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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., Competing Interests: The authors declare no conflicts of interest.

Pulmonary embolism (PE) is the third most prevalent cardiovascular disease. It is associated with high in-hospital mortality and the development of acute and chronic complications. New approaches aimed at improving the prognosis of patients with PE are largely dependent on reliable animal models. Mice, rats, hamsters, and rabbits, are currently most commonly used for PE modeling because of their ethical acceptability and economic feasibility. This article provides an overview of the main approaches to PE modeling, and the advantages and disadvantages of each method. Special attention is paid to experimental endpoints, including morphological, functional, and molecular endpoints. All approaches to PE modeling can be broadly divided into three main groups: 1) induction of thromboembolism, either by thrombus formation in vivo or by injection of in vitro prepared blood clots; 2) introduction of particles of non-thrombotic origin; and 3) surgical procedures. The choice of a specific model and animal species is determined based on the objectives of the study. Rodent models of chronic thromboembolic pulmonary hypertension (CTEPH), which is the most devastating complication of PE, are also described. CTEPH models are especially challenging because of insufficient knowledge about the pathogenesis and high fibrinolytic activity of rodent plasma. The CTEPH model should demonstrate a persistent increase in pulmonary artery pressure and stable reduction of the vascular bed due to recurrent embolism. Based on the analysis of available evidence, one might conclude that currently, there is no single optimal method for modeling PE and CTEPH., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening complication of pulmonary embolism. As existing animal models of CTEPH do not fully recapitulate complex disease pathophysiology, we report a new rat model for CTEPH evoked by repetitive embolization of the distal pulmonary artery branches with partially biodegradable alginate microspheres (MSs). MSs (180 ± 28 μm) were intravenously administered eight times at 4-day intervals; control animals received saline. The validity of the model was confirmed using transthoracic echocardiography, exercise testing, catheterization of the right ventricle, and histological examination of the lung and heart. The animals in the CTEPH group demonstrated a stable increase in right ventricular systolic pressure (RVSP) and decreased exercise tolerance. Histopathological examination revealed advanced medial hypertrophy in the small pulmonary arteries associated with fibrosis. The diameter of the main pulmonary artery was significantly larger in the CTEPH group than in the control group. Marinobufagenin and endothelin-1 serum levels were significantly elevated in rats with CTEPH. In conclusion, repetitive administration of alginate MSs in rats resulted in CTEPH development characterized by specific lung vasculature remodeling, reduced exercise tolerance, and a persistent rise in RVSP. The developed model can be used for pre-clinical testing of promising drug candidates.

Special diets are used for the treatment and prevention of diseases of the digestive system, taking into account individual food intolerance and possible allergic reactions. The monotony of the diet due to the limited range of recommended foods and dishes negatively affects both the effectiveness of the treatment of gluten intolerance, and the provision of the body with essential and replaceable nutrients. The aim of this study was to determine the selenium content in the flour of gluten-free crops (rice, corn, buckwheat and amaranth), their mixtures, as well as in dishes (pancakes) from a mixture of amaranth and buckwheat flours. Material and methods . The following raw materials were used in the study: amaranth flour, unboiled buckwheat groats, whole grain rice flour and corn flour. By mixing the components in a laboratory mixer, dry gluten-free compositions were obtained: a mixture of amaranth flour and flour from native buckwheat; a mixture of amaranth and rice flour and a mixture of amaranth and corn flour in the ratio of 1:2 and 1:1; and a mixture of amaranth, buckwheat and corn flour in equal proportions. In laboratory baking of pancakes, mixtures of amaranth flour and flour from native buckwheat were used. The selenium content was determined by atomic absorption spectroscopy with electrothermal atomization after wet mineralization of the samples. Results . The results of the study showed that amaranth, buckwheat and corn are rich sources of selenium. The most valuable source of selenium was amaranth flour (515 μg/kg). Selenium content in native buckwheat flour and corn flour was 405 and 458 μg/kg, respectively. The lowest selenium content among the studied crops was found in rice flour (135 μg/kg). Selenium content in flour mixtures of the studied cultures ranged from 258 to 522 μg/kg. The highest values of selenium content were observed in mixtures of amaranth with corn flour (516-522 μg/kg). The lowest content of this trace element was found in mixtures containing rice flour (from 258 to 325 μg/kg). Selenium content in pancakes made from mixtures of amaranth flour and native buckwheat flour varied from 290 to 326 μg/kg. The calculation showed that the consumption of a portion of pancakes (50 g) by school-age children will satisfy their daily requirement for selenium by 7.3-8.1%. Conclusion . Regular inclusion of amaranth-based foods in the diet of children with gluten intolerance can positively affect the elimination of selenium deficiency., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Change of state of endothelial cells occurs under the action of viral infection and bacterial lipopolysaccharide (LPS) that leads to cell dysfunction. Therefore, the aim of the current study was to investigate the effect of LPS from Escherichia coli and influenza A virus on proliferative activity of human endothelial cells (ECV-304) and gene expression of several cytokines and cellular factors: TNFá, TGFâ, IFN-ã, MMP-9, NF-êB, Rho A, eNOS and iNOS. It was found that ECV-304 cells once infected with very low infectious doses of influenza virus acquire the ability to long-term active proliferation (over 8 passages). Addition of LPS E. coli reduced the virus-stimulated cell proliferation. It was shown that influenza virus and LPS can affect on gene expression of cytokine and other cellular factors. When endothelial cells had been infected with influenza A virus in the presence of LPS, there was a significant increase in the expression of several genes and replacement of some genes expression on the expression of other genes. Expression of MMP-9 gene was inhibited in the case of separate exposure to the virus and LPS, but it was significantly increased during the first day under the adding of the virus and LPS together, as well as the activity of the IFN-ã gene; gene of TNFá was active for only 1—3 days whereas genes expression of other factors (TGFâ, eNOS, iNOS, NF-êB and Rho A) increased significantly at the 5th day as in the case of adding only LPS. Thus, the change of physiological state of endothelial cells occurs in the presence of influenza A virus and LPS and it can be caused during different time periods (as well as by varying degrees of virus infection of cells) by different cellular factors and possibly with involvement of different signaling pathways.

The electroimpedance indicators' dilution (EIID) technique was used to study the possibility of a simultaneous separate assessment of the biological heart and LVAD performance in the position of LVB. The experimental part of the research was performed on 5 dogs; an artificial ventricle of the pulsing type (USA) with cusps was used as a pump. The clinical part of the work was conducted on 5 patients after open-heart surgery who had the clinical picture of postcardiotomy cardiogenic shock; a centrifugal pump "Biopump" (Medtronic, USA) was used. The authors have shown a principally important possibility of applying the EIID, technique for studying the performance curves which are the integral derivatives of the work of a specific hybrid system--"the biological heart-assist device". From the practical viewpoint the EIID technique permits in the read time mode to control continuously the part of the pumping function which is assumed by the patient's own heart. This information can serve as the basis for making the prognosis and determining the further tactics of treatment; the restoration of the heart performance or its replacement by transplantation.