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Chronotropic action of immobilized subtilisins during the perfusion of an isolated rat heart 固定化枯草菌素在离体大鼠心脏灌注中的变时作用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220505
G. Baikalov, N. Leonov, P. Madonov, K. Ershov, K. I. Bakhareva, M. Soldatova
The pharmacological experiments on isolated organs (ex vivo) are the preferred method for assessing the primary pharmacodynamics of the studied drugs, since this method is completely excluded the systemic influence of neurohumoral regulation. In the last decade, a new group of thrombolytic drugs based on immobilized subtilisins has been formed. At the stage of registrational preclinical and clinical studies, their pleiotropic pharmacological effects have not been studied. Meanwhile, there is a reason to consider that their pharmacological activity in the bloodstream is not limited to thrombolytic action, but may be extended to a systemic effect on the cardiovascular system. The aim of the study was to investigate the chronotropic effects of an isolated heart during its perfusion with solutions of immobilized subtilisins at different concentrations. Material and methods. The isolated rat heart model according to Langendorff was used in the study. The experiment included 50 Wistar rats, which were divided into 5 groups: isolated hearts perfused only with Krebs – Henseleit solution (control) or with immobilized subtilisins in 4 concentrations (170, 340, 510 и 1020 U/l). Results and discussion. The immobilized subtilisins have a negative chronotropic effect. The onset of the effect depends on the drug concentration in the solution: the higher concentration, the earlier effect. From 5 to 10 minutes of perfusion, a negative chronotropic effect is observed using of immobilized subtilisins at any dose. The duration of its increase is manifested up to 10–20 minutes, depending on the drug concentration in solution. After 20 minutes of perfusion, the achieved negative chronotropic effect remains at a plateau level up to 40 minutes. Conclusion. The immobilized subtilisins have an independent pharmacological effect on heart rate.
离体器官药理学实验是评估所研究药物的主要药效学的首选方法,因为该方法完全排除了神经体液调节的全身性影响。在过去的十年中,以固定化枯草菌素为基础的一类新的溶栓药物已经形成。在注册临床前和临床研究阶段,尚未对其多效药理作用进行研究。同时,有理由认为它们在血液中的药理活性不仅限于溶栓作用,还可能扩展到对心血管系统的全身作用。本研究的目的是研究不同浓度的固定化枯草菌素溶液在离体心脏灌注过程中的变时效应。材料和方法。本研究采用Langendorff的离体大鼠心脏模型。实验选用50只Wistar大鼠,将离体心脏分为5组:只灌注Krebs - Henseleit溶液(对照)和固定化枯草菌素4种浓度(170、340、510、1020 U/l)。结果和讨论。固定化枯草菌素具有负变时作用。作用的开始取决于溶液中的药物浓度:浓度越高,作用越早。灌注5 ~ 10分钟,任何剂量的固定化枯草菌素均可观察到负变时效应。其增加的持续时间可达10-20分钟,取决于溶液中的药物浓度。灌注20分钟后,获得的负变时效应保持在平台水平长达40分钟。结论。固定化枯草菌素对心率有独立的药理作用。
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引用次数: 0
Efficiency of using a short-acting β2-agonist for the relief of acute cold bronchospasm in asthma patients with cold airway hyperresponsiveness 短效β2-拮抗剂对哮喘冷气道高反应性患者急性冷性支气管痉挛的缓解作用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220511
A. G. Prihodko, J. Perelman
Excessive sensitivity of the respiratory tract to physical and chemical environmental triggers can vary for many reasons, reducing the therapy effectiveness in a patient with asthma. Aim of the study was to investigate the effectiveness of a short-acting bronchodilator in patients with asthma for the relief of acute cold bronchospasm after a test of isocapnic cold air hyperventilation (ICHV). Material and methods. In 281 (161 women; 120 men, p > 0.05) asthma patients with cold airway hyperresponsiveness (CAHR), the change in airway patency (FEV1) and the efficacy of short-acting β2-agonists (SABA) after a 3-minute isocapnic hyperventilation with cold (–20 ºС) air. Results. According to clinical data, patients had persistent asthma, mean age 35 (26; 44) years, 49 % of patients smoked, ACT 16 (12; 20) points, FEV1 90.0 ± 1.0 % predicted, FEV1/VC 71.4 ± 0.6 %, the increase in FEV1 after inhalation of SABA (∆FEV1β) was 11.1 (5.1; 20.5) %. The change in FEV1 for the ICHV varied within –16 (–22.0; –12.0) %. The use of SABA after the IHCV showed different efficacy for relief of an attack of cold bronchospasm. The median value of ∆FEV1β after ICHV was 21.1 (11.6; 33.3) %, with a range of –48.6 to 108.2 %. In the general group, there was a direct relationship between the level of asthma control in terms of ACT points and the baseline FEV1 (Rs = 0.17; p = 0.007), MEF25-75 (Rs = 0.18; p = 0.008), ∆FEV1β in response to SABA (Rs = –0.17; p = 0.0104), as well as the severity of the bronchial response to the ICHV (Rs = 0.15; p = 0.014). The latter, in turn, correlated with ∆FEV1β after ICHV (Rs = –0.28; p < 0.0001) after HCI. Conclusions. There is a differentiated airway response to SABA after acute cold bronchoprovocation. The results obtained can serve as an important tool for phenotyping of asthma patients with CAHR for the medication correction of сold bronchospasm.
