S. Terekhov, VI Shmygarev, K. Purtov, I. Smirnov, IV Yampolsky, A. Tsarkova
The increasing size and density of the human population is leading to an increasing risk of infectious diseases that threaten to spread yet another pandemics. The widespread use of vaccination has reduced morbidity and mortality associated with viral infections and in some cases eradicated the virus from the population entirely. Regrettably, some virus species retain the ability to mutate rapidly and thus evade the vaccine-induced immune response. New antiviral drugs are therefore needed for the treatment and prevention of viral diseases. Modern research into the structures and properties of viral proteases, which are of key importance in the life cycle of viruses, makes it possible, in our opinion, to turn these enzymes into promising targets for the development of effective viral disease control methods.
{"title":"Drug design strategies for the treatment of coronavirus infection","authors":"S. Terekhov, VI Shmygarev, K. Purtov, I. Smirnov, IV Yampolsky, A. Tsarkova","doi":"10.24075/brsmu.2022.067","DOIUrl":"https://doi.org/10.24075/brsmu.2022.067","url":null,"abstract":"The increasing size and density of the human population is leading to an increasing risk of infectious diseases that threaten to spread yet another pandemics. The widespread use of vaccination has reduced morbidity and mortality associated with viral infections and in some cases eradicated the virus from the population entirely. Regrettably, some virus species retain the ability to mutate rapidly and thus evade the vaccine-induced immune response. New antiviral drugs are therefore needed for the treatment and prevention of viral diseases. Modern research into the structures and properties of viral proteases, which are of key importance in the life cycle of viruses, makes it possible, in our opinion, to turn these enzymes into promising targets for the development of effective viral disease control methods.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42304508","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}
AS Kirshina, AA Kazakova, E. Kolosova, EA Imasheva, O. Vasileva, OV Zaborova, IM Terenin, A. Muslimov, VV Reshetnikov
It has been proven that mRNA vaccines are highly effective against the COVID-19 outbreak, and low prevalence of side effects has been shown. However, there are still many gaps in our understanding of the biology and biosafety of nucleic acids as components of lipid nanoparticles (LNPs) most often used as a system for inctracellular delivery of mRNA-based vaccines. It is known that LNPs cause severe injection site inflammation, have broad biodistribution profiles, and are found in multiple tissues of the body, including the brain, after administration. The role of new medications with such pharmacokinetics in inflammation developing in inaccessible organs is poorly understood. The study was aimed to assess the effects of various doses of mRNA-LNP expressing the reporter protein (0, 5, 10, and 20 μg of mRNA encoding the firefly luciferase) on the expression of neuroinflammation markers (Tnfα, Il1β, Gfap, Aif1) in the prefrontal cortex and hypothalamus of laboratory animals 4, 8, and 30 h after the intramuscular injection of LNP nanoemulsion. It was shown that mRNA-LNP vaccines in a dose of 10–20 μg of mRNA could enhance Aif1 expression in the hypothalamus 8 h after vaccination, however, no such differences were observed after 30 h. It was found that the Gfap, l11β, Tnfα expression levels in the hypothalamus observed at different times in the experimental groups were different. According to the results, mRNA-LNPs administered by the parenteral route can stimulate temporary activation of microglia in certain time intervals in the dose-dependent and site specific manner.
