V. Iljin, E. Litasova, Maksim S. Kvasov, Mariia A. Brusina, L. B. Piotrovskiy
BACKGROUND: It is important to know the ability of a substance to penetrate the cell membrane to assess the bioavailability of drugs. The distribution of matter between the organic phase and water can be used as a model of the distribution between the membrane and extracellular fluid, and can be expressed by a partion coefficient, called logP. AIM: The aim of this work was to determine the logP of 1H-imidazole-4,5-dicarboxylic acid (IDC) derivatives in various media and compare the values with theoretical ones. RESULTS: As a result of the work, the distribution coefficients of the IDC derivatives were determined from the optical density data for a fixed wavelength of 250 nm (without a buffer). The distribution coefficients of the IDC derivatives over the maxima of the UV spectra (in the buffer) were determined. A comparison of theoretical and experimental values of the distribution coefficients of some IDC derivatives is carried out. CONCLUSION: Thus, it has been shown that for a more accurate assessment of the bioavailability of drugs, it is not enough to rely only on the calculated logP index, it is necessary to conduct an experimental test, or introduce some correction factors to recalculate the theoretical logP index, in each specific class of compounds.
{"title":"Evaluation of the bioavailability of 1H-imidazole-4,5-dicarboxylic acid derivatives using the calculated and experimental lipophilicity index of the molecule logP","authors":"V. Iljin, E. Litasova, Maksim S. Kvasov, Mariia A. Brusina, L. B. Piotrovskiy","doi":"10.17816/rcf20155-60","DOIUrl":"https://doi.org/10.17816/rcf20155-60","url":null,"abstract":"BACKGROUND: It is important to know the ability of a substance to penetrate the cell membrane to assess the bioavailability of drugs. The distribution of matter between the organic phase and water can be used as a model of the distribution between the membrane and extracellular fluid, and can be expressed by a partion coefficient, called logP. \u0000AIM: The aim of this work was to determine the logP of 1H-imidazole-4,5-dicarboxylic acid (IDC) derivatives in various media and compare the values with theoretical ones. \u0000RESULTS: As a result of the work, the distribution coefficients of the IDC derivatives were determined from the optical density data for a fixed wavelength of 250 nm (without a buffer). The distribution coefficients of the IDC derivatives over the maxima of the UV spectra (in the buffer) were determined. A comparison of theoretical and experimental values of the distribution coefficients of some IDC derivatives is carried out. \u0000CONCLUSION: Thus, it has been shown that for a more accurate assessment of the bioavailability of drugs, it is not enough to rely only on the calculated logP index, it is necessary to conduct an experimental test, or introduce some correction factors to recalculate the theoretical logP index, in each specific class of compounds.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78596423","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}
AIM: The aim was to assess the efficacy of treatment of asthenic syndrome in patients with combined injuries by means of succinate containing metabolic drugs (Mexidol, Cytoflavine, Metaprot plus) in comparison with non-succinate containing drugs of analogic structure or composition (Emoxipine, Riboxine, Metaprot) to clear up the significance of succinate as a functional structural element of the molecule. MATERIALS AND METHODS: In 134 surgical patients and sufferers with combined injuries, an asthenic syndrome (high anxiety, depression, high psychic and physical tiredness, weakness, absent-mindedness, attention disorders, reduced physical and psychical ability, need in durative rest, high psychic exhaustion, social disadaptation) was revealed by clinical, psychological and instrumental methods. RESULTS: Metabolic drugs containing succinate (Mexidol, Cytoflavine, Metaprot plus) in more degree than non-containing succinate in their structure (Emoxipine, Riboxine, Metaprot) were clinically effective in abolition or reduction of the asthenic syndrome in such patients. Antiasthenic action was represented by proper antiasthenic, antidepressant, anxiolytic, nootropic (cognitive) and positive general somatic effects of the drugs. CONCLUSION: The data confirm that succinate in the structure (composition) of the metabolic drugs significantly enhances protective action against asthenic syndrome in surgical patients with combined injuries.