由于多种原因,呼吸道对物理和化学环境诱因的过度敏感性可能会有所不同,从而降低哮喘患者的治疗效果。本研究的目的是探讨短效支气管扩张剂在哮喘患者进行异负荷冷空气过度通气(ICHV)试验后缓解急性冷支气管痉挛的有效性。材料和方法。281年(161名女性;120名男性,p > 0.05)哮喘患者冷气道高反应性(CAHR),气道通畅度(FEV1)的变化和短效β2激动剂(SABA)在低温(-20ºС)空气下进行3分钟等氧过度通气后的疗效。结果。根据临床资料,患者有持续性哮喘,平均年龄35岁(26岁;44岁,49%的患者吸烟,ACT 16 (12;20)分,FEV1 90.0±1.0%预测,FEV1/VC 71.4±0.6%,吸入SABA后FEV1(∆FEV1β)增加11.1 (5.1;20.5) %。icv的FEV1变化在-16 (-22.0;-12.0) %。在IHCV后使用SABA对缓解寒性支气管痉挛发作有不同的疗效。ICHV后的中位数为21.1 (11.6;33.3%) %,范围为- 48.6%至108.2%。在普通组,哮喘控制水平(ACT积分)与基线FEV1之间存在直接关系(Rs = 0.17;p = 0.007), MEF25-75 (Rs = 0.18;p = 0.008),∆FEV1β对SABA的反应(Rs = -0.17;p = 0.0104),以及支气管对ICHV反应的严重程度(Rs = 0.15;P = 0.014)。后者又与ICHV后的∆FEV1β相关(Rs = -0.28;p < 0.0001)。结论。急性冷支气管刺激后对SABA有不同的气道反应。本研究结果可作为CAHR哮喘患者表型分析的重要工具,为药物治疗支气管痉挛提供参考。
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引用次数: 0
Correlation between actual nutrition and lipid peroxidation and antioxidant defense parameters in aged 14–17 years adolescents living in rural area 农村14-17岁青少年实际营养与脂质过氧化和抗氧化防御参数的相关性
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220504
M. Darenskaya, L. Rychkova, T. Astakhova, A. Pogodina, O. N. Dolgikh, Y. Klimkina, L. Kolesnikova
The aim of the study was to reveal the relationship between the parameters of actual nutrition and the lipid peroxidation and antioxidant defense system in adolescents aged 14–17 in a rural area. Material and methods. 76 adolescents aged 14–17 of the Irkutsk region were examined by the cross-sectional study method. Actual nutrition was studied by the 24-hour nutrition reproduction method. The content of substrates with unsaturated double bonds (DB), diene conjugates (DC), ketodienes and conjugated trienes (KD and CT), thiobarbituric acid reacting species (TBARS), α-tocopherol, retinol, reduced (GSH) and oxidized glutathione (GSSG), total blood antioxidant activity (TAA), superoxide dismutase (SOD) activity in blood by spectrophotometry and fluorometry methods were analyzed. Results. The adolescents’ diet did not meet the principles of a balanced diet – there was reduced protein intake, an imbalance of unsaturated fatty acids, A, C, D, B vitamins deficiency. An excessive element in the diet was sodium. The content of substrates with DB, KD and CT and TBARS increased significantly in the studied group of adolescents, the concentration of DC decreased. Parameters of antioxidant defense both decreased (TAA, retinol content) and increased (α-tocopherol, GSH concentration). Correlation analysis showed relationships between DB and vitamin B1, B2 content; DC level and calories, carbohydrate and vitamin B1 content; concentration of KD and CT and fats, TAA and vitamin A and β-carotene level; level of α-tocopherol in blood and vitamin E in food; GSH and vitamin K; SOD activity and vitamin H content. Multiple negative correlations were between GSSG and fat, vitamins B1, B9, C, K food concentration were found.Conclusions. The calculated vitamin consumption indicators allow to reveal nutritional deviations in adolescents and to connect them with the real provision of the body with these metabolites.
