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Treatment of Radiation Lesions with Mesenchymal Stem Cells 间充质干细胞治疗放射性病变
Pub Date : 2023-08-04 DOI: 10.35825/2587-5728-2023-7-1-24-35
J. Lakota
   Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing radiation. ARS is the deterministic effect of radiation exposure of the whole body or a significant body volume (partial body irradiation) above a threshold dose of about 1 Gy (gray). Radiation accidents, such as those in Chernobyl (1986) and Fukushima (2011), or the possible use of nuclear weapons during the hostilities or terrorist attacks, can lead to the massive development of ARS in humans.   The aim of the work is to introduce a new method of post-radiation treatment – the use of allogeneic mesenchymal stem cells (MSCs).   Materials and methods. The information contained in specialized scientific journals that are freely available and accessible through the global Internet was studied.   Discussion of the results. In the scenario of mass exposure of the population, when from several tens (hundreds) to millions of people can be irradiated, the transfusion of hematopoietic stem cells traditionally used in such cases would be impossible. MSCs can possibly differentiate into specialized cells, that is, turn into cells of various organs and tissues or induce such kind of regeneration. For practical use, there are two main sources of their isolation and reproduction ex vivo – bone marrow and adipose tissue. To date, it has been shown that MSCs derived from adipose tissue can be effective in mitigating the effects of acute radiation illness. Intravenously applied MSCs are migrating mainly to the bone marrow and are partially restoring its function. Deep anatomical structures are also involved in local radiation injuries: bone, muscles, nerves, blood and lymphatic vessels and skin. There is a strong body of evidence suggesting the «repair effect» of MSCs when used to treat such lesions. This is because MSCs can induce the repair and regeneration of the anatomical structures which they are locally applied, possibly by the paracrine effect. The main advantage of allogeneic MSCs over autologous ones is their logistical accessibility. They can be produced in advance in quantities and stored frozen. After thawing, the cells must be cultured for at least 48 hours in humidified incubators with the addition of 5 % CO2.   Findings. Treatment of MSCs should be started as soon as possible after radiation exposure. Rescue of damaged hematopoiesis in the bone marrow can be achieved by multiple intravenous administration of up to 1 million (106) freshly prepared allogeneic MSCs/kg body weight. Locally (around and in the irradiation area), the dose of MSCs may be lower – 20 million cells. Repeated topical application should be carried out at intervals of two to four weeks. Subsequent surgical reconstruction should be performed by an experienced surgeon and in a specialized center with concomitant topicalapplication of MSCs.
