Pub Date : 2024-04-05DOI: 10.33647/2074-5982-20-1-43-51
A. A. Bondarenko, T. L. Gorchakova, A. Y. Bespalov, L. I. Prokopenko, P. D. Shabanov
This work presents the results of primary pharmacological screening of anticholinergic drugs and comparative evaluation of their specific activity in equitoxic concentrations using Daphnia magna Straus hydrobionts as a biological test object. We determine the protective index and the minimum effective concentration in terms of preventing atypical motor hyperactivity of pharmacological substances when poisoning with a reversible acetylcholinesterase inhibitor. On the basis of the results obtained, the list of promising candidates for further research in warm-blooded animals is extended by all of the anticholinergic drugs previously selected in experiments on mammals.
本研究以大型蚤（Daphnia magna Straus hydrobionts）为生物试验对象，对抗胆碱能药物进行了初步药理筛选，并对其在等毒浓度下的特异性活性进行了比较评估。我们确定了可逆性乙酰胆碱酯酶抑制剂中毒时防止药理物质非典型运动亢进的保护指数和最低有效浓度。根据所获得的结果，之前在哺乳动物实验中选定的所有抗胆碱能药物都被列入了有希望在温血动物中开展进一步研究的候选药物名单。
{"title":"Pharmacological Screening of Cholinergic Drugs Using Daphnia magna Straus Hydrobionts as a Biological Test Object","authors":"A. A. Bondarenko, T. L. Gorchakova, A. Y. Bespalov, L. I. Prokopenko, P. D. Shabanov","doi":"10.33647/2074-5982-20-1-43-51","DOIUrl":"https://doi.org/10.33647/2074-5982-20-1-43-51","url":null,"abstract":"This work presents the results of primary pharmacological screening of anticholinergic drugs and comparative evaluation of their specific activity in equitoxic concentrations using Daphnia magna Straus hydrobionts as a biological test object. We determine the protective index and the minimum effective concentration in terms of preventing atypical motor hyperactivity of pharmacological substances when poisoning with a reversible acetylcholinesterase inhibitor. On the basis of the results obtained, the list of promising candidates for further research in warm-blooded animals is extended by all of the anticholinergic drugs previously selected in experiments on mammals.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"37 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737490","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}
Pub Date : 2024-04-05DOI: 10.33647/2074-5982-20-1-33-42
A. V. Sharabanov, E. G. Batotsyrenova, V. Kashuro, M. T. Gasanov, N. V. Kuzmina, K. Shchepetkova
This study examined the effect of peptide extracts from the epiphysis-pituitary gland of Reindeer (Rangifer tarandus) and a delta sleep-inducing peptide, simulating a modified release of drugs, on the spontaneous motor activity of male rats under the conditions of light desynchronosis. The study revealed changes in spontaneous motor activity under the influence of extracts of a peptide nature and a delta sleep-inducing peptide under the following polar light regimes. Under the conditions of constant lighting and constant darkness, an increase and a decrease in activity was observed, respectively. Under normal lighting, peptide extracts showed increased efficacy. This method of pharmacological adjustment of the body’s circadian oscillators using modified-release peptides can be used to develop a scheme for correcting light desynchronosis.
