V.F. Sadykov, R. Poltavtseva, A. Chaplygina, N. Bobkova
The pandemic caused by a new strain of SARS-CоV-2 coronavirus has swept the whole world, however, despite the developed strategic directions for the treatment of coronavirus infection and intensive research in all countries, effective methods for treating this severe pathology have not yet been created. The list of drugs against COVID-19 practically does not use compounds that affect the renin-angiotensin system, in the functioning of which the ACE2 coronavirus binding receptor plays a central role. It is assumed that the virus, causing a decrease in the density of ACE2 receptors, leads to disruption of RAS activity. This review presents current research on the response of the immune system to infection with the SARS-CoV-2 virus, describes adaptive and innate cellular mechanisms, and describes a number of predictors of severe COVID-19. To write this review, a search was made in the PubMed database and the scientific electronic library eLibrary.ru. The selection of articles was carried out manually with the main goal of synthesizing data and describing the mechanisms of influence of SARS-CoV-2 on the renin-angiotensin system, and, as a result, on the activation of the adaptive and innate immune response. This review includes 53 publications, including methodological recommendations of the Ministry of Health of the Russian Federation, data from ongoing clinical trials and patents. Data from selected scientific sources were structured and visualized.
{"title":"Immune status and cytokine spectrum as predictive signs of the severity of the disease and the effectiveness of intensive care in patients with coronavirus infection COVID-19","authors":"V.F. Sadykov, R. Poltavtseva, A. Chaplygina, N. Bobkova","doi":"10.17816/rcf109220","DOIUrl":"https://doi.org/10.17816/rcf109220","url":null,"abstract":"The pandemic caused by a new strain of SARS-CоV-2 coronavirus has swept the whole world, however, despite the developed strategic directions for the treatment of coronavirus infection and intensive research in all countries, effective methods for treating this severe pathology have not yet been created. The list of drugs against COVID-19 practically does not use compounds that affect the renin-angiotensin system, in the functioning of which the ACE2 coronavirus binding receptor plays a central role. It is assumed that the virus, causing a decrease in the density of ACE2 receptors, leads to disruption of RAS activity. This review presents current research on the response of the immune system to infection with the SARS-CoV-2 virus, describes adaptive and innate cellular mechanisms, and describes a number of predictors of severe COVID-19. \u0000To write this review, a search was made in the PubMed database and the scientific electronic library eLibrary.ru. The selection of articles was carried out manually with the main goal of synthesizing data and describing the mechanisms of influence of SARS-CoV-2 on the renin-angiotensin system, and, as a result, on the activation of the adaptive and innate immune response. This review includes 53 publications, including methodological recommendations of the Ministry of Health of the Russian Federation, data from ongoing clinical trials and patents. Data from selected scientific sources were structured and visualized.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80976087","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 analyzes the results of scientific research on the role of aquaporins in the pathogenesis of CNS diseases and the possibility of their pharmacological regulation. Aquaporins (AQP) are proteins involved in the transmembrane transport of water and other substances. They form the water channels of cell membranes and are widely represented in various mammalian cells, including the membranes of human brain and spinal cord cells. To date, about 300 types of proteins of the aquaporin family have been discovered, of which 13 (AQP0AQP12) have been identified in human cells. Localization of different types of AQP in CNS structures, their functional activity and involvement in the development of CNS diseases differ. There are mainly three types of AQPs in the central nervous system: AQP1, AQP4 and AQP9. The results of scientific research indicate the most important role of AQP in maintaining water-salt homeostasis and ensuring physiological processes in the central nervous system, and also confirm the role of AQP in the pathogenesis of a number of diseases of the central nervous system (cerebral edema of various genesis, invasion of tumor cells and the formation of peritumorous edema, in the development of autoimmune diseases opticomyelitis, Alzheimers disease). Pharmacological regulation of the functional activity of aquaporins can influence the course of these diseases. Therefore, there is a natural interest in drugs that can change the expression of AQP. Proteins of the aquaporin family provide transmembrane transport of water and play an essential role in the development of pathological conditions of the central nervous system. They can be potential targets for pharmacological effects in a number of diseases of the central nervous system. The search and study of drugs affecting the expression and functional activity of AQP is pathogenetically justified and is a promising direction in the development of pharmacotherapy strategies for cerebral edema, malignant brain tumors and other CNS diseases.
