K. Derkach, A. Bakhtyukov, V. Sorokoumov, E. A. Didenko, Irina V. Romanova, I. Morina, I. Lebedev, L. V. Bayunova, A. Shpakov
Gonadotropin preparations, primarily human chorionic gonadotropin (hCG), are widely used to induce ovulation and correct reproductive disorders in women, but they are characterized by a number of side effects. A possible alternative is low-molecular-weight allosteric agonists of the luteinizing hormone receptor (LHR), including the thieno[2,3-d]-pyrimidine derivatives we developed. The purpose of the work was a comparative study of the effect of thieno[2,3-d]-pyrimidine TP03 and hCG on ovarian weight, corpus luteum formation, plasma levels of estradiol, progesterone and LH in immature female rats pre-treated with Follimag, as well as their effect on expression of ovarian genes encoding LHR and key components of steroidogenesis. TP03 was administered at a dose of 20 mg/kg (i.p.), hCG at a dose of 15 IU/rat (s.c.), both 48 hours after the Follimag injection. The estimated parameters were studied 1, 2, 4, 8, 16 and 24 hours after administration of TP03 or hCG. Plasma levels of hormones were determined using ELISA, and gene expression in the ovaries was determined using real-time PCR. The allosteric LHR agonist TP03 increased ovarian weight, progesterone production in the blood and the expression of steroidogenic genes encoding the cholesterol-transporting protein StAR and the cytochromes CYP11A1 and CYP17A1, and also stimulated the formation of the corpus luteum (1624 hours after treatment). The temporal dynamics of its stimulating effects were similar to those of hCG, although their magnitude was slightly inferior to those of gonadotropin. The TP03-induced decrease in blood estradiol levels and aromatase gene expression in the ovaries was also more moderate. Unlike hCG, which suppressed the expression of the gene encoding LHR 8 hours after treatment, TP03 maintained a high level of expression of this gene, preventing a decrease in the sensitivity of the ovaries to endogenous LH. Thus, TP03 is a good candidate for the role of an ovulation inducer, acting more mildly than hCG in terms of stimulating ovarian steroidogenesis, which reduces the risks of developing ovarian hyperstimulation syndrome and resistance of ovarian cells to gonadotropins.
{"title":"DYNAMICS OF THE STIMULATING EFFECTS OF GONADOTROPIN AND THIENOPYRIMIDINE DERIVATIVE TP03 ON OVULATION AND OVARIAN STEROIDOGENESIS IN FOLLIMAG-STIMULATED IMMATURE FEMALE RATS","authors":"K. Derkach, A. Bakhtyukov, V. Sorokoumov, E. A. Didenko, Irina V. Romanova, I. Morina, I. Lebedev, L. V. Bayunova, A. Shpakov","doi":"10.17816/rcf622883","DOIUrl":"https://doi.org/10.17816/rcf622883","url":null,"abstract":"Gonadotropin preparations, primarily human chorionic gonadotropin (hCG), are widely used to induce ovulation and correct reproductive disorders in women, but they are characterized by a number of side effects. A possible alternative is low-molecular-weight allosteric agonists of the luteinizing hormone receptor (LHR), including the thieno[2,3-d]-pyrimidine derivatives we developed. The purpose of the work was a comparative study of the effect of thieno[2,3-d]-pyrimidine TP03 and hCG on ovarian weight, corpus luteum formation, plasma levels of estradiol, progesterone and LH in immature female rats pre-treated with Follimag, as well as their effect on expression of ovarian genes encoding LHR and key components of steroidogenesis. TP03 was administered at a dose of 20 mg/kg (i.p.), hCG at a dose of 15 IU/rat (s.c.), both 48 hours after the Follimag injection. The estimated parameters were studied 1, 2, 4, 8, 16 and 24 hours after administration of TP03 or hCG. Plasma levels of hormones were determined using ELISA, and gene expression in the ovaries was determined using real-time PCR. The allosteric LHR agonist TP03 increased ovarian weight, progesterone production in the blood and the expression of steroidogenic genes encoding the cholesterol-transporting protein StAR and the cytochromes CYP11A1 and CYP17A1, and also stimulated the formation of the corpus luteum (1624 hours after treatment). The temporal dynamics of its stimulating effects were similar to those of hCG, although their magnitude was slightly inferior to those of gonadotropin. The TP03-induced decrease in blood estradiol levels and aromatase gene expression in the ovaries was also more moderate. Unlike hCG, which suppressed the expression of the gene encoding LHR 8 hours after treatment, TP03 maintained a high level of expression of this gene, preventing a decrease in the sensitivity of the ovaries to endogenous LH. Thus, TP03 is a good candidate for the role of an ovulation inducer, acting more mildly than hCG in terms of stimulating ovarian steroidogenesis, which reduces the risks of developing ovarian hyperstimulation syndrome and resistance of ovarian cells to gonadotropins.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"73 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140422944","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}