{"title":"Modified Effect of Peptide Preparations on Spontaneous Motor Activity in Male Rats under the Conditions of Light Desynchronosis","authors":"A. V. Sharabanov, E. G. Batotsyrenova, V. Kashuro, M. T. Gasanov, N. V. Kuzmina, K. Shchepetkova","doi":"10.33647/2074-5982-20-1-33-42","DOIUrl":"https://doi.org/10.33647/2074-5982-20-1-33-42","url":null,"abstract":"This study examined the effect of peptide extracts from the epiphysis-pituitary gland of Reindeer (Rangifer tarandus) and a delta sleep-inducing peptide, simulating a modified release of drugs, on the spontaneous motor activity of male rats under the conditions of light desynchronosis. The study revealed changes in spontaneous motor activity under the influence of extracts of a peptide nature and a delta sleep-inducing peptide under the following polar light regimes. Under the conditions of constant lighting and constant darkness, an increase and a decrease in activity was observed, respectively. Under normal lighting, peptide extracts showed increased efficacy. This method of pharmacological adjustment of the body’s circadian oscillators using modified-release peptides can be used to develop a scheme for correcting light desynchronosis.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737616","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}
Pub Date : 2024-04-05DOI: 10.33647/2074-5982-20-1-8-20
N. Karkischenko, V. N. Lazarev, V. A. Manuvera, P. Bobrovsky, N. V. Petrova, E. Koloskova, E. S. Glotova
Genetic differences in different populations influence the mechanism and efficacy of drugs. Biomodels that take into account the peculiarities of genetic polymorphism in different individuals allow to more fully investigate the molecular-genetic mechanisms of action of pharmacological agents, including immunobiological ones. Recombinant DNA encoding a hybrid MHC class I protein containing human ß2-microglobulin fused with antigen-presenting domains (α1 and α2 domains) of the HLA-C*07:02:01:01 molecule and α3 domain of the mouse H2-complex was created. The purified linearized DNA fragment containing the target construct flanked by regulatory fragments ensuring its stable transcription was used to obtain a new line of humanized transgenic mice. The principles of designing humanized transgenic mice by encoding a chimeric MHC class I protein containing antigen-presenting domains HLA-C*07:02:01:01 are similar to those for obtaining mice of the HLA-А*02:01:01 and HLA-B*18:01:01:02 humanized transgenic lines. These transgenic lines of laboratory mice are independent biomodels, and also be used as baselines for obtaining corresponding transgenic and knockout lines.
不同人群的基因差异会影响药物的作用机制和疗效。考虑到不同个体基因多态性特点的生物模型可以更全面地研究药剂（包括免疫生物学药剂）的分子遗传作用机制。重组 DNA 编码一种混合 MHC I 类蛋白，该蛋白含有融合了 HLA-C*07:02:01:01 分子的抗原递呈结构域（α1 和 α2 结构域）和小鼠 H2 复合物的 α3 结构域的人类 ß2 微小球蛋白。纯化的线性化 DNA 片段含有目标构建体，其两侧有确保其稳定转录的调控片段，用于获得新的人源化转基因小鼠品系。通过编码含有抗原递呈结构域 HLA-C*07:02:01:01 的嵌合 MHC I 类蛋白来设计人源化转基因小鼠的原理与获得 HLA-А*02:01:01 和 HLA-B*18:01:01:02 人源化转基因品系小鼠的原理相似。这些实验室小鼠转基因品系是独立的生物模型，也可用作获得相应转基因品系和基因敲除品系的基线。
{"title":"Principles of Creation of a Genetic Engineering Construction for Obtaining Humanized Transgenic Mice with HLA-C*07:02:01:01, as a Promote of Innovative Transgenic and Knockout Biomodels","authors":"N. Karkischenko, V. N. Lazarev, V. A. Manuvera, P. Bobrovsky, N. V. Petrova, E. Koloskova, E. S. Glotova","doi":"10.33647/2074-5982-20-1-8-20","DOIUrl":"https://doi.org/10.33647/2074-5982-20-1-8-20","url":null,"abstract":"Genetic differences in different populations influence the mechanism and efficacy of drugs. Biomodels that take into account the peculiarities of genetic polymorphism in different individuals allow to more fully investigate the molecular-genetic mechanisms of action of pharmacological agents, including immunobiological ones. Recombinant DNA encoding a hybrid MHC class I protein containing human ß2-microglobulin fused with antigen-presenting domains (α1 and α2 domains) of the HLA-C*07:02:01:01 molecule and α3 domain of the mouse H2-complex was created. The purified linearized DNA fragment containing the target construct flanked by regulatory fragments ensuring its stable transcription was used to obtain a new line of humanized transgenic mice. The principles of designing humanized transgenic mice by encoding a chimeric MHC class I protein containing antigen-presenting domains HLA-C*07:02:01:01 are similar to those for obtaining mice of the HLA-А*02:01:01 and HLA-B*18:01:01:02 humanized transgenic lines. These transgenic lines of laboratory mice are independent biomodels, and also be used as baselines for obtaining corresponding transgenic and knockout lines.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"220 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740144","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}
