INTERLEUKIN 33 AND FIBROSIS: PATHOGENESIS UPDATED

Interleukin 33 (IL-33) is a member of the IL-1 family, which is widely expressed on all types of cells. IL-33 was identified as a functional ligand for the plasma membrane receptor complex, which is a heterodimer consisting of a membrane bound ST2 receptor (growth stimulating factor). IL-33 is involved in the development of immune response with predominant release of pro-inflammatory T helper type 2 cytokines. IL-33 is widely expressed on various structure-forming cells, such as epithelial, endothelial and smooth muscle cells. Increased expression of IL-33 is observed during necrosis of these cells (after tissue or cell damage), and it is released into extracellular space, and acts as an endogenous danger signal, sending a sort of warnings to neighboring cells and tissues. Recently, many studies have shown that IL-33 can participate in development and progression of fibrosis in various organs. However, it exerts anti-inflammatory effects upon development of other diseases. This review will discuss biological characteristics of IL-33 and a role of the IL-33/ST2 signaling pathway in the development of fibrosis

A New Chapter in the Treatment of Patients with Heart Failure. The Role of Sodium-Glucose Co-transporter Type 2 Inhibitors

Heart failure (HF) remains one of the major social and medical public health problems worldwide. Despite new advances in the treatment of patients with HF, the prognosis is still poor. According to the European Cardiology Society guidelines for the diagnosis and treatment of acute and chronic heart failure (CHF) 2021, a new class of drugs related to hypoglycemic has been confirmed to be effective in influencing the survival of patients with heart failure with low ejection fraction (HFpEF), regardless of the presence of disorders of carbohydrate metabolism. We are talking about inhibitors of the sodium-glucose co-transporter type 2 (iSGLT-2) or gliflozins. The article presents the results of the latest large clinical trials on the effective use of SGLT-2 in patients with HF, not only with low, but also with intact ejection fraction (HFpEF), for which there is no evidence base at the present stage. The review article presents the results of experimental studies that explored the potential mechanisms of action of gliflozins with an emphasis on new ones that are of fundamental importance for patients with heart failure, and also describes controversial and little-studied issues. Currently, there is no therapy that improves outcomes in patients with acute heart failure. The article presents the results of small analyzes of the use of iSGLT-2 in this category of patients, which are the basis for the hypothesis of their potentially effective and safe use in the case of acute decompensation of CHF, however, the role of gliflozins in this category of patients requires further in-depth study

New biological markers for a prognostic model for assessing the risk of cardiac fibrosis in patients with ST-segment elevation myocardial infarction