急性辐射综合征(ARS)是一种因暴露于高剂量电离辐射而引起的急性疾病。急性辐射反应是指超过约1戈瑞(灰色)阈值剂量的全身照射或大量身体照射(部分身体照射)所产生的确定性效应。切尔诺贝利(1986年)和福岛(2011年)等辐射事故,或在敌对行动或恐怖袭击期间可能使用核武器,都可能导致人类ARS的大规模发展。这项工作的目的是介绍一种新的放射后治疗方法-使用同种异体间充质干细胞(MSCs)。材料和方法。研究了可通过全球互联网络免费提供和获取的专门科学期刊所载的信息。结果的讨论。在人口大规模暴露的情况下,当从几十(数百)到数百万人可以受到辐射时,传统上用于这种情况的造血干细胞的输注将是不可能的。MSCs有可能分化为特化细胞,即转化为各种器官和组织的细胞或诱导这种再生。在实际应用中,它们的分离和体外繁殖有两个主要来源——骨髓和脂肪组织。迄今为止,已经证明来自脂肪组织的间充质干细胞可以有效地减轻急性辐射疾病的影响。静脉注射的间充质干细胞主要迁移到骨髓,并部分恢复其功能。局部辐射损伤还涉及深层解剖结构:骨、肌肉、神经、血液和淋巴管以及皮肤。有大量证据表明,间充质干细胞在治疗此类病变时具有“修复作用”。这是因为MSCs可以诱导局部应用的解剖结构的修复和再生,可能是通过旁分泌效应。异体间充质干细胞相对于自体间充质干细胞的主要优势在于其可获得性。它们可以提前大量生产并冷冻储存。解冻后,细胞必须在加5% CO2的加湿培养箱中培养至少48小时。发现。放射照射后应尽快开始间充质干细胞的治疗。通过多次静脉注射每公斤体重100万(106)个新鲜制备的同种异体间充质干细胞,可以挽救受损的骨髓造血功能。局部(周围和照射区域),MSCs的剂量可能较低- 2000万个细胞。应每隔两至四周重复局部应用。随后的手术重建应由经验丰富的外科医生进行,并在专业中心进行,同时局部应用间充质干细胞。
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引用次数: 0
Analytical Dependence of the Probability of Masking Objects on the Density and Dispersion of the Aerosol 掩蔽物体的概率对气溶胶密度和弥散的解析依赖性
Pub Date : 2023-08-04 DOI: 10.35825/2587-5728-2023-7-1-53-61
A. А. Brusenin, S. Krasilnikov, V. N. Penyaz, D. N. Buryak, I. V. Artamonov, V. D. Burkov
   With the existing method for evaluating the effectiveness of masking objects with aerosols, two parameters are used: the length and width of an invisible smoke screen with a probability of at least 50 %. Both parameters were obtained during the practical tests of aerosol masking means. However, they are insufficient for assessing the masking ability of an aerosol cloud as a spatial formation.   The purpose of this work is to reveal the analytical dependence of the probability of objects masking on the density and dispersion of the aerosol.   Мaterials and methods. An extended approach was used to estimate the probability of masking at any theoretical value of the flux density (integral concentration, g/m2) of aerosol along the line of sight, taking into account its dispersion, by calculating the formation of a probability field from 5 to 95 % over the entire spatial structure of the aerosol cloud. The method used is the simulation on a PC of the dependence of the share of space occlusion for the observer (the eyepiece of an optical device) by aerosol particles of a given dispersion and flux density, which we took as the probability of masking.   Discussion. It is shown in the article, that the resulting analytical expression as a result of processing the accumulated simulation results on a PC fully corresponds to the Bouguer-Lambert-Beer law, which is a generalization of many years of practical field and laboratory experiments with aerosols in the air and dispersed particles in solutions. The obtained probability values allow us to obtain a generalized efficiency criterion in the form of a new concept - the reduced masking zone. This term is mathematically analogous to the reduced impact zone, which is used to assess damage caused by munitions.   Conclusion. For a full assessment of the effectiveness of aerosol countermeasures, the reduced masking zone must be calculated for all possible lines of sight (observation of an object): horizontally, vertically, and along inclined paths. This condition reflects the method of using modern weapons such as Javelin anti-tank systems, which are aimed at the target mainly horizontally, and the final trajectory before the impact is a «hill». The theoretical difference between the values of vertical and horizontal masking screens, obtained by the authors using a new method for calculating the parameters of an aerosol cloud, is presented in the illustrations to the article.
