One of the most investigated and inscrutable eukaryotic proteins is a factor positioned as tumor suppressor which structural changes are observed in 50% of malignant cells. In the literature this protein is referred to as p53. The generalized function of p53 resolves to maintaining of cell genetic stability and preventing cell automatization. Therefore, p53 was called the keeper, or guardian, of the genome. Suppressive activity of p53 in regard to appearance of malignant cells seems to be side function of this protein. The present review prоvides data on the role of p53 in various vital processes in eukaryotic cells. p53 is a complex protein in its domain structure, and the semi-autonomous role of individual domains is clearly discernible. Normally, p53 is not a crucial factor in ontogenesis. At the same time p53 modulates the activity of about 500 different genes and also maintains homeostasis in cells and organism directly via protein-protein interactions. In response to exogenous and endogenous impacts p53 provides a balance of cellular metabolism and either promotes elimination of abnormalities, or triggers an apoptotic cascade. The review summarizes current considerations of p53 multiple functions as well as discusses already established and not yet disclosed mechanisms concerning involvement of said factor in cellular metabolism.
{"title":"Multiple functions of tumor supressor p53","authors":"A. Gudkova, O. Antimonova, M. Shavlovsky","doi":"10.17816/maj79623","DOIUrl":"https://doi.org/10.17816/maj79623","url":null,"abstract":"One of the most investigated and inscrutable eukaryotic proteins is a factor positioned as tumor suppressor which structural changes are observed in 50% of malignant cells. In the literature this protein is referred to as p53. The generalized function of p53 resolves to maintaining of cell genetic stability and preventing cell automatization. Therefore, p53 was called the keeper, or guardian, of the genome. Suppressive activity of p53 in regard to appearance of malignant cells seems to be side function of this protein. The present review prоvides data on the role of p53 in various vital processes in eukaryotic cells. p53 is a complex protein in its domain structure, and the semi-autonomous role of individual domains is clearly discernible. Normally, p53 is not a crucial factor in ontogenesis. At the same time p53 modulates the activity of about 500 different genes and also maintains homeostasis in cells and organism directly via protein-protein interactions. In response to exogenous and endogenous impacts p53 provides a balance of cellular metabolism and either promotes elimination of abnormalities, or triggers an apoptotic cascade. The review summarizes current considerations of p53 multiple functions as well as discusses already established and not yet disclosed mechanisms concerning involvement of said factor in cellular metabolism.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123729213","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}
Sleep deficit disrupts the normal function of systems and organs in humans and becomes epidemic in nature. Knowledge of the physiology of sleep and the impact of sleep deprivation on the body has expanded in recent years and allows a new assessment of the scale and depth of the problem. In the review summarizes current ideas about the effect of lack of sleep on chronic diseases and pathological processes, taking into account various body systems. Different reviews and studies over the past years have been analyzed, related to lack of sleep which contributes to the development of various diseases, have been analyzed. The use of new information about the impact of sleep on human health and the consequences of its lack opens up additional perspectives in understanding experimental and clinical work. This information can be actively used in diagnostics and therapy within the framework of integrative medicine.