{"title":"Prospects of pharmacological regulation of aquaporin function in CNS diseases","authors":"N. Ponamareva, V. Novikov, E. V. Pozhilova","doi":"10.17816/rcf321506","DOIUrl":"https://doi.org/10.17816/rcf321506","url":null,"abstract":"The review analyzes the results of scientific research on the role of aquaporins in the pathogenesis of CNS diseases and the possibility of their pharmacological regulation. \u0000Aquaporins (AQP) are proteins involved in the transmembrane transport of water and other substances. They form the water channels of cell membranes and are widely represented in various mammalian cells, including the membranes of human brain and spinal cord cells. To date, about 300 types of proteins of the aquaporin family have been discovered, of which 13 (AQP0AQP12) have been identified in human cells. Localization of different types of AQP in CNS structures, their functional activity and involvement in the development of CNS diseases differ. There are mainly three types of AQPs in the central nervous system: AQP1, AQP4 and AQP9. The results of scientific research indicate the most important role of AQP in maintaining water-salt homeostasis and ensuring physiological processes in the central nervous system, and also confirm the role of AQP in the pathogenesis of a number of diseases of the central nervous system (cerebral edema of various genesis, invasion of tumor cells and the formation of peritumorous edema, in the development of autoimmune diseases opticomyelitis, Alzheimers disease). Pharmacological regulation of the functional activity of aquaporins can influence the course of these diseases. Therefore, there is a natural interest in drugs that can change the expression of AQP. \u0000Proteins of the aquaporin family provide transmembrane transport of water and play an essential role in the development of pathological conditions of the central nervous system. They can be potential targets for pharmacological effects in a number of diseases of the central nervous system. The search and study of drugs affecting the expression and functional activity of AQP is pathogenetically justified and is a promising direction in the development of pharmacotherapy strategies for cerebral edema, malignant brain tumors and other CNS diseases.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86700044","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: In preclinical studies on laboratory animals, oral administration with special probe for test substances is very in demand. Most studies are devoted to the psychophysiological and clinical-biochemical reaction of the animals body to this effect, but extremely few studies consider the effect of the manipulation itself on the development of pathology in the tissues of the gastrointestinal tract associated with the inevitable mechanical impact of the probe on the mucous membranes. AIM: To identify pathological changes in the organs of the gastrointestinal tract of laboratory rats that are associated with the effects of intragastric administration of the tested substances, and compare the data obtained with the frequency of spontaneous diseases. MATERIALS AND METHODS: The data of pathomorphological observations obtained from Wistar rats involved in the course of scientific work carried out at NPO Dom Pharmacy in the period from 2018 to 2021 were used. 1400 sentinel animals were analyzed, and the same number of intact rats. Intact animals were gavaged with a control substance (distilled water) for 14 days. RESULTS: In less than 5% of clinically healthy animals, inflammatory diseases of insignificant intensity and prevalence in all parts of the intestine can be detected. As a result of the anipulation of intragastric administration, an almost twofold increase in the number of cases of catarrhal esophagitis and gastritis, erosive and ulcerative lesions of the mucous membrane of the esophagus and stomach in its glandular part and hyperkeratosis in its non-glandular part was noted. CONCLUSIONS: The type and frequency of occurrence of the background pathology of the gastrointestinal tract of laboratory rats were determined. It has been proven that repeated traumatization of the mucous membrane associated with mechanical contact of a solid metal probe with the epithelium provokes the development of inflammatory diseases of the esophagus and stomach, without affecting the underlying parts of the intestine.
