Pub Date : 2023-04-27DOI: 10.18413/rrpharmacology.9.10021
A. Eleskina, O. Filippova, Nathalia V. Pyatigorskaya
Introduction: The COVID-19 pandemic situation had a great impact on all spheres of people’s lives. It also affected clinical trials as Sponsors, sites and investigators faced a number of problems, such as systematic IMP taking, adherence to protocol visits, efficacy evaluations, laboratory procedures, and analyses. Materials and Methods: The amendments issued in 2020 were compared with the amendments issued in the previous three years 2017-2019. The literature about COVID-19 and its impact on clinical trials were analyzed. Clinical trial protocol amendments published in 2020 were studied to evaluate pandemic influence on ongoing clinical studies. Statistical processing of the results was carried out using the correlation analysis. Results: The highest quantity of amendments was released in 2020 –14 (36%). Fewer amendments came out in 2019 – 13 (33%), in 2018 – 9 (23%), and the fewest amendments were issued in 2017 – 3 (8%). Conclusion: The existing system of clinical trial protocol creation is dependable and adequate. It allows reacting flexibly to unexpected challenges, like COVID-19, fully complying with the prescribed procedures and carefully observing participants’ safety and well-being. That is why the current pandemic did not affect the number of protocol amendments. Graphical Abstract
{"title":"Impact of COVID-19 on clinical trials protocol amendments","authors":"A. Eleskina, O. Filippova, Nathalia V. Pyatigorskaya","doi":"10.18413/rrpharmacology.9.10021","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10021","url":null,"abstract":"Introduction: The COVID-19 pandemic situation had a great impact on all spheres of people’s lives. It also affected clinical trials as Sponsors, sites and investigators faced a number of problems, such as systematic IMP taking, adherence to protocol visits, efficacy evaluations, laboratory procedures, and analyses.\u0000Materials and Methods: The amendments issued in 2020 were compared with the amendments issued in the previous three years 2017-2019. The literature about COVID-19 and its impact on clinical trials were analyzed. Clinical trial protocol amendments published in 2020 were studied to evaluate pandemic influence on ongoing clinical studies. Statistical processing of the results was carried out using the correlation analysis.\u0000Results: The highest quantity of amendments was released in 2020 –14 (36%). Fewer amendments came out in 2019 – 13 (33%), in 2018 – 9 (23%), and the fewest amendments were issued in 2017 – 3 (8%).\u0000 Conclusion: The existing system of clinical trial protocol creation is dependable and adequate. It allows reacting flexibly to unexpected challenges, like COVID-19, fully complying with the prescribed procedures and carefully observing participants’ safety and well-being. That is why the current pandemic did not affect the number of protocol amendments.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43800523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-19DOI: 10.18413/rrpharmacology.9.10017
P. Galenko-Yaroshevsky, A. Slavinskiy, Mark A. Zadorozhniy, V. K. Leontev, Artur V. Kheigetyan, V. Popkov, A. Zelenskaya, Lyudmila M. Chuprinenko, A. A. Verevkin, Izabella G. Lomsadze, Mariya Yu. Materenchuk, S. Lebedeva
Introduction: Periodontitis is one of the most urgent problems of modern dentistry. The development of new paradigms and regimens of combination therapy of patients with periodontitis is a strategic task for pharmacologists and dentists. In view of this, pathomorphological examination is of high importance, since it allow us to conclude about the therapeutic effectiveness of the administered drugs with high objectivity. Aim of the study: to evaluate the effect of the composition of Soderm®-Forte and Cytoflavin® on the pathomorphological pattern of gum tissues of rats with experimental periodontitis (EP). Materials and Methods: EP was simulated in rats by ligature method. Study design: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with the combination of TDT and Soderm®-Forte gel; and animals with EP treated with the combination of TDT, Soderm®-Forte and Cytoflavin®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. Slides were stained with hematoxylin and eosin, as well as by Masson. Computer morphometry was performed using the ImageJ software. Results: In EP, TDT has a moderate positive effect on pathomorphological changes in the gum. The combination of TDT and Soderm®-Forte and, to a greater degree, the combination of TDT, Soderm®-Forte and Cytoflavin® have high therapeutic efficacy, characterized by rapid regeneration of the gum tissues. Conclusion: The combination of TDT, Soderm®-Forte and Cytoflavin® in EP has a more pronounced therapeutic effect, manifested by early regression of pathological changes and acceleration of tissue regeneration in the gum. Graphical Abstract