HighlightsThe developed prognostic model for assessing the risk of cardiac fibrosis in patients with STEMI with HFmrEF and HFpEF is promising from the point of view of scientific and clinical potential because similar models for predicting the risk of cardiac fibrosis in patients with index MI are not currently validated. The developed scale includes such parameters as age, LVEF, COL-1, BMI, MMP-2. The scale can be used in patients with HFmrEF and HFpEF phenotypes. Identification of patients at high risk of myocardial fibrosis will allow choosing the appropriate treatment method. Aim. To develop a prognostic model for assessing the risk of cardiac fibrosis (CF) in patients with preserved left ventricular ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF) a year after ST-segment elevation myocardial infarction (STEMI) based on clinical, instrumental and biochemical data.Methods. The prospective cohort study included 100 STEMI patients with HFmrEF (LVEF 40–49%) and with HFpEF (50% or more). Echo was performed in all patients on the 1st, 10–12th day and a year after onset of STEMI. Upon admission to the hospital and on the 10–12th day after the onset of the disease, the following serum biomarker levels were determined: those associated with changes in the extracellular matrix; with remodeling and fibrosis; with inflammation, and with neurohormonal activation. At the 1-year follow-up visit, 84 patients underwent contrast-enhanced MRI to assess fibrotic tissue percentage relative to healthy myocardium.Results. The distribution of patients by HFmrEF and HFpEF phenotypes during follow-up was as follows: HFmrEF on the 1st day – 27%, 10th day – 12%, after a year – 11%; HFpEF on the 1st day – 73%, 10th day – 88%, after a year – 89%. According to cardiac MRI at the follow-up visit (n = 84), the median distribution of fibrotic tissue percentage was 5 [1.5; 14]%. Subsequently, the threshold value of 5% was chosen for analysis: CF≥5% was found in 38 patients (the 1st group), whereas CF<5% was noted in 46 patients (the 2nd group). When analyzing the intergroup differences in biological marker concentrations in the in-patient setting and at the annual follow-up, it was determined that the most significant differences were associated with “ST-2” (1st day) that in the “CF≥5%” group was 11.4 ng/mL higher on average compared to the “CF<5%” group (p = 0.0422); “COL-1” (1st day) that in the “CF≥5%” group was 28112.3 pg/mL higher on average compared to the “CF<5%” group (p = 0.0020), and “NT-proBNP” (12th day) that in the “CF<5 %” group was 1.9 fmol/mL higher on average compared to the “CF≥5%” group (p = 0.0339). Certain factors (age, LVEF (12th day), collagen-1 (1st and 12th day), body mass index, matrix metalloproteinase-2 (12th day) were determined and included in the prognostic model for assessing the risk of CF a year after the STEMI (AUC ROC 0.90, Chi-square test <0.0001).Conclusion. Prognostic model (scale) based on factors such as age, left ventricular ejection fraction (12th day), collagen-1 (1st and 12th day), body mass index, matrix metalloproteinase-2 (12th day) shows high prognostic power and enables identification of patients with HFmrEF and HFpEF phenotypes and at high risk of cardiac fibrosis a year after STEMI

Interacting circular nanomagnets

Regular 2D rectangular lattices of permalloy nanoparticles (40 nm in diameter) were prepared by the method of the electron lithography. The magnetization curves were studied by Hall magnetometry with the compensation technique for different external field orientations at 4.2K and 77K. The shape of hysteresis curves indicates that there is magnetostatic interaction between the particles. The main peculiarity is the existence of remanent magnetization perpendicular to easy plain. By numerical simulation it is shown, that the character of the magnetization reversal is a result of the interplay of the interparticle interaction and the magnetization distribution within the particles (vortex or uniform).Comment: 16 pages, 8 figure

Clinical Efficacy and Safety of Empagliflozin in Patients with Acute Heart Failure from the First Day of Hospitalization