{"title":"Effect of intragastric administration on the morphology of laboratory rats’ gastrointestinal tract","authors":"Y. Gushchin, M. Makarova, P. Shabanov","doi":"10.17816/rcf138659","DOIUrl":"https://doi.org/10.17816/rcf138659","url":null,"abstract":"BACKGROUND: In preclinical studies on laboratory animals, oral administration with special probe for test substances is very in demand. Most studies are devoted to the psychophysiological and clinical-biochemical reaction of the animals body to this effect, but extremely few studies consider the effect of the manipulation itself on the development of pathology in the tissues of the gastrointestinal tract associated with the inevitable mechanical impact of the probe on the mucous membranes. \u0000AIM: To identify pathological changes in the organs of the gastrointestinal tract of laboratory rats that are associated with the effects of intragastric administration of the tested substances, and compare the data obtained with the frequency of spontaneous diseases. \u0000MATERIALS AND METHODS: The data of pathomorphological observations obtained from Wistar rats involved in the course of scientific work carried out at NPO Dom Pharmacy in the period from 2018 to 2021 were used. 1400 sentinel animals were analyzed, and the same number of intact rats. Intact animals were gavaged with a control substance (distilled water) for 14 days. \u0000RESULTS: In less than 5% of clinically healthy animals, inflammatory diseases of insignificant intensity and prevalence in all parts of the intestine can be detected. As a result of the anipulation of intragastric administration, an almost twofold increase in the number of cases of catarrhal esophagitis and gastritis, erosive and ulcerative lesions of the mucous membrane of the esophagus and stomach in its glandular part and hyperkeratosis in its non-glandular part was noted. \u0000CONCLUSIONS: The type and frequency of occurrence of the background pathology of the gastrointestinal tract of laboratory rats were determined. It has been proven that repeated traumatization of the mucous membrane associated with mechanical contact of a solid metal probe with the epithelium provokes the development of inflammatory diseases of the esophagus and stomach, without affecting the underlying parts of the intestine.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74041814","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}
S. S. Pyurveev, Mikhail S. Nekrasov, Nikolay S. Dedanishvili, Albina S. Nekrasova, Tatyana V. Brus, A. Lebedev, Nicanor V. Lavrov, A. V. Podrezova, R. Glushakov, P. Shabanov
BACKGROUND: Exposure to acute or chronic stress contributes to the occurrence of various disorders of the central nervous system, psycho-emotional sphere, as well as increases the risks of development of various forms of addiction. AIM: The aim of the study is analyze the influence of maternal deprivation on voluntary alcohol consumption in adolescents and to determine the degree of the signs of compulsive behavior in experimental animals. MATERIALS AND METHODS: Thirty male Wistar rats were taken in the research. A maternal deprivation model was carried out from day 2 to day 12 of the postnatal period (MD). Compulsivity (compulsive tendency) was evaluated in the ball burial test. Voluntary alcoholization with 10% ethyl alcohol solution in a two-bottle test was employed. Level of progesterone in blood plasma was determined by enzyme- immune analyses. RESULTS: Changes in the level of progesterone in blood plasma in MD and control group of animals were detected. In the test of two bottles 10% of ethanol solution presented on days 2 and 3, statistically significant differences in consumption were determined in contrast to the control group. In the test of balloon diapering, MD group of animals showed a statistically proved significant increase in compulsiveness both before the beginning of voluntary alcoholization and on day 3 from the start. CONCLUSIONS: The increase in compulsivity and voluntary ethanol consumption was significantly higher in the MD group, that is comparable to the increased level in blood plasma progesterone samples.