利用现有的评估气溶胶遮蔽目标有效性的方法,使用两个参数:不可见烟幕的长度和宽度,其概率至少为50%。这两个参数都是在气溶胶掩蔽手段的实际试验中得到的。然而,它们不足以评估作为空间形成的气溶胶云的掩蔽能力。这项工作的目的是揭示物体掩蔽的概率对气溶胶的密度和分散的分析依赖性。Мaterials和方法。通过计算在气溶胶云的整个空间结构上形成的5%至95%的概率场,采用了一种扩展的方法来估计在视线上气溶胶的通量密度(积分浓度,g/m2)的任何理论值下被遮蔽的概率,并考虑了其色散。所使用的方法是在PC上模拟给定色散和通量密度的气溶胶粒子对观测者(光学装置目镜)的空间遮挡份额的依赖关系,我们将其作为掩蔽概率。讨论。文中指出,在PC机上对累积的模拟结果进行处理得到的解析表达式完全符合布格-兰伯特-比尔定律,该定律是多年来对空气中的气溶胶和溶液中的分散颗粒进行实际现场和实验室实验的概括。得到的概率值允许我们以一个新概念的形式得到一个广义的效率准则-简化掩蔽区。这个术语在数学上类似于减少冲击区,用于评估弹药造成的损害。结论。为了全面评估气溶胶对抗措施的有效性,必须计算所有可能的视线(对物体的观察)的减少掩蔽区:水平、垂直和沿倾斜路径。这种情况反映了使用标枪反坦克系统等现代武器的方法,这些武器主要是水平瞄准目标,在撞击前的最终轨迹是一个“山丘”。作者用一种计算气溶胶云参数的新方法得到了垂直遮罩和水平遮罩值之间的理论差异,并在文章的插图中给出。
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引用次数: 0
The Contribution of Soviet Military Scientists to the Development of Industrial Technologies for the Production of the First Domestic Antibiotics (Penicillin and Streptomycin) 苏联军事科学家对生产第一批国产抗生素(青霉素和链霉素)的工业技术发展的贡献
Pub Date : 2023-08-04 DOI: 10.35825/2587-5728-2023-7-1-82-92
S. N. Chigrinov, A. V. Mironin, V. D. Soybanov, V. Teterin, A. Tumanov
   In the domestic literature, the industrial production of penicillin and streptomycin is commonly attributed to the representatives of civil institutions and enterprises. However, the key role of military scientists in solving this problem remains in the background.   The purpose of this article is to summarize the available facts about the role of Soviet military scientists in creating a technology for obtaining the first antibiotics in the USSR.   At the beginning of 1942, all the works, related to the penicillin in the Soviet Union, was headed by academician of AMS USSR Z. V. Ermolyeva. At the first stage of the research, the technology for obtaining penicillin was applied, based on the use of a surface method of growing cultures of the antibiotic-producing fungus in mattresses. But this method could not meet the country's needs for the drug. In early 1944, the Soviet government tasked the Research Institute of Epidemiology and Hygiene of the Red Army (NIIEG) in Kirov (now a branch of the Federal State Budgetary Institution «48th Central Research Institute» of the Ministry of Defense of the Russian Federation) to solve the case of mass production of penicillin and streptomycin. In 1944–1945 for the first time in the USSR military specialists from NIIEG developed a technology for the industrial production of penicillin by the deep method with aeration. The deep cultivation was carried out in cultivator devices designed by engineer-Lieutenant Colonel A. V. Krutyakov. During the research, a fungus strain (Penicillium chrysogenum 23248) was selected from a large number of studied strains, the use of which provided the highest yields of penicillin, and the most effective cultivation conditions were selected. The experience, obtained by the Soviet military specialists during the development of the technology for the deep production of penicillin, served in 1946-1947 as the basis for the creation of the method for obtaining domestic streptomycin from the domestic Streptomyces griseus. In 1947, for the first time in the world an employee of the NIIEG Lieutenant Colonel of medical service N. I. Nikolaev and civil doctors D. D. Fedorinov and V. I. Gorokhov used the NIIEG streptomycin successfully for the treatment of patients with pneumonic plague during the plague epidemic in Manchuria. In the late 1940s the technologies for the production of penicillin and streptomycin, as well as the relevant documentation, were transferred to civil healthcare institutions for the industrial development.