{"title":"Does succinate as a structural component of a drug enhance efficacy of treatment of asthenic disorders in patients with somatic injuries?","authors":"G. V. Buznik","doi":"10.17816/rcf20189-98","DOIUrl":"https://doi.org/10.17816/rcf20189-98","url":null,"abstract":"AIM: The aim was to assess the efficacy of treatment of asthenic syndrome in patients with combined injuries by means of succinate containing metabolic drugs (Mexidol, Cytoflavine, Metaprot plus) in comparison with non-succinate containing drugs of analogic structure or composition (Emoxipine, Riboxine, Metaprot) to clear up the significance of succinate as a functional structural element of the molecule. \u0000MATERIALS AND METHODS: In 134 surgical patients and sufferers with combined injuries, an asthenic syndrome (high anxiety, depression, high psychic and physical tiredness, weakness, absent-mindedness, attention disorders, reduced physical and psychical ability, need in durative rest, high psychic exhaustion, social disadaptation) was revealed by clinical, psychological and instrumental methods. \u0000RESULTS: Metabolic drugs containing succinate (Mexidol, Cytoflavine, Metaprot plus) in more degree than non-containing succinate in their structure (Emoxipine, Riboxine, Metaprot) were clinically effective in abolition or reduction of the asthenic syndrome in such patients. Antiasthenic action was represented by proper antiasthenic, antidepressant, anxiolytic, nootropic (cognitive) and positive general somatic effects of the drugs. \u0000CONCLUSION: The data confirm that succinate in the structure (composition) of the metabolic drugs significantly enhances protective action against asthenic syndrome in surgical patients with combined injuries.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"221 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74939523","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: Resistance to hypoxia depends on the type of animal, its condition (fatigue, pre-exposure, pregnancy in females) and the conditions of the experiments. AIM: study the effect of ethylthiobenzimidazole (Metaprot, Bemityl) and fabomotizole (Afobazole), which were antihypoxants with an isothiourea group, on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one of the cerebral hemispheres. MATERIALS AND METHODS: Acute hypoxia with hypercapnia was simulated by the cupping method by placing male mice in a closed hermetic volume (200 cm3) until the death of the animal. Previously, in some mice, one of the cerebral hemispheres was temporarily switched off according to the Leao method. RESULTS: It has been shown that ethylthiobenzimidazole and fabomotizole, administered intraperitoneally in equimolar doses (25 and 32.8 mg/kg, respectively) 30 min before a hypoxic episode, increase the life time of experimental animals when either of the hemispheres (right or left) is turned off approximately equally. CONCLUSIONS: Data are considered in terms of the possibility of using both drugs in the prevention and treatment of ischemic strokes.
{"title":"Assessment of ethylthiobenzimidazole and fabomotizole activity in a model of hypercapnic hypoxia with cutting off the brain hemispheres work","authors":"V. V. Marysheva, V. V. Mikheev, P. Shabanov","doi":"10.17816/rcf20175-82","DOIUrl":"https://doi.org/10.17816/rcf20175-82","url":null,"abstract":"BACKGROUND: Resistance to hypoxia depends on the type of animal, its condition (fatigue, pre-exposure, pregnancy in females) and the conditions of the experiments. \u0000AIM: study the effect of ethylthiobenzimidazole (Metaprot, Bemityl) and fabomotizole (Afobazole), which were antihypoxants with an isothiourea group, on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one of the cerebral hemispheres. \u0000MATERIALS AND METHODS: Acute hypoxia with hypercapnia was simulated by the cupping method by placing male mice in a closed hermetic volume (200 cm3) until the death of the animal. Previously, in some mice, one of the cerebral hemispheres was temporarily switched off according to the Leao method. \u0000RESULTS: It has been shown that ethylthiobenzimidazole and fabomotizole, administered intraperitoneally in equimolar doses (25 and 32.8 mg/kg, respectively) 30 min before a hypoxic episode, increase the life time of experimental animals when either of the hemispheres (right or left) is turned off approximately equally. \u0000CONCLUSIONS: Data are considered in terms of the possibility of using both drugs in the prevention and treatment of ischemic strokes.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82601884","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}
I. Tissen, A. Lebedev, P. Khokhlov, E. Bychkov, S. Tsikunov, P. Shabanov