{"title":"Яркий изобретатель-новатор фармаколог Александр Ливиевич Ураков (к 70-летию со дня рождения)","authors":"Petr D. Shabanov","doi":"10.17816/rcf627547","DOIUrl":"https://doi.org/10.17816/rcf627547","url":null,"abstract":"Яркий изобретатель-новатор фармаколог Александр Ливиевич Ураков (к 70-летию со дня рождения)","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"13 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140423275","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}
V. V. Rusanovsky, A. A. Savelyeva, Z. G. Tadtaeva, Egor S. Astudin, Alexandr E. Krivoshein, Alexandr A. Akimov, N. A. Kuritcyna
The article is devoted to the possibility and prospects of using nitazoxanide in a wide range of diseases. Based on literature data, the authors evaluate the pharmacological effectiveness and substantiate the potential of using nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. This information is of interest and can be used to decide on the need to conduct clinical trials of nitazoxanide in Russia. The goal is to evaluate the pharmacological activity and potential of nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. Materials and methods: A systematic search for current information was conducted in four databases until December 1, 2023: PubMed, EMBASE, Web of Science and Cochrane Library. Work included preclinical studies in vitro and in vivo, as well as randomized clinical trials comparing the pharmacological effectiveness of nitazoxanide and placebo. Conclusions: the broad-spectrum thiazolide drug nitazoxanide has antibacterial, antiprotozoal, anthelmintic, antiviral and antitumor activity. This is achieved through its pharmacological properties, namely: regulation of the cell cycle, apoptosis, cell proliferation and migration; activation of innate immunity; influence on the synthesis and activation of cell proteins, some of which are links in cellular signaling pathways; binding to proteins of viruses, bacteria, protozoa and helminths with disruption of their vital functions; immunomodulating effect by regulating the activity of pro- and anti-inflammatory cytokines. The article systematizes and summarizes current information on the pharmacodynamics of NTZ, as well as the results of preclinical and clinical studies of the drug, and discusses further prospects.
{"title":"Evaluation of the pharmacological efficacy and potential of nitazoxanide, a broad–spectrum thiazolide drug","authors":"V. V. Rusanovsky, A. A. Savelyeva, Z. G. Tadtaeva, Egor S. Astudin, Alexandr E. Krivoshein, Alexandr A. Akimov, N. A. Kuritcyna","doi":"10.17816/rcf624703","DOIUrl":"https://doi.org/10.17816/rcf624703","url":null,"abstract":"The article is devoted to the possibility and prospects of using nitazoxanide in a wide range of diseases. Based on literature data, the authors evaluate the pharmacological effectiveness and substantiate the potential of using nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. This information is of interest and can be used to decide on the need to conduct clinical trials of nitazoxanide in Russia. \u0000The goal is to evaluate the pharmacological activity and potential of nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. \u0000Materials and methods: A systematic search for current information was conducted in four databases until December 1, 2023: PubMed, EMBASE, Web of Science and Cochrane Library. Work included preclinical studies in vitro and in vivo, as well as randomized clinical trials comparing the pharmacological effectiveness of nitazoxanide and placebo. \u0000Conclusions: the broad-spectrum thiazolide drug nitazoxanide has antibacterial, antiprotozoal, anthelmintic, antiviral and antitumor activity. This is achieved through its pharmacological properties, namely: regulation of the cell cycle, apoptosis, cell proliferation and migration; activation of innate immunity; influence on the synthesis and activation of cell proteins, some of which are links in cellular signaling pathways; binding to proteins of viruses, bacteria, protozoa and helminths with disruption of their vital functions; immunomodulating effect by regulating the activity of pro- and anti-inflammatory cytokines. The article systematizes and summarizes current information on the pharmacodynamics of NTZ, as well as the results of preclinical and clinical studies of the drug, and discusses further prospects.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"26 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140418676","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}