Pub Date : 2024-04-05DOI: 10.33647/2074-5982-20-1-21-32
N. S. Ogneva, M. S. Nesterov, D. Khvostov, Y. Fokin, V. Karkischenko
This paper presents a study into the pharmacokinetics of a new inhaled anti-inflammatory hexapeptide, registered as “Leutragin”. This drug is used as a new treatment approach for viral pneumonias, whose severe course is directly related to the cytokine inflammatory cascade referred to as a cytokine storm. The study involved investigation of lung tissue and serum after a single inhalation administration of Leutragin to mice of the C57BL/6Y line at a dose of 150 mg/kg. The time required to reach the maximum concentration (Tmax) of Leutragin in serum and lung was 30 min and 10 min, respectively. The maximum concentration (Cmax) in lung was 358.5 ng/g, which exceeded the concentration maximum for blood (53.84 ng/g) by over six times. It was found that, after inhalation administration, Leutragin is rather rapidly eliminated from the body with the half-life of the drug (t1/2el) from blood serum and lungs ranging from 25.8 to 38.9 min.
{"title":"Comparative Pharmacokinetics Study of the Leutragin Peptide Drug in Blood Serum and Lung Tissue in C57BL/6Y Mice after Single Inhalation Administration","authors":"N. S. Ogneva, M. S. Nesterov, D. Khvostov, Y. Fokin, V. Karkischenko","doi":"10.33647/2074-5982-20-1-21-32","DOIUrl":"https://doi.org/10.33647/2074-5982-20-1-21-32","url":null,"abstract":"This paper presents a study into the pharmacokinetics of a new inhaled anti-inflammatory hexapeptide, registered as “Leutragin”. This drug is used as a new treatment approach for viral pneumonias, whose severe course is directly related to the cytokine inflammatory cascade referred to as a cytokine storm. The study involved investigation of lung tissue and serum after a single inhalation administration of Leutragin to mice of the C57BL/6Y line at a dose of 150 mg/kg. The time required to reach the maximum concentration (Tmax) of Leutragin in serum and lung was 30 min and 10 min, respectively. The maximum concentration (Cmax) in lung was 358.5 ng/g, which exceeded the concentration maximum for blood (53.84 ng/g) by over six times. It was found that, after inhalation administration, Leutragin is rather rapidly eliminated from the body with the half-life of the drug (t1/2el) from blood serum and lungs ranging from 25.8 to 38.9 min.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"24 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140736598","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}
Pub Date : 2023-12-06DOI: 10.33647/2074-5982-19-4-35-46
M.Ю. Раваева, И.В. Чeрeтaeв, Е.Н. Чуян, П.А. Галенко-Ярошевский, M. Ravaeva, I. Cheretaev, Elena N. Chuyan, Pavel A. Galenko-Yaroshevskii
We set out to examine the indicators of microhemodynamics and tissue oxidative metabolism in rats after their tenfold exposure to extremely high-frequency low-intensity electromagnetic radiation (EHF EMR). The aim was to elucidate the specifics of skin microcirculation and tissue oxidative metabolism following exposure to tenfold electromagnetic radiation of extremely high frequency. The experiment was carried out on 40 mature male Wistar rats weighing 200–220 g, which were kept in standard vivarium conditions under natural light regimen. The animals were divided into two groups with 20 rats each. The animals in the first group were biological controls and were exposed to false EHF EMR (placebo); the animals in the second group were exposed to mm-exposure in the morning, 10 sessions daily. On the 10th day of EMR exposure, the indicators of skin tissue fluorescence on the tail base were recorded. Tenfold exposure to low-intensity EHF EMR was shown to increase the concentration and intensity of NADH fluorescence, as well as the FAD and redox ratio. This indicates an increased cellular demand for ATP and the predominance of oxidative phosphorylation over other processes, thus demonstrating the activation of the respiratory chain. At the same time, an increase in endothelium-dependent vasodilation, a decrease in peripheral resistance, an increase in blood flow to the nutritive microvascular bed, and an improvement in venular outflow were observed in the microcirculatory bed. The conclusion is made that the modulating effect of EHF EMR is manifested in the rearrangements of correlations. Thus, the coefficient of variation comes to the fore – the final calculated indicator of microcirculation, which has strong negative associations with all indicators of tissue metabolism (FAD, NADH, RR). In addition, the amplitudes of endothelial rhythms associated with periodic releasing of nitric oxide by the endothelium show a strong negative association with FAD.