BACKGROUND: A number of recent studies have revealed the role of orexins in regulating emotional behavior and emotional memory. The rationale for this role of orexin regulation is the close bi-directional interaction of orexin neurons with emotional structures of the brain, such as the bed nucleus of the stria terminalis, locus ceruleus, central and dorsomedial amygdala, hippocampus, medial prefrontal cortex. There is experimental and clinical evidence that an endogenous or induced deficiency of orexin effects accelerates the elimination of traumatic memory. AIM: To study the effect of the OX1R Orexin Receptor Antagonist SB408124 and orexin on the emotional and exploratory behavior of animals after predator-induced stress. MATERIALS AND METHODS: The experiments were made with 36 male Wistar rats, divided into 4 groups of 8 animals. Animals of 3 groups were exposed to single simulation of post-traumatic stress disorder by exposition with the indian python and subsequent death of one rat as a result of predator activity. The rats of 2 experimental groups received SB408124 OX1R antagonist in a dose of 20 l of 0.1% solution and Orexin A in the same dose intranasally. The other animals received physiological solution in a dose of 20 l intranasally. Behavior tests was made 7 days after the modeling of psychotrauma. A panel of behavioral tests was used: an elevated X-maze, an open field test, and an residentintruder test. The obtained data were statistically processed using the Student t-test and ANOVA dispersion analysis. The differences were considered statistically significant at p 0.01. RESULTS: Orexin antagonist SB408124 showed anxiolytic effects. SB408124 showed anxiolytic properties in stressed rats. It restored the time spent in the light arm of the elevated X-maze to the intact level. In the open field test SB408124 increased (p 0.01) the orientation behavior and reduced the frequency of freezing in stressed animals. Orexin A suppressed (p 0,01) locomotor activity of animals in the open field. In the residentintruder test in stressed animals SB408124 restored suppressed communication activity (p 0,01). Orexin A reduced communicative behavior and increased aggression of animals. CONCLUSIONS: The work shows a moderate anxiolytic action of SB408124 in the post-traumatic stress model in rats.
{"title":"Effect of orexin and its antagonist on the organization of emotional and exploratory behavior of rats in a model of psychic trauma","authors":"I. Tissen, A. Lebedev, P. Khokhlov, E. Bychkov, S. Tsikunov, P. Shabanov","doi":"10.17816/rcf20183-88","DOIUrl":"https://doi.org/10.17816/rcf20183-88","url":null,"abstract":"BACKGROUND: A number of recent studies have revealed the role of orexins in regulating emotional behavior and emotional memory. The rationale for this role of orexin regulation is the close bi-directional interaction of orexin neurons with emotional structures of the brain, such as the bed nucleus of the stria terminalis, locus ceruleus, central and dorsomedial amygdala, hippocampus, medial prefrontal cortex. There is experimental and clinical evidence that an endogenous or induced deficiency of orexin effects accelerates the elimination of traumatic memory. \u0000AIM: To study the effect of the OX1R Orexin Receptor Antagonist SB408124 and orexin on the emotional and exploratory behavior of animals after predator-induced stress. \u0000MATERIALS AND METHODS: The experiments were made with 36 male Wistar rats, divided into 4 groups of 8 animals. Animals of 3 groups were exposed to single simulation of post-traumatic stress disorder by exposition with the indian python and subsequent death of one rat as a result of predator activity. The rats of 2 experimental groups received SB408124 OX1R antagonist in a dose of 20 l of 0.1% solution and Orexin A in the same dose intranasally. The other animals received physiological solution in a dose of 20 l intranasally. Behavior tests was made 7 days after the modeling of psychotrauma. A panel of behavioral tests was used: an elevated X-maze, an open field test, and an residentintruder test. The obtained data were statistically processed using the Student t-test and ANOVA dispersion analysis. The differences were considered statistically significant at p 0.01. \u0000RESULTS: Orexin antagonist SB408124 showed anxiolytic effects. SB408124 showed anxiolytic properties in stressed rats. It restored the time spent in the light arm of the elevated X-maze to the intact level. In the open field test SB408124 increased (p 0.01) the orientation behavior and reduced the frequency of freezing in stressed animals. Orexin A suppressed (p 0,01) locomotor activity of animals in the open field. In the residentintruder test in stressed animals SB408124 restored suppressed communication activity (p 0,01). Orexin A reduced communicative behavior and increased aggression of animals. \u0000CONCLUSIONS: The work shows a moderate anxiolytic action of SB408124 in the post-traumatic stress model in rats.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85847713","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. Shulgina, Kseniya V. Zubova, E. Glinskaya, O. Nechaeva, Natalya V. Bespalova