本研究的目的是揭示农村地区14-17岁青少年的实际营养参数与脂质过氧化和抗氧化防御系统之间的关系。材料和方法。采用横断面研究方法对伊尔库茨克地区76名14-17岁的青少年进行了调查。采用24小时营养繁殖法研究实际营养状况。用分光光度法和荧光法分析了血液中不饱和双键(DB)、二烯共轭物(DC)、酮二烯和共轭三烯(KD和CT)、硫代巴比妥酸反应物(TBARS)、α-生育酚、视黄醇、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)、血液总抗氧化活性(TAA)、超氧化物歧化酶(SOD)活性的含量。结果。青少年的饮食不符合均衡饮食的原则——蛋白质摄入减少,不饱和脂肪酸失衡,a、C、D、B族维生素缺乏。饮食中的一个过量元素是钠。在研究的青少年组中,含有DB、KD、CT和TBARS的底物含量显著增加,DC浓度降低。抗氧化防御参数既降低(TAA,视黄醇含量)又增加(α-生育酚,GSH浓度)。相关分析显示DB与维生素B1、B2含量之间存在相关性;DC水平和热量、碳水化合物和维生素B1含量;KD和CT与脂肪的浓度、TAA和维生素A以及β-胡萝卜素水平;血液中的α-生育酚和食物中的维生素E水平;GSH和维生素K;SOD活性和维生素H含量。GSSG与脂肪、维生素B1、B9、C、K含量呈多重负相关。结论。计算出的维生素消耗指标可以揭示青少年的营养偏差,并将其与身体提供这些代谢产物的实际情况联系起来。
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引用次数: 0
Features of laboratory parameters in children with multisystem inflammatory syndrome associated with SARS-CoV-2 与SARS-CoV-2相关的儿童多系统炎症综合征的实验室参数特征
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220508
O. Obukhova, T. Ryabichenko, G. S. Karpovich, G. Skosyreva, I. V. Kuimova, M. Voevoda
Multisystem inflammatory syndrome (MIS-C) is a new childhood disease associated with coronavirus SARS-CoV-2 that manifests itself 3–4 weeks after infection. The development of MIS-C is possible, despite the asymptomatic course of coronavirus infection. The pathogenetic features of MIS-C remain unclear. The aim of the study was to investigate the state of peripheral blood parameters in children with multisystem inflammatory syndrome associated with SARS-CoV-2 upon admission to a hospital. Material and methods. We examined 52 children with MIS-C from 1 to 14 years old, hospitalized in Children`s Clinical Hospital No. 3 in Novosibirsk in October–December 2020. Testing for the isolation of SARS-CoV-2 RNA in scrapings from the nasopharynx and oropharynx was carried out using real time PCR (test systems of DNA-Technology, Russia). The presence of specific IgM and IgG antibodies to SARS-CoV-2 in blood serum was determined by ELISA using Vector-Best kits (Russia). Results and discussion. It was noted that SARS-CoV-2 virus RNA was found only in 12.8 % of cases, while specific IgG antibodies in blood serum were detected in 100 % of children. IgM to SARS-CoV-2 antigens were detected in the blood serum only in 53.85 % of children with MIS-C. It has been established that unexpressed leukocytosis was found both in children under the age of 7 and in children of 8–14 years old. However, the leukocytes content in children of the older age group was significantly lower than in children aged 1–7 years. At the same time, in both age groups, some children had extremely low values of the indicator. The causes of severe leukopenia against the background of excessive inflammation remain unclear. Age groups (1–7 and 8–14 years) do not differ statistically significantly in the relative content of lymphocytes and neutrophils. In the study of individual values of the relative content of lymphocytes within the age groups, it was noted that only some children had lymphopenia of varying severity. Conclusions. Against the background of minor leukocytosis in children with MIS-C, upon admission to the hospital, there is a tendency to develop both relative and absolute lymphopenia, regardless of age. The study noted an extremely pronounced variability of individual values of the evaluated peripheral blood parameters, regardless of age, which, with similar clinical symptoms, characterized as MIS-C, requires further study in dynamics, taking into account the initial values of the indicators.There is no pronounced relationship between the leukocytes content and specific IgM antibodies to SARS-CoV-2 antigens in the blood.
