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Comparative Immunogenicity of the Gam-COVID-Vac Vaccine under Intranasal and Intramuscular Administration Gam-COVID-Vac 疫苗鞘内和肌肉注射的免疫原性比较
Pub Date : 2023-12-04 DOI: 10.33647/2074-5982-19-4-56-69
E. I. Katorkina, I. V. Lyagoskin, E. N. Bocharova, M. V. Bolotnikova, A. A. Borzov, N. V. Belskaya, A. E. Lisova, K. V. Ulyanova, N. K. Kudina, N. A. Belyanina, O. M. Strizhakova, A. S. Pershin, Ya. A. Bahareva, P. E. Kargopolova, A. P. Vasiliev, A. A. Kazarov, M. Lykov, R. A. Khamitov
In this work, we set out to compare the immunogenicity of the Gam-COVID-Vac two-component vaccine produced by GENERIUM JSC (Russia) following its intranasal or intramuscular administration of the first or both components to BALB/c mice. The immunogenicity was evaluated according to antigen-specific IgG and IgA antibodies in the blood and bronchoalveolar fluid, the number of antigen-specific IFN-γ-producing T-lymphocytes, the number of antigen-specific IFN-γ-producing CD4 and CD8 T-lymphocytes. Intranasal administration was shown to induce the mucosal immunity, significantly exceeding both qualitatively and quantitatively the effect of intramuscular administration (by the number of animals with antigen-specific IgA antibodies and the titer of antibodies in blood serum and bronchoalveolar lavage). At the same time, intramuscular administration slightly exceeded the effect obtained under intranasal administration in terms of the total number of CD8-IFN-γ-producing lymphocytes.
在这项工作中,我们着手比较GENERIUM JSC(俄罗斯)生产的Gam-COVID-Vac双组分疫苗在将第一组分或两组分经鼻或肌肉注射给BALB/c小鼠后的免疫原性。免疫原性根据血液和支气管肺泡液中抗原特异性IgG和IgA抗体、抗原特异性产生IFN-γ的t淋巴细胞数量、抗原特异性产生IFN-γ的CD4和CD8 t淋巴细胞数量进行评价。鼻内给药可诱导粘膜免疫,在定性和定量上均显著超过肌内给药(通过血清和支气管肺泡灌洗液中具有抗原特异性IgA抗体的动物数量和抗体滴度)。同时,在产生CD8-IFN-γ的淋巴细胞总数方面,肌内给药的效果略优于鼻内给药。
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引用次数: 0
Pharmacokinetics of a New Dimethylamineethanol Derivative Administered Orally to Laboratory Animals 实验动物口服二甲胺乙醇新衍生物的药代动力学
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-110-113
A. Kim, E. B. Shustov
A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids (laboratory code ADK-17) was synthesized at the Organic Chemistry Department of the Saint Petersburg State Chemical and Pharmaceutical University (SPSPU). This promising nootropic and anti-asthmatic agent is planned for use in an oral dosage form. The aim was to calculate the pharmacokinetic parameters of the synthesized compound and to determine its possible biotransformation pathways. Rabbits of the Soviet Chinchilla breed were used as a test system in the preclinical study of the compound pharmacokinetics. In accordance with the designed schedule, blood was taken from the marginal vein of the ear, and urine samples were taken. Quantitative determination in biological media was carried out using an Ultimate 3000 liquid chromatograph with a Q-Exactive mass-selective detector with electrospray ionization in accordance with OFS 1.2.1.100015 (Chromatography) of the State Pharmacopoeia by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS). To study the pharmacokinetics of the ADK-17 preparation, a measurement procedure was developed with a detection limit in biological media ranging from 10-6 to 10-3 mg/ml. The determined harmacokinetic parameters show that the absorption of ADK-17 into the systemic circulation from the gastrointestinal tract occurs at an average rate, with its maximum concentration in blood plasma during the oral route of administration being observed between 60–90 min. The elimination half-life from the systemic circulation comprises 4.3 h. Urinary excretion in the first 4 h proceeds at a high rate; however, the compound is detected in the urine within 3 days and in the blood within 2 days from the moment of administration.