BACKGROUND: The construction and application of antimicrobial drugs on the basis of nanoparticles of metals, silver and gold in particular, are staying casual up to now. AIM: was to study the spectrum of antimicrobial activity of nanoparticles of silver and gold developed by means of chemical recovery and stabilized with native and synthetic compounds. MATERIALS AND METHODS: The paper presents the results of a study of the antimicrobial activity of aqueous dispersions of silver and gold nanoparticles against standard and clinical strains of Staphylococcus aureus, which were sensitive to methicillin. Natural (carboxymethylcellulose, sodium oleate) and synthetic (polyvinyl alcohol, sodium dodecyl sulfate, polyazolidylammonium modified with iodine hydrate ions) polymeric compounds were used as stabilizers. RESULTS: The high antistaphylococcal activity of the studied drugs was established, which depended on the stabilizer used. The highest efficiency of biocidal action was revealed for aqueous dispersions of metal nanoparticles stabilized with polyvinyl alcohol and polyazolidylammonium modified with iodine hydrate ions, which did not depend on the strain differences of microorganisms. CONCLUSIONS: The results obtained open up prospects for the use of aqueous dispersions of silver and gold nanoparticles as active components in the development of new antiseptic preparations and photosensitizers for antimicrobial photodynamic therapy.
{"title":"Comparative characteristics of antimicrobial activity of water dispersions of silver and gold nanoparticles stabilized with native and synthetic polymers","authors":"T. Shulgina, Kseniya V. Zubova, E. Glinskaya, O. Nechaeva, Natalya V. Bespalova","doi":"10.17816/rcf194405-411","DOIUrl":"https://doi.org/10.17816/rcf194405-411","url":null,"abstract":"BACKGROUND: The construction and application of antimicrobial drugs on the basis of nanoparticles of metals, silver and gold in particular, are staying casual up to now. \u0000AIM: was to study the spectrum of antimicrobial activity of nanoparticles of silver and gold developed by means of chemical recovery and stabilized with native and synthetic compounds. \u0000MATERIALS AND METHODS: The paper presents the results of a study of the antimicrobial activity of aqueous dispersions of silver and gold nanoparticles against standard and clinical strains of Staphylococcus aureus, which were sensitive to methicillin. Natural (carboxymethylcellulose, sodium oleate) and synthetic (polyvinyl alcohol, sodium dodecyl sulfate, polyazolidylammonium modified with iodine hydrate ions) polymeric compounds were used as stabilizers. \u0000RESULTS: The high antistaphylococcal activity of the studied drugs was established, which depended on the stabilizer used. The highest efficiency of biocidal action was revealed for aqueous dispersions of metal nanoparticles stabilized with polyvinyl alcohol and polyazolidylammonium modified with iodine hydrate ions, which did not depend on the strain differences of microorganisms. \u0000CONCLUSIONS: The results obtained open up prospects for the use of aqueous dispersions of silver and gold nanoparticles as active components in the development of new antiseptic preparations and photosensitizers for antimicrobial photodynamic therapy.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90609235","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 immediate cause of death of patients in the final stage of a new coronavirus infection is hypoxia, which develops due to respiratory obstruction. In accordance with the standard of treatment of patients with the most severe atypical pneumonia with COVID-19, artificial lung ventilation and extrapulmonary blood oxygenation are used to preserve their lives. However, these methods do not eliminate airway obstruction, one of the causes of which is mucus hypersecretion. The review shows that a new vector for the search and development of medicines for the drug elimination of hypoxia in respiratory obstruction has been identified in Russia. The high prospects of solutions of hydrogen peroxide and sodium bicarbonate with original physicochemical properties and local mechanisms of action providing urgent recanalization of the respiratory tract and oxygenation of blood in respiratory obstruction caused by blockage of the respiratory tract with thick sputum, mucus, pus and blood are shown. Domestic inventions are indicated, the essence of which is the basis of this scientific direction. Original formulations of solutions of hydrogen peroxide and sodium bicarbonate are given, as well as new technologies for their local application, providing urgent dissolution of mucus, sputum, pus and blood with simultaneous immediate release of oxygen gas.