BACKGROUND: Osteoporosis is a significant problem in the world with important medical and economic consequences. An important contribution to solving the problem of osteoporosis can be the creation of drugs based on unique biologically active compounds. aim: Evaluate of the processes of osteogenesis, according to the evaluation of markers of bone remodeling in blood serum at the stages of therapy of experimental osteoporosis complicated by diabetes type 2. Materials and methods: The study was performed on an experimental model of osteoporosis, followed by induction of diabetes type 2, using biochemical methods for analyzing markers of osteoporosis in blood serum. Results: According to the results of the study of the content of markers of bone remodeling, the dependence of the anti-osteoporotic activity of a composite preparation based on succinic acid salts on glucose metabolism disorders in DM is shown. High efficacy of the new drug in monotherapy, and in combination with vitamin D3 in the activation of osteogenesis processes in experimental osteoporosis. it was leveled by a violation of metabolic processes, induction of diabetes type 2. Conclusion: The dependence of the pharmacological effectiveness of the anti-osteoporosis agent on the model of osteoporosis in female rats on metabolic disorders in the form of diabetes type 2 is shown. Keywords: osteoporosis, experimental model, markers of osteogenesis, anti-osteoporosis agent, type 2 diabetes.
{"title":"PHARMACOLOGICAL CORRECTION OF EXPERIMENTALLY INDUCED OSTEOPOROSIS COMPLICATED BY DIABETES MELLITUS TYPE 2","authors":"Petr D. Shabanov","doi":"10.17816/rcf623110","DOIUrl":"https://doi.org/10.17816/rcf623110","url":null,"abstract":"BACKGROUND: Osteoporosis is a significant problem in the world with important medical and economic consequences. An important contribution to solving the problem of osteoporosis can be the creation of drugs based on unique biologically active compounds. aim: Evaluate of the processes of osteogenesis, according to the evaluation of markers of bone remodeling in blood serum at the stages of therapy of experimental osteoporosis complicated by diabetes type 2. Materials and methods: The study was performed on an experimental model of osteoporosis, followed by induction of diabetes type 2, using biochemical methods for analyzing markers of osteoporosis in blood serum. Results: According to the results of the study of the content of markers of bone remodeling, the dependence of the anti-osteoporotic activity of a composite preparation based on succinic acid salts on glucose metabolism disorders in DM is shown. High efficacy of the new drug in monotherapy, and in combination with vitamin D3 in the activation of osteogenesis processes in experimental osteoporosis. it was leveled by a violation of metabolic processes, induction of diabetes type 2. Conclusion: The dependence of the pharmacological effectiveness of the anti-osteoporosis agent on the model of osteoporosis in female rats on metabolic disorders in the form of diabetes type 2 is shown. \u0000 Keywords: osteoporosis, experimental model, markers of osteogenesis, anti-osteoporosis agent, type 2 diabetes.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140422674","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}
D. Kachanov, Andrei V. Pavlysh, Tatiana Yurievna Galunova, Galina Ya. Lapkina
When using antibiotics in the treatment of various diseases, the quantitative and qualitative composition of the microbiota, both pathogenic and symbiotic, changes dramatically. Both oral and parenteral use of antibacterial drugs has an impact and changes the quantitative and qualitative composition of the intestinal microbiota, which subsequently entails changes in the pathways of cell development and long-term violations of physiology at all levels of functioning of the macroorganism. In this article, the analysis of available data on modern probiotic drugs drugs that contribute to improving the normal microbiota of the human body was carried out. The undoubted effectiveness of various probiotics in acute and antibiotic-associated diarrhea, eradication of Helicobacter pylori was noted.