多系统炎症综合征(MIS-C)是一种与冠状病毒严重急性呼吸系统综合征冠状病毒2型相关的新型儿童疾病,在感染后3-4周出现。尽管有无症状的冠状病毒感染过程,但MIS-C的发展是可能的。MIS-C的发病特点尚不清楚。该研究的目的是调查与严重急性呼吸系统综合征冠状病毒2型相关的多系统炎症综合征儿童入院时的外周血参数状态。材料和方法。我们检查了2020年10月至12月在新西伯利亚第三儿童临床医院住院的52名1至14岁的MIS-C儿童。使用实时PCR(DNA技术的测试系统,俄罗斯)对鼻咽和口咽刮片中的严重急性呼吸系统综合征冠状病毒2型RNA的分离进行测试。使用Vector Best试剂盒(俄罗斯)通过ELISA测定血清中是否存在针对严重急性呼吸系统综合征冠状病毒2型的特异性IgM和IgG抗体。结果和讨论。值得注意的是,严重急性呼吸系统综合征冠状病毒2型病毒RNA仅在12.8%的病例中发现,而在100%的儿童血清中检测到特异性IgG抗体。仅在53.85%的MIS-C儿童血清中检测到针对严重急性呼吸系统综合征冠状病毒2型的IgM抗原。已经证实,在7岁以下的儿童和8-14岁的儿童中都发现了未表达的白细胞增多症。然而,年龄较大的儿童的白细胞含量明显低于1-7岁的儿童。与此同时,在这两个年龄组中,一些儿童的指标值极低。在过度炎症的背景下,严重白细胞减少的原因尚不清楚。年龄组(1-7岁和8-14岁)在淋巴细胞和中性粒细胞的相对含量方面没有统计学上的显著差异。在研究各年龄组淋巴细胞相对含量的个体值时,注意到只有一些儿童患有不同严重程度的淋巴细胞减少症。结论。在患有MIS-C的儿童出现轻微白细胞增多的背景下,入院后,无论年龄大小,都有发展为相对和绝对淋巴细胞减少症的趋势。该研究注意到,无论年龄大小,评估的外周血参数的个体值都存在极其显著的可变性,具有类似的临床症状,其特征为MIS-C,需要在考虑指标初始值的情况下进行进一步的动力学研究。白细胞含量与血液中针对严重急性呼吸系统综合征冠状病毒2型抗原的特异性IgM抗体之间没有明显关系。
{"title":"Features of laboratory parameters in children with multisystem inflammatory syndrome associated with SARS-CoV-2","authors":"O. Obukhova, T. Ryabichenko, G. S. Karpovich, G. Skosyreva, I. V. Kuimova, M. Voevoda","doi":"10.18699/ssmj20220508","DOIUrl":"https://doi.org/10.18699/ssmj20220508","url":null,"abstract":"Multisystem inflammatory syndrome (MIS-C) is a new childhood disease associated with coronavirus SARS-CoV-2 that manifests itself 3–4 weeks after infection. The development of MIS-C is possible, despite the asymptomatic course of coronavirus infection. The pathogenetic features of MIS-C remain unclear. The aim of the study was to investigate the state of peripheral blood parameters in children with multisystem inflammatory syndrome associated with SARS-CoV-2 upon admission to a hospital. Material and methods. We examined 52 children with MIS-C from 1 to 14 years old, hospitalized in Children`s Clinical Hospital No. 3 in Novosibirsk in October–December 2020. Testing for the isolation of SARS-CoV-2 RNA in scrapings from the nasopharynx and oropharynx was carried out using real time PCR (test systems of DNA-Technology, Russia). The presence of specific IgM and IgG antibodies to SARS-CoV-2 in blood serum was determined by ELISA using Vector-Best kits (Russia). Results and discussion. It was noted that SARS-CoV-2 virus RNA was found only in 12.8 % of cases, while specific IgG antibodies in blood serum were detected in 100 % of children. IgM to SARS-CoV-2 antigens were detected in the blood serum only in 53.85 % of children with MIS-C. It has been established that unexpressed leukocytosis was found both in children under the age of 7 and in children of 8–14 years old. However, the leukocytes content in children of the older age group was significantly lower than in children aged 1–7 years. At the same time, in both age groups, some children had extremely low values of the indicator. The causes of severe leukopenia against the background of excessive inflammation remain unclear. Age groups (1–7 and 8–14 years) do not differ statistically significantly in the relative content of lymphocytes and neutrophils. In the study of individual values of the relative content of lymphocytes within the age groups, it was noted that only some children had lymphopenia of varying severity. Conclusions. Against the background of minor leukocytosis in children with MIS-C, upon admission to the hospital, there is a tendency to develop both relative and absolute lymphopenia, regardless of age. The study noted an extremely pronounced variability of individual values of the evaluated peripheral blood parameters, regardless of age, which, with similar clinical symptoms, characterized as MIS-C, requires further study in dynamics, taking into account the initial values of the indicators.There is no pronounced relationship between the leukocytes content and specific IgM antibodies to SARS-CoV-2 antigens in the blood.","PeriodicalId":33781,"journal":{"name":"Sibirskii nauchnyi meditsinskii zhurnal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44756957","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 effect of silver-containing sorbent on red blood cells during hemosorption: an in vitro study 含银吸附剂在血液吸收过程中对红细胞影响的体外研究
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220503
L. N. Rachkovskaya, A. Smagin, V. Nimaev, A. Demura, E. Rachkovsky, E. Yastrebova, V. Maltsev, M. Korolev, A. Letyagin
The aim of the study was to investigate the influence of the original porous silver–containing sorbent on the morphofunctional parameters of red blood cells during in vitro hemoperfusion. Material and methods. Donor blood was perfused through glass columns filled with a sorbent based on porous aluminum oxide, polydimethylsiloxane and silver nanoclusters and a sorbent without silver. The effect of a silver-containing sorbent on the change in morphofunctional parameters of red blood cells after perfusion through sorbents was determined by scanning flow cytometry. Results and their discussion. Due to the uniformity of the distribution of silver (0.1 %) over the sorbent granules, the parameters of the porous structure – the specific surface area and pore volume – practically do not change compared to the sorbent without silver. Morphological parameters of original donor blood and after hemoperfusion are within the norm. The functional parameters are also normal, although the introduction of silver in to the sorbent slightly increases the number of active band 3 (B3) proteins on erythrocyte membranes, both in comparison with the donor red cell mass as a control and in comparison with the sorbent without silver. There is also an increase in the ultimate extensibility of the erythrocyte membrane compared to the original blood (2.2 times) and the sorbent without silver (1.4 times). Conclusions. A sorbent modified with silver and a sorbent without silver does not have a damaging toxic effect on the morphofunctional parameters of blood under perfusion conditions. The mechanisms affecting the indicators of the ultimate extensibility of the erythrocyte membrane after blood perfusion through a silver-containing sorbent require further research.