{"title":"Effects of various mRNA-LNP vaccine doses on neuroinflammation in BALB/c mice","authors":"AS Kirshina, AA Kazakova, E. Kolosova, EA Imasheva, O. Vasileva, OV Zaborova, IM Terenin, A. Muslimov, VV Reshetnikov","doi":"10.24075/brsmu.2022.068","DOIUrl":"https://doi.org/10.24075/brsmu.2022.068","url":null,"abstract":"It has been proven that mRNA vaccines are highly effective against the COVID-19 outbreak, and low prevalence of side effects has been shown. However, there are still many gaps in our understanding of the biology and biosafety of nucleic acids as components of lipid nanoparticles (LNPs) most often used as a system for inctracellular delivery of mRNA-based vaccines. It is known that LNPs cause severe injection site inflammation, have broad biodistribution profiles, and are found in multiple tissues of the body, including the brain, after administration. The role of new medications with such pharmacokinetics in inflammation developing in inaccessible organs is poorly understood. The study was aimed to assess the effects of various doses of mRNA-LNP expressing the reporter protein (0, 5, 10, and 20 μg of mRNA encoding the firefly luciferase) on the expression of neuroinflammation markers (Tnfα, Il1β, Gfap, Aif1) in the prefrontal cortex and hypothalamus of laboratory animals 4, 8, and 30 h after the intramuscular injection of LNP nanoemulsion. It was shown that mRNA-LNP vaccines in a dose of 10–20 μg of mRNA could enhance Aif1 expression in the hypothalamus 8 h after vaccination, however, no such differences were observed after 30 h. It was found that the Gfap, l11β, Tnfα expression levels in the hypothalamus observed at different times in the experimental groups were different. According to the results, mRNA-LNPs administered by the parenteral route can stimulate temporary activation of microglia in certain time intervals in the dose-dependent and site specific manner.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46284243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Siniavin, L. Russu, D. Vasina, EV Shidlovskaya, N. Kuznetsova, Vadim V. Guschin, A. Gintsburg
The COVID-19 disease pandemic remains a significant global problem, resulting in hundreds of millions of cases and millions of deaths. The search for specific inhibitors of SARS-CoV-2 for the treatment of this infection remains relevant. Drugs such as Favipiravir and Molnupiravir, which exhibit specific antiviral activity against SARS-CoV-2, are already being used to treat patients. However, there is limited evidence of their effectiveness, especially against novel genetic variants of the COVID-19 pathogen. The aim of this study was to investigate the antiviral effect of these drugs using an in vitro experimental model of SARS-CoV-2 infection in Vero E6 cell culture and an animal model of infection using Syrian hamsters. It has been established that Molnupiravir has an inhibitory effect against variants of the SARS-CoV-2 with IC50 values from 16.51 to 7.88 μM in vitro, and reduces the infectious titer of the virus in the lungs of animals by ~1.5 Log10 in vivo, in while Favipiravir shows lower activity and severe toxicity. Dose selection and frequency of use remain unexplored.
{"title":"Efficacy of favipiravir and molnupiravir against novel SARS-CoV-2 variants in vitro and in vivo","authors":"A. Siniavin, L. Russu, D. Vasina, EV Shidlovskaya, N. Kuznetsova, Vadim V. Guschin, A. Gintsburg","doi":"10.24075/brsmu.2022.071","DOIUrl":"https://doi.org/10.24075/brsmu.2022.071","url":null,"abstract":"The COVID-19 disease pandemic remains a significant global problem, resulting in hundreds of millions of cases and millions of deaths. The search for specific inhibitors of SARS-CoV-2 for the treatment of this infection remains relevant. Drugs such as Favipiravir and Molnupiravir, which exhibit specific antiviral activity against SARS-CoV-2, are already being used to treat patients. However, there is limited evidence of their effectiveness, especially against novel genetic variants of the COVID-19 pathogen. The aim of this study was to investigate the antiviral effect of these drugs using an in vitro experimental model of SARS-CoV-2 infection in Vero E6 cell culture and an animal model of infection using Syrian hamsters. It has been established that Molnupiravir has an inhibitory effect against variants of the SARS-CoV-2 with IC50 values from 16.51 to 7.88 μM in vitro, and reduces the infectious titer of the virus in the lungs of animals by ~1.5 Log10 in vivo, in while Favipiravir shows lower activity and severe toxicity. Dose selection and frequency of use remain unexplored.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41958947","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}
AV Gospodaryk, LA Ulakhanova, SS Esiev, EV Polyakova, YD Shansky, J. Bespyatykh
Fecal microbiota transplantation (FMT) is prescribed to treat various gastrointestinal pathologies. One of the most important and significant stages of FMT is selection of the donor. In recent years, special attention has been paid to checking the biomaterial for genes marking resistance to various groups of antibiotics. This study aimed to analyze the occurrence of mef and ermB drug resistance genetic markers in population of various age groups, including breastfed infants, and to determine microbiological composition of the flora of distal part of the intestine of potentially healthy volunteering FMT donors. A total of 52 biological samples (46 stool samples and 6 breast milk samples) were analyzed by real-time polymerase chain reaction. The macrolides resistance gene (mef) was detected in 97.8% of stool samples (different age groups), the gene marking resistance to macrolides, lincosamides, streptogramin (ermB) — in 93.5%. In the isolated "mother-child" group, the mef gene was found in all samples of breast milk and feces. The ermB gene in this group was found in 3 out of 6 breast milk samples and 4 out of 6 infant stool samples. Since the mef and ermB genetic determinants were identified not only among in adults but also in infants, it was suggested that transplant material (feces) containing these genes can be used for FMT. The analysis of microbiological composition of stool samples from 23 healthy volunteers (potential FMT donors) revealed that it rarely (in 8.7% of cases only) corresponds to what is considered to be a normal microbiota of the intestine's distal part.
