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Response of CD68-Positive Thymic Cells in Rats to Selenium and Carcinogen Administration cd68阳性大鼠胸腺细胞对硒和致癌物的反应
Pub Date : 2023-06-10 DOI: 10.33647/2074-5982-19-2-54-60
N. V. Bubnova
Macrophages are the key thymic cells that take part in the antigen-independent differentiation of T-lymphocytes and their further selection. The level of macrophages indicates changes in the functions of the organ under study. As an essential trace element, selenium is part of a variety of proteins and enzymes, which perform cytoprotective, antimutagenic, and anticancerogenic action. Selenium also plays a significant role in the functioning of the immune system, increasing the activity of natural killers, production of interleukins, and stimulation of phagocytosis. This study was aimed at investigating the response of thymic macrophages to the administration of selenium and a chemical carcinogen. During the experiment, an increase in the level of CD68-positive cells was revealed in all experimental animals receiving selenium and a carcinogen, as well as under their combined action. The observed effects were assumed to be related to the immune-stimulating effect of selenium.
巨噬细胞是参与t淋巴细胞抗原非依赖性分化及其进一步选择的关键胸腺细胞。巨噬细胞的水平表明所研究器官功能的变化。作为一种必需的微量元素,硒是多种蛋白质和酶的一部分,具有细胞保护、抗诱变和抗癌作用。硒在免疫系统的功能中也起着重要的作用,增加自然杀手的活性,产生白细胞介素,并刺激吞噬作用。本研究旨在探讨胸腺巨噬细胞对硒和一种化学致癌物的反应。在实验过程中,所有接受硒和一种致癌物的实验动物,以及在它们的共同作用下,cd68阳性细胞的水平都有所增加。观察到的效果被认为与硒的免疫刺激作用有关。
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引用次数: 0
Morphofunctional State of the Adrenal Glands in Rats under Urethane and Selenium Administration 氨基甲酸乙酯和硒对大鼠肾上腺形态功能的影响
Pub Date : 2023-04-09 DOI: 10.33647/2074-5982-19-1-85-94
N. Timofeeva, L. M. Merkulova, G. Struchko, N. V. Bubnova, O. Kostrova, I. S. Stomenskaya, A. A. Kotelkina
The adrenal gland is one of the first organs to respond to external influences. Cortisol, with its important properties affecting the immune system, proliferation and apoptosis in various tissues, is a significant indicator of such a pathological process as malignant growth. Selenium is a powerful antioxidant having an immunomodulatory action and exhibiting anticarcinogenic effects. In this paper, we investigate adrenal morphofunctional changes under experimental carcinogenesis against the background of urethane and selenium administration by determining blood cortisol concentrations and studying the aggregate morphometric index of adrenal glands. The study revealed that carcinogen introduction imitates the adaptation syndrome stages in the organism and is accompanied by changes in the cortisol level and aggregate morphometric index. Maximal values of the studied parameters were detected after 1 month of exposure to carcinogen, which indicated the development of the alarm phase. A further decrease in the indices after 2 and 3 months down to the intact level indicates the development of the resistance stage. A sharp decrease in the indices after 6 months shows the exhaustion stage. An isolated course introduction of selenium leads to a reliable decrease in the aggregate morphometric index practically in all terms that indicates the stress-relieving influence of the microelement. The combined effects of selenium and carcinogen revealed a dropout of the alarm stage, but rapid elimination of the micronutrient from the body could not prevent the development of the exhaustion phase after 6 months.
