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MOLECULAR DOCKING STUDIES OF SOME N-AMIDOALKYLATED DERIVATIVES OF 2-AMINO-1,3,4-OXADIAZOLE AS POTENTIAL INHIBITORS OF GLYCOGEN SYNTHASE KINASE-3β 2-氨基-1,3,4-恶二唑n -氨基烷基化衍生物作为糖原合成酶激酶-3β抑制剂的分子对接研究
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00742
P. Zadorozhnii, Ihor O. Pokotylo
Alzheimer's disease is a neurodegenerative disease characterized by pathological features of neurofibrillary tangles and β-amyloid plaques in the cerebral cortex. In Alzheimer's disease, tau protein undergoes excess phosphorylation, due to which its threads begin to merge and form neurofibrillary tangles within nerve cells. It has been shown that glycogen synthase kinase-3β is a key factor in the phosphorylation of tau protein, its increased activity leading to pathologies of neurofibrillary tangles and, consequently, to neurodegenerative changes in the brain. In this connection, the search for effective inhibitors of GSK-3β is a very important and urgent task, for their further use in the treatment of Alzheimer's disease. Aim of research.The aim of this study is to search new inhibitors of GSK-3β among N-amidoalkylated derivatives of 2-amino-1,3,4-oxadiazole by molecular docking methods. Materials and methods. We have carried out geometry optimization of analyzed structures within PM3 semi-empirical method, and GSK-3β molecular docking using software ArgusLab 4.0.1. The three-dimensional crystal structure of co-crystallizer GSK-3β and inhibitor has been loaded from the data bank of protein molecules (PDB ID: 3F7Z). Results. In this study it has been shown that the structures being studied mainly form stronger complexes with the enzyme compared to the known inhibitor. Based on the results of molecular docking, the compounds leaders N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl)benzamide and 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl)benzamide have been chosen. The structures of the compounds leaders have been tested for compliance with Lipinski criteria. Conclusions. Proposed compounds leaders can be recommended for further studies in the treatment of Alzheimer's disease. Despite the good results obtained in silico analysis, it is mandatory to perform biological tests in vitro and in vivo.
阿尔茨海默病是一种神经退行性疾病,其病理特征是大脑皮层的神经原纤维缠结和β-淀粉样斑块。在阿尔茨海默病中,tau蛋白经历过度磷酸化,因此它的线开始合并并在神经细胞内形成神经原纤维缠结。研究表明,糖原合成酶激酶-3β是tau蛋白磷酸化的关键因素,其活性的增加导致神经原纤维缠结的病理,从而导致大脑的神经退行性改变。因此,寻找GSK-3β的有效抑制剂是一项非常重要和紧迫的任务,以进一步将其用于阿尔茨海默病的治疗。研究目的。本研究的目的是通过分子对接方法在2-氨基-1,3,4-恶二唑n -氨基烷基化衍生物中寻找新的GSK-3β抑制剂。材料和方法。我们使用ArgusLab 4.0.1软件对PM3半经验方法和GSK-3β分子对接进行了分析结构的几何优化。共结晶剂GSK-3β和抑制剂的三维晶体结构已从蛋白质分子数据库(PDB ID: 3F7Z)中加载。结果。在这项研究中已经表明,与已知的抑制剂相比,所研究的结构主要与酶形成更强的配合物。根据分子对接的结果,选择了先导化合物N-((5-(2-溴苯基)-1,3,4-恶二唑-2-基)氨基)甲基)苯酰胺和2,4-二氯-N-(2,2,2-三氯-1-((5-(对甲苯基)-1,3,4-恶二唑-2-基)氨基)乙基)苯酰胺。化合物先导化合物的结构已经过测试,符合利宾斯基标准。结论。提出的先导化合物可以推荐用于阿尔茨海默病治疗的进一步研究。尽管在硅分析中获得了良好的结果,但必须在体外和体内进行生物试验。
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引用次数: 0
ALTERNATIVE METHOD FOR TREATING ARTERIAL HYPERTENSION WITH THE USE OF THE «MOXI» DEVICE 使用“moxi”装置治疗动脉高血压的替代方法
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00777
I. Shuvalova, Lee Sang-kyu
The aim of the article was to study of the influence of the apparatus “MOXI” as an alternative method for the correction of arterial hypertension and improving the quality of life of patients using acupuncture reflexotherapy. Materials and methods. The study was conducted in 36 patients with arterial hypertension of 1 stage, low risk, with the experience of the disease from 1 to 2.5 years, without taking antihypertensive therapy. The average age of patients was 41.3±2.6 years. The state of the psycho-emotional sphere was assessed by the SAN test. The determination of the general non-specific adaptation reaction according to Garkavi-Kvakina-Ukolova was carried out. Control of blood pressure and pulse, was carried out in the center, and by the diaries of self-control. We calculated the arithmetic mean of blood pressure for the day and week. Baseline blood pressure was 152/106 mmHg when measured at the center and 149/102 mmHg at home. Results. The obtained results indicate that the adaptogenic set of acupuncture points allows you to simultaneous selective regulation of the function of organs and systems according to the principle of segmental and vegetative innervation. After a course of preventive recovery, a statistically significant (p<0.05) normalization of well-being indicators according to the SAN test was noted from 4.0 to 4.6 points, activity from 3.9 to 4.4 points, mood from 3.9 to 4.7 points. All patients showed a pronounced reduction of complaints and autonomic disorders. In addition, we revealed improvement in the functional state of the cardiovascular system. So, systolic pressure decreased from 152±1.5 mmHg up to 134±2.4 mmHg, and diastolic from 106±0.7 mmHg to 82±1.8 mmHg. Conclusions. As a result of the prophylactic treatment, all patients registered a normal type of adaptive response, since the training reaction was detected in 44.4 % of cases, the calm activation reaction was 22.2 %, in the area of increased activation - 33.4 %. The use of the “MOXI” device in the treatment of patients with arterial hypertension of 1 type, with a low level of risk gives a positive therapeutic effect in the normalization of the psycho-emotional state of patients. It normalizes non-specific adaptation reactions of the body, and allows you to achieve a decrease in blood pressure to normal levels.