{"title":"The role of mef and ermB drug resistance genetic markers in the selection of fecal microbiota donors","authors":"AV Gospodaryk, LA Ulakhanova, SS Esiev, EV Polyakova, YD Shansky, J. Bespyatykh","doi":"10.24075/brsmu.2022.059","DOIUrl":"https://doi.org/10.24075/brsmu.2022.059","url":null,"abstract":"Fecal microbiota transplantation (FMT) is prescribed to treat various gastrointestinal pathologies. One of the most important and significant stages of FMT is selection of the donor. In recent years, special attention has been paid to checking the biomaterial for genes marking resistance to various groups of antibiotics. This study aimed to analyze the occurrence of mef and ermB drug resistance genetic markers in population of various age groups, including breastfed infants, and to determine microbiological composition of the flora of distal part of the intestine of potentially healthy volunteering FMT donors. A total of 52 biological samples (46 stool samples and 6 breast milk samples) were analyzed by real-time polymerase chain reaction. The macrolides resistance gene (mef) was detected in 97.8% of stool samples (different age groups), the gene marking resistance to macrolides, lincosamides, streptogramin (ermB) — in 93.5%. In the isolated \"mother-child\" group, the mef gene was found in all samples of breast milk and feces. The ermB gene in this group was found in 3 out of 6 breast milk samples and 4 out of 6 infant stool samples. Since the mef and ermB genetic determinants were identified not only among in adults but also in infants, it was suggested that transplant material (feces) containing these genes can be used for FMT. The analysis of microbiological composition of stool samples from 23 healthy volunteers (potential FMT donors) revealed that it rarely (in 8.7% of cases only) corresponds to what is considered to be a normal microbiota of the intestine's distal part.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46573729","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}
Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of female mortality. The development of prognostic models based on multiomics data is the main goal of precision oncology. Aberrant DNA methylation in BC is a diagnostic marker of carcinogenesis. Despite the existing factors of BC prognosis, introduction of methylation markers would make it possible to obtain more accurate prognostic scores. The study was aimed to assess DNA methylation signatures in various BC subtypes for clinical endpoints and patients' clinicopathological characteristics. The data on methylation of CpG dinucleotides (probes) and clinical characteristics of BC samples were obtained from The Cancer Genome Atlas Breast Cancer database. CpG dinucleotides associated with the selected endpoints were chosen by univariate Cox regression method. The LASSO method was used to search for stable probes, while further signature construction and testing of the clinical characteristics independence were performed using multivariate Cox regression. The dignostic and prognostic potential of the signatures was assessed using ROC analysis and Kaplan–Meier curves. It has been shown that the signatures of selected probes have a significant diagnostic (AUC 0.76–1) and prognostic (p < 0.05) potential. This approach has made it possible to identify 47 genes associated with good and poor prognosis, among these five genes have been described earlier. If the genome-wide DNA analysis results are available, the research approach applied can be used to study molecular pathogenesis of BC and other disorders.
