SummaryOver 12 years of cellular therapy in cardiology, some dictinct positive results are obtained in randomized studies. However, exact mechanisms of hematopoietic stem cell actions are still unclear under these clinical conditions. Paracrine effects of cell therapy cannot explain all these effects. Enhanced neoangiogenesis upon stem cell injection is a proven mechanism for improvement of blood supply to the heart. Meanwhile, a decreased revascularization effect 3-4 years after cell therapy is followed by repeated myocardial improvement 6-9 mo after repeated cell infusions with active development of collateral vessels, thus suggesting an additional mechanism for improvement of coronary blood supply. Restoration of regulatory functions of endothelium and smooth muscle cells, including increased NO synthase activity of endothelium and its interactions with myocardiocytes may represent a probable mechanism for this action.
Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the most severe complications of pulmonary embolism (PE), characterized by poor prognosis and insuffcient effectiveness of standard treatment approaches. A small number of representative models of CTEPH make it diffcult to conduct preclinical studies of promising pharmacological substances.Objective – development and validation of the experimental model of CTEPH in rats by embolization of the distal branches of the pulmonary artery with biodegradable microspheres.Material and methods. Male Wistar rats were used for the experiments. Biodegradable microspheres (MS) based on sodium alginate and autologous blood clots (AT) were used as embolizing particles. The animals were divided into groups: control: saline solution was injected 4 times with an interval of 8 days into the tail vein; AT: according to the above protocol, 50 μL of AT was injected; MS was administered intravenously in a volume of 50 μl of MS according to two protocols: MS4: 4 times with an interval of 8 days; MS8: 8 times with an interval of 4 days. After 2 and 6 weeks after the last injection, a histological examination of the lungs was performed; after 6 weeks: echocardiographic study (TTE), right ventricular catheterization (RV) with measurement of right ventricular systolic pressure (RVSP), treadmill test, assessment of serum endothelin1 levels by the immunoassay method.Results. During the experiments, the survival rate in the MS8 group was 50 %. In the other groups, there were no animal losses. According to the treadmill test 6 weeks after the modeling of PE, exercise tolerance was signifcantly reduced in the MC4 and MC8 groups compared with the control group. TTE data indicate a signifcant increase in the diameter of the pulmonary trunk and the right ventricular outflow tract in the MC8 compared with the control and AT. There were signifcant increase in RVSP and the level of endothelin1 compared with the control only in the MS8. After 6 weeks, the index of hypertrophy of vessel wall of the pulmonary artery in the MC4 and MC8 was signifcantly higher compared with the control and AT groups.Conclusion. Based on the use of MS, administered under the MS 8 protocol, a new representative model of CTEPH has been created, which can be used to test promising pharmacological substances.
The in silico modelling of peptides complementary to lactoferrin was carried out using the Protein 3D software package and replication of the natural bonding site between pneumococcal surface protein (PSP) and lactoferrin (LF). The modeling was based on analysis of the conjugated ion–hydrogen bond systems between these proteins (CIHBS). The oligopeptide EEVAPQAQAKIAELENQVHRLE was proposed via computer modelling and synthesized using the solid phase synthesis technique, purified, and analyzed with MS and HPLC methods to confirm >95% purity. The peptide was then studied by capillary electrophoresis (CE). The CE experiments demonstrated the split of peptide zone in the presence of LF, due to complex formation and subsequent mobility change of the system peptide-protein. The reference experiments with homomyeloperoxidase and myoglobin did not show binding with LETI-11.
Coronary artery bypass grafting is one of the most common surgeries performed among all elective cardiac surgery operations. Starting from the first operations, thrombosis not only in the coronary arteries, but also in the venous system was the subject of attention. Over the past two decades it has become evident that the hypercoagulable state, or socalled thrombophilia is multifactorial, genetically determined disorder of the hemostatic system. This article provides an overview of studies on the role of genetic polymorphisms in the development of thrombosis after coronary artery bypass grafting.