本文的目的是研究MOXI器械作为针刺反射疗法治疗动脉高血压的替代方法,对改善患者生活质量的影响。材料和方法。本研究纳入36例1期、低危、发病时间1 ~ 2.5年、未接受降压治疗的动脉高血压患者。患者平均年龄41.3±2.6岁。心理情绪领域的状态采用SAN测试进行评估。根据Garkavi-Kvakina-Ukolova标准测定一般非特异性适应反应。血压和脉搏的控制在中心进行,并通过自我控制日记进行。我们计算了当天和一周血压的算术平均值。在中心测量时基线血压为152/106 mmHg,在家时为149/102 mmHg。结果。所得结果表明,适应性穴位组可以根据节段性和植物性神经支配的原则,同时选择性地调节器官和系统的功能。经过一个预防性恢复过程后,根据SAN测试,幸福感指标的正常化从4.0分到4.6分,活动从3.9分到4.4分,情绪从3.9分到4.7分,具有统计学意义(p<0.05)。所有患者的主诉和自主神经紊乱明显减少。此外,我们还发现了心血管系统功能状态的改善。因此,收缩压从152±1.5 mmHg降至134±2.4 mmHg,舒张压从106±0.7 mmHg降至82±1.8 mmHg。结论。由于预防性治疗的结果,所有患者都登记了正常类型的适应性反应,因为在44.4%的病例中检测到训练反应,平静激活反应为22.2%,在激活增加区域- 33.4%。“MOXI”装置用于1型动脉性高血压患者的治疗,风险水平低,对患者心理情绪状态的正常化具有积极的治疗效果。它使身体的非特异性适应反应正常化,并使你的血压降至正常水平。
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引用次数: 0
PLACENTAL CYTOPATHIC DAMAGE FACTOR DUE TO PARVOVIRUS B19 – AS A HALLMARK OF INTRAUTERINE SYMPTOMATHY OF INFECTED FETUS 细小病毒b19 -引起的胎盘细胞病变损害因子作为受感染胎儿宫内症状的标志
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00782
N. Bondarenko, A. Aksonova
Aim of the work. The focus of this study was to analyze the frequency of fetal intrauterine symptomatic realization as a result of B19 parvovirus infection of pregnant women during I and II gestation periods, with the combination of determination the levels of alpha-fetoprotein in maternal serum blood and histopathological investigation of placenta in cases of negative effects for infected fetuses. Materials and methods. A total of 478 pregnant women were at risk of infection and screened for parvovirus B19. The study was based on serological, morphological and virological testing of fetuses from mothers with confirmed parvovirus B19 infection. Infection of pregnant women was detected by serological diagnosis of specific antibodies IgM and IgG to parvovirus B19. Intrauterine fetal infection was confirmed by polymerase chain reaction method. Levels of alpha-fetoprotein in meternal venous blood were detected using an immunochemical test method. An antenatal diagnosis of hydrops fetalis was confirmed by ultrasound scanning. Placenta from the 8 infected fetuses was studied histologically with hematoxylin and eosin staining using electron microscope during gestational periods of 12-22 weeks. Statistical analysis of the obtained data was carried out using nonparametric statistics with the definition of Fisher's criterion. Results and discussion. The average gestational period of symptomatic manifestations of intrauterine fetal infection was 19.9±0.5 weeks of gestation. It was established that in 33 of cases were confirmed the intrauterine infection due to parvovirus B19 by using the morphological placenta tissue analysis. The research found that the levels of maternal serum alpha-fetoprotein was significantly higher (in 2.17 times) in group of fetuses who suffered from fetal hydrops and in cases of intrauterine fetal death before detecting the general echographic sings of fetal failure (p˂0.05). It will be very important to compare this indicator with the Doppler ultrasound measurements of the human fetal middle cerebral artery peak systolic velocity (MCA PSV) and blood flow parameters in the fetal ductus venosus and to predict the possibility of poor perinatal outcomes. It was identified a cytopathic effect in placental cells viral origin and detected in cells of the cytotrophoblast, syncytiotrophoblast, endothelial cells, and blood cells. Conclusions. Parvovirus B19 fractions were visualized in 100 % of cases of miscarriages with fetal hydrops and placental edema during 12-22 weeks of gestation, while acute maternal parvovirus infection (with the detection of IgM against to parvovirus B19) was diagnosed by immunoassay only in 62.5 % of cases. Detection of B19 particles in placental tissue from fetuses with non-immune origin hydrops is an auxiliary method in the diagnosis of vertical transmission of parvovirus during pregnancy. It is more preferable to estimate the levels of alpha-fetoprotein in maternal serum blood in case of parvovirus B19 affected