{"title":"Probiotics. Review of the current state of the problem from the standpoint of clinical pharmacology and evidence-based medicine","authors":"D. Kachanov, Andrei V. Pavlysh, Tatiana Yurievna Galunova, Galina Ya. Lapkina","doi":"10.17816/rcf321186","DOIUrl":"https://doi.org/10.17816/rcf321186","url":null,"abstract":"When using antibiotics in the treatment of various diseases, the quantitative and qualitative composition of the microbiota, both pathogenic and symbiotic, changes dramatically. Both oral and parenteral use of antibacterial drugs has an impact and changes the quantitative and qualitative composition of the intestinal microbiota, which subsequently entails changes in the pathways of cell development and long-term violations of physiology at all levels of functioning of the macroorganism. In this article, the analysis of available data on modern probiotic drugs drugs that contribute to improving the normal microbiota of the human body was carried out. The undoubted effectiveness of various probiotics in acute and antibiotic-associated diarrhea, eradication of Helicobacter pylori was noted.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"103 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140423573","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}
Mikhail Akimov, P. Dudina, Tatiana Vyunova, A. Kalueff, Natalia Gretskaya, Vladimir V. Bezuglov
Breast cancer is the main cause of death of women from cancer. Endocannabinoids and their exogenous analogues, for example, tetrahydrocannabinol, exhibit antitumor effect on a wide range of animal models of cancer. However, several studies have shown that under certain conditions, treatment with cannabinoids can stimulate the proliferation of cancer cells in vitro and disrupt the immune system's involvement in suppressing tumors. There are also conflicting reports about the antitumor role of the endocannabinoid system itself in cancer. The purpose of this review is to consider the main options for the action of key ligands and receptors of the endocannabinoid system in the context of breast cancer.
{"title":"The role of the key endocannabinoids and their receptros in breast cancer","authors":"Mikhail Akimov, P. Dudina, Tatiana Vyunova, A. Kalueff, Natalia Gretskaya, Vladimir V. Bezuglov","doi":"10.17816/rcf623144","DOIUrl":"https://doi.org/10.17816/rcf623144","url":null,"abstract":"Breast cancer is the main cause of death of women from cancer. Endocannabinoids and their exogenous analogues, for example, tetrahydrocannabinol, exhibit antitumor effect on a wide range of animal models of cancer. However, several studies have shown that under certain conditions, treatment with cannabinoids can stimulate the proliferation of cancer cells in vitro and disrupt the immune system's involvement in suppressing tumors. There are also conflicting reports about the antitumor role of the endocannabinoid system itself in cancer. The purpose of this review is to consider the main options for the action of key ligands and receptors of the endocannabinoid system in the context of breast cancer.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"221 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140417778","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}
E. Andrusenko, R. I. Glushakov, Gregory Aleksandrovich Redkin
There is currently an increasing trend to reduce the amount of synthetic products or additives and replace them with natural ones. Historical experience and developments in human health science demonstrate the adverse effects of xenobiotics on natural metabolism and human health. The trend towards natural products is essential for vitality, social activity, a decent quality of life, and the prevention of adverse events and diseases. The pharmaceutical, cosmetic and food industries place special emphasis on natural and biologically active chemicals isolated from plants or microorganisms. The main task in this direction is the development of effective and environmental methods for their isolation. Deep eutectic solvents (DES) are a mixture of two or more components and are among the solvents with unique properties such as low volatility, low melting points, ease of preparation, inexpensive starting materials and, most importantly, they are practically non-toxic to humans. Deep eutectic solvents are used as an environmentally friendly method for the extraction of biologically active substances (BAS) from medicinal plants, as well as a safe alternative for food, pharmaceutical and various industries. Traditional organic solvent extraction methods have several disadvantages, such as long extraction times, safety of use, environmental damage, high cost, and the need to use large volumes of solvents. This review provides a summary of the research progress regarding the benefits of using deep eutectic solvents for the extraction of bioactive compounds such as phenolic acid, flavonoids, isoflavones, catechins, polysaccharides, curcuminoids, proanthocyanidin, phycocyanin, gingerols, ginsenosides, anthocyanins, rutin, chlorogenic acids and other. The study of the biological activity of extracts is considered: antioxidant, antibacterial and antitumor activity.