Цель -определить тип коронарного шунтирования (КШ), ассоциированный с наименьшим ишемически-реперфузионным повреждением (ИРП) миокарда и воспалительным ответом. Задачи. Оценить степень ИРП, степень воспалительного ответа по уровню тропонина I (TnI), миелопероксидазы (MPO) и С-реактивного белка (СРБ) в плазме крови до и после разных типов операций КШ. Материал и методы. В рамках проспективного нерандомизированного одноцентрового исследования (уровень доказательности II) выполнена оценка ИРП миокарда и воспалительного ответа после КШ у пациентов, поступивших с 2016 по 2019 г. в ПСПбГМУ им. акад. И.П. Павлова для оперативного лечения ишемической болезни сердца (ИБС). ИРП миокарда и воспалительный ответ оценивали по уровням TnI (определяли до операции, после наложения коронарных анастомозов, а также на 1, 2, 3, 4, 5-7-е сутки после КШ), СРБ (определяли до операции на 1, 2, 3, 4, 5-7 и 8-12-е сутки после операции), MPO в плазме крови (определяли до и после наложения коронарных анастомозов) в 3 группах наблюдения. 1-я группа -КШ без искусственного кровообращения (ИК) на работающем сердце (n=177), 2-я группа -КШ с ИК с пережатием аорты (n=128), 3-я группа -КШ с вспомогательным ИК без пережатия аорты (n=33). Результаты. Во 2-й и в 3-й группах повышение TnI на 1-е сутки происходит больше, чем в 1-й группе, затем во 2-й группе уровень TnI плавно снижается. В 1-й и в 3-й группах, наоборот, с 1-го дня уровень TnI хотя и меньше, чем в группе 2, его значение нарастает, достигая пика на 4-е сутки. Операции с ИК сопровождаются меньшим воспалительным ответом в период от 2 до 10 дней после операции, чем операции без ИК. Повышение уровня TnI ассоциировано с увеличением летальности после КШ (площадь под ROC-кривой AUC=0,8), прогностическое значение MPO в отношении летальных исходов (AUC=0,7) требует дальнейших исследований. Заключение. Операции КШ с ИК с пережатием аорты ассоциированы с меньшей степенью проявления ИРП миокарда и меньшим воспалительным ответом.Финансирование. Научно-исследовательская работа: «Оценка регенеративного потенциала пациента при операциях на сердце (2018)».Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.
Background. Bladder cancer is the most common malignancy of the urinary tract and one of the most common neoplasias in this group. The incidence and mortality rates of the population from bladder cancer differ significantly in different geographical regions of Russia.Aim. To assess the main epidemiological indicators of malignant neoplasms of the bladder in residents of Saint Petersburg and the regions of Russia.Materials and methods. The main epidemiological indicators of malignant bladder neoplasms in Saint Petersburg, Russia and individual federal districts for the period 2012–2021 were studied: crude and standardized rates of morbidity, mortality, prevalence, age structure of patients, the number of cases of diagnosis of the disease at various stages, indicators of one-year mortality and 5-year survival, data on completed cases of treatment of bladder neoplasms. Sources of information: Form No. 7 “Information on cases of malignant diseases” and the database of the Medical Information and Analytical Center (Saint Petersburg).Results. During the period 2012–2021 in Russia, there was an increase in the incidence and prevalence of malignant neoplasms of the bladder. At the same time, mortality rates decreased, and 5-year survival rates increased. This fact indicates the effectiveness of the treatment of patients in this category. In more than 50 % of cases, the disease was detected at stage I of the pathological process, which is due to the proper level of diagnosis. The main medical and statistical indicators in patients with malignant bladder neoplasms in Saint Petersburg are comparable to the average Russian data, and in a number of parameters they exceed them.Conclusion. Oncourological assistance to the population with malignant neoplasms of the bladder in Saint Petersburg is provided properly. The study of medical and statistical indicators in dynamics can be used to improve the algorithms of medical and diagnostic care for cancer patients.
Background. Prostate cancer is one of the most common malignant neoplasms in the male population worldwide with high morbidity and mortality rates.Aim. To study the main medial statistical indicators of prostate cancer in Saint Petersburg and other regions of the Russian Federation.Materials and methods. The epidemiological indicators of prostate cancer for 2012-2021 in the Russian Federation, individual federal districts and Saint Petersburg were analyzed.Results. The prevalence of malignant neoplasms of the prostate has increased in recent years. At the same time, the number of cases of early-stage disease diagnosis has increased, one-year mortality has decreased, and 5-year survival has increased, which indicates proper quality of oncological care for the population. In some federal districts, unstable or negative dynamics of indicators compared to the average Russian data are observed, which requires further analysis.Conclusion. Evaluation of statistical measures of morbidity and mortality from malignant neoplasms of the prostate gland can be used to improve diagnostic algorithms and therapeutic tactics for this pathology.
Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5–2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment.
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