乳腺癌(BC)是最常见的癌症，也是女性死亡的主要原因之一。基于多组学数据的预后模型的发展是精确肿瘤学的主要目标。BC异常DNA甲基化是癌变的诊断标志物。尽管存在影响BC预后的因素，但引入甲基化标记物将有可能获得更准确的预后评分。该研究旨在评估不同BC亚型的DNA甲基化特征的临床终点和患者的临床病理特征。CpG二核苷酸(探针)的甲基化和BC样本的临床特征数据来自The Cancer Genome Atlas Breast Cancer数据库。用单变量Cox回归法选择与所选终点相关的CpG二核苷酸。采用LASSO法寻找稳定的探针，进一步的特征构建和临床特征独立性检验采用多变量Cox回归。使用ROC分析和Kaplan-Meier曲线评估特征的诊断和预后潜力。研究表明，所选探针的特征具有显著的诊断(AUC为0.76-1)和预后(p < 0.05)潜力。这种方法已经能够鉴定出47个与预后好坏相关的基因，其中5个基因已经在前面描述过。如果全基因组DNA分析结果可以获得，那么所采用的研究方法可以用于研究BC等疾病的分子发病机制。
{"title":"Identification of prognostically significant DNA methylation signatures in patients with various breast cancer types","authors":"A. Kalinkin, VO Sigin, M. Nemtsova, V. Strelnikov","doi":"10.24075/brsmu.2022.056","DOIUrl":"https://doi.org/10.24075/brsmu.2022.056","url":null,"abstract":"Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of female mortality. The development of prognostic models based on multiomics data is the main goal of precision oncology. Aberrant DNA methylation in BC is a diagnostic marker of carcinogenesis. Despite the existing factors of BC prognosis, introduction of methylation markers would make it possible to obtain more accurate prognostic scores. The study was aimed to assess DNA methylation signatures in various BC subtypes for clinical endpoints and patients' clinicopathological characteristics. The data on methylation of CpG dinucleotides (probes) and clinical characteristics of BC samples were obtained from The Cancer Genome Atlas Breast Cancer database. CpG dinucleotides associated with the selected endpoints were chosen by univariate Cox regression method. The LASSO method was used to search for stable probes, while further signature construction and testing of the clinical characteristics independence were performed using multivariate Cox regression. The dignostic and prognostic potential of the signatures was assessed using ROC analysis and Kaplan–Meier curves. It has been shown that the signatures of selected probes have a significant diagnostic (AUC 0.76–1) and prognostic (p < 0.05) potential. This approach has made it possible to identify 47 genes associated with good and poor prognosis, among these five genes have been described earlier. If the genome-wide DNA analysis results are available, the research approach applied can be used to study molecular pathogenesis of BC and other disorders.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42401418","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. Frankevich, A. Novoselova, N. Starodubtseva, M. Patysheva, IV Larionova, Maria S. Rakina, O. Bragina, J. Kzhyshkowska
Breast cancer is the leading cause of cancer-related death among women worldwide. Tumor-associated macrophages (TAMs) constitute the primary component of innate immunity in breast cancer tissue. During the development of new approaches for breast cancer treatment aimed at editing the epigenome of TAM, precise methods for the analysis of macrophage metabolome are required to examine the effect on new approaches on macrophage metabolism. Our study aimed to develop an HPLC-MS/MS-based analytical approach to characterize the metabolome of human innate immune cells (TAMs and their precursors, monocytes). Analysis of lipid extracts was conducted on a Dionex UltiMate 3000 liquid chromatograph connected to a Maxis Impact qTOF mass analyzer with an ESI ion source. Quantitative analysis of 38 amino acids in the cells was conducted using the Jasem Amino Acids LC-MS/MS Analysis Kit and an HPLC-MS/MS chromatographic system consisting out of an Agilent 6460 triple quadrupole mass spectrometric detector (Agilent), and an Agilent 1260 II liquid chromatograph (Agilent ) with Amino acids-HPLC Column (Jasem). The modified Folch method with double extraction was found to be the optimal approached for the sample preparation, since it enables to simultaneously isolate the lipid extract and water-soluble substances, in particular, amino acids. The method of reversed-phase chromatography yielded more useful data on the cell lipid composition than the method of hydrophilic interaction liquid chromatography (HILIC). The minimum number of cells required to determine the metabolome of immune system cells (TAM and monocytes) was identified as 2 × 106. Thus, we have developed the approach to determine the lipid and amino acid composition of modelled human TAMs and primary monocytes isolated out of breast cancer patients using minimal amount of clinical material.
