Use of selective inhibitors of arginase 2 and tadalafil in combined compensation of homocysteine-induced endothelial dysfunction

Use of selective inhibitors of arginase 2 in combination with tadalafil on in the course of modeling of homocysteine-induced endothelial dysfunction provided endotelio- and cardioprotective effects manifested in preventing of SED increase, adrenoreactivity, maintaining myocardial reserve and normalization of the values of biochemical markers (Total NO, expression of eNOS

Combined use of arginase II inhibitors and tadalafil for the correction of monocrotaline pulmonary hypertension

The concept of the regulatory role of endothelium in the pathogenesis of pulmonary hypertension (PH) is fundamental. To study the protective effects of the selective arginase II inhibitors L207-0525 and L327-0346 in combination with tadalafil in a monocrotaline model of pulmonary hypertension in rat

Role of Arginase 2 as a potential pharmacological target for the creation of new drugs to correct cardiovascular diseases

The review provides relevant information about arginase 2, the role of this enzyme in the formation of endothelial dysfunction and, as a consequence, the development of cardiovascular disease

Dependence of a rabbit's reaction on the frequency of repetition of an impulse and current exposition in experiment

Now electroshock devices are used as a civilian weapon for self-defense and as a non-lethal weapon in the police. Therefore, medical-biological safety testing of electroshock devices should be carried out. Development of hygienic regulations is relevant as well. The aim of our work is the study of the biological effects of pulsed current depending on the pulse frequency, pulse amplitude and exposure. Material and methods. We compared the biological effects with varying frequency of the current pulse (50, 400, and 600 Hz) with varying exposure (0.25, 0.5 and 1.0 s.). Average pulse power in all cases was equal, and the pulse energy was different. Experiments were performed on rabbits. Biological effects of stun device were evaluated by clinical lesions, as well as electrophysiological parameters: ECG and electro-pneumogram. Results. Response was observed only in the current period (0.25 s, 0.5 s or 1 s) was disorientation, convulsing, dyspnea. The degree of severity of the reaction was determined by a combination of pulse repetition frequency and exposure. Immediately after switching off the current noted vocalization, decreased heart rate and breathing. Heart rate and respiration in 5 minutes back to the normal values. Conclusions. In the results of the research has got a comparative classification organism's response (based on a points system) as well as the characteristic of the biological response of the individual systems of the body on the parameters of the current pulse

Characteristics of the state of bone tissue in genetically modified mice with impaired enzymatic regulation of steroid hormone metabolism

The aim was to evaluate the structural and functional changes of bone tissue in mice with null expression of 11β-HSD2 or both 11β-HSD2 and Apolipoprotein

The role of cortisol metabolism in the realization of pathogenetic links in the development of osteoporosis - the rationale for the search for new pharmacotherapeutic targets (review)