{"title":"Pathomorphological analysis of the gum tissues in the application of the combination of Soderm®-Forte gel with Cytoflavin® in experimental periodontitis in rats","authors":"P. Galenko-Yaroshevsky, A. Slavinskiy, Mark A. Zadorozhniy, V. K. Leontev, Artur V. Kheigetyan, V. Popkov, A. Zelenskaya, Lyudmila M. Chuprinenko, A. A. Verevkin, Izabella G. Lomsadze, Mariya Yu. Materenchuk, S. Lebedeva","doi":"10.18413/rrpharmacology.9.10017","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10017","url":null,"abstract":"Introduction: Periodontitis is one of the most urgent problems of modern dentistry. The development of new paradigms and regimens of combination therapy of patients with periodontitis is a strategic task for pharmacologists and dentists. In view of this, pathomorphological examination is of high importance, since it allow us to conclude about the therapeutic effectiveness of the administered drugs with high objectivity.\u0000Aim of the study: to evaluate the effect of the composition of Soderm®-Forte and Cytoflavin® on the pathomorphological pattern of gum tissues of rats with experimental periodontitis (EP).\u0000Materials and Methods: EP was simulated in rats by ligature method. Study design: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with the combination of TDT and Soderm®-Forte gel; and animals with EP treated with the combination of TDT, Soderm®-Forte and Cytoflavin®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. Slides were stained with hematoxylin and eosin, as well as by Masson. Computer morphometry was performed using the ImageJ software.\u0000Results: In EP, TDT has a moderate positive effect on pathomorphological changes in the gum. The combination of TDT and Soderm®-Forte and, to a greater degree, the combination of TDT, Soderm®-Forte and Cytoflavin® have high therapeutic efficacy, characterized by rapid regeneration of the gum tissues.\u0000 Conclusion: The combination of TDT, Soderm®-Forte and Cytoflavin® in EP has a more pronounced therapeutic effect, manifested by early regression of pathological changes and acceleration of tissue regeneration in the gum.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44011710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10007
O. Gaisenok
Aim of the study to analyze the detection of hypercholesterolemia (HCHL) and carotid atherosclerosis (CAS), verified by duplex scanning of the carotid arteries (DSCA) in young adults (YA), and to evaluate the lipid-lowering therapy (LLT) prescription among them according to the local registry database. Material and Methods: The Duplex registry database was used for this study (n=2548). YA up to 45 years old were selected for the final analysis (n=351). Results: HCHL (> 5 mmol/L) was detected in 68.9% of patients (n=241), and only 9.5% of them received LLT (n=23). CAS was detected in 12.8% (n=45), only 17.8% of them had received LLT (n=8). Men and women differed 1.5 times by the incidence of CAS in this age range: 15.7% (30 out of 191) vs 9.4% (15 out of 160), p=0.05. Men also generally have a higher prevalence of other risk factors/diseases: HCHL (78.0% (n=149) vs 58.1% (n=93) in women, p=0.00004), hypertension (AH) (15.7% (n=30) vs 9.4% (n=15) in women, p=0,05), history of myocardial infarction (MI) (1,6% (n=3) vs 0% (n=0) in women, ns). Signs that had a significant impact on LLT intake were the following: CAS (OR 2.8 [1.09;6.6] p=0.036); AH (OR 3.1 [1.32; 7.16] p=0.009); HCHL (> 5 mmol/L) (OR 4.2 [1.12; 26.83] p=0.06); HCHL (ICD-10 code E78) (OR 5.4 [2.04; 13.7] p=0.0003); MI history (OR 22.3 [1.65;675.5] p=0.009). Conclusion: The insufficient LLT prescription in young adults with HCHL and CAS was ascertained in the present study. The use of imaging methods to clarify the degree of cardiovascular risk is advisable for low and intermediate risk patients, which include young adults. DSСA is the main method for subclinical atherosclerosis verification. LLT should be prescribed to all YA patients with CAS (in the absence of contraindications). Graphical Abstract
{"title":"Analysis of the frequency of detection of hypercholesterolemia, carotid atherosclerosis and lipid-lowering therapy prescription in young adults under 45 years old according to the Duplex registry database","authors":"O. Gaisenok","doi":"10.18413/rrpharmacology.9.10007","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10007","url":null,"abstract":"Aim of the study to analyze the detection of hypercholesterolemia (HCHL) and carotid atherosclerosis (CAS), verified by duplex scanning of the carotid arteries (DSCA) in young adults (YA), and to evaluate the lipid-lowering therapy (LLT) prescription among them according to the local registry database. \u0000Material and Methods: The Duplex registry database was used for this study (n=2548). YA up to 45 years old were selected for the final analysis (n=351). \u0000Results: HCHL (> 5 mmol/L) was detected in 68.9% of patients (n=241), and only 9.5% of them received LLT (n=23). CAS was detected in 12.8% (n=45), only 17.8% of them had received LLT (n=8). Men and women differed 1.5 times by the incidence of CAS in this age range: 15.7% (30 out of 191) vs 9.4% (15 out of 160), p=0.05. Men also generally have a higher prevalence of other risk factors/diseases: HCHL (78.0% (n=149) vs 58.1% (n=93) in women, p=0.00004), hypertension (AH) (15.7% (n=30) vs 9.4% (n=15) in women, p=0,05), history of myocardial infarction (MI) (1,6% (n=3) vs 0% (n=0) in women, ns). Signs that had a significant impact on LLT intake were the following: CAS (OR 2.8 [1.09;6.6] p=0.036); AH (OR 3.1 [1.32; 7.16] p=0.009); HCHL (> 5 mmol/L) (OR 4.2 [1.12; 26.83] p=0.06); HCHL (ICD-10 code E78) (OR 5.4 [2.04; 13.7] p=0.0003); MI history (OR 22.3 [1.65;675.5] p=0.009). \u0000Conclusion: The insufficient LLT prescription in young adults with HCHL and CAS was ascertained in the present study. The use of imaging methods to clarify the degree of cardiovascular risk is advisable for low and intermediate risk patients, which include young adults. DSСA is the main method for subclinical atherosclerosis verification. LLT should be prescribed to all YA patients with CAS (in the absence of contraindications). \u0000Graphical Abstract","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43461537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10011