{"title":"Chronic mental stress in early ontogenesis increased risks of development for chemical and non-chemical forms of addiction","authors":"S. S. Pyurveev, Mikhail S. Nekrasov, Nikolay S. Dedanishvili, Albina S. Nekrasova, Tatyana V. Brus, A. Lebedev, Nicanor V. Lavrov, A. V. Podrezova, R. Glushakov, P. Shabanov","doi":"10.17816/rcf321507","DOIUrl":"https://doi.org/10.17816/rcf321507","url":null,"abstract":"BACKGROUND: Exposure to acute or chronic stress contributes to the occurrence of various disorders of the central nervous system, psycho-emotional sphere, as well as increases the risks of development of various forms of addiction. \u0000AIM: The aim of the study is analyze the influence of maternal deprivation on voluntary alcohol consumption in adolescents and to determine the degree of the signs of compulsive behavior in experimental animals. \u0000MATERIALS AND METHODS: Thirty male Wistar rats were taken in the research. A maternal deprivation model was carried out from day 2 to day 12 of the postnatal period (MD). Compulsivity (compulsive tendency) was evaluated in the ball burial test. Voluntary alcoholization with 10% ethyl alcohol solution in a two-bottle test was employed. Level of progesterone in blood plasma was determined by enzyme- immune analyses. \u0000RESULTS: Changes in the level of progesterone in blood plasma in MD and control group of animals were detected. In the test of two bottles 10% of ethanol solution presented on days 2 and 3, statistically significant differences in consumption were determined in contrast to the control group. In the test of balloon diapering, MD group of animals showed a statistically proved significant increase in compulsiveness both before the beginning of voluntary alcoholization and on day 3 from the start. \u0000CONCLUSIONS: The increase in compulsivity and voluntary ethanol consumption was significantly higher in the MD group, that is comparable to the increased level in blood plasma progesterone samples.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77922626","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. Litasova, V. Iljin, M. A. Brusina, L. B. Piotrovskiy
The review is a continuation of the previously published one on the toxicity of spherical nanostructures of carbon, namely fullerenes and nanoonions. This review considers data on the toxicity of carbon nanostructures in sp2-hybridization of carbon atoms, which can be considered as formed from graphene sheets, and nanostructures formed by carbon atoms in sp3-hybridization, namely, nanodiamonds. Unfortunately, it should be repeated the conclusion made in the previous review that at the moment there is not enough data to use carbon nanostructures in practice, and therefore it is necessary to develop more effective and informative tests on animals, taking into account the characteristics of each type of nanomaterials.
{"title":"Toxicology of carbon nanostructures. Part 2. Nanoscale materials based on graphene sheets","authors":"E. Litasova, V. Iljin, M. A. Brusina, L. B. Piotrovskiy","doi":"10.17816/rcf113017","DOIUrl":"https://doi.org/10.17816/rcf113017","url":null,"abstract":"The review is a continuation of the previously published one on the toxicity of spherical nanostructures of carbon, namely fullerenes and nanoonions. This review considers data on the toxicity of carbon nanostructures in sp2-hybridization of carbon atoms, which can be considered as formed from graphene sheets, and nanostructures formed by carbon atoms in sp3-hybridization, namely, nanodiamonds. Unfortunately, it should be repeated the conclusion made in the previous review that at the moment there is not enough data to use carbon nanostructures in practice, and therefore it is necessary to develop more effective and informative tests on animals, taking into account the characteristics of each type of nanomaterials.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89864931","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. I. Vashchenko, Alexey B. Chuklovin, P. Shabanov
Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with limited functionality. However, recent advances in highthroughput genomic technology have allowed circRNAs to be characterized in detail and revealed their important functions in controlling various biological and molecular processes, the most essential being gene regulation. Due to structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA 2 biology. Unlike linear RNAs, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming covalently closed loop-like molecules missing 3' poly-(A) tail or 5' cap structures, thus rendering them resistant to exonuclease-mediated degradation. Previous studies have revealed multiple roles of circRNAs as sponges for miRNA and RNA-binding proteins (RBP), as well as regulators of transcription, translation, and splicing events. Recent advances in the field suggest that the circRNAs are involved in many human disorders, including cancer and neurodegenerative disorders such as Alzheimers and Parkinsons disease, due to their aberrant expression in different pathological conditions. The circRNAs are stable in cells, owing to their circular structure. Participation of circRNAs in programmed cellular destruction by autophagy is discussed in details. The autophagy is a catabolic process which promotes decomposition and recycling of harmful or redundant biological macromolecules and initiates destruction of ageing cells. Processes how circRNAs influence a course of a disease, including an autophagy are in detail discussed, specifying that it joins at the beginning and upon development of various illnesses, and it can influence drug resistance (for example, antitumor efficiency of Cisplatin). The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular actions of circRNAs and their usage as potential therapeutic targets in different human malignancies.