{"title":"Modulating Effect of Extremely High-Frequency Low-Intensity Electromagnetic Radiation on Tissue Oxidative Metabolism and Skin Microhemodynamics","authors":"M.Ю. Раваева, И.В. Чeрeтaeв, Е.Н. Чуян, П.А. Галенко-Ярошевский, M. Ravaeva, I. Cheretaev, Elena N. Chuyan, Pavel A. Galenko-Yaroshevskii","doi":"10.33647/2074-5982-19-4-35-46","DOIUrl":"https://doi.org/10.33647/2074-5982-19-4-35-46","url":null,"abstract":"We set out to examine the indicators of microhemodynamics and tissue oxidative metabolism in rats after their tenfold exposure to extremely high-frequency low-intensity electromagnetic radiation (EHF EMR). The aim was to elucidate the specifics of skin microcirculation and tissue oxidative metabolism following exposure to tenfold electromagnetic radiation of extremely high frequency. The experiment was carried out on 40 mature male Wistar rats weighing 200–220 g, which were kept in standard vivarium conditions under natural light regimen. The animals were divided into two groups with 20 rats each. The animals in the first group were biological controls and were exposed to false EHF EMR (placebo); the animals in the second group were exposed to mm-exposure in the morning, 10 sessions daily. On the 10th day of EMR exposure, the indicators of skin tissue fluorescence on the tail base were recorded. Tenfold exposure to low-intensity EHF EMR was shown to increase the concentration and intensity of NADH fluorescence, as well as the FAD and redox ratio. This indicates an increased cellular demand for ATP and the predominance of oxidative phosphorylation over other processes, thus demonstrating the activation of the respiratory chain. At the same time, an increase in endothelium-dependent vasodilation, a decrease in peripheral resistance, an increase in blood flow to the nutritive microvascular bed, and an improvement in venular outflow were observed in the microcirculatory bed. The conclusion is made that the modulating effect of EHF EMR is manifested in the rearrangements of correlations. Thus, the coefficient of variation comes to the fore – the final calculated indicator of microcirculation, which has strong negative associations with all indicators of tissue metabolism (FAD, NADH, RR). In addition, the amplitudes of endothelial rhythms associated with periodic releasing of nitric oxide by the endothelium show a strong negative association with FAD.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"63 33","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594810","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}
Pub Date : 2023-12-06DOI: 10.33647/2074-5982-19-4-47-55
Ю.Е. Ананьева, О.А. Захарова, В.Д. Федотов, О.М. Лабынцева, Yuliya E. Ananieva, Olga A. Zakharova, V. Fedotov, O. M. Labyntseva, Ananieva Yu., Fedotov Zakharova O.A.
In this work, we investigate the preconditioning action of various modes of pulsed magnetic field (PMF) on the blood biochemical parameters of rats exposed to adrenal toxemia. PMF was shown to trigger adaptive response; however, its rate can differ depending on the selected PMF mode. The possibility of using low-frequency PMF as a protector of stress-induced conditions caused by adrenal toxemia is demonstrated.