{"title":"Acute respiratory syndrome-2 (SARS-CoV-2): A solution of hydrogen peroxide and sodium bicarbonate as an expectorant for recanalization of the respiratory tract and blood oxygenation in respiratory obstruction (review)","authors":"A. Urakov, P. Shabanov","doi":"10.17816/rcf194383-393","DOIUrl":"https://doi.org/10.17816/rcf194383-393","url":null,"abstract":"The immediate cause of death of patients in the final stage of a new coronavirus infection is hypoxia, which develops due to respiratory obstruction. In accordance with the standard of treatment of patients with the most severe atypical pneumonia with COVID-19, artificial lung ventilation and extrapulmonary blood oxygenation are used to preserve their lives. However, these methods do not eliminate airway obstruction, one of the causes of which is mucus hypersecretion. The review shows that a new vector for the search and development of medicines for the drug elimination of hypoxia in respiratory obstruction has been identified in Russia. The high prospects of solutions of hydrogen peroxide and sodium bicarbonate with original physicochemical properties and local mechanisms of action providing urgent recanalization of the respiratory tract and oxygenation of blood in respiratory obstruction caused by blockage of the respiratory tract with thick sputum, mucus, pus and blood are shown. Domestic inventions are indicated, the essence of which is the basis of this scientific direction. Original formulations of solutions of hydrogen peroxide and sodium bicarbonate are given, as well as new technologies for their local application, providing urgent dissolution of mucus, sputum, pus and blood with simultaneous immediate release of oxygen gas.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90930468","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 increasing of morbidity with bronchial asthma, allergic respiratory diseases demand active search not only medicamental treatment. The review of foreign articles states successful using plant drugs and methods of traditional medicines. Proper clinical practice confirms the foreign authors results: the phytotherapy of patients with bronchial asthma is high effective and safe method. It is necessary wide scale, state supported measures for introduction phytotherapy to practice.
{"title":"Examples of positive phytotherapy of patients with bronchial asthma","authors":"O. D. Barnaulov, Y. Timosheva","doi":"10.17816/rcf194451-462","DOIUrl":"https://doi.org/10.17816/rcf194451-462","url":null,"abstract":"The increasing of morbidity with bronchial asthma, allergic respiratory diseases demand active search not only medicamental treatment. The review of foreign articles states successful using plant drugs and methods of traditional medicines. Proper clinical practice confirms the foreign authors results: the phytotherapy of patients with bronchial asthma is high effective and safe method. It is necessary wide scale, state supported measures for introduction phytotherapy to practice.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85810467","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, Juliya E. Romashova, P. Shabanov
Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 2025 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz: TNF-, NF-B and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.