{"title":"Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases","authors":"V. I. Vashchenko, Alexey B. Chuklovin, P. Shabanov","doi":"10.17816/rcf204335-384","DOIUrl":"https://doi.org/10.17816/rcf204335-384","url":null,"abstract":"Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with limited functionality. \u0000However, recent advances in highthroughput genomic technology have allowed circRNAs to be characterized in detail and revealed their important functions in controlling various biological and molecular processes, the most essential being gene regulation. Due to structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA 2 biology. Unlike linear RNAs, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming covalently closed loop-like molecules missing 3' poly-(A) tail or 5' cap structures, thus rendering them resistant to exonuclease-mediated degradation. \u0000Previous studies have revealed multiple roles of circRNAs as sponges for miRNA and RNA-binding proteins (RBP), as well as regulators of transcription, translation, and splicing events. Recent advances in the field suggest that the circRNAs are involved in many human disorders, including cancer and neurodegenerative disorders such as Alzheimers and Parkinsons disease, due to their aberrant expression in different pathological conditions. The circRNAs are stable in cells, owing to their circular structure. Participation of circRNAs in programmed cellular destruction by autophagy is discussed in details. The autophagy is a catabolic process which promotes decomposition and recycling of harmful or redundant biological macromolecules and initiates destruction of ageing cells. Processes how circRNAs influence a course of a disease, including an autophagy are in detail discussed, specifying that it joins at the beginning and upon development of various illnesses, and it can influence drug resistance (for example, antitumor efficiency of Cisplatin). \u0000The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular actions of circRNAs and their usage as potential therapeutic targets in different human malignancies.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79404628","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}
Svetlana A. Doktorova, V. Rafalskiy, Y. Y. Grabovetskaya, S. Korenev
BACKGROUND: For the last decade, physicians and researchers have been actively developing and investigating a novel targeted synthetic disease-modifying antirheumatic drugs. The application of drugs that affect the JAK-STAT pathway and multiple proinflammatory cytokines certainly has great potential for the treatment of different inflammatory diseases. This review provides articles from the past 10 years describing these small-molecule inhibitors: clinical pharmacology, safety, adverse effects and application. There is a growing body of literature that recognises the importance of JAK inhibitors as attractive pharmacological alternative to biologics. AIM: The article aims to explore clinical pharmacology of JAK inhibitors, safety, drug interactions, comparison with biologic disease-modifying antirheumatic drugs and perspective applications for these drugs. MATERIALS AND METHODS: The research data in this review is drawn from five main sources: PubMed, Scopus, Medline, GoogleScholar, eLibrary. A search was conducted for the period from 2012 to 2022 in Russian and English, by combinations of words: janus kinase inhibitors, disease-modifying antirheumatic drugs, safety, adverse effects, autoimmune diseases, pharmacokinetics, pharmacodynamics. RESULTS: The most important clinically relevant findings were that these small-molecule inhibitors have a main advantages like oral administration, rapid therapeutics effect and less of patients-non-responders to therapy. On the other hand, JAK inhibitors have a classic pharmacokinetics and pharmacodynamics, this allows to study such parameters using standard methods. CONCLUSIONS: In this review, the aim was to assess clinical pharmacology of JAK inhibitors, safety, comparison withbiologic disease-modifying antirheumatic drugs and perspective applications for these drugs. In general, it seems that the safety issues of JAK inhibitors unresolved, in particular the development of thromboembolic complications, infectiousdiseases, and malignancies. This is an important issue for future research.