在国内文献中,盘尼西林、链霉素的工业化生产一般都归于民间机构和企业的代表。然而,军事科学家在解决这一问题中的关键作用仍然在幕后。本文的目的是总结关于苏联军事科学家在创造一种技术以获得苏联第一种抗生素方面所起作用的现有事实。1942年初,苏联所有与青霉素有关的工作都是由苏联医学科学院院士埃尔莫耶娃(Z. V. Ermolyeva)领导的。在研究的第一阶段,基于在床垫中培养产生抗生素的真菌的表面方法,应用了获得青霉素的技术。但这种方法不能满足国家对该药的需求。1944年初,苏联政府委托位于基洛夫的红军流行病学和卫生研究所(NIIEG)(现为俄罗斯联邦国防部联邦国家预算机构“第48中央研究所”的分支机构)解决青霉素和链霉素大规模生产的问题。1944-1945年,苏联军事专家第一次从NIIEG开发了一种技术,用于工业生产青霉素的深度方法与曝气。深耕是在工程师A. V. Krutyakov中校设计的耕作装置上进行的。在研究过程中,从大量研究菌株中筛选出一株产青霉素量最高的真菌(青霉菌chrysogenum 23248),并选择最有效的培养条件。苏联军事专家在开发盘尼西林深度生产技术期间获得的经验,在1946年至1947年期间作为创造从国内灰色链霉菌获得国内链霉素方法的基础。1947年,在满洲鼠疫流行期间,NIIEG的医务中校Nikolaev和民间医生Fedorinov和V. I. Gorokhov在世界上首次成功地使用NIIEG链霉素治疗肺鼠疫患者。在20世纪40年代后期,青霉素和链霉素的生产技术以及相关文件被转移到民间医疗机构,用于工业发展。
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引用次数: 0
Bioluminescent ATP-metry: Practical Aspects 生物发光atp测定:实用方面
Pub Date : 2023-08-04 DOI: 10.35825/2587-5728-2023-7-1-93-94
M. V. Supotnitskiy
.
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引用次数: 0
Analysis of the Development and Use of Unmanned Aerial Vehicles Designed for NBC Protection Purposes 基于NBC防护目的的无人机发展与使用分析
Pub Date : 2022-12-23 DOI: 10.35825/2587-5728-2022-6-4-372-385
К.Н. Аккузин, Е.С. Макеев
The lecture is intended for training specialists in higher educational establishments according to the Federal state standard «Robotics for military and special purposes» and also for training operators of robotic complexes (facilities) for military purposes in training centers and military units.The lecture addresses three questions:1) Analysis of sources of radiation, chemical and biological threats in the Russian Federation.2) Analysis of the development and use of foreign unmanned aerial vehicles designed for NBC protection purposes.3) Analysis of the development and use of Russian unmanned aerial vehicles designed for NBC protection purposes.
该讲座旨在根据联邦国家标准“军事和特殊用途机器人”培训高等教育机构的专家,并培训培训中心和军事单位用于军事目的的机器人综合体(设施)的操作员。讲座涉及三个问题:1)分析俄罗斯联邦的辐射源、化学和生物威胁。2)分析为核生化防护目的设计的国外无人机的发展和使用。3)分析为核生化防护目的设计的俄罗斯无人机的发展和使用。
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引用次数: 0
Application of Modern Technical Means of Chemical Reconnaissance and Control for the Detection and Identification of Explosives 现代化学侦察与控制技术手段在爆炸物探测与识别中的应用
Pub Date : 2022-12-23 DOI: 10.35825/2587-5728-2022-6-4-355-364
В.А. Иноземцев, И.Н. Ефимов, А.А. Позвонков, А.С. Самородов, В.Н. Пономарев, С.С. Колбинев
The analysis of the capabilities of modern technical means of chemical reconnaissance and special equipment of chemical control indicates the possibility of quick detection of mined and explosive devices (EDs) by identification of the explosives included in the EDs and related technological impurities. The purpose of this work is to analyze the possibilities of using modern technical means of chemical reconnaissance and control for the detection and identification of explosives. In orderto achieve this goal, the authors assessed the analytical characteristics and features of the technical means of chemical reconnaissance and the indication methods implemented in them to determine the possibility of detecting and identifying the components of the EDs. The article shows the possibility of using special military gas detectors operating on the basis of the ion mobility spectrometry (IMS) method to confirm the presence of the vapor phase of explosives. The assessment was carried out on the basis of an analysis of the physicochemical properties of peroxides and nitrogen-containing explosives and a comparison of the achievable concentrations of the vapor phase of nitrogen-containing explosives (TNT, RDX, pentrite, nitroglycerin, dinitrotoluene) with the results of the calculated sensitivity of the IMS method (~10–10 mg/L). It has been established that trace amounts of explosives in liquid and solid states of aggregation can be identified by portable technical means of chemical control, operating on the basis of infrared Fourier spectroscopy and Raman scattering. The ways of expanding the functionality of these technical means by creating specialized databases of spectral data of explosives and accompanying technological impurities are proposed. The inclusion of an additional spectrum bank in the control software of IMS gas detectors must be combined with the implementation of the possibility of program selection of operating modes and database switching by the operator.
