rats. Unilateral protection also led to uni-directional rotation of the rotenone-exposed rats in the behavioral test. The present study shows, for the first time, the powerful neuroprotective effect offered by the Ndi1 enzyme in a rotenone rat model of PD

    Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

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    Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

    Chronic Administration of Rotenone Induces Parkinsonic Symptoms and Increases Levels of Nitric Oxide in Rat Brain

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    Proceedings of the 9th International Multidisciplinary Conference &laquo;Stress and Behavior&raquo; Saint-Petersburg, Russia, 16&ndash;19 May 2005.Parkinson&rsquo;s disease (PD) is one of the most widespread neurodegenerative diseases. Pathologically, the hallmark of idiopathic PD is the loss of dopaminergic neurons in the substantia nigra (SN), leading to major clinical abnormalities that characterise this disease. The cause of neuronal loss in the brain is still not known. A reduction of complex I activity has been demonstrated in mitochondria of PD patients and complex I inhibitors such as environmental toxins are involved in some cases of toxic, but not in the majority of sporadic PD. It is well known that the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPP) after its conversion to one of the most prominent mitochondrial complex I inhibitors 1-methyl-4-phenylpyridinium (MPP+), produces PD symptoms. However, till now, there is no adequate experimental model of PD. Recently, it was shown that chronic subcutaneous exposure to low doses of rotenone (an inhibitor of mitochondrial NADH dehydrogenase, a naturally occurring toxin and a commonly used pesticide) caused highly selective nigrostriatal dopaminergic lesions. However, while the behavioral effects of rotenone administration are well characterised, the mechanisms underlying rotenone action are unclear. It is hypothesised that PD is accompanied by a number of neurochemical, cellular and molecular disturbances; these include enhanced generation of free radicals. There are a growing number of recent studies concerning the role of nitric oxide (NO), a molecule, which is regarded as universal neuronal messenger in the pathophysiology of neurodegenerative diseases. The aim of this work is to study mechanisms underlying oxidative damage of the various brain areas of rats produced by rotenone and to investigate a possible role of NO and lipid peroxydation (LPO) processes during chronic rotenone administration.Methods: Experiments were carried out on male Sprague-Dawley rats. Rotenone at 1.5 mg/kg i. p. was administered to rats daily for 10, 20, 30 and 60 days and NO and TBARS were measured in the frontal and prefrontal cortices, striatum and nucleus accumbences (NAc). Oil was injected as vehicle to the control rats (1 ml/kg). NO generation was directly measured using Electron Paramagnetic Resonance spectroscopy. Specific indexes of LPO (i.e., thiobarbituric acid reactive substances, TBARS) were measured spectrophotometrically.Results and discussion: NO level in all studied brain structures of rats after first the rotenone injection was not different from that of the control group. In striatum and frontal cortex the level of NO was increased on day 30 and day 6. It has been shown that besides its role as a mediator of several physiological functions, NO appears to be a neurotoxin under conditions of excessive production, which suggests a role for NO in neurodegenerative diseases. NO, generated by the inducible form of nitric oxide synthase (iNOS) in glial cells or the neuronal form (nNOS), can play a key role in the cascade of events leading to the degeneration of neurons. NO-induced catecholamine oxidation could also explain neurotoxcicity in PD by the inherent production of reactive oxygen and nitrogen species. Although NO may act independently, may also act co-operatively with other reactive oxygen species (ROS) to induce neuronal damage. In our study on day 1 and 20 there were slight increases of TBARS in the striatum and frontal cortex but on day 30 and 60 the amount of TBARS was twice higher compared to control in these regions. It was recently demonstrated that a moderate level of complex I inhibition characteristic for PD leads to significant ROS formation. Taken together, these data can be interpreted that dopaminergic neurons may be intrinsically susceptible to oxidative damage as compared to other neurons. Catalepsy was tested by measuring the descent latency after 30 and 60 days using bar and grid test. Rotenone- treated animals showed a prolonged descent latency as compared to control animals. An increase of descent latency from day 30 to 60 was not observed. Thus, the behavioral data point to decreased dopamine activity.Conclusion: The findings indicate that chronic administration of rotenone at low dose 1.5 mg/kg significantly enhances the NO generation in all studied brain areas, especially in the NAc and straitum. Moreover, the results provide the first direct evidence that rotenone increases NO tissue level. Our findings also show that treatment with rotenone during 30 and 60 days increases LPO intensity, which points to acute toxicity. The results of this study should advance the understanding of the mechanism of action for pesticides in the pathogenesis of PD, in particular, a role of oxidative damage in the neurotoxicity phenomena Supported by grants RFBR 03-04-49050 and RFH 03-06-00085а.induced by administration of rotenone.&nbsp;&nbsp

    Humanizing of Education as Mean of Creation of the Personality Oriented Environment

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    У статті розглянуті напрями ефективного управління виховним процесом у школі шляхом упровадження ідей гуманізації, здійснення гуманізації виховного процесу з урахуванням комплексного підходу.In the article considered direction of effective management a educate process at school by introduction of ideas of humanizing, realization of humanizing of an educate process through complex approach

    Age-Related Individual Behavioural Characteristics of Adult Wistar Rats

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    The aim of this work was to study age-related changes in the behaviour of adult Wistar rats using the open field (OF) and elevated plus maze (EPM) tests. Behavioural changes related to motor activity and anxiety were of particular interest. Results showed that as male and female rats progressed from 2 to 5 months of age, there was a decrease in the level of motor and exploratory activities and an increase in their level of anxiety. Age-related changes were dependent upon initial individual characteristics of behaviour. For example, animals that demonstrated high motor activity at 2 months become significantly less active by 5 months, and animals that showed a low level of anxiety at 2 months become more anxious by 5 months. Low-activity and high-anxiety rats did not show any significant age-related changes in OF and EPM tests from 2 to 5 months of age, except for a decrease in the number of rearings in the EPM. Thus, the behaviour of the same adult rat at 2 and 5 months of age is significantly different, which may lead to differences in the experimental results of physiological and pharmacological studies using adult animals of different ages
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