MATHEMATICAL MODEL FOR THE INVESTIGATION OF HYPOXIC STATES IN THE HEART MUSCLE AT VIRAL DAMAGE

The main complications of organism damaged by SARS-CoV-2 virus are various cardiovascular system lesions. As a result, the secondary tissue hypoxia is developed and it is relevant to search the means for hypoxic state alleviation. Mathematical modeling of this process, followed by the imitation of hypoxic states development, and subsequent correction of hypoxia at this model may be one of the directions for investigations. Aim. The purpose of this study was to construct mathematical models of functional respiratory and blood circulatory systems to simulate the partial occlusion of blood vessels during viral infection lesions and pharmacological correction of resulting hypoxic state. Methods. Methods of mathematical modeling and dynamic programming were used. Transport and mass exchange of respiratory gases in organism, partial occlusion of blood vessels and influence of antihypoxant were described by the systems of ordinary nonlinear differential equations. Results. Mathematical model of functional respiratory system was developed to simulate pharmacological correction of hypoxic states caused by the complications in courses of viral infection lesions. The model was based on the theory of functional systems by P. K. Anokhin and the assumption about the main function of respiratory system. The interactions and interrelations of individual functional systems in organism were assumed. Constituent parts of our model were the models of transport and mass exchange of respiratory gases in organism, selforganization of respiratory and blood circulatory systems, partial occlusion of blood vessels and the transport of pharmacological substance. Conclusions. The series of computational experiments for averaged person organism demonstrated the possibility of tissue hypoxia compensation using pharmacological substance with vasodilating effect, and in the case of individual data array, it may be useful for the development of strategy and tactics for individual patient medical treatment.

Behavioral analysis of anxiolytic action of phenazepam in conditions of an acute psychogenic stress (predator presentation) in Danio rerio

We studied the effect of benzodiazepine anxiolytic phenazepam after the predator presentation to Danio rerio. The test of novelty was used: the fish was placed first in a beaker with a dissolved pharmacological substance (or H2O) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing were measured. It is shown that, in response to the novelty of tank, the fish are reacted by submerging to the bottom, increasing the frizing, and reducing the number of movements to the upper half of the novel tank. After phenazepam administration, the fish were not only in the lower, but also in the upper part of the novel tank. The average path length did not change significantly in the range of doses used. The number and time of the frizing, as well as the time spent in the lower part of the novel tank, decreased more than 2 times compared to the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the novel tank for the experiment increased significantly from 1 in the control to 57 after phenazepam in a dose of 1 mg/l. At the same time, the number of movements of fish to the upper part of the novel tank significantly increased more than 2 times from 3th min of the experiment with the use of phenazepam in a dose of 1 mg/l. Predator presentation (Hypsophrys nicaraguensis) caused an increase in the number of freezing (temporary immobilization) and a decrease in the length of the trajectory of movement in the novel tank as compared with the Danio rerio control group. Phenazapam at a dose of 1 mg/l removed the effects of a predator, while exhibiting a typical effect: the number of movements to the upper part of the tank during the experiment significantly increased to 30; the time at the bottom of the tank was halved. It was concluded that the novelty stress test and the test with a predator are highly sensitive for studying anxiety-phobic reactions in Danio rerio.

Study on the Spectrum-Effect Relationship of the Traditional Effect of Saponins in Glycyrrhiza uralensis Fisch

Licorice is a traditional Chinese medicine that has been used for a long time in China and still in great use today. The effect of licorice on tonifying spleen and invigorating qi has been proved for thousands of years, but the material basis of its effect is not clear. In this paper, we established the fingerprints of 21 batches of licorice collected from different origins in China with High-Performance Liquid Chromatography (HPLC) to identify the common peaks. Its effect of tonifying spleen and invigorating qi was confirmed through a series of praxiology experiments. The spectrum-effect relationship between HPLC fingerprints and its effect of tonifying spleen and invigorating qi of licorice was examined by gray relational analysis and partial least squares regression analysis. Results showed that the effect of licorice on tonifying spleen and invigorating qi resulted from various compounds and peaks. X2–X6 is presumed to be the main pharmacological substance base. This research successfully identified the spectrum-effect relationship between HPLC fingerprints and the effect of licorice on tonifying spleen and invigorating qi. The research method based on the spectrum-effect relationship helps provide new research ideas and strategies for the study of the basis of the medicinal materials and quality control of traditional Chinese medicine.