{"title":"Modern understanding of the consequences of lack of sleep","authors":"Yury V. Gavrilov","doi":"10.17816/maj81192","DOIUrl":"https://doi.org/10.17816/maj81192","url":null,"abstract":"Sleep deficit disrupts the normal function of systems and organs in humans and becomes epidemic in nature. Knowledge of the physiology of sleep and the impact of sleep deprivation on the body has expanded in recent years and allows a new assessment of the scale and depth of the problem. In the review summarizes current ideas about the effect of lack of sleep on chronic diseases and pathological processes, taking into account various body systems. Different reviews and studies over the past years have been analyzed, related to lack of sleep which contributes to the development of various diseases, have been analyzed. The use of new information about the impact of sleep on human health and the consequences of its lack opens up additional perspectives in understanding experimental and clinical work. This information can be actively used in diagnostics and therapy within the framework of integrative medicine.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127563110","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: Beta-adrenoblockers nebivolol, carvedilol and propranolol are used in clinical cardiology for the treatment of patients with ischemic heart disease. Pulmonary thromboembolism can develop in such patients. However, its unknown, what will be the pulmonary microcirculatory changes in case of pulmonary thromboembolism after pretreatment with beta-blockers. AIM: The comparative analysis of the pulmonary microhemodynamics changes following experimental pulmonary thromboembolism in rabbits after pretreatment with nebovolol, carvedilol and propranolol. MATERIAL AND METHODS: In 35 isolated perfused rabbit lungs we investigated the changes of pulmonary microcirculation in case of experimental pulmonary thromboembolism after pretreatment with 1-blocker nebivolol, combined blocker of 1- and 1, 2-adrenoceptors carvedilol, and blocker of 1, 2-adrenoceptors propranolol. RESULTS: After administration of 1, 2-adrenoceptors blocker propranolol and 1-blocker nebivolol the most of the pulmonary microcirculatory parameters increased. Combined 1-, 1, 2-blocker carvedilol caused mainly vasodilatory effects of the pulmonary arterial vessels, however, the pulmonary venous resistance increased. Pulmonary thromboembolism after pretreatment with beta-blockers caused pronounced increase of pulmonary artery pressure, precapillary and pulmonary vascular resistance. In that case after pretreatment with carvedilol capillary filtration coefficient was increased two times more than after propranolol administration; after pretreatment with nebivolol capillary filtration coefficient increased less, than after propranolol administration. CONCLUSIONS: Acute pulmonary embolism caused less pronounced increasing of capillary filtration coefficient in case of nebivolol administration, than after pretreatment with carvedilol and propranolol.
{"title":"The impact of nebivolol, carvedilol and propranolol on pulmonary microhemodynamics in case of experimental pulmonary thromboembolism in rabbits","authors":"V. I. Evlakhov, I. Z. Poyassov, T. P. Berezina","doi":"10.17816/maj96368","DOIUrl":"https://doi.org/10.17816/maj96368","url":null,"abstract":"BACKGROUND: Beta-adrenoblockers nebivolol, carvedilol and propranolol are used in clinical cardiology for the treatment of patients with ischemic heart disease. Pulmonary thromboembolism can develop in such patients. However, its unknown, what will be the pulmonary microcirculatory changes in case of pulmonary thromboembolism after pretreatment with beta-blockers. \u0000AIM: The comparative analysis of the pulmonary microhemodynamics changes following experimental pulmonary thromboembolism in rabbits after pretreatment with nebovolol, carvedilol and propranolol. \u0000MATERIAL AND METHODS: In 35 isolated perfused rabbit lungs we investigated the changes of pulmonary microcirculation in case of experimental pulmonary thromboembolism after pretreatment with 1-blocker nebivolol, combined blocker of 1- and 1, 2-adrenoceptors carvedilol, and blocker of 1, 2-adrenoceptors propranolol. \u0000RESULTS: After administration of 1, 2-adrenoceptors blocker propranolol and 1-blocker nebivolol the most of the pulmonary microcirculatory parameters increased. Combined 1-, 1, 2-blocker carvedilol caused mainly vasodilatory effects of the pulmonary arterial vessels, however, the pulmonary venous resistance increased. Pulmonary thromboembolism after pretreatment with beta-blockers caused pronounced increase of pulmonary artery pressure, precapillary and pulmonary vascular resistance. In that case after pretreatment with carvedilol capillary filtration coefficient was increased two times more than after propranolol administration; after pretreatment with nebivolol capillary filtration coefficient increased less, than after propranolol administration. \u0000CONCLUSIONS: Acute pulmonary embolism caused less pronounced increasing of capillary filtration coefficient in case of nebivolol administration, than after pretreatment with carvedilol and propranolol.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132454277","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. Bolkhovitina, J. Vavilova, A. Bogorodskiy, I. Okhrimenko, V. Borshchevskiy, M. Shevchenko