本研究旨在探讨原多孔含银吸附剂对体外血液灌流过程中红细胞形态功能参数的影响。材料和方法。供体血液通过玻璃柱灌注,玻璃柱中填充了一种基于多孔氧化铝、聚二甲基硅氧烷和银纳米团簇的吸附剂和一种不含银的吸附剂。采用扫描流式细胞术研究含银吸附剂对红细胞灌注后形态功能参数变化的影响。结果和讨论。由于银的均匀分布(0.1%)在吸附剂颗粒上,与没有银的吸附剂相比,多孔结构的参数-比表面积和孔体积-实际上没有变化。原供血及血液灌流后的形态学参数均在正常范围内。功能参数也正常,尽管引入银的吸附剂略微增加了红细胞膜上活性带3 (B3)蛋白的数量,无论是与供体红细胞群作为对照,还是与不含银的吸附剂相比。与原始血液(2.2倍)和无银吸附剂(1.4倍)相比,红细胞膜的最终延伸性也有所增加。结论。在灌注条件下,用银修饰的吸附剂和不含银的吸附剂对血液的形态功能参数没有破坏性的毒性作用。含银吸附剂血液灌注后影响红细胞膜最终伸长指标的机制有待进一步研究。
{"title":"The effect of silver-containing sorbent on red blood cells during hemosorption: an in vitro study","authors":"L. N. Rachkovskaya, A. Smagin, V. Nimaev, A. Demura, E. Rachkovsky, E. Yastrebova, V. Maltsev, M. Korolev, A. Letyagin","doi":"10.18699/ssmj20220503","DOIUrl":"https://doi.org/10.18699/ssmj20220503","url":null,"abstract":"The aim of the study was to investigate the influence of the original porous silver–containing sorbent on the morphofunctional parameters of red blood cells during in vitro hemoperfusion. Material and methods. Donor blood was perfused through glass columns filled with a sorbent based on porous aluminum oxide, polydimethylsiloxane and silver nanoclusters and a sorbent without silver. The effect of a silver-containing sorbent on the change in morphofunctional parameters of red blood cells after perfusion through sorbents was determined by scanning flow cytometry. Results and their discussion. Due to the uniformity of the distribution of silver (0.1 %) over the sorbent granules, the parameters of the porous structure – the specific surface area and pore volume – practically do not change compared to the sorbent without silver. Morphological parameters of original donor blood and after hemoperfusion are within the norm. The functional parameters are also normal, although the introduction of silver in to the sorbent slightly increases the number of active band 3 (B3) proteins on erythrocyte membranes, both in comparison with the donor red cell mass as a control and in comparison with the sorbent without silver. There is also an increase in the ultimate extensibility of the erythrocyte membrane compared to the original blood (2.2 times) and the sorbent without silver (1.4 times). Conclusions. A sorbent modified with silver and a sorbent without silver does not have a damaging toxic effect on the morphofunctional parameters of blood under perfusion conditions. The mechanisms affecting the indicators of the ultimate extensibility of the erythrocyte membrane after blood perfusion through a silver-containing sorbent require further research.","PeriodicalId":33781,"journal":{"name":"Sibirskii nauchnyi meditsinskii zhurnal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45306987","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
Evaluation of deadspace effects created by heat and moisture exchange filter during artificial lung ventilation in newborns 新生儿人工肺通气过程中热湿交换过滤器产生的死亡空间效应评价
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220509
A. N. Shmakov, K. V. Budarova, N. L. Elizar’eva, V. N. Kokhno
Heat and moisture exchange filters create additional dead space, comparable in volume to physiological, in premature newborns. It makes carbon dioxide remove difficultу. Reducing the dead space volume by increasing the flow in the ventilator circuit can lead to the hypocapnia. Aim of the study was to determine the safety and efficiency of gas flow boost in the ventilator circuit to hypercapnia compensation created by the additional dead space. Material and methods. The effect of the additional dead space created by a heat and moisture exchange filter on hemoglobin saturation and partial pressure of carbon dioxide at the end of expiration in premature newborns at flows of 5 and 6 l/min was studied. Results and discussion. It has been demonstrated that flows of 5–6 l/min satisfactorily compensate for the effect of additional deadspace without hypocapnia. Conclusions. It is possible to recommend the widespread use of heat and moisture exchange filters in newborn weighing at least 1.0 kg during long-term transportation.