{"title":"Use of Low-Frequency Pulsed Magnetic Field to Modify the Stress-Induced Animal Health Caused by Epinephrine Hydrochloride","authors":"Ю.Е. Ананьева, О.А. Захарова, В.Д. Федотов, О.М. Лабынцева, Yuliya E. Ananieva, Olga A. Zakharova, V. Fedotov, O. M. Labyntseva, Ananieva Yu., Fedotov Zakharova O.A.","doi":"10.33647/2074-5982-19-4-47-55","DOIUrl":"https://doi.org/10.33647/2074-5982-19-4-47-55","url":null,"abstract":"In this work, we investigate the preconditioning action of various modes of pulsed magnetic field (PMF) on the blood biochemical parameters of rats exposed to adrenal toxemia. PMF was shown to trigger adaptive response; however, its rate can differ depending on the selected PMF mode. The possibility of using low-frequency PMF as a protector of stress-induced conditions caused by adrenal toxemia is demonstrated.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"89 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138595958","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}
Pub Date : 2023-12-06DOI: 10.33647/2074-5982-19-4-70-80
O. Rybalkina, O. V. Neupokoeva, O. Voronova, T. Razina, G. I. Kalinkina, V. Y. Andreeva, E. A. Kiseleva, A. A. Churin, E. Zueva, V. V. Zhdanov
Anthocyanins are flavonoid compounds belonging to the group of polyphenols. A. melanocarpa (Michx.) Elliott chokeberry is known to be rich in these bioactive substances. The previously conducted chemical analysis showed that an anthocyanin-containing complex obtained from A. melanocarpa fruits comprise anthocyanins, flavonoids, phenolic acids, and catechins, with anthocyanins being the dominant components. A large amount of data indicates that Aronia fruits exhibit a wide spectrum of pharmacological activity. In this work, we assess the safety of an anthocyanin-containing complex obtained from A. melanocarpa fruits by its genotoxic study followed by an analysis of its effect on mutagenesis. To this end, a model of doxorubicin-induced genotoxicity in bone marrow cells of C57Bl/6 mice was used. The plant complex under study at a dose of 225 mg/kg had no effect the cytogenetic parameters of animal bone marrow cells after a single or double administration. The use of the anthocyanin-containing complex led to a decrease in DNA damage caused by the administration of doxorubicin, 24 and 48 hours after the introduction of a cytostatic agent. Hence, the data obtained can serve as the basis for the creation of a drug corrector for cycplasms.
{"title":"Genoprotective Activity of Aronia melanocarpa Anthocyanin-Containing Complex","authors":"O. Rybalkina, O. V. Neupokoeva, O. Voronova, T. Razina, G. I. Kalinkina, V. Y. Andreeva, E. A. Kiseleva, A. A. Churin, E. Zueva, V. V. Zhdanov","doi":"10.33647/2074-5982-19-4-70-80","DOIUrl":"https://doi.org/10.33647/2074-5982-19-4-70-80","url":null,"abstract":"Anthocyanins are flavonoid compounds belonging to the group of polyphenols. A. melanocarpa (Michx.) Elliott chokeberry is known to be rich in these bioactive substances. The previously conducted chemical analysis showed that an anthocyanin-containing complex obtained from A. melanocarpa fruits comprise anthocyanins, flavonoids, phenolic acids, and catechins, with anthocyanins being the dominant components. A large amount of data indicates that Aronia fruits exhibit a wide spectrum of pharmacological activity. In this work, we assess the safety of an anthocyanin-containing complex obtained from A. melanocarpa fruits by its genotoxic study followed by an analysis of its effect on mutagenesis. To this end, a model of doxorubicin-induced genotoxicity in bone marrow cells of C57Bl/6 mice was used. The plant complex under study at a dose of 225 mg/kg had no effect the cytogenetic parameters of animal bone marrow cells after a single or double administration. The use of the anthocyanin-containing complex led to a decrease in DNA damage caused by the administration of doxorubicin, 24 and 48 hours after the introduction of a cytostatic agent. Hence, the data obtained can serve as the basis for the creation of a drug corrector for cycplasms.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138597237","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}
Pub Date : 2023-12-06DOI: 10.33647/2074-5982-19-4-81-93