工作的目的。本研究的重点是结合母体血清中甲胎蛋白水平的测定和胎盘组织病理学检查,分析妊娠1期和妊娠2期孕妇感染B19细小病毒后胎儿宫内症状实现的频率。材料和方法。共有478名孕妇面临感染风险,并接受了细小病毒B19筛查。该研究基于对确诊细小病毒B19感染的母亲所生胎儿的血清学、形态学和病毒学检测。采用细小病毒B19特异性抗体IgM和IgG的血清学诊断检测孕妇感染情况。采用聚合酶链反应法确诊宫内胎儿感染。采用免疫化学方法检测母体静脉血中甲胎蛋白水平。超声扫描证实胎儿积水的产前诊断。在妊娠12-22周期间,用电镜对8例感染胎儿的胎盘进行苏木精和伊红染色。根据Fisher准则的定义,采用非参数统计方法对所得数据进行统计分析。结果和讨论。宫内胎儿感染有症状表现的平均妊娠期为19.9±0.5周。经胎盘组织形态学分析,33例确诊为细小病毒B19宫内感染。研究发现,在常规超声检测胎儿衰竭之前,患有胎儿水肿的胎儿组和宫内胎儿死亡的孕妇血清甲胎蛋白水平明显较高(2.17倍)(p小于0.05)。将该指标与胎儿大脑中动脉收缩峰值速度(MCA PSV)和胎儿静脉导管血流参数的多普勒超声测量结果进行比较,并预测围产期不良结局的可能性,将具有重要意义。在胎盘细胞中发现了病毒起源的细胞病变效应,并在细胞滋养层细胞、合胞滋养层细胞、内皮细胞和血细胞中检测到。结论。在妊娠12-22周的胎儿水肿和胎盘水肿的流产病例中,100%可见到细小病毒B19的部分,而通过免疫分析法诊断急性母体细小病毒感染(检测针对细小病毒B19的IgM)的病例仅占62.5%。在非免疫性积水胎儿胎盘组织中检测B19颗粒是诊断妊娠期细小病毒垂直传播的辅助方法。在细小病毒B19感染妊娠的情况下,估计母体血清中甲胎蛋白的水平是更可取的,因为该标志物的升高可能是不良胎儿结局的早期预测标志。
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引用次数: 0
EFFECT OF VITAMIN D STATUS ON LIPID METABOLISM OF CHILDREN 维生素d对儿童脂质代谢的影响
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00750
E. Stroy
It has been proven that the functions of vitamin D are not limited to the control of calcium-phosphorus metabolism, but its other pleiotropic effects are being studied. The aim of our study was to study vitamin D status and its effect on the lipid profile in children of risk group for the development of dyslipoproteinemia. Materials and methods 30 children aged 6–7 years (mean age 6.4±0.6 years) who were born to women with diabetes were examined. The control group – 30 children 6–7 years old (6.5±0.5 years) from healthy mothers. An assessment of physical development was carried out with the calculation of body mass index. We studied lipid metabolism indicators - total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol (mmol / l) in blood, atherogenic index. All children were determined with the content of 25-OH-D in the serum, the level of glucose. Results 10 (33.3 %) children from mothers with diabetes are overweight, 5 (16.7 %) – obesity, which is 2 times higher than in the control group. The fasting glucose level in all the examined children from mothers with diabetes was within physiological fluctuations. The level of 25-OH-D in children from mothers with diabetes mellitus, compared with the control group, was significantly reduced. Dyslipoproteinemia was found in children from diabetic mothers: a significant increase in serum triglyceride and cholesterol levels, higher levels of low-density lipoprotein cholesterol and lower levels of high-density lipoprotein cholesterol than in the control group (p <0.05), atherogenic index was significantly higher. Prospects for further research are to explore the possibility of using vitamin D for the primary prevention and treatment of metabolic syndrome, diabetes in children. Conclusions Vitamin D deficiency in the body of the surveyed can be one of the causes of their dyslipidemia, in addition, overweight and obesity are also risk factors for the development of atherosclerosis, metabolic syndrome. Children at risk need dynamic monitoring of anthropometric indicators, control of body mass index, lipid and carbohydrate blood profile, level 25-OH-D.
已经证明,维生素D的功能并不局限于控制钙磷代谢,它的其他多效作用正在研究中。本研究的目的是研究维生素D的状态及其对发生脂蛋白异常血症危险组儿童血脂的影响。材料与方法对糖尿病妇女所生6 ~ 7岁儿童30例(平均6.4±0.6岁)进行调查。对照组:健康母亲6-7岁(6.5±0.5岁)儿童30例。通过计算身体质量指数对身体发育进行评估。我们研究了血脂代谢指标——血液中总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇(mmol / l)、动脉粥样硬化指数。所有患儿均测定血清中25-OH-D含量、葡萄糖水平。结果糖尿病母亲所生儿童超重10例(33.3%),肥胖5例(16.7%),是对照组的2倍。所有被检查的糖尿病母亲所生的孩子的空腹血糖水平都在生理波动范围内。与对照组相比,母亲患有糖尿病的孩子的25-OH-D水平显著降低。糖尿病母亲所生儿童存在脂蛋白异常血症:血清甘油三酯和胆固醇水平显著升高,低密度脂蛋白胆固醇水平高于对照组,高密度脂蛋白胆固醇水平低于对照组(p <0.05),动脉粥样硬化指数显著升高。进一步研究的前景是探索维生素D用于儿童代谢综合征、糖尿病一级预防和治疗的可能性。结论被调查者体内维生素D缺乏可能是其血脂异常的原因之一,此外,超重和肥胖也是动脉粥样硬化、代谢综合征发生的危险因素。有危险的儿童需要动态监测人体测量指标,控制体重指数,血脂和碳水化合物血谱,25-OH-D水平。
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引用次数: 0
SUBSTANTIATION OF THE MECHANISM OF LOGISTIC EXPENDITURE MINIMIZATION BY SUBJECTS OF THE PHARMACEUTICAL INDUSTRY 医药行业主体物流支出最小化机制实证研究
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00783
R. Sahaidak-Nikitiuk, S. Velma