{"title":"Methodology of determining the metabolomic profile of tumor-associated macrophages and monocytes in oncological diseases","authors":"V. Frankevich, A. Novoselova, N. Starodubtseva, M. Patysheva, IV Larionova, Maria S. Rakina, O. Bragina, J. Kzhyshkowska","doi":"10.24075/brsmu.2022.049","DOIUrl":"https://doi.org/10.24075/brsmu.2022.049","url":null,"abstract":"Breast cancer is the leading cause of cancer-related death among women worldwide. Tumor-associated macrophages (TAMs) constitute the primary component of innate immunity in breast cancer tissue. During the development of new approaches for breast cancer treatment aimed at editing the epigenome of TAM, precise methods for the analysis of macrophage metabolome are required to examine the effect on new approaches on macrophage metabolism. Our study aimed to develop an HPLC-MS/MS-based analytical approach to characterize the metabolome of human innate immune cells (TAMs and their precursors, monocytes). Analysis of lipid extracts was conducted on a Dionex UltiMate 3000 liquid chromatograph connected to a Maxis Impact qTOF mass analyzer with an ESI ion source. Quantitative analysis of 38 amino acids in the cells was conducted using the Jasem Amino Acids LC-MS/MS Analysis Kit and an HPLC-MS/MS chromatographic system consisting out of an Agilent 6460 triple quadrupole mass spectrometric detector (Agilent), and an Agilent 1260 II liquid chromatograph (Agilent ) with Amino acids-HPLC Column (Jasem). The modified Folch method with double extraction was found to be the optimal approached for the sample preparation, since it enables to simultaneously isolate the lipid extract and water-soluble substances, in particular, amino acids. The method of reversed-phase chromatography yielded more useful data on the cell lipid composition than the method of hydrophilic interaction liquid chromatography (HILIC). The minimum number of cells required to determine the metabolome of immune system cells (TAM and monocytes) was identified as 2 × 106. Thus, we have developed the approach to determine the lipid and amino acid composition of modelled human TAMs and primary monocytes isolated out of breast cancer patients using minimal amount of clinical material.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44422425","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}
NF Nuralieva, MYu Yukina, E. Troshina, O. Zhukova, V. Petrov, VA Volnukhin
There is evidence in the literature about more frequent association of vitiligo with autoimmune endocrine diseases (AEDs) compared to general population. No full-fledged studies aimed at assessing the prevalence of AEDs in the Russian cohort of adult vitiligo patients have been conducted. The study was aimed to assess the prevalence of AEDs in the cohort of Russian adult vitiligo patients. Patients with vitiligo monitored in two clinics, the Endocrinology Research Centre (Clinic 1; n = 39) and the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology (Clinic 2; n = 26), were enrolled. Along with clinical examination, screening laboratory tests were performed in all patients in order to reveal AEDs. The majority of patients (more than 95% of cases) had nonsegmental vitiligo. Among patients monitored in Clinic 1, AEDs were diagnosed in 85% of cases: isolated AEDs accounted for 39%, while multiple AEDs were found in 46% of cases. Autoimmune thyroid diseases were diagnosed in 69% of cases. Autoimmune adrenal insufficiency was found in 28% of patients, type 1 diabetes mellitus in 21%, hypoparathyroidism in 13%, hypergonadotropic hypogonadism in 10%, endocrine ophthalmopathy in 10% of patients. Among patients monitored in Clinic 2, AEDs were diagnosed in four patients (15% of cases): three patients had primary hypothyroidism in the outcome of autoimmune thyroiditis, one patient had Graves' disease. Thus, the prevalence of AEDs in patients with vitiligo may vary between 15–85%. Vitiligo is most often associated with autoimmune thyroid diseases (15–69%). Vitiligo patients should undergo annual screening aimed at detection of autoimmune endocrine disorders, especially thyroid diseases.