{"title":"Pathophysiology of miR-146a in lung cancer. Prospects of rising of efficiency of targeted therapy","authors":"V. I. Vashchenko, Juliya E. Romashova, P. Shabanov","doi":"10.17816/rcf194359-381","DOIUrl":"https://doi.org/10.17816/rcf194359-381","url":null,"abstract":"Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 2025 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz: TNF-, NF-B and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81966610","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}
I. Spivak, A. Zhekalov, A. I. Glushakov, A. V. Lemeshchenko, Vladislav A. Nyrov, Aleksandra E. Trandina, P.A. Shapovalov, Andrei G. Zakharchuk, Dmitry L. Spivak
BACKGROUND: The ability of a person in the process of active activity to adapt to changing environmental conditions is largely related to his creative potential. Creativity, like other physical and mental personality traits, has its own genetic base, which has not been sufficiently studied to date. Certain genes involved in this process are regularly described. The search for an association with new candidate genes for the creative potential of practically healthy, young respondents selected for work in the extreme conditions of the North is extremely important in the selection of people for work and service in difficult conditions. AIM: Search for the correlation of candidate gene polymorphism and the psychological state of the examined. MATERIALS AND METHODS: The psychological block of the pilot study included determining the degree of creativity, as well as the degree of tension of key psychological defense mechanisms. All the techniques used within its framework are part of the standard psychodiagnostic tools that have been tested in domestic conditions. Genotyping was performed by real-time PCR, determining the corresponding alleles of candidate genes, and then the data were compared by the method of analysis of variance. RESULTS: As candidate genes, we selected the angiotensin-converting enzyme gene, the serotonin 2A receptor gene, the neurotrophic factor BDNF, and alpha-actinin-3. According to the literature, all these genes are associated with the ability to adapt and / or psychotic states, which suggests their possible connection with creativity. The most interesting results are associated with the polymorphism of the BDNF gene: respondents with the BDNF Val/Val genotype are characterized by the maximum level of creativity and the minimum level of intensity of basic psychological defenses and coping strategies by types of distancing, as well as seeking social support. On the contrary, their maximum level is associated with the Met/Met genotype. Thus, it has been reliably shown that optimal adaptation to extreme external conditions is most likely to be ensured genetically by the presence of the Val / Val genotype, and psychologically by enhanced use of creative ability. The respondents with the ACTN3 RX genotype (with increased cold resistance) are characterized by a minimum level of creativity, and those with the RR genotype its maximum level. It is also shown that respondents with the ACE DD genotype are characterized by a minimum level of creativity. There were no associations with creativity with the serotonin 2A receptor gene polymorphism. CONCLUSIONS: The totality of the results obtained as a result of this pilot study allows us to consider a systematic study of creative ability and its molecular biological correlates to be correct and constructive for the development of a fundamental problem of the interaction of molecular biological and psychological mechanisms that provide active adaptation, as well as very expedient for solv
{"title":"Genetic correlates of creativity in military personnel under extreme conditions of the Arctic Zone of the Russian Federation: a pilot study","authors":"I. Spivak, A. Zhekalov, A. I. Glushakov, A. V. Lemeshchenko, Vladislav A. Nyrov, Aleksandra E. Trandina, P.A. Shapovalov, Andrei G. Zakharchuk, Dmitry L. Spivak","doi":"10.17816/rcf194431-442","DOIUrl":"https://doi.org/10.17816/rcf194431-442","url":null,"abstract":"BACKGROUND: The ability of a person in the process of active activity to adapt to changing environmental conditions is largely related to his creative potential. Creativity, like other physical and mental personality traits, has its own genetic base, which has not been sufficiently studied to date. Certain genes involved in this process are regularly described. The search for an association with new candidate genes for the creative potential of practically healthy, young respondents selected for work in the extreme conditions of the North is extremely important in the selection of people for work and service in difficult conditions. \u0000AIM: Search for the correlation of candidate gene polymorphism and the psychological state of the examined. \u0000MATERIALS AND METHODS: The psychological block of the pilot study included determining the degree of creativity, as well as the degree of tension of key psychological defense mechanisms. All the techniques used within its framework are part of the standard psychodiagnostic tools that have been tested in domestic conditions. Genotyping was performed by real-time PCR, determining the corresponding alleles of candidate genes, and then the data were compared by the method of analysis of variance. \u0000RESULTS: As candidate genes, we selected the angiotensin-converting enzyme gene, the serotonin 2A receptor gene, the neurotrophic factor BDNF, and alpha-actinin-3. According to the literature, all these genes are associated with the ability to adapt and / or