{"title":"JAK-inhibitors: clinical pharmacology and application perspectives","authors":"Svetlana A. Doktorova, V. Rafalskiy, Y. Y. Grabovetskaya, S. Korenev","doi":"10.17816/rcf204421-434","DOIUrl":"https://doi.org/10.17816/rcf204421-434","url":null,"abstract":"BACKGROUND: For the last decade, physicians and researchers have been actively developing and investigating a novel targeted synthetic disease-modifying antirheumatic drugs. The application of drugs that affect the JAK-STAT pathway and multiple proinflammatory cytokines certainly has great potential for the treatment of different inflammatory diseases. This review provides articles from the past 10 years describing these small-molecule inhibitors: clinical pharmacology, safety, adverse effects and application. There is a growing body of literature that recognises the importance of JAK inhibitors as attractive pharmacological alternative to biologics. \u0000AIM: The article aims to explore clinical pharmacology of JAK inhibitors, safety, drug interactions, comparison with biologic disease-modifying antirheumatic drugs and perspective applications for these drugs. \u0000MATERIALS AND METHODS: The research data in this review is drawn from five main sources: PubMed, Scopus, Medline, GoogleScholar, eLibrary. A search was conducted for the period from 2012 to 2022 in Russian and English, by combinations of words: janus kinase inhibitors, disease-modifying antirheumatic drugs, safety, adverse effects, autoimmune diseases, pharmacokinetics, pharmacodynamics. \u0000RESULTS: The most important clinically relevant findings were that these small-molecule inhibitors have a main advantages like oral administration, rapid therapeutics effect and less of patients-non-responders to therapy. On the other hand, JAK inhibitors have a classic pharmacokinetics and pharmacodynamics, this allows to study such parameters using standard methods. \u0000CONCLUSIONS: In this review, the aim was to assess clinical pharmacology of JAK inhibitors, safety, comparison withbiologic disease-modifying antirheumatic drugs and perspective applications for these drugs. In general, it seems that the safety issues of JAK inhibitors unresolved, in particular the development of thromboembolic complications, infectiousdiseases, and malignancies. This is an important issue for future research.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73848712","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}
Llya Yu. Tissen, L. Magarramova, Mihail D. Ayzup, A. Lebedev, P. Shabanov
BACKGROUND: Melanocortins, including -melanocyte stimulating hormone (MSH), MSH, MSH, and adrenocorticotropic hormone, are products of the polypeptide proopiomelanocortin. These products bind to five different melanocortin receptors (MC1R, MC2R, MC3R, MC4R, MC5R) with different affinities. Because MC3R and MC4R are the major types expressed in the brain, these two receptors can mediate the behavioral effects of melanocortins. AIM: To clear the role of MC4R in sexual behavior of male rats after social isolation from relatives. MATERIALS AND METHODS: In the present study, 40 naive male Wistar rats divided into 4 groups, 3 of which were grown in complete social and partial sensory isolation, received saline, PT-141 (MC3R/MC4R agonist) in a dose 0.3 g intraperitoneally, and THIQ (MC4R agonist) in a dose 0.1 g intranasally. Behavioral effects were registered in a cage with unreachable reinforcement in which the female in the estrus phase, separated by a transparent perforated barrier, was kept for 10 minutes under red light. Blood samples were taken 30 minutes after administration from the tail vein. Testosterone concentrations were measured by ELISA. RESULTS: Social isolation had no significant effect on latent time before trying to reach a female but decreased the time spent near the cage with a female. Isolated animals did not show genital grooming acts during the experiment. PT-141 decreased the latent time to approach the female, increased the time spent near the female cage, and stimulated genital grooming. THIQ decreased the latent time to reach a female and stimulated genital grooming. At the same time, THIQ had no effect on the time spent near the female cage. Social isolation reduced testosterone levels more than twice compared to controls. The administration of PT-141 and THIQ had no effect on testosterone concentration. CONCLUSIONS: The results confirm the depressing effect of chronic social isolation stress on the sexual motivation of male rats and demonstrate different roles of melanocortin MC3R/MC4R receptors in the realization of sexual behavior.