热量和水分交换过滤器创造额外的死空间,在体积上可与生理,在早产的新生儿。它使二氧化碳难以去除。通过增加呼吸机回路中的流量来减少死腔容积可导致低碳酸血症。该研究的目的是确定呼吸机回路中气体流量增加的安全性和效率,以补偿由额外死区产生的高碳酸血症。材料和方法。研究了在流量为5和6 l/min的早产新生儿呼气结束时,热湿交换过滤器产生的额外死空间对血红蛋白饱和度和二氧化碳分压的影响。结果和讨论。已经证明,5-6升/分钟的流量令人满意地补偿了额外的死亡空间而没有低碳酸血症的影响。结论。对于体重在1.0 kg以上的新生儿,建议在长期运输过程中广泛使用换热换湿过滤器。
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引用次数: 0
Effect of benzoyl taurine dipotassium salt on coagulation, hemostasis and vascular activity in the microvasculature of the brain in violation of cerebral circulation 苯甲酰牛磺酸二钾盐对违反脑循环的脑微血管凝血、止血及血管活性的影响
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220507
V. E. Pustynnikov, S. S. Tsaruk, E. A. Fomichev, E. A. Miloserdova, D. Kurkin, D. A. Bakulin, T. M. Andriashvili, A. Sokolova, N. V. Atapina, A. K. Brel, Yu. N. Budaeva, I. Tyurenkov
Cerebral circulation disorders (CCD) are one of the most common causes of mortality and disability in the population. Improving the microcirculation of brain tissue is one of the main directions in the treatment and prevention of CCD.Aim of the study was to evaluate the effect of a new derivative of hydroxybenzoic (salicylic) acid on neurological deficit, hemostasis and functional state of arterial pial vessels in the study of prostacyclin-synthetic activity and evaluation of NOmediated endothelial dysfunction in rats under experimental CCD conditions. Material and methods. The experiment was carried out on 50 Wistar rats, which were simulated for CCD by occlusion of common carotid arteries. Within 7 days after the operation, the animals received treatment according to the group: saline, C-60 (N-(3-hydroxybenzoyl)taurine dipotassium salt) and acetylsalicylic acid. After treatment, the activity of the prostacyclin-synthetic system was assessed by the reaction of pial vessels to indomethacin, endothelial dysfunction was estimated by tests with acetylcholine and L-NAME. The parameters of plasma and platelet hemostasis were also studied, and behavioral tests (open field, adhesion test, rotarod, Morris water maze, passive avoidance task) were used to assess neurological deficits in animals. Results. When studying the level of neurological deficit in animals with brain ischemia after a course of administration of the test compound, it was noted that in the treated groups, compared with the control group, there was a significant increase in motor and exploratory activity, improvement in sensory-motor function and coordination of movements (p < 0.05). Also, in the group treated with the salicylic acid derivative, normalization of the parameters of platelet and plasma hemostasis, improvement of the functional state of the vascular endothelium was observed. According to the results of assessing the prostacyclin-synthesizing activity of the endothelium of the cerebral vessels, it follows that the test compound inhibits cyclooxygenase at a level comparable with effect of acetylsalicylic acid. Conclusions. A new derivative of salicylic acid, the dipotassium salt of N-(3-hydroxybenzoyl)taurine, reduces the severity of neurological deficit, improves hemostasis parameters and the functional state of cerebral vessels in rats with brain ischemia in the experiment.