O. S. Levchenkova, V. V. Vorobieva, V. Novikov, T. I. Legonkova, Elena N. Volkova
Introduction: Thrombopoietin receptor agonists are commonly second-line drugs in immune thrombocytopenia (ITP) pharmacotherapy in children and prescribed for chronic ITP refractory to first-line therapy. Standard ITP pharmacotherapy in children: includes prescribing glucocorticoids or intravenous immunoglobulins. Thrombopoietin receptor agonists: Currently Romiplostim and Eltrombopag are used in the Russian Federation pediatrics. Their pharmacodynamic features in comparison with other drugs used in ITP are presented in the paper. Increased thrombocytopoiesis is the dominant, but not the only component of Romiplostim and Eltrombopag mechanism of action. It is relevant to study their effect on immune tolerance in ITP, which may be associated with a persistent platelet response in some patients after drug discontinuation. Conclusion: The issue of thrombopoietin receptor agonist efficacy and safety as well as the mode of their use in ITP children treatment continues to be studied. The high cost of drugs continues to be a limiting factor to their earlier prescription. Generic drugs – Romiplostim and Eltrombopag partly solve the problem, promote their earlier prescription in ITP, but require additional study of their bioequivalence and therapeutic equivalence in comparison with the original drugs. Graphical Abstract
{"title":"Thrombopoietin receptor agonists in pharmacotherapy of pediatric immune thrombocytopenia","authors":"O. S. Levchenkova, V. V. Vorobieva, V. Novikov, T. I. Legonkova, Elena N. Volkova","doi":"10.18413/rrpharmacology.9.10011","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10011","url":null,"abstract":"Introduction: Thrombopoietin receptor agonists are commonly second-line drugs in immune thrombocytopenia (ITP) pharmacotherapy in children and prescribed for chronic ITP refractory to first-line therapy. \u0000Standard ITP pharmacotherapy in children: includes prescribing glucocorticoids or intravenous immunoglobulins. \u0000Thrombopoietin receptor agonists: Currently Romiplostim and Eltrombopag are used in the Russian Federation pediatrics. Their pharmacodynamic features in comparison with other drugs used in ITP are presented in the paper. Increased thrombocytopoiesis is the dominant, but not the only component of Romiplostim and Eltrombopag mechanism of action. It is relevant to study their effect on immune tolerance in ITP, which may be associated with a persistent platelet response in some patients after drug discontinuation. \u0000Conclusion: The issue of thrombopoietin receptor agonist efficacy and safety as well as the mode of their use in ITP children treatment continues to be studied. The high cost of drugs continues to be a limiting factor to their earlier prescription. Generic drugs – Romiplostim and Eltrombopag partly solve the problem, promote their earlier prescription in ITP, but require additional study of their bioequivalence and therapeutic equivalence in comparison with the original drugs. \u0000Graphical Abstract \u0000 \u0000 ","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43619867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10004
E. Orlova, B. Kuzmichev, M. A. Orlov, I. Dorfman
Introduction: Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality. Using the evidence obtained about various clinical phenotypes of patients with the same disease allowed us to expand our understanding of the treatment of COPD. Nowadays the only option for solving the problem will be the definition of the clinical phenotype of COPD, and the receipt of expanded data on its correlation with respiratory and other significant biomarkers. Materials and methods: We analyzed the correlations between FKN, CRP and TBA-active lipid peroxidation products in 373 patients with various COPD phenotypes and 60 healthy volunteers. Enzyme immunoassay was used to study the levels of inflammatory biomarkers. Results: We have identified a statistically significant increase in the levels of inflammatory biomarkers in patients with COPD compared with the control. The FKN level in the group of patients with COPD was 1.3 ng/ml, which was higher (p<0.001) than in the control (FKN level of 0.3 ng/ml, p<0.001). The CRP level in patients with COPD was 27.8 mg/L, whereas in control the CRP level was 1.2 mg/L (p<0.001). The TBA-active lipid peroxidation products level in patients with COPD was 14.5 mmol/L, which was higher when compared to the control (p<0.001). Discussion: The correlation analysis revealed very strong relationships between the levels of all the biomarkers studied. The highest values of the Kendall rank correlation coefficient (τ) were determined between the levels of all the inflammatory biomarkers in subgroups of patients with chronic bronchitis and mixed COPD phenotypes. Conclusion: Detection of the COPD phenotype will help actively monitor the therapy of COPD exacerbations. Graphical Abstract