{"title":"Effects of agonists of melanocortin receptors MC3Rand MC4R on components of sexual behavior of male rats reared in condition of chronic social isolation","authors":"Llya Yu. Tissen, L. Magarramova, Mihail D. Ayzup, A. Lebedev, P. Shabanov","doi":"10.17816/rcf204415-420","DOIUrl":"https://doi.org/10.17816/rcf204415-420","url":null,"abstract":"BACKGROUND: Melanocortins, including -melanocyte stimulating hormone (MSH), MSH, MSH, and adrenocorticotropic hormone, are products of the polypeptide proopiomelanocortin. These products bind to five different melanocortin receptors (MC1R, MC2R, MC3R, MC4R, MC5R) with different affinities. Because MC3R and MC4R are the major types expressed in the brain, these two receptors can mediate the behavioral effects of melanocortins. \u0000AIM: To clear the role of MC4R in sexual behavior of male rats after social isolation from relatives. \u0000MATERIALS AND METHODS: In the present study, 40 naive male Wistar rats divided into 4 groups, 3 of which were grown in complete social and partial sensory isolation, received saline, PT-141 (MC3R/MC4R agonist) in a dose 0.3 g intraperitoneally, and THIQ (MC4R agonist) in a dose 0.1 g intranasally. Behavioral effects were registered in a cage with unreachable reinforcement in which the female in the estrus phase, separated by a transparent perforated barrier, was kept for 10 minutes under red light. Blood samples were taken 30 minutes after administration from the tail vein. Testosterone concentrations were measured by ELISA. \u0000RESULTS: Social isolation had no significant effect on latent time before trying to reach a female but decreased the time spent near the cage with a female. Isolated animals did not show genital grooming acts during the experiment. PT-141 decreased the latent time to approach the female, increased the time spent near the female cage, and stimulated genital grooming. THIQ decreased the latent time to reach a female and stimulated genital grooming. At the same time, THIQ had no effect on the time spent near the female cage. Social isolation reduced testosterone levels more than twice compared to controls. The administration of PT-141 and THIQ had no effect on testosterone concentration. \u0000CONCLUSIONS: The results confirm the depressing effect of chronic social isolation stress on the sexual motivation of male rats and demonstrate different roles of melanocortin MC3R/MC4R receptors in the realization of sexual behavior.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80644920","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}
Andrey I. Danilov, A. V. Evseev, M. A. Evseeva, Olga V. Pavluchenkova, V. A. Pereverzev
Chronic heart failure is in the vast majority of cases the outcome of many cardiovascular diseases. Despite significant achievements in the early diagnosis and treatment of cardiological pathology, the prevalence of chronic heart failure is steadily increasing, increasing the material costs of the healthcare system. Experts explain this aspect by the aging of the population of the developed countries of the world due to an increase in life expectancy. The presented review highlights the possibilities of using sacubitril/valsartan in clinical practice in order to inhibit the progression of chronic heart failure.
