STUDY OF ANTI-OSTEOPOROTIC ACTION OF DRUGS FROM THE GROUP OF STATINS

In an experiment on female Wistar white rats, the osteoprotective effect of atorvastatin, simvastatin and rosuvastatin was studied in a model of experimental osteoporosis caused by bilateral ovariectomy. It was found that after ovariectomy in female rats develops endothelial dysfunction, including the vessels of the microcirculatory of the bone, leading to a deterioration of blood supply to bone tissue and the occurrence of osteoporosis. It was found that atorvastatin, simvastatin and rosuvastatin, possessing endothelioprotective activity, prevent deterioration of blood supply to bone tissue and thinning of bone trabeculae, thus having anti-osteoporotic activity. Key words: osteoporosis, endothelial dysfunction, statins, atorvastatin, simvastatin, rosuvastatin, strontium ranelate

PRECLINICAL INVESTIGATION OF THE ALLERGENIC EFFECT OF THE DRUG BASED ON THE PHENOLIC COMPOUND KUD975

Introduction: Vascular endothelium is a cellular monolayer that covers the internal lumen of all blood vessels, thus separating blood from the vessel wall and tissues. The study of the role of endothelium in the pathogenesis of cardiovascular diseases led to an understanding of the concept of it as a target for the prevention and treatment of these pathologies. Research tasks: The purpose of this study was preclinical study of the allergic effect of the drug KUD975, based on a phenolic compound, which is a selective inhibitor of arginase 2. Methods: Experiments on the allergic properties of the phenolic compound KUD975, which is a selective inhibitor of arginase II, were carried out on albino sexually mature guinea pigs weighing 300 ± 20 g. The preparation was administered intragastrically as a suspension in a 1% starch paste using a specially prepared atraumatic probe at 0, 1 ml of suspension per 10 g of body weight of animals. As a control, we used data obtained in animals with intragastric administration of the corresponding volume of placebo-1% starch paste. Results: In the course of the study of the allergic properties of KUD975, when the reaction of active cutaneous anaphylaxis was formulated, it was found that the studied preparation in two and eight times daily therapeutic dosages did not possess allergic properties In the course of the study of the allergic properties of KUD975 in the formulation of a delayed-type hypersensitivity reaction, it was found that the study drug in two and eight times daily therapeutic dosages had no allergenic properties. Erythema, or, especially, infiltration and the appearance of ulcers at the site of administration as a resolving dose of the drug, as well as in the control of reactivity, were not observed in any animal participating in the experiment. Conclusion: When investigating the allergenic properties of the phenolic compound KUD975, which is a selective inhibitor of arginase II in the reaction of active cutaneous anaphylaxis, it was found that the study preparation in two and eight times daily therapeutic dosages does not have allergic properties. In the reaction of active cutaneous anaphylaxis in guinea pigs, the allergic properties of KUD975 in two and eight times daily therapeutic dosages were not detected Key words: compounds of phenolic nature, allergic action, endothelium, inhibitors of arginase I

Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

This paper is about a way of correction of endothelial dysfunction with the inhibitor of arginase: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction

3D organotypic cell structures for drug development and Microorganism-Host interaction research

Introduction: The article describes a new method of tissue engineering, which is based on the use of three-dimensional multicellular constructs consisting of stem cells that mimic the native tissue in vivo – organoids. 3D cell cultures: The currently existing model systems of three-dimensional cultures are described. Characteristics of organoids and strategies for their culturing: The main approaches to the fabrication of 3D cell constructs using pluripotent (embryonic and induced) stem cells or adult stem cells are described. Brain organoids (Cerebral organoids): Organoids of the brain, which are used to study the development of the human brain, are characterized, with the description of biology of generating region-specific cerebral organoids. Lung organoids: Approaches to the generation of lung organoids are described, by means of pluripotent stem cells and lung tissue cell lines. Liver organoids: The features of differentiation of stem cells into hepatocyte-like cells and the creation of 3D hepatic organoids are characterized. Intestinal organoids: The formation of small intestine organoids from stem cells is described. Osteochondral organoids: Fabrication of osteochondral organoids is characterised. Use of organoids as test systems for drugs screening: The information on drug screening using organoids is provided. Using organoids to model infectious diseases and study adaptive responses of microorganisms when interacting with the host: The use of organoids for modeling infectious diseases and studying the adaptive responses of microorganisms when interacting with the host organism is described. Conclusion: The creation of three-dimensional cell structures that reproduce the structural and functional characteristics of tissue in vivo, makes it possible to study the biology of the body’s development, the features of intercellular interactions, screening drugs and co-cultivating with viruses, bacteria and parasites

Eleven-amino acid peptides that mimic the erythropoietin α-helix B increases cell survival in endotheliocyte culture