肾上腺是最先对外界影响作出反应的器官之一。皮质醇具有影响免疫系统、各种组织的增殖和凋亡的重要特性,是恶性生长等病理过程的重要指标。硒是一种强大的抗氧化剂,具有免疫调节作用和抗癌作用。在本文中,我们通过测定血液皮质醇浓度和研究肾上腺的聚集形态计量指数来研究在氨基甲酸乙酯和硒的背景下实验性癌变下肾上腺形态功能的变化。研究表明,致癌物的引入模仿了生物体的适应综合征阶段,并伴随着皮质醇水平和聚集形态计量指数的变化。在接触致癌物1个月后检测到研究参数的最大值,表明警戒阶段的发展。2个月和3个月后,指数进一步下降到完整水平,表明阻力阶段的发展。6个月后,指数急剧下降,显示出枯竭阶段。在孤立的课程中引入硒会导致总体形态测量指数的可靠下降,实际上在所有方面都表明微量元素的应力缓解作用。硒和致癌物的联合作用显示警报阶段的消失,但快速从体内消除微量营养素并不能阻止6个月后的衰竭阶段的发展。
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引用次数: 0
Study Into Antinociceptive Activity of a New Molecule from the Class of Hexaazaizowurzitane 六氮杂唑脲酮类新分子抗伤性的研究
Pub Date : 2023-04-09 DOI: 10.33647/2074-5982-19-1-61-72
E. A. Kiseleva, S. Krylova, T. N. Povet`eva, Y. Nesterova, O. G. Afanas`eva, P. V. Kul`pin, D. A. Kulagina, E. Zueva, N. Suslov, V. V. Eremina, O. Baibakova, S. Sysolyatin, V. V. Zhdanov
In this work, we studied the pharmacological activity of a newly-synthesized compound 4-(3,4- dibromothiophenylcarbonyl)-10-(2-ethoxyacetyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,0,03,11,05,9]dodecane (M3) using somatogenic pain models of various genesis (thermal and visceral pain, mechanical compression of a paw). The compound showed a high antinociceptive efficacy, comparable to or exceeding that of tramadol. It was shown that the new molecule from the class of hexaazaisowurtzitane effectively blocks nociceptive reactions at the supraspinal and peripheral levels of pain sensitivity organization. The results obtained confirm the possibility of creating new pharmacologically active molecules based on the high-energy substance of hexaazaisowurtzitane, which is a priority in domestic pharmaceutical production.
在这项工作中,我们研究了新合成的化合物4-(3,4-二溴噻吩羰基)-10-(2-乙氧基乙酰基)-2,6,8,12-四乙酰基-2,4,6,8,10,12-六氮杂四环[5,5,0,03,11,05,9]十二烷(M3)的药理活性,并利用不同原因的体源性疼痛模型(热痛和内脏痛,机械压迫爪子)。该化合物显示出很高的抗伤感受力,与曲马多相当或超过曲马多。结果表明,六氮杂索乌兹坦类的新分子有效地阻断了疼痛敏感组织的棘上和外周水平的伤害性反应。研究结果证实了以六氮杂索乌尔齐坦的高能物质为基础制备新型药理活性分子的可能性,这是国内制药生产的重点。
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引用次数: 0
Experimental Pharmacokinetics, Metabolism and Tissue Distribution Studies Fluorothiazinon, a of Novel Antivirulence Drug 新型抗毒药物氟噻嗪农的实验药代动力学、代谢及组织分布研究
Pub Date : 2023-04-09 DOI: 10.33647/2074-5982-19-1-73-84
M. V. Savitskii, N. Moskaleva, N. A. Zigangirova, A. Soloveva, A. Sheremet, N. Bondareva, N. L. Lubenec, N. V. Pyatigorskaya, S. Appolonova
We studied the pharmacokinetics, tissue availability and metabolism of fluorothiazinon, a novel antivirulence drug, in mouse blood, liver, kidneys and lungs by administering the substance intragastrically at dose of 400 mg/kg. Fluorothiazinon was established to exhibit good tissue availability and long residential time. This drug is metabolized mainly by glucuronidation.
研究了新型抗毒药物氟噻嗪农(氟噻嗪农)在小鼠血液、肝脏、肾脏和肺中的药代动力学、组织利用度和代谢。氟噻嗪具有良好的组织利用度和较长的停留时间。这种药物主要通过葡萄糖醛酸化代谢。
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引用次数: 0
Comparability of the Reference Drug Pulmozim and a Similar Drug Tigerase in Terms of their Pharmacodynamic, Toxicological and Pharmacokinetic Properties 对照药Pulmozim与同类药物Tigerase药效学、毒理学和药动学性质的比较
Pub Date : 2023-04-07 DOI: 10.33647/2074-5982-19-1-47-60
M. Aksenova, E. Bocharova, S. Abbasova, A. S. Ponomarev, V. V. Loginova, M. V. Bolotnikova, N. V. Belskaya, A. A. Kazarov, A. E. Lisova, N. K. Kudina, M. S. Pantyushenko, M. V. Zhilyaeva, D. S. Kopein, Yu. M. Karelov, G. G. Erastov, M. Lykov, R. A. Chamitov
This work presents research studies into the comparability of Tigerase® (inhalation solution, manufactured by JSC «GENERIUM», Russia) to the reference drug Pulmozim® (inhalation solution, manufactured by Hoffmann-La Roche Ltd., Switzerland). Both drugs contain human recombinant deoxyribonuclease I – dornase alpha as an active substance and are intended for the treatment of cystic fibrosis with pulmonary manifestations (cystic fibrosis). The specific enzymatic activity of dornase alpha was studied in vitro and ex vivo using samples of patients’ purulent sputum. The pharmacokinetic parameters of the drugs were studied in the blood serum, bronchi and lungs. The main physiological parameters (body weight and temperature, the state of the cardiovascular, respiratory, excretory systems, hematological and biochemical blood parameters, pathomorphological changes in the internal organs, including the state of the cornea of the eyes, mortality rates) were assessed in comparative studies of subchronic toxicity in juvenile and sexually mature rats using 28-day inhalation in doses of 0.2 mg/kg to sexually mature and 0.26 mg/kg to juvenile animals (the dose was 6 times higher than the recommended dose for clinical use). It was concluded that the drugs were comparable in terms of their enzymatic, mucolytic (secretolytic) DNase activity, safety profile, and basic pharmacokinetic parameters.