ОБЗОР СОВРЕМЕННЫХ МЕТОДОВ ПРОИЗВОДСТВА ИМПРЕГНИРОВАННЫХ ШОВНЫХ МАТЕРИАЛОВ

The modern medical process poses new challenges, classical suture materials have ceased to satisfy surgeons with both their sanogenetic properties and physical properties. These properties are capable of giving threads the production methods described in the article. Among these methods, there are two fundamental differences: an active pharmacological substance is applied in the process of creating a thread, and a substance is applied to an already finished thread, which fundamentally affects the physical and biological parameters.

Evaluation of the cumulative properties of the drug Delcid 7,5®

Cumulative properties (accumulation of a substance or its effect upon repeated administration in equal doses) is determined on the basis of a quantitative indicator – the cumulation coefficient. Before carrying out chronic toxicological experiments, it is necessary to determine the cumulation index of the pharmacological substance – the ratio of LD50 with a single administration to LD50 with multiple administration. According to the Lim method, the cumulative properties of the drug Delcid 7,5® were studied, the cumulation coefficient of the drug was Kkum = 1,09. In accordance with the classification of chemicals, including pesticides by L.I. For a bear, the drug belongs to a group of substances with pronounced cumulation.

Benzodiazepine tranquilizers abolish the stress-induced increase of the brain ghrelin level in DANIO RERIO

Danio reriohas firmly established itself as a successful model for research in many areas of biology and medicine, first of all for developing new medicines. The aimof our study was to evaluate ghrelin level in zebrafish brain after stress and after phenazepam usage on stressed fish. Methods.In our study 96Danio rerio, predatorCichlasoma nicaraguensishave been used. The fish have been kept at anormal room temperature (2223C) with standard feeding time (twice per day). The level of neuropeptides has been tested by ELISA test. During experiment a fish has been firstly placed in a beaker with a dissolved pharmacological substance, then has been transferred into a tank with predator. In the end of experiment, it has been put into a novel tank for 6 min. The decapitation has been made. Thebrain has been divided into three anatomical parts:telencephalonjust behind the olfactory bulb, the middle partcorpora bigemiaandcerebellum, which is situated behind thecorpora bigemia. After that the material for ELISA test was made using GhrelinFISH, MyBioSource ELISA kit. Results.In the control group ghrelin has been determined only in thecerebellumin 57.14% of all fish. In the experiment with predator ghrelin has been found in all tested brain parts of fish, but in thetelencephalonthere was the highest level. Inthe experiment with phenazepam usage only and phenazepam administration after predator stress, the ghrelin value has not been determined atall. Conclusion.Thus we have found out that the ghrelin value increases after predator stress and the drug phenazepam eliminated it completely after its administration. We may suppose that the administration of anxiolytics such as phenazepam can reduce the anxiety inDanio rerio.

Benzodiazepine tranquilizers abolish the stress-induced increase of the brain ghrelin level in DANIO RERIO

Danio reriohas firmly established itself as a successful model for research in many areas of biology and medicine, first of all for developing new medicines. The aimof our study was to evaluate ghrelin level in zebrafish brain after stress and after phenazepam usage on stressed fish. Methods.In our study 96Danio rerio, predatorCichlasoma nicaraguensishave been used. The fish have been kept at anormal room temperature (2223C) with standard feeding time (twice per day). The level of neuropeptides has been tested by ELISA test. During experiment a fish has been firstly placed in a beaker with a dissolved pharmacological substance, then has been transferred into a tank with predator. In the end of experiment, it has been put into a novel tank for 6 min. The decapitation has been made. Thebrain has been divided into three anatomical parts:telencephalonjust behind the olfactory bulb, the middle partcorpora bigemiaandcerebellum, which is situated behind thecorpora bigemia. After that the material for ELISA test was made using GhrelinFISH, MyBioSource ELISA kit. Results.In the control group ghrelin has been determined only in thecerebellumin 57.14% of all fish. In the experiment with predator ghrelin has been found in all tested brain parts of fish, but in thetelencephalonthere was the highest level. Inthe experiment with phenazepam usage only and phenazepam administration after predator stress, the ghrelin value has not been determined atall. Conclusion.Thus we have found out that the ghrelin value increases after predator stress and the drug phenazepam eliminated it completely after its administration. We may suppose that the administration of anxiolytics such as phenazepam can reduce the anxiety inDanio rerio.