Aim: to determine the factors of influence on the magnitude of logistics costs and developing measures to minimize them. Materials and methods. The methods used in the study include the expert, systematic method of scientific knowledge, structural analysis, the method of abstract modeling. An expert method was conducted with the help of questionnaires of specialists of pharmaceutical companies, pharmacies and wholesale pharmaceutical companies. 118 respondents participated in the survey. The degree of consistency of expert opinions was determined with the help of the coefficient of concordance, which is 0.8374 (the normative value of the coefficient of concordance is 0.75), the Pearson criterion also exceeds the table value for the corresponding number of degrees of freedom, which testifies to the non-randomness of their judgments. Results. The factors influencing the amount of logistics costs are determined. The internal factors of influence include the activities of the subject of the pharmaceutical industry, assortment structure and structure of the use of substances and materials, the magnitude of stocks, etc. External factors of influence are the level of prices for logistics services provided by outside organizations; rate of transport tax; environmental taxes etc.; competitors suppliers of substances and materials; consumers; intermediaries; legislative base, etc. The conducted questioning of specialists and taking into account the current experience of leading foreign pharmaceutical companies allowed to determine the main measures to minimize logistics costs for all parts of the logistics system - procurement, production, transportation, storage, distribution and recycling, and types of flows - material, financial, information, labor. Conclusions. Based on the carried out research, the factors influencing the magnitude of logistics costs, which experts are divided into external and internal, are determined. The matrix of the components of LV savings is proposed, which takes into account the type of flow and the links of the logistic system. The constructed matrix allows to minimize the amount of LV, which helps to reduce the price of drugs for the end user.
目的:确定影响物流成本大小的因素,并制定最小化这些因素的措施。材料和方法。研究中采用的方法包括专家法、系统科学知识法、结构分析法、抽象建模法等。采用专家法,对医药企业、药店和批发医药企业的专家进行问卷调查。118名受访者参与了调查。通过一致性系数确定专家意见的一致性程度,一致性系数为0.8374(一致性系数的规范性值为0.75),相应的自由度的Pearson判据也超过了表值,证明了专家意见判断的非随机性。结果。确定了影响物流成本金额的因素。内部影响因素包括医药行业主体的活动、物质和材料的分类结构和使用结构、库存规模等。外部影响因素是外部组织提供的物流服务的价格水平;运输税税率;环境税等;竞争对手、物质和材料供应商;消费者;中介机构;立法基础等等。通过对专家的询问,并考虑到国外领先制药公司的当前经验,可以确定物流系统所有部分(采购、生产、运输、储存、分销和回收)以及流动类型(材料、财务、信息、劳动力)的物流成本最小化的主要措施。结论。在进行研究的基础上,确定了影响物流成本大小的因素,专家将其分为外部因素和内部因素。在考虑物流系统的物流类型和环节的基础上,提出了低压节约的组成矩阵。构建的矩阵允许最小化LV的数量,这有助于降低最终用户的药品价格。
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引用次数: 0
EVALUATION OF THE MAIN DATA OF INFLAMMATORY RESPONSE TO THE BASE THERAPY OF THE JUVENILE IDIOPATHIC ARTHRITIS 青少年特发性关节炎基础治疗炎症反应的主要资料评价
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00762
Y. Vyzhga
The activity of the juvenile idiopathic arthritis evaluates the speed of the process progression, intense of its clinical manifestation, effect of the carried treatment. The aim of our study was to estimate changes of the inflammatory response signs as well as content of NF-kB due to basic therapy of the JIA. Materials and methods. At our study, we had checked 68 children with JIA, who passed their treatment at Vinnytsya regional children’s hospital within the period from 2011 to 2014 years. Results. At the patients we studied currency of the JIA was characterized with articular variant of the disease, mainly in monoarthritis type. Laboratory activity of the inflammatory response characterized with increased content of the C-reactive protein (71.2±3.7 %), inflammatory cytokines – ІL-1β (54.8±4.1 %) and ІL-6 (56.2±2.4 %), as well high quantity of the nuclear factor-kB (70.5±3.1 %). Currency of the JIA in children characterized with high increasing of the inflammatory response signs especially C-reactive protein (6.55(4.2;9.8)), ІL-1β (7.3(3.5;11.9)), ІL-6 (6.8(4.5;10.6)) and NF-kB (6.76 (4.8; 9.1)), that are in correlative connections with clinical signs (number of the injured and swelled joints, evaluation of the general condition of the child according to doctors and own response) of the disease activity (rxy = +0.34 up to 0.62, p< 0.01). Conclusion. During the managing of the basic therapy in children with JIA we estimated decreasing of the IL-1β content in patients at the background of methotrexate administration (38.7±3.7 %), at the second group with use of sulfasalazine (28.5±3.5 %) and the third with leflunomide prescription (29.1±5.1 %), but significant decreasing of the ІL-6 content, that is one of the main inflammatory mediators and as well NF-kB was found just in group of the patients with methotrexate administration (on 36.3±3.8 % and 32.4±2.4 % for NF-kB).