这项工作介绍了对Tigerase®(吸入溶液,由俄罗斯JSC«GENERIUM»生产)与参比药物Pulmozim®(吸入溶液,由瑞士Hoffmann-La Roche Ltd生产)的可比性的研究。这两种药物都含有人重组脱氧核糖核酸酶I - dornase α作为活性物质,用于治疗有肺部表现的囊性纤维化(囊性纤维化)。利用患者化脓痰标本,在体外和离体研究了dornase α的特异性酶活性。研究了药物在血清、支气管和肺中的药动学参数。主要生理参数(体重和体温,心血管、呼吸、排泄系统的状态,血液和生化血液参数,内脏器官的病理形态学变化,包括眼睛角膜的状态,在幼鼠和性成熟大鼠的亚慢性毒性比较研究中评估了死亡率),使用28天吸入剂量,性成熟大鼠0.2 mg/kg,幼年动物0.26 mg/kg(剂量比临床使用推荐剂量高6倍)。结论是,这两种药物在酶促、溶黏液酶活性、安全性和基本药代动力学参数方面具有可比性。
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引用次数: 0
Pilot-Scale Technology for Obtaining a Substance of Lipid-Stabilized Nanoparticles Containing a Complex of Biologically Active Substances Isolated from Gland Secretion of Musk Deer with Specified Stability Parameters 从麝腺体分泌物中提取含有生物活性物质复合物的脂质稳定纳米颗粒的中试技术,具有特定的稳定性参数
Pub Date : 2023-04-07 DOI: 10.33647/2074-5982-19-1-8-21
S. L. Lyublinskiy, I. N. Lyublinskaya, E. Koloskova, L. F. Keremetskaya, A. Azizov, V. Karkischenko, M. Nesterov, A. V. Kaptsov, A. V. Sharabanov, R. Ageldinov, V. N. Gerasimov
In the course of improving the pilot-scale technology for manufacturing a liposomal substance of biologically active substances (BAS) isolated from the gland secretion of musk deer, the authors established operations and modes to ensure the production of liposomes with the specified stability parameters (shape, hydrodynamic diameter, charge, and polydispersity index) in full compliance with GMP requirements and the maximum inclusion of BAS from deer musk into liposomes with the preservation of the initial biological activity of its most important components. The established modes provide for a two-fold reduction in the technological cycle duration with the substance yield of more than 90%. The improved technology ensures the production of at least 80% of liposomes with the main liposome fraction in experimental samples in the range of 200+50 nm and 250+100 nm for the final substance (before lyophilization) and after its recovery (rehydration), respectively, which is considered optimal for transmucosal drug administration. The polydispersity index was less than 0.3, and the zeta (Z)-potential was less than -35 mV. The quality indicators characterizing the dispersity of the resulting liposomal substance were studied by conventional analytical methods (dynamic light scattering, electron microscopy). On the basis of the obtained results, a draft specification for a liposomal substance (powder) containing a complex of BAS isolated from deer musk was finalized.