BACKGROUND: Airborne pathogens such as virus particles undergo elimination from the respiratory tract by mucociliary clearance and phagocytosis by immune cells. The data about phagocytic cell type infiltration and stimuli that attract phagocytic cells to conducting airway are required for the anti-virus immune response mechanism understanding and the treatment strategy development. AIM: To detect the role of the receptor-binding domain of SARS-CoV-2 in neutrophil immune response activation in conducting airway mucosa after 100 nm particles application. MATERIALS AND METHODS: C57BL/6 mice received an oropharyngeal application of fluorescent 100 nm particles suspended in the receptor-binding domain of SARS-CoV-2 solution. 24 hours after, conducting airways of mice were dissected and subjected for immunohistochemistry as whole-mounts. Three-dimensional images of conducting airway regions were obtained using confocal microscopy. Quantitative image analysis was performed to estimate the ingestion activity of neutrophils in conducting airway mucosa. RESULTS: Neutrophil migration to conducting airway mucosa was detected in case of the application of particles in receptor-binding domain solution, but not in phosphate buffer or bovine serum albumin solution. Receptor-binding domain solution alone also induced neutrophil migration to conducting airway mucosa. Infiltrating conducting airway wall mucosa neutrophils contributed to particles internalization. CONCLUSIONS: The receptor-binding domain of SARS-CoV-2 can activate the neutrophil-mediated response in conducting airway mucosa.
{"title":"Receptor-binding domain of SARS-CoV-2 contribution to the neutrophil activation during 100 nm particle-induced immune response in conduction airway mucosa of mice","authors":"E. Bolkhovitina, J. Vavilova, A. Bogorodskiy, I. Okhrimenko, V. Borshchevskiy, M. Shevchenko","doi":"10.17816/maj79206","DOIUrl":"https://doi.org/10.17816/maj79206","url":null,"abstract":"BACKGROUND: Airborne pathogens such as virus particles undergo elimination from the respiratory tract by mucociliary clearance and phagocytosis by immune cells. The data about phagocytic cell type infiltration and stimuli that attract phagocytic cells to conducting airway are required for the anti-virus immune response mechanism understanding and the treatment strategy development. \u0000AIM: To detect the role of the receptor-binding domain of SARS-CoV-2 in neutrophil immune response activation in conducting airway mucosa after 100 nm particles application. \u0000MATERIALS AND METHODS: C57BL/6 mice received an oropharyngeal application of fluorescent 100 nm particles suspended in the receptor-binding domain of SARS-CoV-2 solution. 24 hours after, conducting airways of mice were dissected and subjected for immunohistochemistry as whole-mounts. Three-dimensional images of conducting airway regions were obtained using confocal microscopy. Quantitative image analysis was performed to estimate the ingestion activity of neutrophils in conducting airway mucosa. \u0000RESULTS: Neutrophil migration to conducting airway mucosa was detected in case of the application of particles in receptor-binding domain solution, but not in phosphate buffer or bovine serum albumin solution. Receptor-binding domain solution alone also induced neutrophil migration to conducting airway mucosa. Infiltrating conducting airway wall mucosa neutrophils contributed to particles internalization. \u0000CONCLUSIONS: The receptor-binding domain of SARS-CoV-2 can activate the neutrophil-mediated response in conducting airway mucosa.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121122878","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}
Z. V. Zharkova, A. Yasenyavskaya, I. B. Nikitina, I. V. Goretova, I. Fedoseev, O. Bashkina, M. Samotrueva
Cardiovascular disease is the leading cause of death in the population. Unfortunately, cardiovascular disease and its associated risks are often difficult to diagnose due to the many factors associated with age and other comorbidities that lead to significant uncertainty in diagnostic classification and therapeutic decision making. Therefore, there is a great need to find new biomarkers for more accurate diagnosis, risk assessment and treatment recommendations for both acute and chronic cardiovascular disease. This article presents an analysis of metabolomic and genomic markers used for the diagnosis of cardiovascular disease. The study of the metabolome in combination with the genome and proteome can provide important information about both the pathogenesis of cardiovascular disease and the ability to search for and identify new cardiovascular disease biomarkers. Along with the fundamental data on new cardiovascular disease biomarkers, there is an urgent need for further research confirming their great potential for practical health care.