幼年特发性关节炎的活动性评价其病程进展的速度、临床表现的强烈程度、进行治疗的效果。我们的研究目的是评估JIA基础治疗后炎症反应体征和NF-kB含量的变化。材料和方法。在我们的研究中,我们检查了68名患有JIA的儿童,他们在2011年至2014年期间在Vinnytsya地区儿童医院接受治疗。结果。在我们研究的患者中,JIA的主要特征是疾病的关节变异,主要是单关节炎型。实验室炎症反应活性的特征是c反应蛋白(71.2±3.7%),炎症细胞因子- ІL-1β(54.8±4.1%)和ІL-6(56.2±2.4%)的含量增加,以及核因子- kb的高含量(70.5±3.1%)。JIA在儿童中的传播特征是炎症反应体征特别是c反应蛋白(6.55(4.2;9.8))、ІL-1β(7.3(3.5;11.9))、ІL-6(6.8(4.5;10.6))和NF-kB (6.76 (4.8;9.1)),与疾病活动性的临床体征(损伤和肿胀关节数、医生对患儿一般情况的评价和自身反应)相关(rxy = +0.34 ~ 0.62, p< 0.01)。结论。在JIA患儿基础治疗过程中,我们估计甲氨蝶呤组患者IL-1β含量降低(38.7±3.7%),第二组使用柳氮磺胺吡啶组(28.5±3.5%),第三组使用来氟米特组(29.1±5.1%),但ІL-6含量显著降低。仅在甲氨蝶呤组患者中发现NF-kB和主要炎症介质之一(NF-kB分别为36.3%±3.8%和32.4±2.4%)。
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引用次数: 0
CONTENT OF DIENE KOH'UGATIVES AND MALONIC DIALDEHYDE IN BLOOD FOR RATS IN DYNAMICS OF FORMATION OF IMMOBILIZATIONAL STRESS 大鼠血液中二烯koh '阴性物和丙二醛含量对固定应激形成的动态影响
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00751
O. Lys
Nowadays, one of the most important problems are stressful reaction of human and animal systems. The purpose of our study was to find out the peculiarities of the dynamics of changes in the indices of diene conjugates and malonic dialdehyde in blood in rats under the conditions of development of immobilization stress. Material and methods of research. The experiments were carried out on white male rats of the Vistar line weighing 180–200 g which were divided into 3 groups for 10 animals (one control and three tested). The control group of rats was injected with 1 mg physiological saline per kg body weight intraperitoneally. The animals were decapitated under anes the siaca used by sodium thiopental (intraperitoneal injection of 1 % solution of 50 mg / kg) and withdrawn from the experiment after 1, 3, and 5 days. In blood plasma was determined the content of diene conjugates and malonic dialdehyde in stress-induced rats, the groups were compared with the control group rats. Results. The state of the processes (POFs) was assessed by the content of blood vessels detected in different periods (1 st, 3 rd, and 5 th day) after conducting of IS in rats. Under the conditions of the development of the IS, an increase in the content of DK was observed at 116.96 % (p<0.05) in the experimental group1 accordingly on the 1st day after the IS compared with the control. For the 3rd day of the study, the level of DK increased by 44.24 % (p<0.05) in experimental group 2, against the intact group of animals. Experimental group 3, in which animals were withdrawn from the IS for the 5th day, was characterized by an increase in the content of DK by 41.84 % (p<0.05) compared with the control group. Another indicator of MDA in the blood for 1 day of the experiment in experimental group 1 increased by 104.15 % (p<0.05) in the case of IS in relation to the intact group. On the 3rd day of the experiment under the conditions of development of IP, the level of MDA increased by 83.9 % (p<0.05), against control. At the 5th day of the experiment, MDA level was 30.1 % (p<0.05) for IS, when compared with control Conclusion. Consequently, the experiment made it possible to establish the significant activation of the LP processes, which we determined with increasing levels of DC and MDA in animals under IS conditions, the most of it was on the 1th day of the experiment.
目前,人类和动物系统的应激反应是最重要的问题之一。本研究的目的是了解大鼠在固定应激条件下血液中二烯偶联物和丙二醛指标变化的动力学特点。研究材料和方法。实验选用体重180 ~ 200 g的Vistar系雄性白种大鼠,分为3组,每组10只(对照组1只,试验组3只)。对照组大鼠腹腔注射生理盐水1 mg / kg体重。用硫喷妥钠(1%溶液50 mg / kg腹腔注射)灌胃,分别于1、3、5 d后退出实验。测定应激诱导大鼠血浆中二烯缀合物和丙二醛的含量,并与对照组大鼠进行比较。结果。通过大鼠灌胃后不同时期(第1、3、5天)血管含量的测定来评价灌胃过程的状态(POFs)。在IS发育条件下,实验组1在IS发生后第1天DK含量较对照组增加了116.96% (p<0.05)。试验第3天,实验2组DK水平较对照组提高44.24% (p<0.05)。实验3组在第5天停止给药,与对照组相比,DK含量提高了41.84% (p<0.05)。另一项指标丙二醛(MDA),实验1组在IS情况下,在实验1天内较正常组升高104.15% (p<0.05)。试验第3天,在IP发育条件下,MDA水平比对照提高了83.9% (p<0.05)。实验第5天,与对照组相比,IS组MDA含量为30.1% (p<0.05)。因此,实验使LP过程的显著激活成为可能,我们确定在IS条件下动物的DC和MDA水平增加,其中大部分是在实验的第11天。