{"title":"Correlation analysis between inflammatory biomarkers and significant clinical phenotypes of chronic obstructive pulmonary disease","authors":"E. Orlova, B. Kuzmichev, M. A. Orlov, I. Dorfman","doi":"10.18413/rrpharmacology.9.10004","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10004","url":null,"abstract":"Introduction: Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality. Using the evidence obtained about various clinical phenotypes of patients with the same disease allowed us to expand our understanding of the treatment of COPD. Nowadays the only option for solving the problem will be the definition of the clinical phenotype of COPD, and the receipt of expanded data on its correlation with respiratory and other significant biomarkers.\u0000Materials and methods: We analyzed the correlations between FKN, CRP and TBA-active lipid peroxidation products in 373 patients with various COPD phenotypes and 60 healthy volunteers. Enzyme immunoassay was used to study the levels of inflammatory biomarkers.\u0000Results: We have identified a statistically significant increase in the levels of inflammatory biomarkers in patients with COPD compared with the control. The FKN level in the group of patients with COPD was 1.3 ng/ml, which was higher (p<0.001) than in the control (FKN level of 0.3 ng/ml, p<0.001). The CRP level in patients with COPD was 27.8 mg/L, whereas in control the CRP level was 1.2 mg/L (p<0.001). The TBA-active lipid peroxidation products level in patients with COPD was 14.5 mmol/L, which was higher when compared to the control (p<0.001).\u0000Discussion: The correlation analysis revealed very strong relationships between the levels of all the biomarkers studied. The highest values of the Kendall rank correlation coefficient (τ) were determined between the levels of all the inflammatory biomarkers in subgroups of patients with chronic bronchitis and mixed COPD phenotypes.\u0000Conclusion: Detection of the COPD phenotype will help actively monitor the therapy of COPD exacerbations.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45718829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10006
Vladimir D. Dergachev, E. E. Yakovleva, M. A. Brusina, E. Bychkov, L. B. Piotrovskiy, P. Shabanov
Introduction: To study the antiparkinsonian activity of new ligands of the glutamate NMDA receptor complex – 1,2–substituted imidazole-4,5-dicarboxylic acids – on an experimental model of catalepsy caused by haloperidolintraabdominal injections in rats. Materials and methods: The experiments were performed on Wistar rats weighing 300-350 g, obtained from the Rappolovo nursery of the Russian Academy of Medical Sciences (Leningrad Region). The animals were kept in standard plastic cages in vivarium conditions with free access to water and food at a temperature of 22±2 °C and in the experiment were divided into several groups (6 animals each). All the experiments were carried out in the autumn-winter period. The animals were kept in accordance with the rules of laboratory practice (GLP), regulatory documents ”Sanitary Rules for the Device, Equipment and Maintenance of Vivarium” and the Order of the Ministry of Health and Social Development of the Russian Federation dated 23.08.2010 No. 708n “On Approval of the Rules of Laboratory Practice”. Imidazole-dicarboxylic acid derivatives (IEM-2295, IEM-2296) were injected intraperitoneally at doses from 5 mg/kg to 40 mg/kg simultaneously with haloperidol at a dose of 1 mg/kg, after which the duration and severity of catalepsy were evaluated after 30, 60, 120 minutes from 0 to 6 points according to the Morpurgo method. Results: The severity of catalepsy with the injection of IEM-2295 decreased on average to 3 points, while in the control group it remained at the level of 6 points throughout the observation. However, the severity of catalepsy with the introduction of IEM-2296 decreased to an average of 4 points, but the effect itself lasted longer than with the introduction of IEM-2295. Thus, it was noted that by the 120th minute of observation, the severity of catalepsy in rats receiving the IEM-2295 compound averaged 5 points, whereas in animals receiving IEM-2296 – 3 points. Discussion: Basing on the results of our work and similar experiments, we can conclude that the studied compounds, which are not channel blockers, have an active effect on dopaminergic neurotransmission, because of which the symptoms of catalepsy that occur when haloperidol is injected to rats were stopped to one degree or another. Conclusion: The studied substances exhibit antiparkinsonian activity on an experimental haloperidol model of catalepsy in rats and are promising for development as potential therapies for neurodegenerative diseases. Further study of these compounds and other ligands from the NMDA-blocker group in a wider sample on the catalepsy model, as well as on other models of Parkinsonism, is required. Graphical Abstract