{"title":"Analysis of metabolomic and genomic markers for diagnosing cardiovascular diseases","authors":"Z. V. Zharkova, A. Yasenyavskaya, I. B. Nikitina, I. V. Goretova, I. Fedoseev, O. Bashkina, M. Samotrueva","doi":"10.17816/maj76043","DOIUrl":"https://doi.org/10.17816/maj76043","url":null,"abstract":"Cardiovascular disease is the leading cause of death in the population. Unfortunately, cardiovascular disease and its associated risks are often difficult to diagnose due to the many factors associated with age and other comorbidities that lead to significant uncertainty in diagnostic classification and therapeutic decision making. Therefore, there is a great need to find new biomarkers for more accurate diagnosis, risk assessment and treatment recommendations for both acute and chronic cardiovascular disease. This article presents an analysis of metabolomic and genomic markers used for the diagnosis of cardiovascular disease. The study of the metabolome in combination with the genome and proteome can provide important information about both the pathogenesis of cardiovascular disease and the ability to search for and identify new cardiovascular disease biomarkers. Along with the fundamental data on new cardiovascular disease biomarkers, there is an urgent need for further research confirming their great potential for practical health care.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128224833","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.N. Shvedova, O. Kopteva, Polina Kudar, A. Lerner, Yuliya A. Desheva
BACKGROUND: Despite the continuing global spread of the coronavirus infection COVID-19 caused by the SARS-CoV-2 coronavirus, the mechanisms of the pathogenesis of severe infections remain poorly understood. The role of comorbidity with other seasonal viral infections, including influenza, in the pathogenesis of the severe course of COVID-19 remains unclear. MATERIALS AND METHODS: The present study used sera left over from ongoing laboratory studies of patients with varying degrees of severity of COVID-19. The study was approved by the Local Ethics Committee of the Federal State Budgetary Scientific Institution IEM (protocol 3/20 from 06/05/2020). We studied 28 paired samples obtained upon admission of patients to the hospital and after 57 days of hospital stay. Paired sera of patients with COVID-19 were tested for antibodies to influenza A and B viruses. The presence of IgG antibodies specific to the SARS-CoV-2 spike (S) protein was studied using an enzyme-linked immunosorbent assay (ELISA). The serum concentration of C-reactive protein and the neutrophil-lymphocyte ratio on the day of hospitalization were also assessed. RESULTS: At least a 4-fold increase in serum IgG antibodies to SARS-CoV-2 S protein was found both in patients with PCR-confirmed SARS-CoV-2 infection and without PCR confirmation. It was shown that out of 18 patients with moderate and severe forms of COVID-19 infection, six of them showed at least a 4-fold increase in antibodies to influenza A/H1N1, in one to influenza A/H3N2 and in two cases to the influenza B. Laboratory data in these two groups were characterized by significant increases in serum C-reactive protein and neutrophil-lymphocyte ratio concentrations compared with the moderate COVID-19 group. CONCLUSIONS: Serological diagnostics can additionally detect cases of coronavirus infection when the virus was not detected by PCR. In moderate and severe cases of COVID-19, coinfections with influenza A and B viruses have been identified. The results obtained confirm the need for anti-influenza immunization during the SARS-CoV-2 pandemic. Influenza virus screening can significantly improve patient management because recommended antiviral drugs (neuraminidase inhibitors) are available.