{"title":"CONTENT OF DIENE KOH'UGATIVES AND MALONIC DIALDEHYDE IN BLOOD FOR RATS IN DYNAMICS OF FORMATION OF IMMOBILIZATIONAL STRESS","authors":"O. Lys","doi":"10.21303/2585-663.2018.00751","DOIUrl":"https://doi.org/10.21303/2585-663.2018.00751","url":null,"abstract":"Nowadays, one of the most important problems are stressful reaction of human and animal systems. The purpose of our study was to find out the peculiarities of the dynamics of changes in the indices of diene conjugates and malonic dialdehyde in blood in rats under the conditions of development of immobilization stress. Material and methods of research. The experiments were carried out on white male rats of the Vistar line weighing 180–200 g which were divided into 3 groups for 10 animals (one control and three tested). The control group of rats was injected with 1 mg physiological saline per kg body weight intraperitoneally. The animals were decapitated under anes the siaca used by sodium thiopental (intraperitoneal injection of 1 % solution of 50 mg / kg) and withdrawn from the experiment after 1, 3, and 5 days. In blood plasma was determined the content of diene conjugates and malonic dialdehyde in stress-induced rats, the groups were compared with the control group rats. Results. The state of the processes (POFs) was assessed by the content of blood vessels detected in different periods (1 st, 3 rd, and 5 th day) after conducting of IS in rats. Under the conditions of the development of the IS, an increase in the content of DK was observed at 116.96 % (p<0.05) in the experimental group1 accordingly on the 1st day after the IS compared with the control. For the 3rd day of the study, the level of DK increased by 44.24 % (p<0.05) in experimental group 2, against the intact group of animals. Experimental group 3, in which animals were withdrawn from the IS for the 5th day, was characterized by an increase in the content of DK by 41.84 % (p<0.05) compared with the control group. Another indicator of MDA in the blood for 1 day of the experiment in experimental group 1 increased by 104.15 % (p<0.05) in the case of IS in relation to the intact group. On the 3rd day of the experiment under the conditions of development of IP, the level of MDA increased by 83.9 % (p<0.05), against control. At the 5th day of the experiment, MDA level was 30.1 % (p<0.05) for IS, when compared with control Conclusion. Consequently, the experiment made it possible to establish the significant activation of the LP processes, which we determined with increasing levels of DC and MDA in animals under IS conditions, the most of it was on the 1th day of the experiment.","PeriodicalId":33846,"journal":{"name":"Technology Transfer Innovative Solutions in Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89668217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FORECASTING OF TRIAZOLE, AMIDE, PIPEREDINYLE THIAZOL ISOXAZOLINE, OXAZOLE FUNGICIDES HAZARDOUS EFFECT ON HUMAN HEALTH IN CONSUMPTION OF VEGETABLES GROWED IN THEIR APPLICATION 预测三唑类、酰胺类、哌啶类噻唑类异恶唑啉类、恶唑类杀菌剂在食用蔬菜种植中对人体健康的危害影响及其应用
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00763
A. Antonenko, O. Vavrinevych
The chemical plant protection products application is an integral part of intensive crop production technologies. However, scientists have proven that the increase in chemical pollution of the environment in 2 times increases the general level of morbidity of the adult population by 25%. That is why the risk assessment of pesticide-contaminated products consumption is an important part of the regulatory process. Methods. The parameters of fungicides difenoconazole, tebuconazole, cyflufenamid, oxathiapiprolin, famoxadone persistence in agricultural crops were studied in the field experiments. For the integrated assessment of the potential risk of pesticide-contaminated products consumption for human (RPCPC), a methodology developed on the basis of the Institute of Hygiene and Ecology was used. The acceptable daily intake (ADI), the half-life period (τ50) in plants and the average daily consumption of the product have been evaluated using four-graded scale. Results. According to the persistency in tomatoes and potatoes, fungicides difenoconazole, cyflufenamid, famoxadone are pertained to 3 classes of hazard (5-14 days); tebuconazole - to 2 class (15-30 days); oxathiapiprolin - to 4 class (less than 5 days). After the addition of all the obtained points, the RPCPC value (tomatoes and potatoes) for difenoconazole, cyflufenamid, famoxadone amounted 8 points (2+2+2× 2 and 2+2+4, respectively); tebuconazole - 8 points (3+1+2×2 or 3+1+4, respectively); oxathiapiprolin - 6 points (1+1+2×2 or 1+1+4, respectively). Discussion. Thus, the studied compounds belong to the 3rd class of hazard according to pesticide-contaminated products consumption for human index value. The results obtained by us correlate with the studies carried out in the previous stage. The exception was only difenoconazole, which was classified as hazard class 2 due to its high toxicity for human.