圣彼得堡国立化学与制药大学(SPSPU)有机化学系合成了二甲基氨基乙醇、丁二酸和反式丁二酸的新衍生物(实验室代码 ADK-17)。计划将这种有前景的促智剂和抗哮喘剂用于口服剂型。研究的目的是计算合成化合物的药代动力学参数,并确定其可能的生物转化途径。在化合物药代动力学的临床前研究中,使用了苏联栗鼠品种的兔子作为试验系统。按照设计的时间表,从耳朵边缘静脉抽取血液,并采集尿液样本。根据《国家药典》OFS 1.2.1.100015(色谱法),使用 Ultimate 3000 型液相色谱仪和 Q-Exactive 质量选择检测器,通过超高效液相色谱-质谱法(UPLC-MS)对生物介质进行定量测定。为研究 ADK-17 制剂的药代动力学,开发了一种测量程序,其在生物介质中的检测限为 10-6 至 10-3 mg/ml。测定的药代动力学参数表明,ADK-17 从胃肠道进入体循环的吸收率一般,口服给药过程中血浆中的最高浓度在 60-90 分钟之间。从全身循环中排出的半衰期为 4.3 小时。在最初的 4 小时内,尿液的排泄率较高;不过,从给药后 3 天内和 2 天内,尿液和血液中均可检测到该化合物。
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引用次数: 0
Influence of Etomersol Fumarate on Cognitive Functions of Rats During Mercury Acetate Poisoning 富马酸依托摩醇对醋酸汞中毒大鼠认知功能的影响
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-124-129
K. Shchepetkova, E. G. Batotsyrenova, E. B. Shustov, V. Kashuro, A. V. Sharabanov, N. P. Ramenskaya
Research into the consequences of human exposure to heavy metals acquires particular significance in the context of life and working age prolongation. Such consequences can be manifested either in the form of selective damage to any organ, organ system or function, or in the form of a general violation of the functions of a number of systems and organs and the organism as a whole, in the form of “disintegration of functions”. In this work, we set out to study the neuroprotective effect of etomerzol fumarate after a subchronic low-dose administration of mercury acetate to Wistar rats. After an intragastric administration of an aqueous solution of mercury acetate at a dose of 4 mg/kg for 30 days, a violation of the learning process was identified in an active avoidance by swimming test. The use of the test substance at a dose of 12.5 mg/kg for 14 days had a positive effect on the long-term memory of animals, contributing to the preservation and reproduction of mercury information received.
研究人类接触重金属的后果对于延长寿命和工作年龄具有特别重要的意义。这种后果既可以表现为对任何器官、器官系统或功能的选择性损害,也可以表现为对多个系统和器官以及整个机体功能的普遍损害,即 "功能解体"。在这项工作中,我们研究了富马酸依托美唑对 Wistar 大鼠亚慢性低剂量服用醋酸汞后的神经保护作用。在连续 30 天以 4 毫克/千克的剂量给大鼠胃内注射醋酸汞水溶液后,在游泳主动回避试验中发现大鼠的学习过程出现了异常。以 12.5 毫克/千克的剂量连续 14 天使用试验物质,对动物的长期记忆产生了积极影响,有助于保存和再现接收到的汞信息。
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引用次数: 0
Effect of L-thyroxine, a Human Serum Albumin Natural Ligand, on the Kinetics of β-amyloid Peptide Fibril Formation 人血清白蛋白天然配体 L-甲状腺素对 β 淀粉样肽纤维形成动力学的影响
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-114-118
E. Litus, E. Nemashkalova, A. A. Vologzhannikova, E. Deryusheva
Ligands of human serum albumin (HSA) are capable of modulating its interaction with β-amyloid peptide (Aβ), which is a key factor in the pathogenesis of Alzheimer’s disease (AD). L-thyroxine (L-Tr), a natural HSA ligand, is associated with the pathogenesis of AD according to epidemiological and animal model studies. In this work, we studied the kinetics of Aβ fibril formation in the presence of L-Tr and HSA using a fluorescent test with thioflavin T. L-Tr had no significant effect on the inhibitory effect of HSA on fibril growth. At the same time, L-Tr itself had an inhibitory effect similar to that of HSA. Our data can partially explain the relationship between AD and thyroid pathologies.