脑循环障碍(CCD)是人群中最常见的死亡和残疾原因之一。改善脑组织微循环是CCD治疗和预防的主要方向之一,在实验CCD条件下研究前列环素合成活性和评估NO介导的大鼠内皮功能障碍中动脉血管的止血和功能状态。材料和方法。实验在50只Wistar大鼠上进行,通过阻断颈总动脉来模拟CCD。术后7天内,动物按组接受治疗:生理盐水、C-60(N-(3-羟基苯甲酰基)牛磺酸二钾盐)和乙酰水杨酸。治疗后,通过pial血管对吲哚美辛的反应来评估前列环素合成系统的活性,通过乙酰胆碱和L-NAME测试来评估内皮功能障碍。还研究了血浆和血小板止血的参数,并使用行为测试(开放视野、粘附测试、旋转棒、Morris水迷宫、被动回避任务)来评估动物的神经功能缺陷。结果。在研究试验化合物给药一个疗程后脑缺血动物的神经功能缺损水平时,注意到,与对照组相比,治疗组的运动和探索活动显著增加,感觉运动功能和运动协调性改善(p<0.05),水杨酸衍生物治疗组血小板及血浆止血参数正常化,血管内皮功能状态改善。根据评估脑血管内皮的前列环素合成活性的结果,可以得出试验化合物抑制环氧合酶的水平与乙酰水杨酸的作用相当。结论。水杨酸的一种新衍生物,N-(3-羟基苯甲酰基)牛磺酸二钾盐,在实验中降低了脑缺血大鼠神经功能缺损的严重程度,改善了止血参数和脑血管的功能状态。
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引用次数: 0
Toxicity of new monophenolic synthetic activator of Keap1/Nrf2/ARE redox-sensitive signaling system in vitro and in vivo 新型单酚类合成激活剂Keap1/Nrf2/ARE氧化还原敏感信号系统的体外和体内毒性研究
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220502
M. Khrapova, S. E. Khrapov, A. Chechushkov, P. Kozhin, L. Romakh, A. E. Serykh, S. Kholshin, N. Kandalintseva, E. Menshchikova
One of the promising areas of modern pharmacology is the development of «indirect antioxidants» capable of activating redox-sensitive signaling systems, primarily the Keap1/Nrf2/ARE system. Among its chemical inductors is the hydrophilic monosubstituted monophenol (3’-tert-butyl-4’-hydroxyphenyl)sodium propylthiosulfonate (TS-13) in development. The aim of the study was to investigate TS-13 antiproliferative activity against tumor cell line BT-474 in vitro and acute oral toxicity in mice in vivo. Material and methods. The relationship between TS-13 concentration and proliferative activity of human breast ductal carcinoma cell line BT-474 was determined using the MTT test, the IC50 was calculated and compared to the previously obtained for MCF-7 line; results were correlated with the functional properties of cells based on gene expression (in silico GSEA). In vivo acute toxicity was studied in 50 female C57Bl/6J mice, who received a TS-13 solution in distilled water at various doses by intragastric gavage. LD50 obtained experimentally and predicted in silico using the GUSAR web service were compared. Results and discussion. TS-13 inhibited the proliferation of BT-474 cells in a concentration-dependent manner (exponential approximation, IC50 = 59.5 μM) and was 2.2 times more toxic than for MCF-7 cells. This may be due to functional differences between the BT-474 and MCF-7 lines, as evidenced by the GSEA results. The LD50 value established in the in vivo experiment was 936 mg/kg body weight, the obtained value satisfactorily corresponds to the predicted in silico (561 mg/kg), although in reality the compound turned out to be somewhat less toxic than could be expected based on its structure. Conclusions. A study of the acute toxicity of the new water-soluble monophenol TC-13 allows the classification of it as slightly toxic (toxicity rating level 4) according to the Hodge – Sterner scale) or as moderately hazardous (hazard class 3) according to GOST 12.1.007-76.
现代药理学最有前途的领域之一是开发能够激活氧化还原敏感信号系统的“间接抗氧化剂”,主要是Keap1/Nrf2/ARE系统。其化学诱导剂之一是正在开发的亲水单取代单酚(3′-叔丁基-4′-羟基苯基)丙基硫磺酸钠(TS-13)。研究了TS-13对肿瘤细胞系BT-474的体外抗增殖活性和小鼠急性口服毒性。材料和方法。采用MTT法测定TS-13浓度与人乳腺导管癌细胞BT-474增殖活性的关系,计算其IC50并与MCF-7细胞株进行比较;结果与基于基因表达(在硅GSEA)的细胞功能特性相关。用不同剂量的TS-13蒸馏水灌胃50只雌性C57Bl/6J小鼠,研究其体内急性毒性。比较了实验得到的LD50和利用GUSAR web service在计算机上预测的LD50。结果和讨论。TS-13对BT-474细胞的抑制呈浓度依赖性(指数近似,IC50 = 59.5 μM),其毒性是MCF-7细胞的2.2倍。正如GSEA结果所证明的那样,这可能是由于BT-474和MCF-7系之间的功能差异。体内实验中建立的LD50值为936 mg/kg体重,所得值与计算机预测值(561 mg/kg)相吻合,尽管实际上该化合物的毒性比根据其结构可以预期的要小一些。结论。一项对新型水溶性单酚TC-13急性毒性的研究允许将其分类为轻度毒性(毒性等级4)(根据Hodge - Sterner等级)或中度危险(危害等级3)(根据GOST 12.1.007-76)。
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引用次数: 0
Influence of physical loading on behavioral reactions of rats in cerebral hypoperfusion 体力负荷对脑灌注不足大鼠行为反应的影响
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220506
V. V. Сhrishtop, T. Rumyantseva, V. Nikonorova, I. Fateev
A number of clinical studies demonstrate that individual characteristics such as stress tolerance and cognitive ability can be considered not only as diagnostic variables but also as risk factors for severe cerebral hypoperfusion. The aim of the study was to identify the typological features of the effect of physical activity on the behavioral reactions of rats during cerebral hypoperfusion. Material and methods. Cerebral hypoperfusion was modeled by bilateral carotid artery ligation. The study involved 280 rats, divided into equal subgroups, according to sex, stress tolerance and learning capacity. Of these, 112 animals were subjected to daily short-term swimming as a rehabilitation model. Before the simulation, and at 6, 8, 14, 21, 28, 35, 60 and 90 days postoperatively, the animals were tested using a Morris water maze and an “open field” test. Results and discussion. The dynamics of stress resistance and learning ability are related to the periodicity of inflammatory, necrotic, circulatory and reparative remodeling in the model used. After 2-3 months of study, cerebral hypoperfusion causes stabilization of indices characterizing stress resistance and cognitive functions below control values. A decrease in stress resistance begins earlier from day 6 of the study, while the index characterizing cognitive functions first decreases significantly after 3 weeks of study. Factors reducing the damaging effects of cerebral hypoperfusion were female gender, high baseline stress tolerance and learning ability. When assessing learning ability under physical load, animals with high baseline cognitive development showed earlier recovery dynamics during urgent adaptation and a significant increase during long-term adaptation.
