Vol 19, No 2 (2021)

The literature review is devoted to the study of the mechanisms of the cardioprotective action of a new class of glucose-lowering drugs glyflozins, which inhibit the joint transport of sodium and glucose in the proximal renal tubules. Favorable changes in ion transport in cardiomyocytes with the use of these drugs are considered. The inhibition of the activity of the sodium-hydrogen exchanger (NHE) was found, followed by a decrease in the activity of Na⁺/ Ca²⁺ exchange on the mitochondrial membranes of the cardiomyocytes, which leads to a decrease in the concentration of Ca²⁺ in the cytoplasm with a simultaneous increase in mitochondria. This initiates a number of intracellular signaling cascades that contribute to the optimization of mitochondrial homeostasis. The use of glyflozins, apparently, provides a balance between the fusion and fission of mitochondria, which determines the bioenergetic adaptation of the cell to the state of intracellular metabolism, weakens the development of the inflammatory response, fibrosis and oxidative stress in the myocardium, which are activated under conditions of diabetes mellitus. The point of view is discussed, according to which the mechanism of anti-inflammatory action of glyflozins is associated with inhibition of the activity of the NLRP3 inflammasome, which contributes to the progression of myocardial dysfunction and subsequent chronic heart failure. The results of clinical trials and experimental data on the beneficial effect of glyflozins in the development of various phenotypes of heart failure with reduced and preserved ejection fraction are analyzed. The assumption is substantiated about the prospects for wider use of these hypoglycemic drugs in heart failure, which is not limited to diabetes mellitus. The assumptions made require further experimental and clinical studies.

A review of the literature shows that the physical-chemical properties of infusion solutions can be an integral part of the mechanism of their local action on the routes of administration. This new scientific and practical direction in clinical pharmacology was born at the end of the 20th century in Russia. Initially, it was found that isotonic solutions of glucose, mannitol, and sodium chloride with different temperatures have different local effects on the metabolism and viability of isolated biological objects such as mitochondria and blood plasma. At the same time, it was shown that increasing the temperature of solutions from +37 to +45°C accelerates the metabolism of these biological objects, increases their reactivity and enhances their response to the action of many drugs-activators of metabolism and function. And vice versa, lowering the temperature of these solutions from +37 to +20°C and below (up to 0°C) slows down their metabolism, reduces their reactivity, weakens their response to the action of drugs-activators of metabolism and function, and also increases survival in conditions of ischemia and hypoxia. These results allowed us to recommend warm infusion solutions as universal means of activating aerobic metabolism in tissues and the response of tissues to drugs with local physical-chemical action, and cold infusion solutions as universal means of inhibiting aerobic metabolism in tissues and increasing the resistance of tissues to the action of drugs on them. Following this, it was shown that many infusion solutions do not have isoosmotic activity, since the osmotic activity of drugs is not controlled. Therefore, one part of the solutions has hypotonic activity, and the other part has hypertonic activity. Therefore, sometimes the infusion solution can increase the hypoosmotic or hyperosmotic activity of the blood plasma. Then it was shown that the absolute majority of infusion solutions do not have a pH of 7.4. At the same time, very many infusion solutions have acidic activity, so they have an acidifying effect on the blood. The chronology of the development of inventions based on the achievements of the physical-chemical pharmacology of infusion agents is shown.

BACKGROUND: New laboratory and instrumental technologies for analyzing the adaptive capabilities of a biological organism to acute stressful effects including hypoxic ones have significantly facilitated the diagnosis and fixation of adaptive behavioral reactions, physiological and biochemical changes. Much attention has been paid to the phenomenon of preconditioning — a positive effect from exposure to small doses of pathogenic factors. Hypoxia-inducible factor 1 (HIF-1) is one of the most promising markers for fixing the phenomenon of hypoxic preconditioning.

AIM: To study the mechanisms of neuroadaptation to acute stressful effects.

MATERIALS AND METHODS: Using models of immobilization, hypothermic exposure, and electrocutaneous irritation of rat paws were carried out for the assessment of the mechanisms of neuroadaptation. Changes in the HIF-1 concentration were recorded in the blood and in the structures of the brain.

RESULTS: The maximum concentration of HIF-1 was found in the amygdala (±230 pg / mg), in the prefrontal cortex it was ±50.8 pg / mg in the control group. Hypothermal exposure increased the HIF-1 content in the amygdala by more than 4 times, while emotionally pain and immobilization showed a slight decrease in HIF-1 in the amygdala. All types of stressors significantly increased the concentration of HIF-1 in the prefrontal cortex of animals. The most pronounced changes were observed when using the model of emotional pain stress. The obtained experimental data allow us to draw with caution a conclusion about the universality and unity of multicomponent mechanisms of adaptation to acute stressful effects.

BACKGROUND: The work is devoted to the analysis of the elements the reactivity of grelin system in the model of psychogenic stress. In recent years, it has been shown that the ghrelin brain system is not limited only to the regulation of energy balance and eating behavior. Along with other peptide regulatory systems, it plays an important role in the mechanisms of stress, reward and addiction. Therefore, the elements of this system should be considered primarily as molecular targets of pharmacological action in order to correct the states of addiction and post-stress disorders.