Aim. Evaluation of the safety, clinical and hemodynamic effects of empagliflozin in patients with acute decompensated heart failure (ADHF) from the first day of hospitalization in the absence of signs of hemodynamic instability.Material and methods. A prospective, comparative, randomized study included 46 patients admitted to the hospital in connection with ADHF in the absence of signs of hemodynamic instability. Inclusion in the study and randomization to receive empagliflozin was carried out in the first 24 hours from the moment of admission to the hospital. The main group (n=23) from the first day of hospitalization and the entire subsequent follow-up period took empagliflozin at a daily dose of 10 and 25 mg (for patients with type 2 diabetes mellitus) in addition to basic therapy, the control group (n=23) received standard therapy without gliflozines. The observation period was 3 months and included 3 control points: 1st day of hospitalization, 7th-12th day, 3rd month of observation. Clinical, anamnestic and instrumental data were evaluated at all control points.Results. In the hospital period, by the 7th-12th day, only in the main group there was an improvement in all clinical indicators (p<0.01), an increase in the rate of diuresis (p><0.01), a decrease in the daily dose of the parenteral diuretic furosemide from 54 mg to 26 mg (p><0.01). A decrease in systolic blood pressure (SBP) occurred in both groups (p><0.01), but it was more pronounced in the comparison group [from 141 (110; 160) to 110 (90; 120) mm Hg) compared to the main group [from 140 (120; 160) to 120 (110; 130) mm Hg]. According to echocardiography data in the main group, there was a decrease in the indexed volume of the right atrium, the end-systolic volume of the left ventricle (LV ESV) and systolic pressure in the pulmonary artery, an increase in the LV ejection fraction (LV EF) (p><0.05). In the comparison group, only an increase in LV ESV was noted (p=0.04). The index of the indexed volume of the left atrium did not show significant dynamics in the main group (p=0.79), but showed a significant decrease>˂0.01), a decrease in the daily dose of the parenteral diuretic furosemide from 54 mg to 26 mg (p<0.01). A decrease in systolic blood pressure (SBP) occurred in both groups (p>˂0.01), but it was more pronounced in the comparison group [from 141 (110; 160) to 110 (90; 120) mm Hg) compared to the main group [from 140 (120; 160) to 120 (110; 130) mm Hg]. According to echocardiography data in the main group, there was a decrease in the indexed volume of the right atrium, the end-systolic volume of the left ventricle (LV ESV) and systolic pressure in the pulmonary artery, an increase in the LV ejection fraction (LV EF) (p˂0.05). In the comparison group, only an increase in LV ESV was noted (p=0.04). The index of the indexed volume of the left atrium did not show significant dynamics in the main group (p=0.79), but showed a significant decrease in the 2nd and 3rd control points compared to the control group (p=0.01 and p=0.02). Complications, against the background of taking empagliflozin, were not noted: there were no episodes of hypotension (SBP˂90 mm Hg), hypoglycemia, acute kidney injury.Conclusion. The results obtained indicate the safety of empagliflozin in patients with ADHF, regardless of the status of carbohydrate metabolism and LV EF, as well as taking into account the clinical (more intense positive dynamics of clinical symptoms of ADHF) and hemodynamic (smooth decrease in SBP, increased diuretic effect) effects of empagliflozin, this drug should be considered as an effective and safe supplement to the main therapy from the first day of hospitalization in patients with stable hemodynamic parameters

Thrombocyte aggregation activity in the conditions of intensive light deprivation

The aim of the research was to study the effect of photoperiodism disturbances on platelet aggregation activity. Material and methods. The experiment was conducted in two stages in 5 groups of male rats: the control group and four experimental groups. At the first stage, the animals were exposed to 24 h/day continuous light (24L:0D) for 10 and 21 days. In the second stage, animals after 10 and 21 days of round-the-clock lighting were returned to natural lighting for a period of 21 days to study the reversibility of changes. Animals were withdrawn from the experiment by intramuscular injection based on body weight of drugs for anesthesia (telazol, xylanite). Blood sampling was performed by puncture of the right heart. The functional activity of platelets was determined no later than 3 hours after the collection of blood. Results and discussion. The results of the experiment indicate a direct effect of light desynchronosis on the increase in platelet aggregation ability, while it was noted that the degree of increase in aggregation activity and reversibility of changes directly depend on the duration of round-the-clock lighting. So, a 10-day stay of animals in conditions of abnormal lighting leads to an increase in aggregation indices, which remain at a high level even when animals return to normal conditions. In animals that were under round-the-clock illumination for 21 days, a more pronounced increase in platelet aggregation values relative to animals on day 10 was noted. In this regard, it can be argued that circadian rhythm disturbances provoke the development of microvasculature disorders

Two novel mutations associated with ataxia-telangiectasia identified using an ion ampliSeq inherited disease panel