在对麝鹿腺分泌物生物活性物质(BAS)脂质体的中试生产工艺进行改进的过程中,建立了保证脂质体的生产具有规定的稳定性参数(形状、流体动力学直径、电荷、和多分散性指数)完全符合GMP要求,并最大限度地将鹿香中的BAS包含到脂质体中,同时保留了其最重要成分的初始生物活性。所建立的模式可将技术周期缩短两倍,物质收率超过90%。改进后的技术可确保在200+50 nm和250+100 nm范围内生产至少80%的脂质体,其中实验样品中的主要脂质体部分分别用于最终物质(冻干前)和回收后(再水化),这被认为是经黏膜给药的最佳选择。多分散性指数小于0.3,zeta (Z)电位小于-35 mV。采用常规分析方法(动态光散射、电子显微镜)对表征所得脂质体物质分散性的质量指标进行了研究。在所得结果的基础上,确定了从麝麝香中分离出的含有BAS复合物的脂质体物质(粉末)的规范草案。
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引用次数: 0
Features of Heart Rate Variability in Male and Female Wistar Rats 雄性和雌性Wistar大鼠心率变异性的特征
Pub Date : 2023-04-07 DOI: 10.33647/2074-5982-19-1-22-33
V. N. Korobova, I. Bobyntsev, A. O. Vorvul
In this study, we investigated the heart rate variability (HRV) of awake male and female Wistar rats using a non-invasive technique of electrocardiosignal recording. We established significant differences in the value of HRV indicators in groups of animals differing in spectral parameters (total power of the spectrum (TP), high-(HF) and low-frequency (LF) components of the spectrum). The following HRV indicators were shown to be highly informative: statistical (SDNN — the standard deviation of the complete array of RR intervals, RMSSD — the square root of the standard deviations of successive RR intervals, CV — the coefficient of variation) and spectral (TP, HF, LF, VLF is a very low–frequency component of the HRV spectrum, LF/HF is the vagosympathetic interaction index, IC — centralization index). The data obtained should be taken into account when advancing the existing methodology for studying the pathogenetic mechanisms of HRV changes and determining the prognostic value of these HRV parameters.
在这项研究中,我们使用无创心电信号记录技术研究了醒着的雄性和雌性Wistar大鼠的心率变异性(HRV)。我们确定了不同光谱参数(光谱总功率(TP)、光谱高(HF)和低频(LF)分量)的动物组中HRV指标的值存在显著差异。以下HRV指标具有很高的信息量:统计(SDNN - RR区间完整序列的标准差,RMSSD -连续RR区间标准差的平方根,CV -变异系数)和频谱(TP, HF, LF, VLF是HRV频谱的极低频成分,LF/HF是迷走交感相互作用指数,IC -集中化指数)。在推进研究HRV变化的发病机制和确定这些HRV参数的预后价值的现有方法时,应考虑所获得的数据。
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引用次数: 0
Analysis of Main World Trends in Objectivization of Protocols for Behavioral Testing of Laboratory Animals with Brain Pathology 世界脑病理实验动物行为测试方案客观化的主要趋势分析
Pub Date : 2023-04-07 DOI: 10.33647/2074-5982-19-1-34-46
A. Salmina, Y. Gorina, A. Bolshakova, O. Vlasova
Behavioral phenotyping of rodents using neurodegeneration models has received much research attention over the past three decades. However, some difficulties still exist in understanding the variability of behavior caused by genetic, environmental, and biological factors, human intervention and poorly standardized experimental protocols, which can negatively affect the interpretation of the results obtained. In this article, we discuss factors that have a negative impact on the performance of behavioral testing of laboratory animals, modern approaches to overcome them, as well as new technologies, such as visualization of neuronal activity using ion-dependent fluorescent indicators (optogenetics), which expand the boundaries of the study of neuronal networks responsible for behavior by evaluating neuronal function at both the cellular and population levels. Ultimately, this will increase the reliability of the results obtained and provide an opportunity to take a fresh look at the ethological paradigms of a particular transgenic mouse model.
在过去的三十年中,使用神经变性模型进行啮齿动物的行为表型研究受到了广泛的关注。然而,在理解由遗传、环境和生物因素、人为干预和不规范的实验方案引起的行为变异性方面仍然存在一些困难,这可能会对所获得的结果的解释产生负面影响。在本文中,我们讨论了对实验动物行为测试性能产生负面影响的因素,克服这些因素的现代方法,以及新技术,例如使用离子依赖性荧光指示器(光遗传学)可视化神经元活动,通过在细胞和群体水平上评估神经元功能,扩展了负责行为的神经元网络研究的边界。最终,这将增加所获得结果的可靠性,并提供一个机会,以一个新的视角来看待一个特定的转基因小鼠模型的行为学范式。
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引用次数: 1
Study of Acute Toxicity of an Herbal Extract of Astragalus vulpinus 黄芪提取物的急性毒性研究
Pub Date : 2022-12-12 DOI: 10.33647/2074-5982-18-4-86-93
M. Sergalieva, A. A. Tsibizova, O. Bashkina, M. Samotrueva
This paper studies the acute toxicity of an herbal extract of Astragalus vulpinus Willd. growing in the Astrakhan Oblast. Experiments were carried out on white nonlinear rats. The animals were divided into several groups (n = 6): the control group receiving intragastric distilled water and the experimental groups receiving intragastric extract of the Astragalus vulpinus extract once at doses of 100, 500, 1000, 2000, and 4000 mg/kg. On the first day after extract administration, the animals were under continuous observation. During the entire observation period for 14 days, the animals were monitored in terms of their general condition, body weight, food refusal, and coat appearance, as well as their response to sound, light, and tactile stimuli. The response to sound was evaluated by a sudden sharp knock on the cage and identification of the animal’s flinching. The response to light was assessed by shining light into the eye with a penlight to control eye lid closure. Tactile stimuli were evaluated by compressing the basal part of the tail. After removing the animals from the experiment, macroscopic examination of internal organs (brain, liver, spleen, heart, stomach) and hematological analysis of blood smears were performed. During the research, the LD50 of the Astragalus vulpinus herbal extract under study was established. When the extract was administered at a dose of 4000 mg/kg, animal mortality was recorded (3 individuals died by the third day). In the remaining animals, a decrease in weight and leukocyte count was observed along with changes in the gastric mucosa. In terms of acute toxicity, the extract under study was found to belong to low-toxic substances with an LD50 of 4000 mg/kg. However, its administration at a dose of 4000 mg/kg led to changes in leukocyte count and gastric mucosa. Therefore, the chronic toxicity of Astragalus vulpinus herbal extracts requires additional research.