psychotic states, which suggests their possible connection with creativity. The most interesting results are associated with the polymorphism of the BDNF gene: respondents with the BDNF Val/Val genotype are characterized by the maximum level of creativity and the minimum level of intensity of basic psychological defenses and coping strategies by types of distancing, as well as seeking social support. On the contrary, their maximum level is associated with the Met/Met genotype. Thus, it has been reliably shown that optimal adaptation to extreme external conditions is most likely to be ensured genetically by the presence of the Val / Val genotype, and psychologically by enhanced use of creative ability. The respondents with the ACTN3 RX genotype (with increased cold resistance) are characterized by a minimum level of creativity, and those with the RR genotype its maximum level. It is also shown that respondents with the ACE DD genotype are characterized by a minimum level of creativity. There were no associations with creativity with the serotonin 2A receptor gene polymorphism. \u0000CONCLUSIONS: The totality of the results obtained as a result of this pilot study allows us to consider a systematic study of creative ability and its molecular biological correlates to be correct and constructive for the development of a fundamental problem of the interaction of molecular biological and psychological mechanisms that provide active adaptation, as well as very expedient for solv","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76120755","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 the early postnatal period, the activation of cholinergic regulation was shown to reveal that lead to development of atypical cardiac rhythm in form of alteration of normal and weak bradycardic rhythm and periods of significant bradycardia. AIM: To study the change in the rhythmic activity of cardiac, respiratory and somatomotor systems after Na+/K+-ATPase blockade by ouabain in rats of 3 and 16 days old MATERIALS AND METHODS: In 3- (P3) and 16-day-old (P16) rats the change in the rhythmic activity of cardiac, respiratory and somatomotor systems after Na+/K+-ATPase blockade by ouabain was studied. RESULTS: It was found that injection of the drug at a dose of 3/4 DL50 leads to changes in heart rhythm variability and motor activity pattern, more pronounced on P16. In the motor activity pattern in 3-day-old rats, there is a tendency to a reduction in the rhythms of the near- and multiminute ranges, while in older rats, on the contrary, their enhancement. The coefficient of variation of motor excitation periods decreased by 12% in 3-day-olds and increased by 35% in 16-day-olds. The decrease in heart rate and respiration is comparable in P3 and P16 rats. Heart rhythm disturbances occur in 37% of 3-day-old and 25% of 16-day-old rats; the arrhythmia rate increases 1,7-2-fold more in animals on P16 than on P3. CONCLUSIONS: The severity of pathological heart rhythm disturbances, including periods of normo/bradycardia, increases with age. Comparison of the character of arrhythmia arising after sodium-potassium pump blockade with pathological heart rhythm observed under conditions of excessive activation of cholinoreactive structures does not allow us to speak about the common mechanisms of their occurrence.
{"title":"Effects of high doses of ouabain on cardiac, respiratory, and motor activity at newborn rats","authors":"S. V. Kuznetsov, Nalalia N. Kuznetsova","doi":"10.17816/rcf194395-403","DOIUrl":"https://doi.org/10.17816/rcf194395-403","url":null,"abstract":"BACKGROUND: In the early postnatal period, the activation of cholinergic regulation was shown to reveal that lead to development of atypical cardiac rhythm in form of alteration of normal and weak bradycardic rhythm and periods of significant bradycardia. \u0000AIM: To study the change in the rhythmic activity of cardiac, respiratory and somatomotor systems after Na+/K+-ATPase blockade by ouabain in rats of 3 and 16 days old \u0000MATERIALS AND METHODS: In 3- (P3) and 16-day-old (P16) rats the change in the rhythmic activity of cardiac, respiratory and somatomotor systems after Na+/K+-ATPase blockade by ouabain was studied. \u0000RESULTS: It was found that injection of the drug at a dose of 3/4 DL50 leads to changes in heart rhythm variability and motor activity pattern, more pronounced on P16. In the motor activity pattern in 3-day-old rats, there is a tendency to a reduction in the rhythms of the near- and multiminute ranges, while in older rats, on the contrary, their enhancement. The coefficient of variation of motor excitation periods decreased by 12% in 3-day-olds and increased by 35% in 16-day-olds. The decrease in heart rate and respiration is comparable in P3 and P16 rats. Heart rhythm disturbances occur in 37% of 3-day-old and 25% of 16-day-old rats; the arrhythmia rate increases 1,7-2-fold more in animals on P16 than on P3. \u0000CONCLUSIONS: The severity of pathological heart rhythm disturbances, including periods of normo/bradycardia, increases with age. Comparison of the character of arrhythmia arising after sodium-potassium pump blockade with pathological heart rhythm observed under conditions of excessive activation of cholinoreactive structures does not allow us to speak about the common mechanisms of their occurrence.","PeriodicalId":21186,"journal":{"name":"Reviews on Clinical Pharmacology and Drug Therapy","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78550215","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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