对现代化学侦察技术手段和化学管制专用设备能力的分析表明,通过识别地雷和爆炸装置中包含的炸药和相关的工艺杂质,可以快速探测地雷和爆炸装置。这项工作的目的是分析利用现代化学侦察和控制技术手段探测和识别爆炸物的可能性。为了实现这一目标,作者对化学侦察技术手段的分析特点和特点及其所实施的指示方法进行了评价,以确定检测和识别电子能谱成分的可能性。本文介绍了利用离子迁移率谱法(IMS)的特殊军用气体探测器来确定炸药气相存在的可能性。对过氧化物和含氮炸药的理化性质进行了分析,并将含氮炸药(TNT、RDX、渗透石、硝化甘油、二硝基甲苯)的气相可达浓度与IMS方法的计算灵敏度(~10 ~10 mg/L)进行了比较。利用红外傅立叶光谱和拉曼散射的便携式化学控制技术手段,可以对液体和固体聚集态的痕量炸药进行鉴别。提出了通过建立爆炸物及其伴生工艺杂质光谱数据专用数据库来扩展这些技术手段功能的方法。在IMS气体探测器的控制软件中加入额外的频谱库,必须与操作员实现操作模式的程序选择和数据库切换的可能性相结合。
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引用次数: 0
Scientific Сompany of the NBC Protection Troops NBC保护部队的科学Сompany
Pub Date : 2022-12-23 DOI: 10.35825/2587-5728-2023-6-4-386-390
In accordance with the decision of the President of the Russian Federation, in 2013, the creation of scientific companies began in the Armed Forces of Russia. In 2015, such a company was created in the troops of radiation, chemical and biological protection as part of the Military Academy of Radiation, Chemical and Biological Protection named after Marshal of the Soviet Union S.K. Timoshenko (Kostroma).The purpose of the work is to show the history of the creation of a scientific company, the order of recruitment, organization and main indicators of the effectiveness of its research activities. The selection of candidates is carried out on the basis of the list of areas of training (specialties) of higher education of candidates for scientific companies, approved by the Office of the Chief of the NBC Protection Troops. The main criteria in the selection of candidates are the ability to conduct independent scientific activities in specialized areas, as well as the scientific potential of the candidate. The average GPA of the selected candidates is usually at least 4.7. With the young replenishment of the scientific company after the next call-up, the program of combat training of military personnel of the Armed Forces of the Russian Federation, who first entered (called up) for military service, is being mastered. Then the young replenishment of the company is given the military oath. Each serviceman is assigned a supervisor from among scientific and pedagogical workers who have a scientific degree and academic title, as well as practical experience in carrying out scientific research. After the end of the service, military personnel are provided with the opportunity is given: to conclude a contract for military service with the assignment of the military rank of "lieutenant"; stay as a researcher in universities and research organizations of the Ministry of Defense of the Russian Federation with the subsequent possibility of defending a dissertation and conferring the academic title of candidate of sciences; find employment in scientific organizations that are part of the military-industrial complex of Russia.