人血清白蛋白(HSA)的配体能够调节其与β-淀粉样肽(Aβ)的相互作用,而β-淀粉样肽是阿尔茨海默病(AD)发病机制中的一个关键因素。根据流行病学和动物模型研究,天然 HSA 配体 L-甲状腺素(L-Tr)与阿尔兹海默病的发病机制有关。在这项工作中,我们使用硫黄素 T 荧光测试法研究了在 L-Tr 和 HSA 存在下 Aβ 纤维的形成动力学。同时,L-Tr 本身的抑制作用与 HSA 相似。我们的数据可以部分解释AD与甲状腺病变之间的关系。
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引用次数: 0
Development and Preclinical Trials of Castomized Porous Titanium Implants with Bioactive Coatings in Model Systems 带有生物活性涂层的铸造多孔钛植入体在模型系统中的开发和临床前试验
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-104-109
P. A. Karalkin, K. G. Kudrin, D. Svyatoslavov, D. Usatov, I. V. Reshetov
This paper presents a technology for creating customized porous titanium implants with bioactive coatings, manufactured using additive technologies. The stages of creating an implant include obtaining primary data from the bone defect area using computed tomography; 3D modeling of the defect area and the corresponding implant; production of a customized implant from titanium alloys using selective laser fusion technology; application of bioactive coatings. The as-created customized implant can have several functional structures. Samples of titanium implants with bioactive coatings were subjected to extensive testing. Mathematical modeling and experiments were used to verify the correspondence of the mechanical properties of the developed structures to natural bone tissue. In vitro tests of the studied samples showed the absence of acute toxicity along with high levels of biocompatibility. In vivo tests of the studied samples on Soviet chinchilla rabbits and Anubis baboon monkeys approved by local ethical committees showed their adequate biomechanical and high osteoinductive properties. The successful results of preclinical studies, as well as toxicological and technical tests in certified laboratories, made it possible to create a registration dossier for state registration of customized porous titanium implants with bioactive coatings, manufactured using additive technologies.
本文介绍了一种利用添加剂技术制造带有生物活性涂层的定制多孔钛植入体的技术。制作植入体的各个阶段包括:使用计算机断层扫描获取骨缺损区域的原始数据;缺损区域和相应植入体的三维建模;使用选择性激光熔融技术用钛合金制作定制植入体;应用生物活性涂层。制作完成的定制植入体可具有多种功能结构。对带有生物活性涂层的钛植入体样品进行了大量测试。通过数学建模和实验验证了所开发结构的机械性能与天然骨组织的对应关系。对所研究样品进行的体外测试表明,这些样品没有急性毒性,同时具有很高的生物相容性。经当地伦理委员会批准,在苏联栗鼠兔和阿努比斯狒狒猴身上对所研究样品进行的体内测试表明,这些样品具有适当的生物力学特性和较高的骨诱导特性。临床前研究的成功结果,以及在认证实验室进行的毒理学和技术测试,使得利用添加剂技术生产的带有生物活性涂层的定制多孔钛植入物的国家注册档案得以建立。
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引用次数: 0
Clinical Course and Therapy Methods of Aquagenic Urticaria 水源性荨麻疹的临床过程和治疗方法
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-130-135
O. M. Kudelina, E. Gantsgorn, Yu. S. Maklyakov, D. L. Tkachenko, L. A. Avakyan, P. A. Chubyreva, Y. G. Amirova, Yu. A. Karpova, A. N. Dulskaya, I. B. Meshi
Aquagenic urticaria is one of the rarest forms of allergic reaction in the body. Aquagenic urticaria is clinically manifested by itching and urticarial rashes 5–10 min after contact with water. The signs disappear within 30–60 min. The standard therapy regimen includes the administration of second-generation H1-histamine receptor blockers and barrier creams with ceramides. In recent years, the use of monoclonal antibody therapy (omalizumab) has been considered in cases where antihistamines are ineffective.