{"title":"Frequent association of vitiligo with autoimmune endocrine diseases: primary data of the Russian cohort of adult patients","authors":"NF Nuralieva, MYu Yukina, E. Troshina, O. Zhukova, V. Petrov, VA Volnukhin","doi":"10.24075/brsmu.2022.055","DOIUrl":"https://doi.org/10.24075/brsmu.2022.055","url":null,"abstract":"There is evidence in the literature about more frequent association of vitiligo with autoimmune endocrine diseases (AEDs) compared to general population. No full-fledged studies aimed at assessing the prevalence of AEDs in the Russian cohort of adult vitiligo patients have been conducted. The study was aimed to assess the prevalence of AEDs in the cohort of Russian adult vitiligo patients. Patients with vitiligo monitored in two clinics, the Endocrinology Research Centre (Clinic 1; n = 39) and the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology (Clinic 2; n = 26), were enrolled. Along with clinical examination, screening laboratory tests were performed in all patients in order to reveal AEDs. The majority of patients (more than 95% of cases) had nonsegmental vitiligo. Among patients monitored in Clinic 1, AEDs were diagnosed in 85% of cases: isolated AEDs accounted for 39%, while multiple AEDs were found in 46% of cases. Autoimmune thyroid diseases were diagnosed in 69% of cases. Autoimmune adrenal insufficiency was found in 28% of patients, type 1 diabetes mellitus in 21%, hypoparathyroidism in 13%, hypergonadotropic hypogonadism in 10%, endocrine ophthalmopathy in 10% of patients. Among patients monitored in Clinic 2, AEDs were diagnosed in four patients (15% of cases): three patients had primary hypothyroidism in the outcome of autoimmune thyroiditis, one patient had Graves' disease. Thus, the prevalence of AEDs in patients with vitiligo may vary between 15–85%. Vitiligo is most often associated with autoimmune thyroid diseases (15–69%). Vitiligo patients should undergo annual screening aimed at detection of autoimmune endocrine disorders, especially thyroid diseases.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47546688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Gerasimova, YuV Shevchenko, PA Klimenko, LA Asyrafyan
Prediction of ovarian tumor type in pregnant women is of great clinical significance, however, it is vastly difficult. In the last 5–10 years gynecologists were suggested to use RMI (Risk of Malignancy Index) in non-pregnant women, however the value of the test for obstetric practice has yet to be established. The study was aimed to determine RMI-IV and RMI-V during preoperative non-invasive prediction of ovarian tumor type in pregnant women. Retrospective and prospective clinical and laboratory data of 114 pregnant women aged 20–38 were collected. Among them 15 patients had malignant ovarian tumors (MOTs), 28 had borderline ovarian tumors (BOTs), and 71 had benign ovarian tumors. Color Doppler and pulsed wave Doppler ultrasound was performed. The levels of СА-125 were defined by enzyme immunoassay. Models IV, V were used to assess the risk of ovarian cancer. A moderate non-significant increase in blood levels of СА-125 compared to patients with benign ovarian tumors and BOTs was found in pregnant women with MOTs. Patients with BOTs and MOTs showed higher RMI-IV and RMI-V values compared to the group of pregnant women with benign ovarian tumors. Extreme values are required to guarantee the differences in the diagnosis of tumors (RMI-IV > 3500 indicate the presence of MOTs, the values below 100 indicate no malignancy). Similar RMI-V values are 1500 and 60. However, in most cases, availability of RMI-IV and RMI-V is insufficient for decision making, and a comprehensive approach has to be used. Thus, it is difficult to define ovarian mass type in pregnant women using RMI only. Comprehensive clinical assessment with the use of imaging methods is required for preoperative prediction of ovarian mass type in pregnant women, along with the use of prognostic models taking into account the majority of descriptive “morphological” tumor characteristics.
{"title":"Comparative assessment of RMI-IV and RMI-V in preoperative prediction of ovarian tumor type in pregnant women","authors":"A. Gerasimova, YuV Shevchenko, PA Klimenko, LA Asyrafyan","doi":"10.24075/brsmu.2022.050","DOIUrl":"https://doi.org/10.24075/brsmu.2022.050","url":null,"abstract":"Prediction of ovarian tumor type in pregnant women is of great clinical significance, however, it is vastly difficult. In the last 5–10 years gynecologists were suggested to use RMI (Risk of Malignancy Index) in non-pregnant women, however the value of the test for obstetric practice has yet to be established. The study was aimed to determine RMI-IV and RMI-V during preoperative non-invasive prediction of ovarian tumor type in pregnant women. Retrospective and prospective clinical and laboratory data of 114 pregnant women aged 20–38 were collected. Among them 15 patients had malignant ovarian tumors (MOTs), 28 had borderline ovarian tumors (BOTs), and 71 had benign ovarian tumors. Color Doppler and pulsed wave Doppler ultrasound was performed. The levels of СА-125 were defined by enzyme immunoassay. Models IV, V were used to assess the risk of ovarian cancer. A moderate non-significant increase in blood levels of СА-125 compared to patients with benign ovarian tumors and BOTs was found in pregnant women with MOTs. Patients with BOTs and MOTs showed higher RMI-IV and RMI-V values compared to the group of pregnant women with benign ovarian tumors. Extreme values are required to guarantee the differences in the diagnosis of tumors (RMI-IV > 3500 indicate the presence of MOTs, the values below 100 indicate no malignancy). Similar RMI-V values are 1500 and 60. However, in most cases, availability of RMI-IV and RMI-V is insufficient for decision making, and a comprehensive approach has to be used. Thus, it is difficult to define ovarian mass type in pregnant women using RMI only. Comprehensive clinical assessment with the use of imaging methods is required for preoperative prediction of ovarian mass type in pregnant women, along with the use of prognostic models taking into account the majority of descriptive “morphological” tumor characteristics.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41986337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Ermakova, N. Dolgushina, I. Menzhinskaya, N. Lomova, VV Vtorushina
Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, β2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%); p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy.