{"title":"NATURAL DEEP EUTECTIC SOLVENTS ARE PROMISING AGENTS FOR THE EXTRACTION OF SUBSTANCES FROM PLANT MATERIALS","authors":"E. Andrusenko, R. I. Glushakov, Gregory Aleksandrovich Redkin","doi":"10.17816/rcf611034","DOIUrl":"https://doi.org/10.17816/rcf611034","url":null,"abstract":"There is currently an increasing trend to reduce the amount of synthetic products or additives and replace them with natural ones. Historical experience and developments in human health science demonstrate the adverse effects of xenobiotics on natural metabolism and human health. The trend towards natural products is essential for vitality, social activity, a decent quality of life, and the prevention of adverse events and diseases. The pharmaceutical, cosmetic and food industries place special emphasis on natural and biologically active chemicals isolated from plants or microorganisms. The main task in this direction is the development of effective and environmental methods for their isolation. Deep eutectic solvents (DES) are a mixture of two or more components and are among the solvents with unique properties such as low volatility, low melting points, ease of preparation, inexpensive starting materials and, most importantly, they are practically non-toxic to humans. Deep eutectic solvents are used as an environmentally friendly method for the extraction of biologically active substances (BAS) from medicinal plants, as well as a safe alternative for food, pharmaceutical and various industries. Traditional organic solvent extraction methods have several disadvantages, such as long extraction times, safety of use, environmental damage, high cost, and the need to use large volumes of solvents. This review provides a summary of the research progress regarding the benefits of using deep eutectic solvents for the extraction of bioactive compounds such as phenolic acid, flavonoids, isoflavones, catechins, polysaccharides, curcuminoids, proanthocyanidin, phycocyanin, gingerols, ginsenosides, anthocyanins, rutin, chlorogenic acids and other. The study of the biological activity of extracts is considered: antioxidant, antibacterial and antitumor activity.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"34 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140457141","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}
The review presents literature data analysis devoted to the study of structural changes in the heart in patients with vibration disease, identified by echocardiographic methods in the form of concentric remodeling of the left ventricle chambers and disturbance of its diastolic function, a decrease in the intensity of the heart structure work compared to healthy ones in 1.2 times (p0.05). The changes in morphometric and bioenergetic parameters of cardiomyocytes against the background of various experimental vibration modes (7 and 56 sessions with a frequency of 8 Hz) confirms the violation of the ideal relationship between the spatial configuration of the heart cavities, the ability to contract and the energy supply potential. The loss of cardiac myofibrils symbolizes the convertion of myocardial hypertrophy to the decompensation stage and the increase in degenerative (dystrophic) signs, in particular the loss of sarcomeres of cardiomyocytes. To realize the processes of pathological structural (morphological) and energy restructuring of tissue under the influence of vibration-mediated hemodynamic and ischemic factors, it is necessary to involve in the process numerous mediators that regulate metabolism, proliferation, growth and survival of cells, such as STIM (stromal interaction molecule), SERCA (calcium ATPase of the endo(sarco)plasmic reticulum), IP3R (inositol-1,4,5-triphosphate receptor), Orai (protein that forms CRAC channels), TRPC (transient receptor potential canonical), etc. As one of the most important link of structural cardiac remodeling is performed by the degradation system of the extracellular matrix, including matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), which regulate the rate of mRNA synthesis on the DNA matrix by binding to specific DNA regions that control cardiac nutrition and plasticity. A lot of analyzed facts make it possible to explain some patterns of the development of cardiac remodeling in patients with vibration disease and to determine the direction of pathogenetically based approaches to therapy, taking into account not only the vibration-protective effect of drugs, but also their ability to inhibit and regress myocardial remodeling.