Aim. To study the cytoprotective activity of peptides that mimic the spatial structure of the erythropoietin α-helix B in vitro. Material and methods. The experiment was performed on the primary cell culture of human endotheliocytes (HUVEC). Hydrogen peroxide (H2O2) was used to mimic oxidative stress. Cells were scattered in 96-well gelatin-coated plates with a density of 5 thousand cells per well. After 24 hours of incubation, the studied peptides were introduced - the basic peptide - Helix B surface peptide HBSP (QEQLERALNSS) and its derivatives EP-11-1 (UEHLERALNSS), EP-11-2 (UEQLERALNCS), EP-11-3 (UEQLERALNTS) in 3 concentrations - 5 μg/ml, 30 μg/ml and 50 μg/ml. Cell viability was measured using the MTT test. Results. Initial screening of the cytoprotective activity of innovative peptides that mimic the erythropoietin α-helix B in vitro was performed.  Our results demonstrate that the original HBSP peptide and its derivatives EP-11-1, EP-11-2, EP-11-3 have a pronounced (p<0.05, compared with the control) cytoprotective effect. Derivatives EP-11-1, EP-11-2 does not differ from the base peptide HBSP in terms of the level of detected activity. When comparing the density of the formazan solution and the percentage of surviving endotheliocytes between the series of experiments with the base peptide HBSP and its derivatives, EP-11-3 showed significant superior cytoprotective effects when compared with HBSP (p<0.05), all over the entire range studied concentrations. Conclusion.  Derivatives of the original peptide with laboratory code EP-11-1, EP-11-2 do not differ in their cytoprotective action from the base peptide HBSP. While the derivatives with laboratory code EP-11-3 presented a higher and significant cytoprotective activity when compared to the base peptide HBS

Comparative study of the pharmacological effects of Venarus Plus, Venarus, and Detralex on L-NAME-induced endothelial dysfunction, venous tone and platelet aggregation

In the present study we compared the pharmacological activity of Venarus Plus, Venarus and Detralex 1000 mg on the reversion of endothelial dysfunction (ED), and on the effect on venous tone, vascular permeability, and platelet aggregation. We used 150 Wistar male rats, weighing 180-220 g, and 80 adult albino rabbits weighing 2800 - 3200 g. Endothelial dysfunction (ED) was induced with the non-selective inhibitor of NO synthase, N-nitro-L-arginine-methyl ether (L-NAME). Functional vascular tests and biochemical markers were used to determine the reversion of the functional disorders. The anti-inflammatory effects of the drugs was evaluated in rabbits using o-xylene. The venotonic effects of the compounds was carried out on an isolated segment of the rat portal vein with Ca2+ solutions at a concentration of 0.08-1.75 mM. Our results show that the maximum daily therapeutic dose of Venarus Plus, produces a significant decrease in the ED coefficient (СED), an increase in NO synthesis, and an extended ADP-induced platelet aggregation time. The studied drugs dose-dependently reduce vascular permeability disorders caused by the application of o-xylene, which was manifested in a profound decrease the size of spots and the extension of the time interval before their onset. To study the Ca2+-mediated smooth muscle response, showed that the maximum force of vein contraction occurs with a higher dosage of drugs in the presence of a lower concentration of Ca2+, the effects of the drugs are comparable

The anti-aggregation activity of new 11-amino acid of erythropoietin derivate containing tripeptide motifs

Objective. To study the platelet antiaggregant activity of new 11-amino acid derivatives of erythropoietin, containing tripeptide motifs. Materials and methods. The platelet aggregation degree was determined using the platelet-rich plasma of male Wistar rats. Formation of platelet aggregates results in an increase in light transmission through the sample; the kinetics of the responses and maximal aggregation provide a quantitative assessment of platelet aggregation The degree of platelet aggregation is estimated by the magnitude of the amplitude of aggregatograms, and the time of onset of light transmission level as well the time of onset of 85% of light transmission. Results. When blood was incubated with the studied peptides P-αB1, P-αB3, and P-αB4, a pronounced antiplatelet effect was observed. This is evidenced by a decrease in the maximum light transmittance of the plasma to 28.4±1.00%, 29.7±1.13% and 30.1±0.97%, respectively, and a delay in its onset to 134.4±2,90, 135.8±3.72 and 132.0 ± 3.59 seconds, respectively. In this case, a shift in the plasma light transmission curve to the right was observed which characterizes the platelet aggregation process.   Conclusion. The addition of P-αB1, P-αB3, and P-αB4 produces antiplatelet activity, which is reflected by the shifting to the right of the platelet aggregation curve. The data obtained indicate a prolongation of platelet aggregation time and a decrease in its degre