{"title":"Investigation of antiparkinsonian activity of new imidazole-4,5-dicarboxylic acid derivatives on the experimental model of catalepsy","authors":"Vladimir D. Dergachev, E. E. Yakovleva, M. A. Brusina, E. Bychkov, L. B. Piotrovskiy, P. Shabanov","doi":"10.18413/rrpharmacology.9.10006","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10006","url":null,"abstract":"Introduction: To study the antiparkinsonian activity of new ligands of the glutamate NMDA receptor complex – 1,2–substituted imidazole-4,5-dicarboxylic acids – on an experimental model of catalepsy caused by haloperidolintraabdominal injections in rats.\u0000Materials and methods: The experiments were performed on Wistar rats weighing 300-350 g, obtained from the Rappolovo nursery of the Russian Academy of Medical Sciences (Leningrad Region). The animals were kept in standard plastic cages in vivarium conditions with free access to water and food at a temperature of 22±2 °C and in the experiment were divided into several groups (6 animals each). All the experiments were carried out in the autumn-winter period. The animals were kept in accordance with the rules of laboratory practice (GLP), regulatory documents ”Sanitary Rules for the Device, Equipment and Maintenance of Vivarium” and the Order of the Ministry of Health and Social Development of the Russian Federation dated 23.08.2010 No. 708n “On Approval of the Rules of Laboratory Practice”. Imidazole-dicarboxylic acid derivatives (IEM-2295, IEM-2296) were injected intraperitoneally at doses from 5 mg/kg to 40 mg/kg simultaneously with haloperidol at a dose of 1 mg/kg, after which the duration and severity of catalepsy were evaluated after 30, 60, 120 minutes from 0 to 6 points according to the Morpurgo method.\u0000Results: The severity of catalepsy with the injection of IEM-2295 decreased on average to 3 points, while in the control group it remained at the level of 6 points throughout the observation. However, the severity of catalepsy with the introduction of IEM-2296 decreased to an average of 4 points, but the effect itself lasted longer than with the introduction of IEM-2295. Thus, it was noted that by the 120th minute of observation, the severity of catalepsy in rats receiving the IEM-2295 compound averaged 5 points, whereas in animals receiving IEM-2296 – 3 points.\u0000Discussion: Basing on the results of our work and similar experiments, we can conclude that the studied compounds, which are not channel blockers, have an active effect on dopaminergic neurotransmission, because of which the symptoms of catalepsy that occur when haloperidol is injected to rats were stopped to one degree or another.\u0000Conclusion: The studied substances exhibit antiparkinsonian activity on an experimental haloperidol model of catalepsy in rats and are promising for development as potential therapies for neurodegenerative diseases. Further study of these compounds and other ligands from the NMDA-blocker group in a wider sample on the catalepsy model, as well as on other models of Parkinsonism, is required.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41539364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10003
S. Lebedeva, P. A. Galenko-Yaroshevsky (Jr.), M. Samsonov, Arkadiy B. Erlich, A. Zelenskaya, Arus G. Margaryan, M. Materenchuk, I. R. Arshinov, Yuriy V. Zharov, O. V. Shelemekh, Isabella Yu. Lomsadze, T. Demura
Introduction: In the course of evolution, humans developed a number of complex multi-step wound healing mechanisms which limit the infectious agents access to the bloodstream, protect the organism from blood loss, and restore skin integrity. The process of skin wound healing includes the following stages: haemostasis, inflammation, proliferation, and remodeling. These processes are possible because of modulators, growth factors, cytokines, matrix metalloproteinases and cellular receptors, as well as some trace elements like zinc. Materials and Methods: The presented data was analyzed and compiled using all relevant articles describing the role of zinc in blood coagulation, proliferation, damaged tissues regeneration and angiogenesis. Results and Discussion: There are some on-going studies about zinc effects on blood coagulation, proliferation, damaged tissues regeneration and angiogenesis. However, molecular mechanisms of these processes are not yet fully understood and require further study. The analysis of scientific efforts to investigate the role of zinc in wound healing molecular mechanisms is especially relevant to the understanding of treatment of skin wound injuries. Conclusion: Wound healing is a complex multi-phase process consisting of several phases. Each stage involves metal ions, primarily zinc, which stimulates re-epithelialization, decreases inflammation and bacterial growth. The use of known zinc-based drugs is accompanied by side effects and low efficacy due to low skin absorption. These factors significantly limit use of such drugs and highlight the urgency of finding new, more effective and safe treatment. The emerging field of nanobiotechnology may provide an alternative platform to develop new therapeutic agents for the wound healing process. Graphical Abstract