本综述介绍了专门研究振动病患者心脏结构变化的文献数据分析，通过超声心动图方法确定了左心室腔同心重塑和舒张功能紊乱的形式，与健康人相比，心脏结构工作强度降低了1.2倍（P0.05）。在各种实验振动模式（频率为 8 赫兹的 7 次和 56 次）背景下，心肌细胞形态计量和生物能参数的变化证实，心腔的空间结构、收缩能力和能量供应潜力之间的理想关系受到了破坏。心肌纤维的损失象征着心肌肥大向失代偿阶段的转化和退化（萎缩）迹象的增加，特别是心肌细胞肌节的损失。在振动介导的血流动力学因素和缺血因素影响下，要实现组织的病理结构（形态）和能量重组过程，就必须让众多调节新陈代谢、增殖、生长和存活的介质参与其中，如细胞、细胞核和细胞膜、如 STIM（基质相互作用分子）、SERCA（肌浆网内的钙 ATP 酶）、IP3R（肌醇-1,4,5-三磷酸受体）、Orai（形成 CRAC 通道的蛋白质）、TRPC（瞬时受体电位）等。心脏结构重塑的最重要环节之一是细胞外基质降解系统，包括基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs），它们通过与控制心脏营养和可塑性的特定 DNA 区域结合，调节 DNA 基质上 mRNA 的合成速度。通过分析大量事实，可以解释振动病患者心脏重塑的一些发展模式，并确定基于病因的治疗方法的方向，不仅要考虑到药物的振动保护作用，还要考虑到药物抑制和缓解心肌重塑的能力。
{"title":"MECHANISMS OF STRUCTURAL MYOCARDIAL REMODELING UNDER THE INFLUENCE OF VIBRATION","authors":"O. Levchenkova, V. V. Vorobieva","doi":"10.17816/rcf624185","DOIUrl":"https://doi.org/10.17816/rcf624185","url":null,"abstract":"The review presents literature data analysis devoted to the study of structural changes in the heart in patients with vibration disease, identified by echocardiographic methods in the form of concentric remodeling of the left ventricle chambers and disturbance of its diastolic function, a decrease in the intensity of the heart structure work compared to healthy ones in 1.2 times (p0.05). The changes in morphometric and bioenergetic parameters of cardiomyocytes against the background of various experimental vibration modes (7 and 56 sessions with a frequency of 8 Hz) confirms the violation of the ideal relationship between the spatial configuration of the heart cavities, the ability to contract and the energy supply potential. The loss of cardiac myofibrils symbolizes the convertion of myocardial hypertrophy to the decompensation stage and the increase in degenerative (dystrophic) signs, in particular the loss of sarcomeres of cardiomyocytes. \u0000To realize the processes of pathological structural (morphological) and energy restructuring of tissue under the influence of vibration-mediated hemodynamic and ischemic factors, it is necessary to involve in the process numerous mediators that regulate metabolism, proliferation, growth and survival of cells, such as STIM (stromal interaction molecule), SERCA (calcium ATPase of the endo(sarco)plasmic reticulum), IP3R (inositol-1,4,5-triphosphate receptor), Orai (protein that forms CRAC channels), TRPC (transient receptor potential canonical), etc. As one of the most important link of structural cardiac remodeling is performed by the degradation system of the extracellular matrix, including matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), which regulate the rate of mRNA synthesis on the DNA matrix by binding to specific DNA regions that control cardiac nutrition and plasticity. A lot of analyzed facts make it possible to explain some patterns of the development of cardiac remodeling in patients with vibration disease and to determine the direction of pathogenetically based approaches to therapy, taking into account not only the vibration-protective effect of drugs, but also their ability to inhibit and regress myocardial remodeling.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"23 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140457705","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}
T. V. Shushpanova, Anna I. Mandel, N. A. Bokhan, E. D. Schastnyy
BACKGROUND: The development of new drugs to improve the effectiveness of treatment and rehabilitation programs for patients suffering from addiction diseases, which are non-addictive and have a stimulating effect on detoxification processes in the body, can increase the effectiveness of therapy and reduce the cost of treatment. A deficiency of GABAergic inhibition in brain structures plays a leading role in the occurrence of paroxysmalness. The innovative anticonvulsant Galodif® (1-[(3-chlorophenyl)(phenyl)methyl]urea), a GABAA receptor modulator, has low toxicity and hepatoprotective properties, which allows it to be recommended for use in the treatment of patients with alcohol dependence. AIM: The aim of this study is to evaluation of