Assessment of dose-dependent effects of anxiolytics of benzodiazepine structure with diazepam as an example in Danio Rerio

The effect of benzodiazepine anxiolytic diazepam in Danio rerio was investigated. Methods. A stress test on novelty situation was used: a fish was placed first in a beaker with a dissolved pharmacological substance (or water) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing of the experiment were measured. Results. In response to the novelty of tank, the fish was shown to react by submerging to the bottom, increasing the freezing, and reducing the number of movements to the upper half of the novel tank. After diazepam exposure (administration), the fish was not only in the lower, but also in the upper part of the novel tank. A pharmacological analysis of diazepam effect in Danio rerio showed that in a certain dose range of 110 mg/l anxiolytic reduces (in comparison with the control group of fish) the number and time of freezing, increases the number of movements in the upper half of the tank and the swimming time in upper part of the tank. Diazepam causes a disinhibition of motor activity at doses of 1 and 5 mg/l, which may be explained by the effect of small doses of tranquilizers on presynaptic GABA-A autoreceptors. Diazepam 20 mg/l has a depriving effect. Conclusion. Diazepam acts in a higher dose range (110 mg/l) than phenazepam (0.11 mg/l) in Danio rerio. At the same time, diazepam is characterized by a domed dose-dependent effect, in contrast to the action of phenazepam. The prospect of using Danio rerio as an animal model in behavioral pharmacology is not inferior to studies in rodents.

Coffee and Endothelial Function: A Coffee Paradox?

Coffee is a popular beverage throughout the world. Coffee contains various chemical compounds (e.g., caffeine, chlorogenic acids, hydroxyhydroquinone, kahweol, cafestol, and complex chemical mixtures). Caffeine is also the most widely consumed pharmacological substance in the world and is included in various beverages (e.g., coffee, tea, soft drinks, and energy drinks), products containing chocolate, and drugs. The effects of coffee and caffeine on cardiovascular diseases remain controversial. It is well known that there are J-curve-type or U-curve-type associations of coffee consumption with cardiovascular events including myocardial infarction and stroke. However, there is little information on the direct and indirect effects of coffee consumption on endothelial function in humans. It is likely that the coffee paradox or caffeine paradox exists the association of coffee intake with cardiovascular diseases, cardiovascular outcomes, and endothelial function. This review focusses on the effects of coffee and caffeine on endothelial function from molecular mechanisms to clinical perspectives.

ACUTE CHRONICAL TOXICITY AND INTOLERANCE OF SM - COMPLEX

The researchers elaborated pharmacological complex of SM at the Chair of Morphology, Physiology and Pharmacology atSouth-UralStateAgrarianUniversity. The complex contains butafosfan, vitamins, vitamin-like substances, selected on the basis of synergistic effect on the body. The parameters of acute toxicity of the SM-complex were explored in the experiment on clinically healthy adult white mice of both genders by a single injection of the solution in the maximum permissible dose according to GOST 31926-2013. Intolerance on the skin of animals was detected in line with GOST R ISO 10993.10-2009. GOST R ISO 10993.10-99 became a guideline for evaluating SM-complex intolerance on the eye conjunctiva. Chronic toxicity was investigated on non-linear rats; the rates were divided into 4 groups of 6. The first group became a control group, the second group received the SM-complex in a therapeutic dose (255mg/kg), the third group - in a 5 -fold therapeutic dose (1275mg/kg), the fourth group - in a 10-fold dose (2550mg/kg). Pharmacological substance was applied through the probe in the form of an aqueous solution for 30 days. The researchers found out that at single oral introduction of SM-complex in the maximum possible doses it does not affect mice organism and it is referred to the 4th class of danger according to GOST 12.1.007-76. Local application in the form of applications on the skin and mucous membranes of rabbits, the complex does not have a local irritant effect. Long-term application of pharmacological composition (30 days) in high doses causes functional and morphological changes of the liver in the form of gray foci and flabbiness, as well as it increases the volume of the organ. Due to the fact that the therapeutic doses are 5 and 10 times lower than the toxic ones and the period of application does not exceed 7-14 days, the authors make a conclusion that SM-complex is safe and secure and can be used in the recommended doses.