化学植保产品的应用是集约化作物生产技术的重要组成部分。然而,科学家已经证明,环境化学污染增加2倍,成年人的总体发病率就会增加25%。这就是为什么农药污染产品消费风险评估是监管过程的重要组成部分。方法。通过田间试验研究了杀菌剂异丙康唑、戊康唑、氟虫胺、恶唑匹林、法莫沙酮在农作物中的持久性。为了综合评估人类食用农药污染产品的潜在风险,采用了卫生与生态研究所开发的一种方法。采用四级量表对该产品的可接受日摄入量(ADI)、植物半衰期(τ50)和平均日摄入量进行了评价。结果。根据对番茄和土豆的持久性,杀菌剂异虫康唑、氟虫胺、法莫沙酮被划分为3类危害(5-14天);替布康唑-至2级(15-30天);Oxathiapiprolin -至4级(少于5天)。各所得点相加后,异虫康唑、氟虫胺、法莫沙酮(番茄、土豆)的RPCPC值分别为8点(2+2+ 2x2和2+2+4);替布康唑- 8分(分别为3+1+2×2或3+1+4);Oxathiapiprolin - 6分(分别为1+1+2×2或1+1+4)。讨论。因此,根据农药污染产品的人体消费指标值,所研究的化合物属于第三类危害。我们得到的结果与前一阶段进行的研究是相关联的。唯一的例外是异丙康唑,由于其对人体的高毒性,被列为二级危害。
{"title":"FORECASTING OF TRIAZOLE, AMIDE, PIPEREDINYLE THIAZOL ISOXAZOLINE, OXAZOLE FUNGICIDES HAZARDOUS EFFECT ON HUMAN HEALTH IN CONSUMPTION OF VEGETABLES GROWED IN THEIR APPLICATION","authors":"A. Antonenko, O. Vavrinevych","doi":"10.21303/2585-663.2018.00763","DOIUrl":"https://doi.org/10.21303/2585-663.2018.00763","url":null,"abstract":"The chemical plant protection products application is an integral part of intensive crop production technologies. However, scientists have proven that the increase in chemical pollution of the environment in 2 times increases the general level of morbidity of the adult population by 25%. That is why the risk assessment of pesticide-contaminated products consumption is an important part of the regulatory process. Methods. The parameters of fungicides difenoconazole, tebuconazole, cyflufenamid, oxathiapiprolin, famoxadone persistence in agricultural crops were studied in the field experiments. For the integrated assessment of the potential risk of pesticide-contaminated products consumption for human (RPCPC), a methodology developed on the basis of the Institute of Hygiene and Ecology was used. The acceptable daily intake (ADI), the half-life period (τ50) in plants and the average daily consumption of the product have been evaluated using four-graded scale. Results. According to the persistency in tomatoes and potatoes, fungicides difenoconazole, cyflufenamid, famoxadone are pertained to 3 classes of hazard (5-14 days); tebuconazole - to 2 class (15-30 days); oxathiapiprolin - to 4 class (less than 5 days). After the addition of all the obtained points, the RPCPC value (tomatoes and potatoes) for difenoconazole, cyflufenamid, famoxadone amounted 8 points (2+2+2× 2 and 2+2+4, respectively); tebuconazole - 8 points (3+1+2×2 or 3+1+4, respectively); oxathiapiprolin - 6 points (1+1+2×2 or 1+1+4, respectively). Discussion. Thus, the studied compounds belong to the 3rd class of hazard according to pesticide-contaminated products consumption for human index value. The results obtained by us correlate with the studies carried out in the previous stage. The exception was only difenoconazole, which was classified as hazard class 2 due to its high toxicity for human.","PeriodicalId":33846,"journal":{"name":"Technology Transfer Innovative Solutions in Medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87904577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
ANALYSIS OF PROGNOSTIC VALUE OF LEUKOCYTE AND HEMATOLOGICAL INDEXES OF INTOXICATION IN THE DIAGNOSIS OF SURGICAL SEPSIS 中毒白细胞及血液学指标对外科败血症诊断的预后价值分析
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00772
A. Pavliak
The mortality from surgical sepsis remains high and ranges from 17 to 83.7 %. The cause of high lethality is endogenous intoxication and multiple organ failure. The most common laboratory markers for determining the syndrome of endogenous intoxication in surgical sepsis are leukocyte and hematological intoxication indices, such as LII, HII, NII. Aim of the work: to study the predictive value of laboratory and hematological indicators of intoxication in the diagnosis of surgical sepsis. Materials and methods. A retrospective analysis of disease history and prospective follow-up of 41 patients treated for surgical sepsis in the Ivano-Frankivsk (Ukraine) Surgical Department of the CCCH in period between August 2015 and August 2018 was conducted. In the first day after the operation, all the patients been calculated the leukocyte index of intoxication, the hematological index of intoxication and the nuclear index of intoxication to assess their predictive and diagnostic significance. Methods of nonparametric statistics were used in the study: ROC-analysis, Mann-Whitney U-test, Spierman's criterion (Rs). Results. The results of the diagnostic and prognostic significance of LII, HII, NII for 1 day postoperative period, with regard to the prediction of lethality by means of ROC analysis, Mann-Whitney U-test, Spirman criteria (Rs) showed low sensitivity and specificity in patients with surgical sepsis. Common laboratory leukocyte and hematological non-specific indicators of endogenous intoxication determination have low prognostic and diagnostic significance in assessing the degree of endotoxicosis in surgical sepsis and can not serve as prognostic criteria for lethality. Conclusions. The problem of diagnosing endotoxicosis in surgical sepsis requires the further study and introduction into clinical practice of new specific and integrated clinical and laboratory methods for the quantitative determination of endotoxicosis, which could serve as a reliable diagnostic criterion in assessing the severity of the condition and the prediction of hospital mortality.