the effectiveness of the use of the anticonvulsant drug galodif1 in complex therapy in patients with alcohol dependence with compulsive and paroxysmal disorders with pathological craving for alcohol when withdrawing of alcohol. MATERIALS AND METHODS: A limited open-type clinical study of the therapeutic effectiveness of the innovative anticonvulsant galodif1 included 128 male patients (average age 38.3 ± 8.9 years) with a diagnosis of “Mental and behavioral disorders as a result of alcohol consumption, dependence syndrome” (F10.232) and “Mental and behavioral disorders as a result of alcohol consumption, withdrawal states” (F10.302). 68 patients received Galodif® 300 mg per day as an anticonvulsant for 21 days. 60 patients made up the comparison group, receiving carbamazepine at a dose of 400 mg per day. RESULTS: The use of the anticonvulsant Galodif® in complex therapy of patients revealed: normothymoleptic activity of the drug; when assessing depression on the Hamilton Depression Rating Scale (HDRS), the average total score decreased from 28.3 ± 1.3 to 5.7 ± 1.9, and a reduction in unmotivated fear and anxiety was noted; vegetative stabilizing effect with a sympathicolytic component with normalization of heart rate; reduction of headaches; weakening or disappearance of pathological desire during withdrawal syndrome in 88% of cases, in the post-withdrawal state — in 57% of cases; taking the drug did not cause any unwanted side effects. CONCLUSIONS: The use of the anticonvulsant Galodif®, which modulates GABAA receptors, has low toxicity and detoxification properties and does not cause side effects, has been proposed as one of the modern pharmacotherapeutic approaches in the treatment of patients with alcohol dependence.
{"title":"The effectiveness of the original anticonvulsant Galodif® — a GABAA receptor modulator for alcohol withdrawal syndrome","authors":"T. V. Shushpanova, Anna I. Mandel, N. A. Bokhan, E. D. Schastnyy","doi":"10.17816/rcf607434","DOIUrl":"https://doi.org/10.17816/rcf607434","url":null,"abstract":"BACKGROUND: The development of new drugs to improve the effectiveness of treatment and rehabilitation programs for patients suffering from addiction diseases, which are non-addictive and have a stimulating effect on detoxification processes in the body, can increase the effectiveness of therapy and reduce the cost of treatment. A deficiency of GABAergic inhibition in brain structures plays a leading role in the occurrence of paroxysmalness. The innovative anticonvulsant Galodif® (1-[(3-chlorophenyl)(phenyl)methyl]urea), a GABAA receptor modulator, has low toxicity and hepatoprotective properties, which allows it to be recommended for use in the treatment of patients with alcohol dependence. \u0000AIM: The aim of this study is to evaluation of the effectiveness of the use of the anticonvulsant drug galodif1 in complex therapy in patients with alcohol dependence with compulsive and paroxysmal disorders with pathological craving for alcohol when withdrawing of alcohol. \u0000MATERIALS AND METHODS: A limited open-type clinical study of the therapeutic effectiveness of the innovative anticonvulsant galodif1 included 128 male patients (average age 38.3 ± 8.9 years) with a diagnosis of “Mental and behavioral disorders as a result of alcohol consumption, dependence syndrome” (F10.232) and “Mental and behavioral disorders as a result of alcohol consumption, withdrawal states” (F10.302). 68 patients received Galodif® 300 mg per day as an anticonvulsant for 21 days. 60 patients made up the comparison group, receiving carbamazepine at a dose of 400 mg per day. \u0000RESULTS: The use of the anticonvulsant Galodif® in complex therapy of patients revealed: normothymoleptic activity of the drug; when assessing depression on the Hamilton Depression Rating Scale (HDRS), the average total score decreased from 28.3 ± 1.3 to 5.7 ± 1.9, and a reduction in unmotivated fear and anxiety was noted; vegetative stabilizing effect with a sympathicolytic component with normalization of heart rate; reduction of headaches; weakening or disappearance of pathological desire during withdrawal syndrome in 88% of cases, in the post-withdrawal state — in 57% of cases; taking the drug did not cause any unwanted side effects. \u0000CONCLUSIONS: The use of the anticonvulsant Galodif®, which modulates GABAA receptors, has low toxicity and detoxification properties and does not cause side effects, has been proposed as one of the modern pharmacotherapeutic approaches in the treatment of patients with alcohol dependence.