根据俄罗斯联邦总统的决定,2013年开始在俄罗斯武装部队中创建科学公司。2015年,在辐射、化学和生物防护部队中成立了这样一个公司,作为以苏联元帅S.K.季莫申科(科斯特罗马)命名的辐射、化学和生物防护军事学院的一部分。这项工作的目的是展示一个科学公司的创建历史,招聘的顺序,组织和其研究活动有效性的主要指标。候选人的选拔是根据国家广播公司保护部队负责人办公室批准的科学公司候选人高等教育培训领域(专业)清单进行的。选择候选人的主要标准是在专业领域进行独立科学活动的能力,以及候选人的科学潜力。入选候选人的平均绩点通常不低于4.7。随着科学公司在下一次征召后的年轻补充,首次进入(征召)服兵役的俄罗斯联邦武装部队军事人员的战斗训练方案正在掌握。然后,连队的年轻补充人员进行军训宣誓。每名军人从具有科学学位、学术职称和从事科学研究的实际经验的科学工作者和教学工作者中指派一名主管。军事人员服完兵役后,有机会签订军衔为“中尉”的兵役合同;在俄罗斯联邦国防部的大学和研究机构担任研究员,随后有可能进行论文答辩并授予科学候选人的学术头衔;在隶属于俄罗斯军工联合体的科研机构中找到工作。
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引用次数: 0
Nanoparticles as Potential Agents of Chemical and Biological Weapons 纳米粒子作为化学和生物武器的潜在制剂
Pub Date : 2022-12-23 DOI: 10.35825/10.35825/2587-5728-2022-6-4-304-319
Ján Lakota
The wide distribution in industry, medicine, agriculture, and other areas of human activity of nanoscale objects raise the question of the possibility of their dual use, which in this work means the use for deliberate mass destruction of people. The aim of the work is to consider nanoparticlesas potential agents of chemical and biological weapons. Nanoparticles of any type have been shown to have biological activity. This is due to an increase in the surface activity of particles during the transition from microscale to nanoscale and their ability to penetrate the cell, especially cell nucleus. Being non-biological objects, interacting with cell receptors, distorting intracellular signaling pathways and affecting the genetic regulation of the cell, they can cause a variety of pathological effects (oxidative stress, neuroinflammation, neurodegeneration, etc.). Therefore, with the transition from microscales to nanoscales, essentially remaining chemical compounds, particles of non-toxic materials can transform into potential biological and chemical damaging agents. The existing possibilities of their mass use through the respiratory system, skin, gastrointestinal tract and through the introduction of injectable forms of drugs suggest that based on damaging agents of this type, weapons of mass destruction of a new type that are not subject to the Conventions on the Prohibition of Chemical and Biological Weapons can be developed. It is necessary to start developing methods for detecting nanoparticles and other nanoobjects in various environments surrounding a person, food and dosage forms
纳米物体在工业、医药、农业和其他人类活动领域的广泛分布引发了它们双重用途的可能性的问题,在这项工作中,这意味着用于故意大规模毁灭人类。这项工作的目的是考虑纳米粒子作为化学和生物武器的潜在代理人。任何类型的纳米颗粒都已被证明具有生物活性。这是由于粒子在从微尺度到纳米尺度的转变过程中表面活性的增加以及它们穿透细胞,特别是细胞核的能力。作为非生物物质,它们与细胞受体相互作用,扭曲细胞内信号通路,影响细胞的遗传调控,可引起多种病理作用(氧化应激、神经炎症、神经变性等)。因此,随着从微尺度到纳米尺度的过渡,基本上剩余的化学化合物,无毒材料的颗粒可以转化为潜在的生物和化学破坏剂。通过呼吸系统、皮肤、胃肠道和注射形式的药物大量使用它们的现有可能性表明,可以在这类破坏剂的基础上开发出不受《禁止化学武器和生物武器公约》约束的新型大规模毁灭性武器。有必要开始开发在人、食物和剂型周围的各种环境中检测纳米粒子和其他纳米物体的方法
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引用次数: 0
New Enzymatic Targets for Organophosphorus Compounds 有机磷化合物的新酶靶点
Pub Date : 2022-12-23 DOI: 10.35825/2587-5728-2022-6-4-342-354