{"title":"Molecular mechanisms of wound healing: the role of zinc as an essential microelement","authors":"S. Lebedeva, P. A. Galenko-Yaroshevsky (Jr.), M. Samsonov, Arkadiy B. Erlich, A. Zelenskaya, Arus G. Margaryan, M. Materenchuk, I. R. Arshinov, Yuriy V. Zharov, O. V. Shelemekh, Isabella Yu. Lomsadze, T. Demura","doi":"10.18413/rrpharmacology.9.10003","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10003","url":null,"abstract":"Introduction: In the course of evolution, humans developed a number of complex multi-step wound healing mechanisms which limit the infectious agents access to the bloodstream, protect the organism from blood loss, and restore skin integrity. The process of skin wound healing includes the following stages: haemostasis, inflammation, proliferation, and remodeling. These processes are possible because of modulators, growth factors, cytokines, matrix metalloproteinases and cellular receptors, as well as some trace elements like zinc.\u0000Materials and Methods: The presented data was analyzed and compiled using all relevant articles describing the role of zinc in blood coagulation, proliferation, damaged tissues regeneration and angiogenesis.\u0000Results and Discussion: There are some on-going studies about zinc effects on blood coagulation, proliferation, damaged tissues regeneration and angiogenesis. However, molecular mechanisms of these processes are not yet fully understood and require further study. The analysis of scientific efforts to investigate the role of zinc in wound healing molecular mechanisms is especially relevant to the understanding of treatment of skin wound injuries.\u0000Conclusion: Wound healing is a complex multi-phase process consisting of several phases. Each stage involves metal ions, primarily zinc, which stimulates re-epithelialization, decreases inflammation and bacterial growth. The use of known zinc-based drugs is accompanied by side effects and low efficacy due to low skin absorption. These factors significantly limit use of such drugs and highlight the urgency of finding new, more effective and safe treatment. The emerging field of nanobiotechnology may provide an alternative platform to develop new therapeutic agents for the wound healing process.\u0000\u0000\u0000\u0000Graphical Abstract\u0000\u0000\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44375325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10001
T. Berezhnova, Yelena A. Lunyova, Kseniya S. Dyadina, V. Borisov
Introduction: Lung carcinoma is the leading cause of death in men and is closely related to smoking. The article focuses on the current statistics of this pathology in the world. Materials and methods: The literature review was carried out using PubMed database and included articles published from 2006 to 2021. The current schemes of chemotherapy and diagnostic options of small cell lung cancer were analyzed. The mechanisms of drug action on tumor cells were considered. An analysis of the publication activity in PubMed database related to pharmacotherapy of small cell lung cancer allows reporting a twofold increase in the number of publications over the period from 2007 to 2017. Results and discussion: A systematic review presenting staging of small cell lung cancer (SCLC) and its radiation diagnostics has been conducted. As demonstrated, there are no current methods with proven effectiveness to early detect this pathology. However, it has been found that annual low-dose CT screenings helped detect a significant number of lung cancer cases at the early stage, although, the proportion of small cell carcinoma is still very high. Analyses of clinical outcomes of small cell lung cancer have showed that cisplatin/etoposide (EP) or carboplatin/etoposide (EC) appear to be the key combinations with high treatment efficacy. The article also discusses chemotherapy for small cell lung cancer, namely and the principle of its effect on tumor cells. However, this chemotherapy remains very toxic and causes a number of life-threatening side effects. It is necessary to assess the effectiveness of chemotherapy immediately after the start of treatment in order to balance benefits and risks. Conclusion: The search is currently under way for less toxic but effective compounds, this fact being a crucial issue of healthcare in providing high-quality medical and pharmaceutical care for cancer patients. Chemotherapy of the pathology under study requires high costs; therefore, a pharmacoeconomical assessment of the prescription of chemotherapy for small cell lung cancer is necessary to compare the costs of treatment and its effectiveness Graphical Abstract