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"48 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139683631","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}
A review of the literature data covering topical issues of the use of bacteriophages in clinical practice is presented. Traditionally, phage therapy is based on the use of natural phages for the lysis of bacteria at the infection site. Despite some limitations, it has significant advantages over antibiotic therapy. The use of biotechnological methods currently makes it possible to eliminate the disadvantages of phage therapy by creating recombinant drugs and, in the future, expand its capabilities through the use of lytic phage proteins and their modified derivatives. Currently, bacteriophages are used not only for the treatment of infections but also for prevention and diagnosis (phagotyping to identify the source of infection). Bacteriophages are also used in genetic engineering as vectors for transferring DNA sections. Few side effects have been described about bacteriophages. Particularly, they do not negatively affect the intestinal microbiota, and compared with antibiotics, they are much less likely to be associated with allergic reactions. Moreover, existing randomized clinical trials, which are the gold standard of clinical trials, in phage therapy are extremely insufficient, which dictates the need to concentrate the efforts of all stakeholders in this direction.
本文综述了有关在临床实践中使用噬菌体的热点问题的文献资料。传统的噬菌体疗法是利用天然噬菌体溶解感染部位的细菌。尽管存在一些局限性，但与抗生素疗法相比，噬菌体疗法具有明显的优势。目前，生物技术方法的使用使得通过制造重组药物来消除噬菌体疗法的缺点成为可能，未来还可以通过使用溶菌噬菌体蛋白及其改良衍生物来扩大噬菌体疗法的能力。目前，噬菌体不仅用于治疗感染，还用于预防和诊断（通过噬菌体分型确定感染源）。噬菌体还可用于基因工程，作为转移 DNA 片段的载体。噬菌体几乎没有副作用。特别是，噬菌体不会对肠道微生物群产生负面影响，与抗生素相比，噬菌体引起过敏反应的可能性要小得多。此外，噬菌体疗法的现有随机临床试验（临床试验的黄金标准）还极不充分，这就决定了所有利益相关者都需要集中精力朝这个方向努力。
{"title":"Bacteriophages: Clinical significance and application prospects","authors":"Andrey I. Danilov, A. V. Evseev","doi":"10.17816/rcf624214","DOIUrl":"https://doi.org/10.17816/rcf624214","url":null,"abstract":"A review of the literature data covering topical issues of the use of bacteriophages in clinical practice is presented. Traditionally, phage therapy is based on the use of natural phages for the lysis of bacteria at the infection site. Despite some limitations, it has significant advantages over antibiotic therapy. The use of biotechnological methods currently makes it possible to eliminate the disadvantages of phage therapy by creating recombinant drugs and, in the future, expand its capabilities through the use of lytic phage proteins and their modified derivatives. Currently, bacteriophages are used not only for the treatment of infections but also for prevention and diagnosis (phagotyping to identify the source of infection). Bacteriophages are also used in genetic engineering as vectors for transferring DNA sections. Few side effects have been described about bacteriophages. Particularly, they do not negatively affect the intestinal microbiota, and compared with antibiotics, they are much less likely to be associated with allergic reactions. Moreover, existing randomized clinical trials, which are the gold standard of clinical trials, in phage therapy are extremely insufficient, which dictates the need to concentrate the efforts of all stakeholders in this direction.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"6 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139683407","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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