手术败血症的死亡率仍然很高,从17%到83.7%不等。高致死率的原因是内源性中毒和多器官衰竭。判断外科脓毒症内源性中毒综合征最常见的实验室标志物是白细胞和血液学中毒指标,如LII、HII、NII。目的:探讨中毒的实验室及血液学指标对外科败血症诊断的预测价值。材料和方法。回顾性分析2015年8月至2018年8月在乌克兰伊凡诺-弗兰科夫斯克(Ivano-Frankivsk) CCCH外科接受手术败血症治疗的41例患者的病史和前瞻性随访。术后第1天计算所有患者的中毒白细胞指数、中毒血液学指数和中毒核指数,评估其预测和诊断意义。本研究采用非参数统计方法:roc分析、Mann-Whitney u检验、Spierman标准(Rs)。结果。术后1天LII、HII、NII的诊断及预后意义,ROC分析、Mann-Whitney u检验、Spirman标准(Rs)对手术脓毒症患者的致死率预测敏感性和特异性较低。常规实验室白细胞和血液学非特异性指标检测内源性中毒对外科脓毒症内毒程度的评估预后和诊断意义较低,不能作为判定致死率的预后标准。结论。外科脓毒症的内毒素诊断问题,需要进一步研究并将新的特异性的、综合的临床和实验室方法引入临床实践,以定量确定内毒素,作为评估病情严重程度和预测住院死亡率的可靠诊断标准。
{"title":"ANALYSIS OF PROGNOSTIC VALUE OF LEUKOCYTE AND HEMATOLOGICAL INDEXES OF INTOXICATION IN THE DIAGNOSIS OF SURGICAL SEPSIS","authors":"A. Pavliak","doi":"10.21303/2585-663.2018.00772","DOIUrl":"https://doi.org/10.21303/2585-663.2018.00772","url":null,"abstract":"The mortality from surgical sepsis remains high and ranges from 17 to 83.7 %. The cause of high lethality is endogenous intoxication and multiple organ failure. The most common laboratory markers for determining the syndrome of endogenous intoxication in surgical sepsis are leukocyte and hematological intoxication indices, such as LII, HII, NII. Aim of the work: to study the predictive value of laboratory and hematological indicators of intoxication in the diagnosis of surgical sepsis. Materials and methods. A retrospective analysis of disease history and prospective follow-up of 41 patients treated for surgical sepsis in the Ivano-Frankivsk (Ukraine) Surgical Department of the CCCH in period between August 2015 and August 2018 was conducted. In the first day after the operation, all the patients been calculated the leukocyte index of intoxication, the hematological index of intoxication and the nuclear index of intoxication to assess their predictive and diagnostic significance. Methods of nonparametric statistics were used in the study: ROC-analysis, Mann-Whitney U-test, Spierman's criterion (Rs). Results. The results of the diagnostic and prognostic significance of LII, HII, NII for 1 day postoperative period, with regard to the prediction of lethality by means of ROC analysis, Mann-Whitney U-test, Spirman criteria (Rs) showed low sensitivity and specificity in patients with surgical sepsis. Common laboratory leukocyte and hematological non-specific indicators of endogenous intoxication determination have low prognostic and diagnostic significance in assessing the degree of endotoxicosis in surgical sepsis and can not serve as prognostic criteria for lethality. Conclusions. The problem of diagnosing endotoxicosis in surgical sepsis requires the further study and introduction into clinical practice of new specific and integrated clinical and laboratory methods for the quantitative determination of endotoxicosis, which could serve as a reliable diagnostic criterion in assessing the severity of the condition and the prediction of hospital mortality.","PeriodicalId":33846,"journal":{"name":"Technology Transfer Innovative Solutions in Medicine","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83595340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
THE ASPECTS OF DEVELOPMENT AND STANDARDIZATION OF CHILDREN’S SUPPOSITORIES WITH EXTRACT OF LICORICE ROOT 甘草提取物儿童栓剂的研制与标准化
Pub Date : 2018-11-21 DOI: 10.21303/2585-663.2018.00739
T. Yarnykh, O. Rukhmakova
The aim of this work was the development of technology of rectal suppositories of immunomodulatory action for children and their standardization. To obtain suppositories, a licorice root extract, chamomile and tea tree essential oils were used. Given that the introduction of ingredients in a dissolved form is preferable, we studied the possibility of using emulsion suppository bases. To evaluate the compositions, the homogeneity and colloidal stability of the suppositories obtained were studied. Estimation of homogeneity, melting temperature, decay time, average mass was carried out according to the State Pharmacopoeia. To confirm the authenticity of the active ingredients, a chromatography method was used. The quantitative determination of glycyrrhizin acid was carried out by spectrophotometric method. Suppositories were prepared by the pouring method. The licorice root extract was added to the suppository when dissolved in the hydrophilic phase of the base. Essential oils of chamomile and tea tree were introduced when a solid fat of type A dissolved in a melt, at a temperature of (42.0±2.0) ºC. Optimum indices for the criteria of “homogeneity” and “colloidal stability” were noted for the samples of the composition: purified water, polysorbate-80, lecithin, solid fat type A. To prove the authenticity of the licorice root extract in suppositories, the chloroform-methanol-water system was optimal (26:14:3). Identification of essential oils on a gas chromatograph showed that on the chromatogram the peaks and retention times of the solution under study coincide with the peaks and retention times of the reference solutions. The conducted studies of quantitative determination of glycyrrhizin acid have shown that its content in one suppository is not less than 0.035 g in terms of glycyram.
本工作的目的是开发具有免疫调节作用的儿童直肠栓剂的技术及其标准化。为了获得栓剂,使用了甘草根提取物、洋甘菊和茶树精油。考虑到以溶解形式引入成分是可取的,我们研究了使用乳液栓剂的可能性。为评价栓剂的组成,对所制栓剂的均匀性和胶体稳定性进行了研究。均质性、熔化温度、衰变时间、平均质量按国家药典进行估计。为证实其有效成分的真实性,采用了色谱法。采用分光光度法测定甘草酸的含量。采用灌注法制备栓剂。甘草根提取物溶解于碱的亲水性相后加入栓剂。在(42.0±2.0)℃的温度下,将a型固体脂肪溶解在熔体中,引入洋甘菊精油和茶树精油。在“均匀性”和“胶体稳定性”两项指标上,组份样品分别为纯净水、聚山梨酸酯-80、卵磷脂、a型固体脂肪。为了证明栓剂中甘草根提取物的真实性,以氯仿-甲醇-水体系为最佳(26:14:3)。在气相色谱仪上对精油的鉴定表明,在色谱图上,所研究溶液的峰和保留时间与参比溶液的峰和保留时间一致。对甘草酸的定量测定研究表明,甘草酸在一个栓剂中的含量以甘草酸为单位不小于0.035 g。
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引用次数: 0
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Technology Transfer Innovative Solutions in Medicine
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