{"title":"The role of coinfection with influenza viruses in the pathogenesis of severe infection in patients with COVID-19","authors":"T.N. Shvedova, O. Kopteva, Polina Kudar, A. Lerner, Yuliya A. Desheva","doi":"10.17816/maj78155","DOIUrl":"https://doi.org/10.17816/maj78155","url":null,"abstract":"BACKGROUND: Despite the continuing global spread of the coronavirus infection COVID-19 caused by the SARS-CoV-2 coronavirus, the mechanisms of the pathogenesis of severe infections remain poorly understood. The role of comorbidity with other seasonal viral infections, including influenza, in the pathogenesis of the severe course of COVID-19 remains unclear. \u0000MATERIALS AND METHODS: The present study used sera left over from ongoing laboratory studies of patients with varying degrees of severity of COVID-19. The study was approved by the Local Ethics Committee of the Federal State Budgetary Scientific Institution IEM (protocol 3/20 from 06/05/2020). We studied 28 paired samples obtained upon admission of patients to the hospital and after 57 days of hospital stay. Paired sera of patients with COVID-19 were tested for antibodies to influenza A and B viruses. The presence of IgG antibodies specific to the SARS-CoV-2 spike (S) protein was studied using an enzyme-linked immunosorbent assay (ELISA). The serum concentration of C-reactive protein and the neutrophil-lymphocyte ratio on the day of hospitalization were also assessed. \u0000RESULTS: At least a 4-fold increase in serum IgG antibodies to SARS-CoV-2 S protein was found both in patients with PCR-confirmed SARS-CoV-2 infection and without PCR confirmation. It was shown that out of 18 patients with moderate and severe forms of COVID-19 infection, six of them showed at least a 4-fold increase in antibodies to influenza A/H1N1, in one to influenza A/H3N2 and in two cases to the influenza B. Laboratory data in these two groups were characterized by significant increases in serum C-reactive protein and neutrophil-lymphocyte ratio concentrations compared with the moderate COVID-19 group. \u0000CONCLUSIONS: Serological diagnostics can additionally detect cases of coronavirus infection when the virus was not detected by PCR. In moderate and severe cases of COVID-19, coinfections with influenza A and B viruses have been identified. The results obtained confirm the need for anti-influenza immunization during the SARS-CoV-2 pandemic. Influenza virus screening can significantly improve patient management because recommended antiviral drugs (neuraminidase inhibitors) are available.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"167 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124668238","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}
P. Prokopenko, Виктория A. Matyushenko, I. Isakova-Sivak, L. Rudenko
BACKGROUND: Vaccination is the most effective means of fighting influenza epidemics, but the immunogenicity of licensed influenza vaccines is not always satisfactory. One of the ways to increase the immunogenicity of an attenuated live influenza vaccine is to shorten the open reading frame of the NS1 protein, a modulator of innate antiviral immunity. In addition, the T-cell response to vaccination can be optimized by including the NP gene from the epidemic parental virus into the genome of vaccine strains. MATERIALS AND METHODS: The open reading frame of the NS1 protein of the master donor virus A/Leningrad/134/17/57 was truncated to 126 amino acids by site-directed mutagenesis. The HA, NA, and NP genes of the model virus A/Anhui/1/2013 (H7N9) were cloned into the pCIPolISapIT vector. The rescue of recombinant influenza viruses was performed by transfection of Vero cells with a desired set of plasmids. The growth properties of the recombinant viruses were determined in embryonated chicken eggs incubated at different temperatures, as well as in the tissues of the respiratory tract of mice (nasal turbinates, lungs). RESULTS: Experimental live influenza vaccine strains of subtype H7N9 with genome compositions 6:2 and 5:3 and carrying a full-length or truncated NS1 gene were actively replicated in eggs under optimal conditions, while maintaining the temperature-sensitive and cold-adapted phenotypes characteristic of classical live influenza vaccine strains. All viruses lacked the ability to grow in the lungs of C57BL/6J mice, which confirms the attenuated phenotype of the viruses. In the nasal passages of mice, only viruses with the full-length NS1 gene replicated, while viruses expressing the truncated NS1 protein were not detected in the respiratory tract of animals. CONCLUSIONS: The results indicate that modification of the NS1 gene of the vaccine virus and the inclusion of wild-type NP gene in its genome does not affect its growth characteristics in eggs. A decrease in the activity of viral replication in the upper respiratory tract of mice with a shortening of the NS1 open reading frame indicates an increase in the attenuating properties of modified vaccines, which opens up prospects for the use of new vaccines in children under three years of age.