Background: Osteoporosis is an important medical and social public health problem in an aging or elderly society. Osteoporosis is caused by an imbalance in bone remodeling, which is a continuous process of destruction of mature bone tissue by osteoclasts (bone resorption) and the formation of new bone tissue by osteoblasts (bone formation). The system of bone homeostasis that regulates the functional activity of osteoclasts and osteoblasts is represented by a wide range of molecules. The understanding of the molecular mechanisms of bone homeostasis achieved today makes it possible to significantly change and expand the paradigms of treatment and prevention of osteoporosis. The aim of the study: To consider the main pathogenetic pathways through which the effect of the cortisol metabolism system on the development of osteoporosis is realized and to identify ways to find new therapeutic approaches to the treatment and prevention of this pathology. Materials and methods: To achieve this goal, we analyzed the literature on the influence of cortisol metabolism on the development of osteoporosis published in the last 10 years. Results: To date, there are significant prerequisites in the literature for a direct connection of disorders of steroid hormone metabolism with the development of osteoporosis and a violation of osteoreparative processes. This literature review presents the main pathogenetic pathways that cause the processes leading to a decrease in bone density in disorders of cortisol metabolism. The enzyme 11b-hydroxysteroid dehydrogenase (11b-HSD), represented by two isoforms, performs the mutual conversion of cortisone and cortisol in tissues. Using the methods of reverse genetics, we have established the systemic consequences of knockout of both isoforms. Convincing evidence demonstrates that both enzymes are involved in the pathogenesis of osteoporosis. Since animals with type 11b-HSD deficiency are characterized by proinflammatory activation of the endothelium, we assume that further study of the interaction between the endothelium and bone tissue is of particular interest. Conclusion: The effects of glucocorticoids on eNOS expression seem to be significantly modulated by 11ß-HSD isoenzymes. The established relationship between 11ß-HSD and NO can be considered a promising pharmacotherapeutic target. In this regard, a pharmacotherapeutic approach aimed at restoring the balance of nitric oxide in bone and endothelial tissues, currently considered as one of the most relevant ways to correct osteoporosis, may also be relevant in case of cortisol metabolism disorders due to 11ß-HSD2 deficiency. © 2022 by the Author(s).Russian Science Foundation, RSF, (22-25-00376)Исследование выполнено за счет гранта Российского научного фонда № 22-25- 00376 (https://rscf.ru/project/22-25-00376). Financial support The study was supported by the Russian Science Foundation, Project № 22-25-00376 (https://rscf.ru/project/22-25-00376)

Use of selective inhibitors of arginase 2 and tadalafil in combined compensation of homocysteine-induced endothelial dysfunction

Use of selective inhibitors of arginase 2 in combination with tadalafil on in the course of modeling of homocysteine-induced endothelial dysfunction provided endotelio- and cardioprotective effects manifested in preventing of SED increase, adrenoreactivity, maintaining myocardial reserve and normalization of the values of biochemical markers (Total NO, expression of eNOS

Conversion of Phenol and Lignin as Components of Renewable Raw Materials on Pt and Ru-Supported Catalysts

Hydrogenation of phenol in aqueous solutions on Pt-Ni/SiO2, Pt-Ni-Cr/Al2O3, Pt/C, and Ru/C catalysts was studied at temperatures of 150–250 °C and pressures of 40–80 bar. The possibility of hydrogenation of hydrolysis lignin in an aqueous medium in the presence of a Ru/C catalyst is shown. The conversion of hydrolysis lignin and water-soluble sodium lignosulfonate occurs with the formation of a complex mixture of monomeric products: a number of phenols, products of their catalytic hydrogenation (cyclohexanol and cyclohexanone), and hydrogenolysis products (cyclic and aliphatic C2–C7 hydrocarbons)

Role of Arginase 2 as a potential pharmacological target for the creation of new drugs to correct cardiovascular diseases

Introduction: The review provides relevant information about arginase 2, the role of this enzyme in the formation of endothelial dysfunction and, as a consequence, the development of cardiovascular diseases. History of the discovery of arginase and its functions: The discovery of arginase took place long before its active study as a substance that affects the formation of endothelial dysfunction. Role of arginase 2 in the development of a number of cardiovascular diseases: The role of NO synthase and arginase 2 in the formation of oxidative stress is determined. The pathophysiological mechanisms of the development of a number of cardiovascular diseases, such as coronary heart disease, atherosclerosis, and aortic aneurysm, are described. The modern possibilities of treatment of endothelial dysfunction in the pathology of the cardiovascular system and the possibility of creation of new drugs are considered. An increase in the activity of arginase 2 was proven to occur in the case of the development of coronary heart disease (CHD), hypertension, type II diabetes mellitus, hypercholesterolemia, as well as in the process of aging. According to the WHO, coronary heart disease and apoplectic attack have topped the list of causes of death worldwide over the past 15 years. Arginase 2 as a potential pharmacological target: The purpose of this literature review is to determine the possibilities of use of arginase 2 as a new target for the pharmacological correction of cardiovascular diseases