{"title":"Pharmacotherapy of small cell lung cancer: Current state-of-the-art","authors":"T. Berezhnova, Yelena A. Lunyova, Kseniya S. Dyadina, V. Borisov","doi":"10.18413/rrpharmacology.9.10001","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10001","url":null,"abstract":"Introduction: Lung carcinoma is the leading cause of death in men and is closely related to smoking. The article focuses on the current statistics of this pathology in the world. \u0000Materials and methods: The literature review was carried out using PubMed database and included articles published from 2006 to 2021. The current schemes of chemotherapy and diagnostic options of small cell lung cancer were analyzed. The mechanisms of drug action on tumor cells were considered. An analysis of the publication activity in PubMed database related to pharmacotherapy of small cell lung cancer allows reporting a twofold increase in the number of publications over the period from 2007 to 2017. \u0000Results and discussion: A systematic review presenting staging of small cell lung cancer (SCLC) and its radiation diagnostics has been conducted. As demonstrated, there are no current methods with proven effectiveness to early detect this pathology. However, it has been found that annual low-dose CT screenings helped detect a significant number of lung cancer cases at the early stage, although, the proportion of small cell carcinoma is still very high. Analyses of clinical outcomes of small cell lung cancer have showed that cisplatin/etoposide (EP) or carboplatin/etoposide (EC) appear to be the key combinations with high treatment efficacy. The article also discusses chemotherapy for small cell lung cancer, namely and the principle of its effect on tumor cells. However, this chemotherapy remains very toxic and causes a number of life-threatening side effects. It is necessary to assess the effectiveness of chemotherapy immediately after the start of treatment in order to balance benefits and risks. \u0000Conclusion: The search is currently under way for less toxic but effective compounds, this fact being a crucial issue of healthcare in providing high-quality medical and pharmaceutical care for cancer patients. Chemotherapy of the pathology under study requires high costs; therefore, a pharmacoeconomical assessment of the prescription of chemotherapy for small cell lung cancer is necessary to compare the costs of treatment and its effectiveness \u0000Graphical Abstract","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41336596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-31DOI: 10.18413/rrpharmacology.9.10015
S. P. Bairamova, D. Petelin, R. Akhapkin, N. Kudryashov, O. Sorokina, S. A. Semin, Veronika Panfilova, B. A. Volel
Introduction: Although neurosteroids have been relatively recently discovered, their significant role in the neurochemical processes and pathogenesis of a number of psychiatric and neurological disorders is now quite clear. First of all, it seems important to clarify the definition of the endogenous neurosteroids as a class of steroids, taking into account the variability of approaches to their description. Currently, neurosteroids include endogenous steroids synthesized in the central nervous system, gonads, or adrenal glands and interacting with GABAA, NMDA, and sigma-1 receptors. Neurosteroid biosynthesis: Biosynthesis of neurosteroids begins with rate-limiting reaction of TSPO binding cholesterol and transporting it into the mitochondria, where pregnenolone is synthesized following the cytochrome P450scc (CYP11A1) impact. Interaction with GABAА, NMDA and sigma-1 receptors: According to the experimental data, neurosteroids act as the most highly potent endogenous allosteric modulators of the GABA receptor; some types of neurosteroids (ALLO, DHEA, etc.) can produce a rapid anxiolytic and anticonvulsant effect. There is some experimental evidence for antipsychotic effects of some neurosteroids realized through NMDA receptors: intracerebral administration of ALLO to laboratory animals can prevent further appearance of motor agitation and other equivalents of psychosis after administration of high doses of amphetamines. It has also been proven in several studies on animal models that neurosteroids exhibit anxiolytic effects through sigma-1 receptors. Conclusion: The article describes the process of neurosteroidogenesis and the effect of neurosteroids on listed receptorsin accordance with already available scientific data. In addition, this paper describes the specific role of various neurosteroids in the development of mental illnesses, including anxiety disorders, depression, and schizophrenia Graphical Abstract
{"title":"The endogenic neurosteroid system and its role in the pathogenesis and therapy of mental disorders","authors":"S. P. Bairamova, D. Petelin, R. Akhapkin, N. Kudryashov, O. Sorokina, S. A. Semin, Veronika Panfilova, B. A. Volel","doi":"10.18413/rrpharmacology.9.10015","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10015","url":null,"abstract":"Introduction: Although neurosteroids have been relatively recently discovered, their significant role in the neurochemical processes and pathogenesis of a number of psychiatric and neurological disorders is now quite clear. First of all, it seems important to clarify the definition of the endogenous neurosteroids as a class of steroids, taking into account the variability of approaches to their description. Currently, neurosteroids include endogenous steroids synthesized in the central nervous system, gonads, or adrenal glands and interacting with GABAA, NMDA, and sigma-1 receptors. \u0000Neurosteroid biosynthesis: Biosynthesis of neurosteroids begins with rate-limiting reaction of TSPO binding cholesterol and transporting it into the mitochondria, where pregnenolone is synthesized following the cytochrome P450scc (CYP11A1) impact. \u0000Interaction with GABAА, NMDA and sigma-1 receptors: According to the experimental data, neurosteroids act as the most highly potent endogenous allosteric modulators of