{"title":"Growth characteristics of experimental live influenza vaccine strains with modified NP and NS genes","authors":"P. Prokopenko, Виктория A. Matyushenko, I. Isakova-Sivak, L. Rudenko","doi":"10.17816/maj77800","DOIUrl":"https://doi.org/10.17816/maj77800","url":null,"abstract":"BACKGROUND: Vaccination is the most effective means of fighting influenza epidemics, but the immunogenicity of licensed influenza vaccines is not always satisfactory. One of the ways to increase the immunogenicity of an attenuated live influenza vaccine is to shorten the open reading frame of the NS1 protein, a modulator of innate antiviral immunity. In addition, the T-cell response to vaccination can be optimized by including the NP gene from the epidemic parental virus into the genome of vaccine strains. \u0000MATERIALS AND METHODS: The open reading frame of the NS1 protein of the master donor virus A/Leningrad/134/17/57 was truncated to 126 amino acids by site-directed mutagenesis. The HA, NA, and NP genes of the model virus A/Anhui/1/2013 (H7N9) were cloned into the pCIPolISapIT vector. The rescue of recombinant influenza viruses was performed by transfection of Vero cells with a desired set of plasmids. The growth properties of the recombinant viruses were determined in embryonated chicken eggs incubated at different temperatures, as well as in the tissues of the respiratory tract of mice (nasal turbinates, lungs). \u0000RESULTS: Experimental live influenza vaccine strains of subtype H7N9 with genome compositions 6:2 and 5:3 and carrying a full-length or truncated NS1 gene were actively replicated in eggs under optimal conditions, while maintaining the temperature-sensitive and cold-adapted phenotypes characteristic of classical live influenza vaccine strains. All viruses lacked the ability to grow in the lungs of C57BL/6J mice, which confirms the attenuated phenotype of the viruses. In the nasal passages of mice, only viruses with the full-length NS1 gene replicated, while viruses expressing the truncated NS1 protein were not detected in the respiratory tract of animals. \u0000CONCLUSIONS: The results indicate that modification of the NS1 gene of the vaccine virus and the inclusion of wild-type NP gene in its genome does not affect its growth characteristics in eggs. A decrease in the activity of viral replication in the upper respiratory tract of mice with a shortening of the NS1 open reading frame indicates an increase in the attenuating properties of modified vaccines, which opens up prospects for the use of new vaccines in children under three years of age.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130324201","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 aim of this study is to analyze the scientific literature data on the frequency and characteristics of infectious complications during the treatment of patients with lymphoproliferative diseases with a new class of drugs, selective inhibitors of Brutons tyrosine kinase (BTK). This work describes the indications for appointing these drugs as well as the participation of BTK in the development and activation of B cells. We have studied the main characteristics of BTK inhibitors used in clinical practice and associated disorders in the activity of off-target tyrosine kinases. The work describes the main types of known infectious complications developing during the treatment with the drugs of this group, the period of their appearance, and characteristic pathogens.