大量临床研究表明,应激耐受性和认知能力等个体特征不仅可以作为诊断变量,而且可以作为严重脑灌注不足的危险因素。本研究旨在探讨运动对脑灌注不足大鼠行为反应影响的类型学特征。材料和方法。通过双侧颈动脉结扎建立脑灌注不足模型。这项研究涉及280只大鼠,根据性别、压力承受能力和学习能力被分成相等的小组。其中,112只动物每天进行短期游泳作为康复模型。在模拟前和术后6、8、14、21、28、35、60和90天,采用Morris水迷宫和“开放场地”测试对动物进行测试。结果和讨论。应激抵抗和学习能力的动态变化与模型中炎症、坏死、循环和修复性重构的周期性有关。研究2-3个月后,脑灌注不足导致表征应激抵抗和认知功能的指标稳定在控制值以下。抗压能力的下降从研究的第6天就开始了,而表征认知功能的指数在研究的第3周后开始显著下降。降低脑灌注不足损伤效应的因素有女性、高基线应激耐受性和学习能力。在评估体力负荷下的学习能力时,高基线认知发展的动物在紧急适应中表现出更早的恢复动态,在长期适应中表现出显著的恢复动态。
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引用次数: 0
Preparing the upper gastrointestinal tract for an esophagogastroduodenoscopy to identify the source of acute bleeding 准备上消化道进行食管胃十二指肠镜检查以确定急性出血的来源
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-27 DOI: 10.18699/ssmj20220512
A. Ilkanich, V. Darvin, M. G. Ryzhikov, A. V. Oganian
Esophagogastroduodenoscopy (EGDS) is the main way to diagnose bleeding from the upper gastrointestinal tract. Diagnostic accuracy of the study depends on the preparation. Aim of the study was to evaluate the preparation of the upper parts of the digestive tract in case of esophagogastroduodenal bleeding. Material and methods. The retrospective analysis of 2570 case histories was carried out. Gastric lavage through nasogastric tube was carried out in the main group (1299 patients). Preparation for the primary EGDS was not carried out in the control group (1271 patients). A comparison of the number of EGDS performed and the detection of the bleeding source in the control and the main groups as well as the period of investigation up to the detection of the bleeding source were performed. Results. EGDS without preparation of the upper gastrointestinal tract in case of acute bleeding and determination of the diagnosis is possible in 85,6 % of patients. Preparation of the upper gastrointestinal tract for EGDS prolongs the study period by 30–60 minutes, but allows establishing the diagnosis in 93.7 % of cases that is by 8.1 % more than without preparation.
食管胃十二指肠镜(EGDS)是诊断上消化道出血的主要方法。研究的诊断准确性取决于准备工作。本研究的目的是评估食管胃十二指肠出血时消化道上部的准备情况。材料和方法。对2570例病史进行了回顾性分析。主要组(1299例)采用鼻胃导管洗胃。对照组(1271名患者)未进行原发性EGDS的准备工作。对对照组和主要组中进行的EGDS的数量和出血源的检测进行了比较,并对检测出血源之前的研究周期进行了比较。结果。在急性出血的情况下,在不准备上消化道的情况下进行EGDS,85.6%的患者可以确定诊断。上消化道EGDS的准备将研究时间延长了30-60分钟,但93.7%的病例可以确定诊断,比没有准备的病例多8.1%。
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引用次数: 0
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Sibirskii nauchnyi meditsinskii zhurnal
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