И.А. Помыткин, В. В. Писарев, М.Е. Меркулов, Л.В. Лукиных, М.В. Моржухина, Н.Н. Каркищенко, I. A. Pomytkin, V. Pisarev, M. E. Merkulov, L. V. Lukinykh, Marina V. Morzhukhinа, N. Karkischenko
Direkord is an original drug containing the active substance of dicholine succinate, which improves the sensitivity of insulin receptors in neurons to insulin. The aim of this work was to evaluate the efficacy and safety of the drug in ischemic stroke patients in the early recovery period. In total, 160 patients after the first ischemic stroke in the carotid system, confirmed by computed or magnetic resonance imaging, with a stroke duration from 3 weeks to 2 months, mean age 63.2±8.4 years, were randomized into two treatment groups. The first group (n=80) received Direkord intramuscularly at a dose of 600 mg/day for two weeks; the second group (n=80) received a placebo. Treatment response was defined as an improvement in neurological status, functional status, and cognitive function of the patients: at least a two-fold decrease in the total NIHSS score, the total Barthel score ≥ 95, and the total MoCA score ≥ 26. The analysis of the primary endpoint of the study using exact Fisher’s test showed that Direkord was statistically significantly superior to the placebo (p=0.017) in the number of patients who responded to the therapy — 23.7 and 8.7% of patients in groups, respectively. The secondary end point analysis revealed a statistically significant superiority of Direkord over the placebo in reducing neurological deficits on the NIHSS scale (p=0.004), on the Rankin scale (p=0.0357), and on the CGI-I (p<0.001) and PGI-I (p<0.001) global clinical impression scales. Direkord has a good safety profile; thus, no statistically significant differences were found with the placebo in any of the safety parameters, including the number of adverse events, vital signs, laboratory parameters, and ECG. Overall, Direkord is statistically significantly more effective than placebo in recovering function and daily activities after ischemic stroke.
{"title":"Results of Phase III Clinical Trial: a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Direkord in Ischemic Stroke Patients in Early Recovery Period","authors":"И.А. Помыткин, В. В. Писарев, М.Е. Меркулов, Л.В. Лукиных, М.В. Моржухина, Н.Н. Каркищенко, I. A. Pomytkin, V. Pisarev, M. E. Merkulov, L. V. Lukinykh, Marina V. Morzhukhinа, N. Karkischenko","doi":"10.33647/2074-5982-19-4-81-93","DOIUrl":"https://doi.org/10.33647/2074-5982-19-4-81-93","url":null,"abstract":"Direkord is an original drug containing the active substance of dicholine succinate, which improves the sensitivity of insulin receptors in neurons to insulin. The aim of this work was to evaluate the efficacy and safety of the drug in ischemic stroke patients in the early recovery period. In total, 160 patients after the first ischemic stroke in the carotid system, confirmed by computed or magnetic resonance imaging, with a stroke duration from 3 weeks to 2 months, mean age 63.2±8.4 years, were randomized into two treatment groups. The first group (n=80) received Direkord intramuscularly at a dose of 600 mg/day for two weeks; the second group (n=80) received a placebo. Treatment response was defined as an improvement in neurological status, functional status, and cognitive function of the patients: at least a two-fold decrease in the total NIHSS score, the total Barthel score ≥ 95, and the total MoCA score ≥ 26. The analysis of the primary endpoint of the study using exact Fisher’s test showed that Direkord was statistically significantly superior to the placebo (p=0.017) in the number of patients who responded to the therapy — 23.7 and 8.7% of patients in groups, respectively. The secondary end point analysis revealed a statistically significant superiority of Direkord over the placebo in reducing neurological deficits on the NIHSS scale (p=0.004), on the Rankin scale (p=0.0357), and on the CGI-I (p<0.001) and PGI-I (p<0.001) global clinical impression scales. Direkord has a good safety profile; thus, no statistically significant differences were found with the placebo in any of the safety parameters, including the number of adverse events, vital signs, laboratory parameters, and ECG. Overall, Direkord is statistically significantly more effective than placebo in recovering function and daily activities after ischemic stroke.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"43 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138597551","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}