{"title":"Infectious complications in patients with chronic lymphocytic leukemia treated with bruton’s tyrosine kinase inhibitors","authors":"Yulia S. Torshina, N. Serebryanaya","doi":"10.17816/maj76060","DOIUrl":"https://doi.org/10.17816/maj76060","url":null,"abstract":"The aim of this study is to analyze the scientific literature data on the frequency and characteristics of infectious complications during the treatment of patients with lymphoproliferative diseases with a new class of drugs, selective inhibitors of Brutons tyrosine kinase (BTK). This work describes the indications for appointing these drugs as well as the participation of BTK in the development and activation of B cells. We have studied the main characteristics of BTK inhibitors used in clinical practice and associated disorders in the activity of off-target tyrosine kinases. The work describes the main types of known infectious complications developing during the treatment with the drugs of this group, the period of their appearance, and characteristic pathogens.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123852355","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}
Alena V. Kuleshova, Inna P. Iskova, E. Kiseleva, Vitaliy N. Chebotkevich
BACKGROUND: Patients with cancer are prone to developing infectious complications. They significantly aggravate the course of the underlying disease and worsen the quality of life of patients. The emergence of infections is largely promoted by immunosuppression associated with the use of cytostatic drugs, high-dose chemotherapy and hematopoietic stem cell transplantation in hematological cancer patients. Among infectious agents, respiratory viruses, especially influenza viruses, play an important role. The urgency of this problem has increased many times in connection with the development of the COVID-19 pandemic. AIM: To study the features of the course of respiratory infections, including coronavirus (seasonal and COVID-19), infections in cancer and oncohematological patients during hospitalization and in outpatient settings. MATERIALS AND METHODS: The study of the frequency and course of infectious complications in cohorts of patients with oncological diseases, who were under dispensary supervision in the polyclinic in Kirovsk, Leningrad region. Retrospective analysis of the frequency and characteristics of the course of coronavirus infection caused by HCoVs (OC43, 229E, NL63, HKU1) in patients treated at the clinics of the Russian research institute of Hematology and Transfusionology. Prospective study of the coronavirus COVID-19 of patients hospitalized at the Russian research institute of Hematology and Transfusionology and at the Kirov interdistrict hospital in Leningrad Region during the period of its conversion to specialized infection diseases hospital. RESULTS: Coronavirus infection caused by HCoVs (OC43, 229E, NL63, HKU1), occurs in hematological cancer patients more often in association with other respiratory viruses. In the cases of detection of the SARS-CoV-2 in hospitalized patients, they need to be transferred to specialized infectious hospitals. CONCLUSIONS: Respiratory viral infections are risk factors in cancer and oncohematological patients. Outpatient oncological and oncohematological patients require constant dispensary observation and special attention during the COVID-19 pandemic, outbreaks of influenza and other viral infections.
{"title":"Respiratory viral infections including caused by coronaviruses in oncological and oncohematological patients","authors":"Alena V. Kuleshova, Inna P. Iskova, E. Kiseleva, Vitaliy N. Chebotkevich","doi":"10.17816/maj78565","DOIUrl":"https://doi.org/10.17816/maj78565","url":null,"abstract":"BACKGROUND: Patients with cancer are prone to developing infectious complications. They significantly aggravate the course of the underlying disease and worsen the quality of life of patients. The emergence of infections is largely promoted by immunosuppression associated with the use of cytostatic drugs, high-dose chemotherapy and hematopoietic stem cell transplantation in hematological cancer patients. Among infectious agents, respiratory viruses, especially influenza viruses, play an important role. The urgency of this problem has increased many times in connection with the development of the COVID-19 pandemic. \u0000AIM: To study the features of the course of respiratory infections, including coronavirus (seasonal and COVID-19), infections in cancer and oncohematological patients during hospitalization and in outpatient settings. \u0000MATERIALS AND METHODS: The study of the frequency and course of infectious complications in cohorts of patients with oncological diseases, who were under dispensary supervision in the polyclinic in Kirovsk, Leningrad