本文研究了黄芪提取物的急性毒性。生长在阿斯特拉罕州。实验采用白色非线性大鼠。将实验动物分为几组(n = 6):对照组灌胃蒸馏水,试验组灌胃黄芪提取物1次,剂量分别为100、500、1000、2000、4000 mg/kg。给药后第1天连续观察。在整个14 d的观察期内,监测动物的一般状况、体重、拒食、被毛外观以及对声、光、触觉刺激的反应。对声音的反应是通过对笼子的突然猛烈敲击和动物畏缩的识别来评估的。对光线的反应是通过用笔灯照射眼睛来控制眼睑闭合来评估的。通过压缩尾部基部来评估触觉刺激。将动物从实验中取出后,进行内脏器官(脑、肝、脾、心、胃)的宏观检查和血液涂片的血液学分析。在研究过程中,确定了所研究的黄芪提取物的LD50。以4000mg /kg剂量给药时,记录动物死亡率(3只死亡)。在其余的动物中,观察到体重和白细胞计数的减少以及胃粘膜的变化。在急性毒性方面,所研究的提取物属于低毒物质,LD50为4000 mg/kg。然而,4000mg /kg的剂量可导致白细胞计数和胃粘膜的变化。因此,黄芪提取物的慢性毒性有待进一步研究。
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引用次数: 0
Hystostructure Features of the Sacra-Caudal (Coccygeal) Dorsal Lateral Muscle when Modeling Posterior Arthodesis of the Ileosacral Joint 模拟回骶关节后固定术时骶尾部(尾骨)背外侧肌的结构特征
Pub Date : 2022-12-12 DOI: 10.33647/2074-5982-18-4-102-111
G. Filimonova, O. V. Diuriagina, N. I. Antonov
Paravertebral muscles play an important role in the development of deformities and degenerative diseases of the spine. The impact of posterior arthrodesis of the ileosacral articulation (sacrum-iliac joint) on the morphological characteristics of the m. sacrocaudalis (coccygeus) dorsalis lateralis of mongrel dogs was studied in animal experiments. Titanium cages were used, followed by stabilization with an external fixation device for 30 days. The advantages of posterior arthrodesis include a small incision, minimal blood loss, preservation of the integrity of most ligaments, and a short immobilization period. Nevertheless, when modeling arthrodesis experimentally in animals, fibrosis of the interstitial space and fatty infiltration in the adjacent muscle were revealed at the end of the experiment, which amounted to 240% and 310% of the intact parameters, respectively. In addition, fibrosis of the vessel membranes of the arterial link was observed. When performing surgical interventions on the spine, traumatization of the muscles should be reduced in order to minimize fibrogenesis and fatty involution of the paravertebral muscles.
椎旁肌肉在脊柱畸形和退行性疾病的发展中起重要作用。动物实验研究了回骶关节(骶骨-髂关节)后路关节融合术对杂种犬骶尾肌(尾骨)背外侧肌形态特征的影响。使用钛笼,然后用外固定装置稳定30天。后路关节融合术的优点包括切口小,出血量少,保留大部分韧带的完整性,固定时间短。然而,在动物实验模拟关节融合术时,实验结束时发现间质间隙纤维化,邻近肌肉脂肪浸润,分别占完整参数的240%和310%。此外,观察到动脉连接血管膜纤维化。当对脊柱进行手术干预时,应减少对肌肉的创伤,以尽量减少脊柱旁肌肉的纤维形成和脂肪累及。
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引用次数: 0
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