水源性荨麻疹是人体最罕见的过敏反应之一。水源性荨麻疹的临床表现为接触水后 5-10 分钟出现瘙痒和荨麻疹。症状在 30-60 分钟内消失。标准治疗方案包括使用第二代 H1 组胺受体阻断剂和含神经酰胺的隔离霜。近年来,在抗组胺药无效的情况下,也考虑使用单克隆抗体疗法(奥马珠单抗)。
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引用次数: 0
The effect of L. reuteri on Nonspecific Resistance and Hematological Parameters of Laboratory Animals 纽崔莱对实验动物非特异性抵抗力和血液学参数的影响
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-119-123
A. Ovcharova, N. V. Belova
Probiotics are microbial preparations, which have a positive effect on the composition of the intestinal microflora and the immune system of animals. These preparations are widely used for correcting and preventing violations of the microflora of the gastrointestinal tract. Lactobacilli play a special role in the formation of normal microflora. They exhibit a pronounced antagonistic activity against pathogenic and opportunistic microorganisms, as well as possess a number of other positive effects. This study is aimed at determining the effect of new probiotic strains of L. reuteri on the indicators of nonspecific resistance, hematological and biochemical parameters of laboratory rabbits. The studied strains were found to have a pronounced positive effect on the indicators of nonspecific resistance. Thus, compared to the control, the indicators of phagocytic activity and bactericidal activity in the experimental group were by 22% and 32% higher, respectively. The content of hemoglobin, erythrocytes and total protein in the blood serum also increased.
益生菌是一种微生物制剂,对动物肠道微生物区系的组成和免疫系统有积极作用。这些制剂被广泛用于纠正和预防胃肠道微生物菌群失调。乳酸菌在正常微生物区系的形成过程中发挥着特殊作用。乳酸菌对病原微生物和机会性微生物具有明显的拮抗活性,并具有许多其他积极作用。本研究旨在确定新的 L. reuteri 益生菌株对实验兔的非特异性抵抗力指标、血液学和生化指标的影响。研究发现,所研究的菌株对非特异性抵抗力指标有明显的积极影响。因此,与对照组相比,实验组的吞噬活性和杀菌活性指标分别提高了 22% 和 32%。血清中的血红蛋白、红细胞和总蛋白含量也有所增加。
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引用次数: 0
Influence of Dioscorea Extracts on Physical Load Tolerance in the Setting of Hypoxic and Temperature Factors 薯蓣皂苷提取物在缺氧和温度因素下对物理负荷耐受性的影响
Pub Date : 2023-11-21 DOI: 10.33647/2713-0428-19-3e-99-103
A. Ivkina, D. Ivkin, E. B. Shustov, M. N. Povydysh
A comparative evaluation of the effectiveness of dry alcoholic extracts of Dioscorea from pharmacopoeial raw materials and cell cultures was carried out on a model of combined exposure to hypoxic and temperature factors and swimming of laboratory animals (mice) with a load of 5% of body weight. Dioscorea preparations had a pronounced thermoprotective effect and increased physical performance; however, the aftereffect was confirmed only for the cell culture extract.