{"title":"Sacubitril/valsartan as a component of therapy for chronic heart failure","authors":"Andrey I. Danilov, A. V. Evseev, M. A. Evseeva, Olga V. Pavluchenkova, V. A. Pereverzev","doi":"10.17816/rcf204407-413","DOIUrl":"https://doi.org/10.17816/rcf204407-413","url":null,"abstract":"Chronic heart failure is in the vast majority of cases the outcome of many cardiovascular diseases. Despite significant achievements in the early diagnosis and treatment of cardiological pathology, the prevalence of chronic heart failure is steadily increasing, increasing the material costs of the healthcare system. Experts explain this aspect by the aging of the population of the developed countries of the world due to an increase in life expectancy. The presented review highlights the possibilities of using sacubitril/valsartan in clinical practice in order to inhibit the progression of chronic heart failure.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"516 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77122735","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}
This review discusses information about the structure and function of calcium channels in the plasma membrane and mitochondria of the heart, and pharmacological methods for modulating their conductance. Experimental data are presented that characterize the change in the energy metabolism of cardiomyocytes against the background of the transformation of the conductivity of L-type calcium channels of the cell membrane in a non-invasive model of vibration-mediated (56 sessions of total vertical vibration, with a frequency of 44 Hz and an amplitude of 0.5 mm) hypoxia. It was shown that in animals treated with calcium channel blocker adalat (nifedipine INN) against the background of vibration, the rate of endogenous respiration (Ve), measured by the polarographic method using a closed Clark electrode in native homogenate of rabbit myocardial tissue, remained at the level of intact animals and amounted to 16.3 4.3 ng-O atom/ min mg of protein, amytal sensitivity increased by 39% (p 0.05) compared to the group of vibrated animals, low-natality decreased by 40% (p 0.05). The dynamics of the rate of substrate respiration (Vac and Vglu + mal) in the group with adalat returned to that of intact animals, which indicated the restoration of the physiological predominance of the activity of theNADH CoQ-reductase complex in redox reactions. It was found that the blockade of transport of Ca2+ ions at the level of high-threshold (HVA) voltage-dependent ion channels of the L-type of the cell membrane, normalizing the activity of the I enzyme-substrate complex of the respiratory chain and regulatoryly restraining the hyperactivity of succinate dehydrogenase in zone II of the enzyme-substrate complex, has an energy-protective effect. Adalat prevented a low-energy shift and the development of bioenergetic hypoxia in the myocardial tissue of experimental animals.
{"title":"Biochemical mechanisms of the energy-protective action of blockers of slow high-threshold L-type calcium channels","authors":"V. V. Vorobieva, O. S. Levchenkova, P. Shabanov","doi":"10.17816/rcf204395-405","DOIUrl":"https://doi.org/10.17816/rcf204395-405","url":null,"abstract":"This review discusses information about the structure and function of calcium channels in the plasma membrane and mitochondria of the heart, and pharmacological methods for modulating their conductance. Experimental data are presented that characterize the change in the energy metabolism of cardiomyocytes against the background of the transformation of the conductivity of L-type calcium channels of the cell membrane in a non-invasive model of vibration-mediated (56 sessions of total vertical vibration, with a frequency of 44 Hz and an amplitude of 0.5 mm) hypoxia. \u0000It was shown that in animals treated with calcium channel blocker adalat (nifedipine INN) against the background of vibration, the rate of endogenous respiration (Ve), measured by the polarographic method using a closed Clark electrode in native homogenate of rabbit myocardial tissue, remained at the level of intact animals and amounted to 16.3 4.3 ng-O atom/ min mg of protein, amytal sensitivity increased by 39% (p 0.05) compared to the group of vibrated animals, low-natality decreased by 40% (p 0.05). The dynamics of the rate of substrate respiration (Vac and Vglu + mal) in the group with adalat returned to that of intact animals, which indicated the restoration of the physiological predominance of the activity of theNADH CoQ-reductase complex in redox reactions. It was found that the blockade of transport of Ca2+ ions at the level of high-threshold (HVA) voltage-dependent ion channels of the L-type of the cell membrane, normalizing the activity of the I enzyme-substrate complex of the respiratory chain and regulatoryly restraining the hyperactivity of succinate dehydrogenase in zone II of the enzyme-substrate complex, has an energy-protective effect. Adalat prevented a low-energy shift and the development of bioenergetic hypoxia in the myocardial tissue of experimental animals.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89017436","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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