Pub Date : 2023-12-05DOI: 10.33647/2074-5982-19-4-25-34
Т. В. Кириченко, Л.А. Бочкарева, Л. В. Недосугова, Ю.В. Маркина, И. А. Кузина, Н. А. Петунина, Т.В. Толстик, А.И. Богатырева, В.А. Антонов, А.М. Маркин, Tatiana V. Kirichenko, L. A. Bochkareva, L. Nedosugova, Y. Markina, I. A. Kuzina, N. Petunina, T. Tolstik, A. Bogatyreva, Valeriy A. Antonov, Alexander M Markin
Сhronic inflammation is considered as a key factor in the development of type 2 diabetes mellitus. Impaired tolerance of the inflammatory response of monocytes is regarded as an important mechanism in the pathogenesis of chronic inflammation. In this work, we study the inflammatory activation and tolerance of the immune response of monocytes in diabetes. In total, 40 patients with newly diagnosed diabetes and 40 control group participants were included in the study. The level of basal, LPS-stimulated and re-stimulated secretion of the TNF-α, IL-1β, and MCP-1 cytokines was assessed in a monocyte culture isolated from the blood by immunomagnetic separation of CD14+ cells. The level of basal, LPS-stimulated and re-stimulated TNF-α secretion was significantly higher in patients with diabetes; the level of IL-1β secretion did not differ significantly between the groups; basal and re-stimulated MCP-1 secretion was also significantly higher in the diabetes group. Re-stimulated secretion of TNF-α and IL-1β was reduced compared to primary-stimulated secretion in both groups, demonstrating the tolerance of the macrophage immune response to these cytokines. Re-stimulated secretion of MCP-1 in 42% of diabetes patients was higher than primary stimulated secretion, thus revealing an impaired tolerance of the immune response of macrophages. A correlation was found between TNF-α secretion and body mass index, r=0.631, p<0.001, and with glycemic level, r=0.427, p=0.037. The results obtained demonstrate inflammatory activation of monocytes with hypersecretion of TNF-α and MCP-1, impaired tolerance of the immune response of monocytes in diabetes regarding the secretion of MCP-1, as well as a correlation of TNF-α secretion with body mass index and glycemic level. This indicates an important role of TNF-α and MCP-1 in the pathogenesis of chronic inflammation in type 2 diabetes, thus allowing these cytokines to be considered as potential therapeutic targets for pathogenetic therapy of type 2 diabetes.
{"title":"Inflammatory Status of Monocytes in Type 2 Diabetes Mellitus","authors":"Т. В. Кириченко, Л.А. Бочкарева, Л. В. Недосугова, Ю.В. Маркина, И. А. Кузина, Н. А. Петунина, Т.В. Толстик, А.И. Богатырева, В.А. Антонов, А.М. Маркин, Tatiana V. Kirichenko, L. A. Bochkareva, L. Nedosugova, Y. Markina, I. A. Kuzina, N. Petunina, T. Tolstik, A. Bogatyreva, Valeriy A. Antonov, Alexander M Markin","doi":"10.33647/2074-5982-19-4-25-34","DOIUrl":"https://doi.org/10.33647/2074-5982-19-4-25-34","url":null,"abstract":"Сhronic inflammation is considered as a key factor in the development of type 2 diabetes mellitus. Impaired tolerance of the inflammatory response of monocytes is regarded as an important mechanism in the pathogenesis of chronic inflammation. In this work, we study the inflammatory activation and tolerance of the immune response of monocytes in diabetes. In total, 40 patients with newly diagnosed diabetes and 40 control group participants were included in the study. The level of basal, LPS-stimulated and re-stimulated secretion of the TNF-α, IL-1β, and MCP-1 cytokines was assessed in a monocyte culture isolated from the blood by immunomagnetic separation of CD14+ cells. The level of basal, LPS-stimulated and re-stimulated TNF-α secretion was significantly higher in patients with diabetes; the level of IL-1β secretion did not differ significantly between the groups; basal and re-stimulated MCP-1 secretion was also significantly higher in the diabetes group. Re-stimulated secretion of TNF-α and IL-1β was reduced compared to primary-stimulated secretion in both groups, demonstrating the tolerance of the macrophage immune response to these cytokines. Re-stimulated secretion of MCP-1 in 42% of diabetes patients was higher than primary stimulated secretion, thus revealing an impaired tolerance