在实验动物(小鼠)联合暴露于缺氧和温度因素以及负重 5%游泳的模型中,对从药典原料和细胞培养物中提取的薯蓣干酒精提取物的功效进行了比较评估。薯蓣皂苷制剂具有明显的热保护作用,并能提高体能;不过,只有细胞培养提取物的后效应得到了证实。
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引用次数: 0
HLDF-6-H Peptide Exhibits an Anti-inflammatory Effect in the Development of Depression in an MPTP Model of Parkinson's Disease HLDF-6-H肽在帕金森病MPTP模型抑郁发展过程中表现出抗炎作用
Pub Date : 2023-11-20 DOI: 10.33647/2713-0428-19-3e-90-94
S. A. Zozulya, O. Sokolov, N. Kost, N. V. Baimeeva, A. K. Dadayan, Yu. A. Zolotarev
In this work, we investigate the anti-inflammatory effect of the HLDF-6-H peptide (Thr-Gly-Glu-HseHis-Arg) in a model of the presymptomatic stage of Parkinson’s disease (PD). This peptide is a bioactive fragment of the HLDF leukocyte differentiation factor. The presymptomatic stage of PD was modelled by introducing moderate doses of MPTP toxin to C57Bl/6 mice. HLDF-6-H was administered intranasally at a dose of 300 μg/kg daily for three weeks. The severity of depression was determined by the time of immobilization in a Porsolt test. The serum levels of 10 steroids were determined using MS analysis. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined using kinetic methods. The development of an inflammatory process under the influence of MPTP is evidenced by an increase in the activity of α1-PI; the anti-inflammatory effect of the peptide is manifested in a decreased activity of LE and α1-PI. At the same time, the immobilization time of mice in a Porsolt test positively correlated with α1-PI and LE, which may indicate the role of inflammation in the development of depression. A positive correlation between estradiol and LE was found in the general sample of mice. In the group of mice treated with the peptide, α1-PI correlated positively with corticosterone and negatively with estradiol and androstenedione. It can be assumed that the anti-inflammatory effect of the peptide is associated with the regulation of corticosteroids and sex hormones. Hence, the applied experimental model confirmed the development of a depressive-like syndrome and neuroendocrine disorders in the presymptomatic stage of PD. The long-term use of HLDF-6-H has antidepressant and anti-inflammatory effects.
在这项工作中,我们研究了 HLDF-6-H 肽(Thr-Gly-Glu-HseHis-Arg)在帕金森病(PD)症状前期模型中的抗炎作用。该肽是 HLDF 白细胞分化因子的生物活性片段。通过向 C57Bl/6 小鼠注射中等剂量的 MPTP 毒素,模拟帕金森病的症状前期。HLDF-6-H以每天300微克/千克的剂量经鼻给药,持续三周。抑郁的严重程度由 Porsolt 试验中的固定时间决定。通过质谱分析测定了血清中 10 种类固醇的水平。用动力学方法测定了炎症标志物白细胞弹性蛋白酶(LE)和α1-蛋白酶抑制剂(α1-PI)的活性。在 MPTP 的影响下,炎症过程的发展表现为 α1-PI 活性的增加;多肽的抗炎作用表现为 LE 和 α1-PI 活性的降低。同时,小鼠在波尔索尔特试验中的固定时间与α1-PI和LE呈正相关,这可能表明炎症在抑郁症的发展中起了作用。在小鼠的总体样本中发现,雌二醇与 LE 呈正相关。在接受多肽治疗的小鼠组中,α1-PI 与皮质酮呈正相关,与雌二醇和雄烯二酮呈负相关。由此可以推断,该肽的抗炎作用与皮质类固醇和性激素的调节有关。因此,应用的实验模型证实,在帕金森病的症状前期,会出现类似抑郁的综合征和神经内分泌紊乱。长期服用HLDF-6-H具有抗抑郁和抗炎作用。
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引用次数: 0
Influence of a Nanoform of 9-phenyl-2,3,4,5,6,7,8,9-octahydro-1H-selenoxanthene on the Reproductive Function of White Rats 9-苯基-2,3,4,5,6,7,8,9-八氢-1H-硒氧蒽纳米形式对白鼠生殖功能的影响
Pub Date : 2023-11-20 DOI: 10.33647/2713-0428-19-3e-85-89
O. V. Buyuklinskayа, S. M. Napalkova, E. D. Kubasova, D. S. Makarova
Despite the diversity of modern treatment methods, infertility rates remain high both in Russian and globally. In the present experimental study, we study the effect of a nanopreparation based on a selenoxanthene derivative and cyclodextrin on the reproduction of white outbred rats (females) after the administration of mifepristone. Selenoxanthene at a dose of 0.35 mg/kg and 0.7 mg/kg intragastrically for 5 days increased the reproductive activity of animals.
尽管现代治疗方法多种多样,但俄罗斯和全球的不孕不育率仍然居高不下。在本实验研究中,我们研究了一种基于硒氧蒽衍生物和环糊精的纳米制剂在米非司酮给药后对雌性白种大鼠繁殖的影响。硒氧蒽以 0.35 毫克/千克和 0.7 毫克/千克的剂量胃内注射 5 天,可提高动物的生殖活性。
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引用次数: 0
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