MATERIALS AND METHODS: To produce psychoemotional stress, we used an acute single traumatic situation in male Wistar rats. The animals were placed in the tiger python, one animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. One week after exposure to python, the animals were decapitated, and the brain structures were isolated. Aliquots of the brain structures suspensions were examined for the content of desacyl ghrelin (DAG) using a highly sensitive enzyme-linked immunosorbent assay (ELISA). In another group, rats were decapitated on the 4th day after exposure to python, stomachs were removed, which were fixed in 10% formalin solution. In horizontal paraffin sections of the gastric mucosa, after staining with hematoxylin and eosin, the heights of superficial and dimple mucous cells, the height of the dimple stroma, the area of superficial, dimple mucocytes and stroma of the dimples, and the number of dead mucocytes were calculated. To clarify the differentiation of epithelial cells, they were stained with alcian blue

RESULTS: DAG was detected in all studied brain structures: amygdala, hippocampus, and hypothalamus. The highest concentration of DAG was noted in the hypothalamus (p < 0.05), which may serve as an indirect confirmation of the data on the presence of ghrelin-containing neurons in the nuclei of the hypothalamus. After exposure to stress, a sharp decrease in the level of DAG was observed in all studied brain structures (8–12 times, p < 0.01): amygdala, hippocampus, and hypothalamus. It has been established that the experience of the stress of the death of a partner is expressed by erosive inflammation of the gastric mucosa, the death of many mucous cells, and an increase in mucus production in viable epithelial cells.

CONCLUSION: Psychoemotional stress completely suppresses the content of desacyl ghrelin of the brain in rats, which may be based on both a disturbance of the central mechanisms of limbic regulation and a violation of peripheral mechanisms, in particular, reactive changes in the gastric mucosa.

BACKGROUND: The retina of the eye, with its wide range of neurotransmitter systems, can be the point of application in the action of the psychotropic drugs, given their synaptotropic properties.

MATERIALS AND METHODS: In this regard, a complex of studies was carried out with the participation of volunteers to assess the effect of psychotropic substances with a depressing (melatonin, grandaxin, motherwort tincture) type of action on the functional state of the retina, registered by the campimetric method. In the course of the research, the photosensitivity of the retina and its ability to distinguish colors were evaluated. Moreover, the capabilities of the technique made it possible to assess retinal activity in the field of view from 0 to 21°. Such an approach can not only demonstrate the interest of retinal cellular elements in the action of substances, but also raise the question of the participation of the visual system in the psychopharmacological effect more broadly.

RESULTS: The work of the visual apparatus was studied both in healthy volunteers of different ages and in persons with emotional disorders, which were identified using special questionnaire tests. It was found that violations of the emotional status are often accompanied by a limitation of the photosensitivity of the retina of varying severity. These facts can be interpreted in different ways. On the one hand, violations of visual functions can lead to psychoemotional disorders and be a pathogenetic link in their development, and on the other hand, primary disorders of retinal light and color sensitivity can provoke the development of psychopathology. However, regardless of the pharmacological characteristics of the studied drugs with psychodeprimating activity, the connection between their anti-anxiety effect and changes in visual function seems to be obvious, which allows us to raise the question of the advisability of taking into account the photosensitivity of the retina for a comprehensive assessment of both the mental state of emotionally labile subjects and the pharmacodynamics of psychodemitting drugs.

CONCLUSIONS: Thus, it is legitimate to conclude that taking into account the light and color sensitivity of the retina can be one of the quantitative criteria for the severity and effectiveness of psychopharmacotherapy.

AIM: of the study is to analyze the results of pharmacoeconomical studies of preventive chemotherapy in children from high-risk groups of tuberculosis to optimize measures for the prevention of tuberculosis infection in children.

MATERIALS AND METHODS: Collection, systematization and analysis of data from the scientific literature and the results of their own research on the relevant problem.

RESULTS: On the problem of chemoprophylaxis of tuberculosis infection in children from high-risk groups, there is insufficient information on the pharmacoeconomical aspects of this problem. Most studies include a pharmacoeconomical assessment of the management of adult patients with tuberculosis infection. There are isolated scientific papers devoted to the pharmacoeconomical analysis of the preventive treatment of latent tuberculosis infection (LTI) in children. Different clinical and economic efficiency of the applied methods of immunodiagnostics and regimens of chemoprophylaxis of tuberculosis in children is shown. To improve the epidemic situation of tuberculosis among children, it is important to improve preventive chemotherapy regimens. Their effectiveness is largely determined by the sensitivity of Mycobacterium tuberculosis (MBT) to anti-tuberculosis drugs (PTP) and the rational choice of a chemotherapy regimen. The current chemoprophylaxis regimens for children with LTI do not take into account the sensitivity of MBT to PTP at a possible source of infection.

CONCLUSION: The analysis shows the high relevance of pharmacoeconomical studies and the practical significance of the results of such studies for optimizing preventive chemotherapy in children from high-risk groups for tuberculosis. Scientific research on the assessment of the clinical and economic effectiveness of various regimens of chemoprophylaxis of tuberculosis in children allows us to identify the most effective and least expensive ways to prevent tuberculosis through the rational use of medicines and methods of immunodiagnostics.

The effect was studied of dry leaf extract of Serratula centauroides L. on the behavior of white rats (Wistar) in tests with positive reinforcement. It was revealed that the extract of S. centauroides at doses of 50–200 mg/kg promotes in animals a decrease in the level of anxiety, adaptation to unfamiliar conditions, and as a consequence, to an increase in the volume of food intake. And also a more rapid formation of a conditioned reflex with positive reinforcement. In animals treated with S. centauroides extract, the volume of food taken in “hypophagia” test was 1.4–2.7 times higher than the control value. In the T-shaped maze, 50–80% of the animals in the experimental groups developed a conditioned reflex to positive reinforcement, while none of the animals in the control group reached the learning criterion. The S. centauroides extract showed the most pronounced effect on the behavior of animals in tests with positive reinforcement at a dose of 100 mg/kg.