{"title":"Antiphospholipid antibodies and outcomes of assisted reproductive technology programs in patients with a history of COVID-19","authors":"D. Ermakova, N. Dolgushina, I. Menzhinskaya, N. Lomova, VV Vtorushina","doi":"10.24075/brsmu.2022.048","DOIUrl":"https://doi.org/10.24075/brsmu.2022.048","url":null,"abstract":"Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, β2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%); p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48743597","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}
Post-stroke lower extremity vein thrombosis can be the reason behind complications of embolic nature and death. This study aimed to investigate the influence of provoking factors, frequency and localization of acute thrombosis, post-thrombotic changes in the lower extremity veins during stroke recovery period. The study involved 1315 patients, 885 (67.3%) male and 430 (32.7%) female, ages 18–94 years, mean age 59.23 ± 13.7 years. All participants underwent lower extremity venous duplex scanning in the early and late stages of stroke recovery period. We found no evidence of interconnections between presence of signs of thrombosis and/or its consequences and the pathogenetic variant of stroke the patient had. Acute deep vein thrombosis was diagnosed significantly more often (p < 0.05) in the early stage of stroke recovery period. The frequency of acute lower extremity vein thrombosis was 7.8%, post-thrombotic changes — 5.6%. Isolated lesion of the lower leg veins was the most common complication associated with deep veins (49.6%). We have discovered a significant relationship between the side of lower extremity paresis (plegia) of and the side of deep vein thrombosis (p < 0.001). No relationship was found between lower extremity superficial and deep vein thrombosis and use of anticoagulants and antiplatelet agents (p > 0.05). Excess body weight was associated with damage to the lower extremity proximal veins (p < 0.05). Women had lower extremity vein thrombosis significantly more often (p < 0.05). Repeated lower extremity venous duplex scanning upon admission to the rehabilitation hospital allowed reducing the risk of venous thromboembolic complications that may develop during the stroke recovery period.
{"title":"Lower extremity vein thrombosis and its consequences in stroke recovery period","authors":"E. Orlova, A. Berdalin, V. Lelyuk","doi":"10.24075/brsmu.2022.053","DOIUrl":"https://doi.org/10.24075/brsmu.2022.053","url":null,"abstract":"Post-stroke lower extremity vein thrombosis can be the reason behind complications of embolic nature and death. This study aimed to investigate the influence of provoking factors, frequency and localization of acute thrombosis, post-thrombotic changes in the lower extremity veins during stroke recovery period. The study involved 1315 patients, 885 (67.3%) male and 430 (32.7%) female, ages 18–94 years, mean age 59.23 ± 13.7 years. All participants underwent lower extremity venous duplex scanning in the early and late stages of stroke recovery period. We found no evidence of interconnections between presence of signs of thrombosis and/or its consequences and the pathogenetic variant of stroke the patient had. Acute deep vein thrombosis was diagnosed significantly more often (p < 0.05) in the early stage of stroke recovery period. The frequency of acute lower extremity vein thrombosis was 7.8%, post-thrombotic changes — 5.6%. Isolated lesion of the lower leg veins was the most common complication associated with deep veins (49.6%). We have discovered a significant relationship between the side of lower extremity paresis (plegia) of and the side of deep vein thrombosis (p < 0.001). No relationship was found between lower extremity superficial and deep vein thrombosis and use of anticoagulants and antiplatelet agents (p > 0.05). Excess body weight was associated with damage to the lower extremity proximal veins (p < 0.05). Women had lower extremity vein thrombosis significantly more often (p < 0.05). Repeated lower extremity venous duplex scanning upon admission to the rehabilitation hospital allowed reducing the risk of venous thromboembolic complications that may develop during the stroke recovery period.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45666517","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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