region. Retrospective analysis of the frequency and characteristics of the course of coronavirus infection caused by HCoVs (OC43, 229E, NL63, HKU1) in patients treated at the clinics of the Russian research institute of Hematology and Transfusionology. Prospective study of the coronavirus COVID-19 of patients hospitalized at the Russian research institute of Hematology and Transfusionology and at the Kirov interdistrict hospital in Leningrad Region during the period of its conversion to specialized infection diseases hospital. \u0000RESULTS: Coronavirus infection caused by HCoVs (OC43, 229E, NL63, HKU1), occurs in hematological cancer patients more often in association with other respiratory viruses. In the cases of detection of the SARS-CoV-2 in hospitalized patients, they need to be transferred to specialized infectious hospitals. \u0000CONCLUSIONS: Respiratory viral infections are risk factors in cancer and oncohematological patients. Outpatient oncological and oncohematological patients require constant dispensary observation and special attention during the COVID-19 pandemic, outbreaks of influenza and other viral infections.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115569665","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}
J. Vavilova, E. Bolkhovitina, A. Bogorodskiy, I. Okhrimenko, V. Borshchevskiy, M. Shevchenko
BACKGROUND: Daily, people inhale airborne viral particles, some of which have a size of about 100 nm, such as particles of SARS-CoV-2. Kinetics of such 100 nm particle distribution in the respiratory tract is important, however, not a properly investigated question. AIM: To estimate the dissemination of inert viral particles based on the analysis of the spatial distribution of fluorescent 100 nm particles in the mouse lungs at different time points after the application. MATHERIALS AND METHODS: Fluorescent particles of 100 nm size were applied to C57BL/6 mice. 6, 24, 48 and 72 hours after, lungs were excised and fixed. Lung lobes were stained with immunohistochemistry as whole-mounts and then underwent optical clearance. Three-dimensional images of whole-mount mouse lung lobes were acquired using confocal laser scanning microscopy. RESULTS: 6 hours after the particle application particles were detected in lungs both as single particles and as particle agglomerates. Particles were both free and internalized by phagocytic cells. 24 hours after the application particles were detected both in bronchial lumen and in the alveolar space. Particles were detected in the mouse lungs up to 72 hours after the application. CONCLUSIONS: Reaching the respiratory tract of mammalian, inert particles which size equal to SARS-CoV-2 particle size distribute both in bronchi and in alveoli and undergoes internalization of phagocytic cells.
{"title":"Estimation of 100 nm particle distribution kinetics in mouse lung using confocal laser scanning microscopy","authors":"J. Vavilova, E. Bolkhovitina, A. Bogorodskiy, I. Okhrimenko, V. Borshchevskiy, M. Shevchenko","doi":"10.17816/maj79200","DOIUrl":"https://doi.org/10.17816/maj79200","url":null,"abstract":"BACKGROUND: Daily, people inhale airborne viral particles, some of which have a size of about 100 nm, such as particles of SARS-CoV-2. Kinetics of such 100 nm particle distribution in the respiratory tract is important, however, not a properly investigated question. \u0000AIM: To estimate the dissemination of inert viral particles based on the analysis of the spatial distribution of fluorescent 100 nm particles in the mouse lungs at different time points after the application. \u0000MATHERIALS AND METHODS: Fluorescent particles of 100 nm size were applied to C57BL/6 mice. 6, 24, 48 and 72 hours after, lungs were excised and fixed. Lung lobes were stained with immunohistochemistry as whole-mounts and then underwent optical clearance. Three-dimensional images of whole-mount mouse lung lobes were acquired using confocal laser scanning microscopy. \u0000RESULTS: 6 hours after the particle application particles were detected in lungs both as single particles and as particle agglomerates. Particles were both free and internalized by phagocytic cells. 24 hours after the application particles were detected both in bronchial lumen and in the alveolar space. Particles were detected in the mouse lungs up to 72 hours after the application. \u0000CONCLUSIONS: Reaching the respiratory tract of mammalian, inert particles which size equal to SARS-CoV-2 particle size distribute both in bronchi and in alveoli and undergoes internalization of phagocytic cells.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"70 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117021268","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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