of the immune response of macrophages. A correlation was found between TNF-α secretion and body mass index, r=0.631, p<0.001, and with glycemic level, r=0.427, p=0.037. The results obtained demonstrate inflammatory activation of monocytes with hypersecretion of TNF-α and MCP-1, impaired tolerance of the immune response of monocytes in diabetes regarding the secretion of MCP-1, as well as a correlation of TNF-α secretion with body mass index and glycemic level. This indicates an important role of TNF-α and MCP-1 in the pathogenesis of chronic inflammation in type 2 diabetes, thus allowing these cytokines to be considered as potential therapeutic targets for pathogenetic therapy of type 2 diabetes.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"105 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138600017","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}
Pub Date : 2023-12-05DOI: 10.33647/2074-5982-19-4-8-24
В.Н. Каркищенко, И.А. Помыткин, Н.В. Петрова, И.А. Васильева, О.В. Алимкина, Н.В. Станкова, Н.А. Ларюшина, V. Karkischenko, I. A. Pomytkin, N. V. Petrova, I. A. Vasil’eva, Oksana V. Alimkina, Nataliia V. Stankova, N. A. Laryushina
In this work, we investigate the effect of a number of pharmaceutical preparations on the expression of genes, which are used as molecular targets under the conditions of debilitating physical exercise in minipigs. In the conducted experiment, the effectiveness of the following preparations was compared: “Mio-Activ-Sport” dietary supplement, a liposomal deer musk extract, intranasal insulin, and a liposomal ginseng preparation. The selected biomarkers included the leukocyte blood fraction and mRNA expression of NFE2L2 and HMGB1 genes in lymphocytes. Among the studied preparations, the liposomal deer musk extract showed the highest effectiveness. Thus, during seven days of therapy, this preparation almost completely prevented the pro-inflammatory effect of physical load. At the same time, the liposomal deer musk extract led to a manyfold increase in the expression of NFE2L2 gene, which is responsible for antioxidant defense of the organism. In terms of action, the liposomal deer musk extract outperformed insulin – the reference drug, whose protective effects are well known from the scientific literature. These findings confirm the prospects of deer musk preparations for medical rehabilitation.
{"title":"Evaluation of Approaches for Correcting the State of Animals under Debilitating Physical Exertion by Cellular and Genetic Biomarkers","authors":"В.Н. Каркищенко, И.А. Помыткин, Н.В. Петрова, И.А. Васильева, О.В. Алимкина, Н.В. Станкова, Н.А. Ларюшина, V. Karkischenko, I. A. Pomytkin, N. V. Petrova, I. A. Vasil’eva, Oksana V. Alimkina, Nataliia V. Stankova, N. A. Laryushina","doi":"10.33647/2074-5982-19-4-8-24","DOIUrl":"https://doi.org/10.33647/2074-5982-19-4-8-24","url":null,"abstract":"In this work, we investigate the effect of a number of pharmaceutical preparations on the expression of genes, which are used as molecular targets under the conditions of debilitating physical exercise in minipigs. In the conducted experiment, the effectiveness of the following preparations was compared: “Mio-Activ-Sport” dietary supplement, a liposomal deer musk extract, intranasal insulin, and a liposomal ginseng preparation. The selected biomarkers included the leukocyte blood fraction and mRNA expression of NFE2L2 and HMGB1 genes in lymphocytes. Among the studied preparations, the liposomal deer musk extract showed the highest effectiveness. Thus, during seven days of therapy, this preparation almost completely prevented the pro-inflammatory effect of physical load. At the same time, the liposomal deer musk extract led to a manyfold increase in the expression of NFE2L2 gene, which is responsible for antioxidant defense of the organism. In terms of action, the liposomal deer musk extract outperformed insulin – the reference drug, whose protective effects are well known from the scientific literature. These findings confirm the prospects of deer musk preparations for medical rehabilitation.","PeriodicalId":14837,"journal":{"name":"Journal Biomed","volume":"125 31","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138599224","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}
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