the GABA receptor; some types of neurosteroids (ALLO, DHEA, etc.) can produce a rapid anxiolytic and anticonvulsant effect. There is some experimental evidence for antipsychotic effects of some neurosteroids realized through NMDA receptors: intracerebral administration of ALLO to laboratory animals can prevent further appearance of motor agitation and other equivalents of psychosis after administration of high doses of amphetamines. It has also been proven in several studies on animal models that neurosteroids exhibit anxiolytic effects through sigma-1 receptors. \u0000Conclusion: The article describes the process of neurosteroidogenesis and the effect of neurosteroids on listed receptorsin accordance with already available scientific data. In addition, this paper describes the specific role of various neurosteroids in the development of mental illnesses, including anxiety disorders, depression, and schizophrenia \u0000Graphical Abstract \u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46843157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-22DOI: 10.3897/rrpharmacology.8.80376
Dmitry V. Shcheblykin, Anton A. Bolgov, M. Pokrovskii, Julia V. Stepenko, Julia M. Tsuverkalova, Olesya V. Shcheblykina, P. A. Golubinskaya, L. Korokina
Introduction: Every year the importance of the normal functioning of the endothelial layer of the vascular wall in maintaining the health of the body becomes more and more obvious. The physiological role of the endothelium: The endothelium is a metabolically active organ actively involved in the regulation of hemostasis, modulation of inflammation, maintenance of hemovascular homeostasis, regulation of angiogenesis, vascular tone, and permeability. Risk factors for the development of endothelial dysfunction: Currently, insufficient bioavailability of nitric oxide is considered the most significant risk factor for endothelial dysfunction. Mechanisms of development of endothelial dysfunction: The genesis of endothelial dysfunction is a multifactorial process. Among various complex mechanisms, this review examines oxidative stress, inflammation, hyperglycemia, vitamin D deficiency, dyslipidemia, excess visceral fat, hyperhomocysteinemia, hyperuricemia, as well as primary genetic defect of endotheliocytes, as the most common causes in the population underlying the development of endothelial dysfunction. Markers of endothelial dysfunction in various diseases: This article discusses the main biomarkers of endothelial dysfunction currently used, as well as promising biomarkers in the future for laboratory diagnosis of this pathology. Therapeutic strategies: Therapeutic approaches to the endothelium in order to prevent or reduce a degree of damage to the vascular wall are briefly described. Conclusion: Endothelial dysfunction is a typical pathological process involved in the pathogenesis of many diseases. Thus, pharmacological agents with endothelioprotective properties can provide more therapeutic benefits than a drug without such an effect.
{"title":"Endothelial dysfunction: developmental mechanisms and therapeutic strategies","authors":"Dmitry V. Shcheblykin, Anton A. Bolgov, M. Pokrovskii, Julia V. Stepenko, Julia M. Tsuverkalova, Olesya V. Shcheblykina, P. A. Golubinskaya, L. Korokina","doi":"10.3897/rrpharmacology.8.80376","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.80376","url":null,"abstract":"Introduction: Every year the importance of the normal functioning of the endothelial layer of the vascular wall in maintaining the health of the body becomes more and more obvious.\u0000 The physiological role of the endothelium: The endothelium is a metabolically active organ actively involved in the regulation of hemostasis, modulation of inflammation, maintenance of hemovascular homeostasis, regulation of angiogenesis, vascular tone, and permeability.\u0000 Risk factors for the development of endothelial dysfunction: Currently, insufficient bioavailability of nitric oxide is considered the most significant risk factor for endothelial dysfunction.\u0000 Mechanisms of development of endothelial dysfunction: The genesis of endothelial dysfunction is a multifactorial process. Among various complex mechanisms, this review examines oxidative stress, inflammation, hyperglycemia, vitamin D deficiency, dyslipidemia, excess visceral fat, hyperhomocysteinemia, hyperuricemia, as well as primary genetic defect of endotheliocytes, as the most common causes in the population underlying the development of endothelial dysfunction.\u0000 Markers of endothelial dysfunction in various diseases: This article discusses the main biomarkers of endothelial dysfunction currently used, as well as promising biomarkers in the future for laboratory diagnosis of this pathology.\u0000 Therapeutic strategies: Therapeutic approaches to the endothelium in order to prevent or reduce a degree of damage to the vascular wall are briefly described.\u0000 Conclusion: Endothelial dysfunction is a typical pathological process involved in the pathogenesis of many diseases. Thus, pharmacological agents with endothelioprotective properties can provide more therapeutic benefits than a drug without such an effect.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44189872","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}