It is known that several decarboxylases (aromatic amino acid decarboxylase (AAD), histidine decarboxylase (HD) and glutamate decarboxylase (GD) with different molecular weights catalyze the most important reactions of neurotransmitter and neuromodulator biosynthesis. Pyridoxal phosphate, which serves as a cofactor for these enzymes, is one of organophosphorus compounds (OPC) having a structure similar to highly toxic substances such as warfare agents (WA) sarin, soman, Vx, a substance of type Vx, tabun and the so-called «Novichoks» (A230, A232, A234), as well as pesticides, widely used in agriculture (chlorpyrifos, malathion, glyphosate, mipafox, diazinon, paraoxon), based on their inhibitory effect on cholinesterases (ChE). The purpose of this work wasto use computer modeling methods to evaluate the possible binding of various OPC to the catalytic centers of these enzymes instead of a cofactor, as well as similar interactions of decarboxylases (DC)with OPC when the active centers of DC already contain a built-in cofactor. Molecular docking has shown that a number of these OPC can compete with the cofactor for binding to the active centers of DC, and absolutely all the studied OPC (pesticides and WA) create obstacles to embeddingthe cofactor in the active center of AAD and HD. Such interactions will lead to a decrease in the level of formation of products of the corresponding catalytic reactions (dopamine, serotonin, phenylethylamine, serotonin, γ-aminobutyric acid) and the manifestation of their physiologicalfunctions. It was found that in the presence of a cofactor in the active center of the studied DC, the interaction of a number of OPC with the surface of these enzymes near the active center increases and exceeds the strength of the interaction of same enzymes with their typical substrates. At the same time, the maximum interaction that can lead to a significant inactivation of all the studied DC was revealed for the pesticides, while the effect of their presence was lower for WA. One of the highest levels of possible influence on the activity of DC was revealed for chlorpyrifos and diazinon. In total, for DC, the more dangerous substances with high potential neurotoxicity turned out to be not WA at all, including «Novichoks», namely pesticides, which, according to their known effect on ChE, are considered as low-toxic OPC. The conducted new theoretical studies indicate that, firstly, direct experimental studies are required that will confirm the bioinformatics calculations made; secondly, a revision of long-standing approaches to assessing the neurotoxicity of various OPC, based mainly on the use of ChE for these purposes, is necessary; thirdly, it may be necessary to formulate tasks for the development and the use of new systems for the determination of potentially neurotoxic substances,the effect of which will be based on the use of different DC; fourth, to study the possible using DC as a basis for the development of new catalytic e
已知几种不同分子量的脱羧酶(芳香氨基酸脱羧酶(AAD)、组氨酸脱羧酶(HD)和谷氨酸脱羧酶(GD)催化了神经递质和神经调节剂生物合成的最重要反应。磷酸吡哆醛作为这些酶的辅助因子,是有机磷化合物(OPC)的一种,其结构类似于剧毒物质,如战剂(WA)沙林、索曼、Vx、Vx型物质、塔本和所谓的“诺维乔克”(A230、A232、A234),以及农业中广泛使用的农药(毒死蜱、马拉硫磷、草甘膦、米帕fox、二嗪农、对氧磷),基于它们对胆碱酯酶(ChE)的抑制作用。这项工作的目的是使用计算机建模方法来评估各种OPC与这些酶的催化中心而不是辅助因子的可能结合,以及当DC的活性中心已经含有内置辅助因子时,脱羧酶(DC)与OPC的类似相互作用。分子对接表明,许多OPC可以与辅助因子竞争结合到DC的活性中心,并且绝对所有被研究的OPC(农药和WA)都对辅助因子嵌入到AAD和HD的活性中心产生障碍。这种相互作用会导致相应的催化反应产物(多巴胺、血清素、苯乙胺、血清素、γ-氨基丁酸)的形成水平及其生理功能的表现降低。研究发现,在研究的DC的活性中心存在辅助因子时,许多OPC与活性中心附近这些酶表面的相互作用增加,并超过了相同酶与其典型底物的相互作用强度。与此同时,杀虫剂的最大相互作用可导致所有研究的DC显着失活,而它们的存在对WA的影响较低。毒死蜱和二嗪农对DC活性的影响最大。总的来说,对于DC来说,具有高潜在神经毒性的更危险的物质根本不是WA,包括“诺维乔克”,即农药,根据它们对ChE的已知影响,被认为是低毒的OPC。新的理论研究表明,首先,需要直接的实验研究来证实所做的生物信息学计算;其次,有必要修订长期以来评估各种OPC神经毒性的方法,主要基于对这些目的的ChE使用;第三,可能有必要制定开发和使用新系统的任务,以确定潜在的神经毒性物质,其效果将取决于使用不同的DC;第四,研究以DC为基础开发新型催化酶法解毒剂(解毒剂)和CNS再生器的可能性。