© 2017 Kuznetsova, Trofimov, Shubina, Kochetkova, Karetnikova, Barkov, Bakharev, Gusev and Sukhikh. Ataxia-telangiectasia (A-T), or Louis-Bar syndrome, is a rare neurodegenerative disorder associated with immunodeficiency. For families with at least one affected child, timely A-T genotyping during any subsequent pregnancy allows the parents to make an informed decision about whether to continue to term when the fetus is affected. Mutations in the ATM gene, which is 150 kb long, give rise to A-T; more than 600 pathogenic variants in ATM have been characterized since 1990 and new mutations continue to be discovered annually. Therefore, limiting genetic screening to previously known SNPs by PCR or hybridization with microarrays may not identify the specific pathog enic genotype in ATM for a given A-T family. However, recent developments in next-generation sequencing technology offer prompt high-throughput full-length sequencing of genomic fragments of interest. This allows the identification of the whole spectrum of mutations in a gene, including any novel ones. We report two A-T families with affected children and current pregnancies. Both families are consanguineous and originate from Caucasian regions of Russia and Azerbaijan. Before our study, no ATM mutations had been identified in the older children of these families. We used ion semiconductor sequencing and an Ion AmpliSeq ™ Inherited Disease Panel to perform complete ATM gene sequencing in a single member of each family. Then we compared the experimentally determined genotype with the affected/normal phenotype distribution in the whole family to provide unambiguous evidence of pathogenic mutations responsible for A-T. A single novel SNP was allocated to each family. In the first case, we found a mononucleotide deletion, and in the second, a mononucleotide insertion. Both mutations lead to truncation of the ATM protein product. Identification of the pathogenic mutation in each family was performed in a timely fashion, allowing the fetuses to be tested and diagnosed. The parents chose to continue with both pregnancies as both fetuses had a healthy genotype and thus were not at risk of A-T

ИНФАРКТ МИОКАРДА 2-ГО ТИПА: СОВРЕМЕННЫЙ ВЗГЛЯД НА ПРОБЛЕМУ

HighlightsThe article describes the main differences between the types of myocardial infarction, in particular, differences between type 1 and type 2 myocardial infarction, the complexity of diagnosis and management of patients with myocardial infarction type 2, and summarizes data on the prevalence of patients with myocardial infarction type 2. The arguments supporting the need for further researches to differentiate various phenotypes of myocardial infarction are provided. AbstractDespite the high interest in the study of type 2 MI, many unresolved issues concerning diagnosis, criteria for diagnosis and, especially, therapeutic tactics remain unresolved. The available data regarding type 2 MI remain limited and inconsistent, and are based on sources that include the analysis of type 1 MI. According to various predictions, the prevalence of type 2 MI will increase even more. Type 2 MI management strategy should be patient-specific and in accordance with the etiology and pathogenesis, therefore, timely diagnosis, and MI differentiation according to universally accepted definitions is a relevant scientific topic and a practical necessity.Thus, summarizing all the above, we can say that type 2 myocardial infarction is a topic that encompasses many unresolved issues concerning diagnosis, patient management and further secondary prevention.Основные положенияВ обзоре освещены основные различия типов инфаркта миокарда, в частности отличия инфаркта 2-го типа от 1-го типа, описаны сложности диагностики и ведения пациентов с инфарктом миокарда 2-го типа, обобщены данные о частоте выявления данного типа заболевания. Представлены аргументы в пользу необходимости дальнейших исследований, посвященных изучению различных фенотипов инфаркта миокарда. РезюмеНесмотря на высокий интерес к изучению инфаркта миокарда (ИМ) 2-го типа, остается множество нерешенных вопросов, связанных с диагностикой, критериями постановки диагноза и, прежде всего, тактикой лечения заболевания. Доступная информация об ИМ 2-го типа основана на зарубежных источниках, включающих анализ ИМ 1-го типа, и носит ограниченный и разрозненный характер. По прогнозам, распространенность ИМ 2-го типа будет только увеличиваться. Тактика ведения больных ИМ 2-го типа должна определяться индивидуально в каждой конкретной клинической ситуации в соответствии с этиологией и патогенезом, поэтому своевременная диагностика и конкретизация типа ИМ по Универсальному определению представляют не только научный, но и практический интерес. Таким образом, вопросы диагностики инфаркт миокарда 2-го типа, ведения пациентов и вторичной профилактики требуют дальнейшего исследования