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引用次数: 0
Modern Psychoactive Substances and Their Detection in Biomedical Samples 现代精神活性物质及其在生物医学样品中的检测
Pub Date : 2022-12-23 DOI: 10.35825/10.35825/2587-5728-2022-6-4-320-341
Scientific and technological advancement of the mid- and late twentieth century led to the creation of a large number of new psychoactive substances (NPS), diverse in composition and spectrum of action.The primary stages of fight the spread of NPS are awareness of their characteristics, as well as the possibility of detecting both the substances themselves and biomarkers of their use (metabolites) in human biological objects. The purpose of the work is to review psychoactive compounds and methods of their detection performed for diagnostic purposes. The paper presents brief characteristics of the most common NPS, as well as features of their metabolism in the human. It is shown that the analysisof biological specimens collected from susceptive drug users is difficult due to the low content of analytes, the matrix influences, metabolism and the formation of various artifacts. The general scheme of screening of biological objects assumes the presence of two stages – a preliminary express analysis performed using immunochemical test systems, and a confirmatory analysis performed by gas and liquid chromatography-mass spectrometry. The article discusses the possibilities and limitations oftargeted and non-targeted screening. The subject of special consideration was the problems of using chromatography-mass spectrometry methods of NPS analysis in Russian – issues of accessibility of standard substances, search libraries, etc. The article also presents brief characteristics of individual families of NPS, such as stimulants, synthetic cannabinoids, synthetic opioids and hallucinogens. In addition, the article shows that in a number of foreign armies, in particular, in the Armed forces of Ukraine (AFU), drugs and psychostimulants are used to create «fearless soldiers». Thus, methadone, amphetamine and other psychoactive substances, as well as a psychotomimetic – a structural and pharmacological similarity of the prohibited BZ – were found in objects delivered from the positions of the AFU for analysis.
20世纪中后期的科学和技术进步导致了大量新的精神活性物质(NPS)的产生,这些物质的成分和作用谱各不相同。防治NPS传播的初级阶段是了解其特征,以及检测物质本身及其在人类生物物体中使用的生物标志物(代谢物)的可能性。这项工作的目的是审查精神活性化合物及其用于诊断目的的检测方法。本文简要介绍了最常见的NPS的特征,以及它们在人体中的代谢特征。结果表明,由于分析物含量低、基质影响、代谢和各种伪影的形成,对敏感吸毒者采集的生物标本进行分析是困难的。生物对象筛选的一般方案假定存在两个阶段-使用免疫化学测试系统进行初步表达分析,以及通过气相和液相色谱-质谱法进行确认分析。本文讨论了靶向和非靶向筛查的可能性和局限性。特别考虑的主题是在俄罗斯使用色谱-质谱法分析NPS的问题-标准物质的可及性、检索库等问题。本文还简要介绍了兴奋剂、合成大麻素、合成阿片类药物和致幻剂等NPS各科的特点。此外,文章显示,在一些外国军队中,特别是在乌克兰武装部队(AFU)中,使用药物和精神兴奋剂来创造“无畏的士兵”。因此,美沙酮、安非他明和其他精神活性物质,以及一种拟精神物质——与违禁BZ在结构和药理学上相似——被发现从AFU的位置送出供分析。
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引用次数: 0
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Journal of NBC Protection Corps
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