Background. In some cases, a new coronavirus infection demonstrates non-standard clinical manifestations, an integral characteristic of which is a tendency to thrombotic and hemorrhagic complication.

Objective. To study the predisposing factors for the development of thrombotic and hemorrhagic complications in patients with COVID-19.

Design and methods. The work was based on observations of 403 patients who were hospitalized for pneumonia of viral etiology (COVID-19). The features of comorbid pathology, markers of inflammation and coagulation, characteristics of the identified complications in the main group (75 people who had thrombotic and hemorrhagic complications) were prospectively collected in comparison with the control (328 patients), where no such consequences were detected.

Results. There were no significant differences between the groups in terms of age and gender. In the main group, a large number of overweight patients were registered in comparison with the control. The levels of CRP, ferritin, and D-dimer in patients with complications significantly exceeded the reference values more often. Among the complications, spontaneous hematomas, gastrointestinal bleeding, acute cerebral circulatory disorders, acute myocardial infarction and venous thromboembolic complications were recorded.

Conclusion. In patients with thrombotic and hemorrhagic complications of COVID-19, the level of markers of the inflammatory process (CRP, ferritin) increases. These negative consequences are most characteristic for patients with chronic kidney disease, severe hypertension, COPD and generalized atherosclerotic process (myocardial infarction, stroke).

Backround. It is known that both subclinical hypothyroidism (SHT) and subclinical thyrotoxicosis (STT) can influence the outcome of coronary heart disease. The feasibility of routinely determining thyroid status in patients without obvious signs of thyroid dysfunction with acute coronary syndrome without ST-segment elevation (NSTEACS) to assess the effect on the status of implanted stents has not been determined.

Objective. To evaluate the effect of subclinical hypothyroidism and subclinical thyrotoxicosis on lumen loss and the degree of endothelialization of drug-eluting stents after stenting for NSTE-ACS.

Design and methods. The study included 173 patients who were urgently stented for NSTE-ACS, and who subsequently underwent repeat coronary angiography within a year on a planned or emergency basis with a targeted assessment of the condition of the installed stents. In 40 patients with everolimus-eluting stents, the condition of the coronary arteries was assessed 6.3 + 0.3 months after stenting using optical coherence tomography (OCT). All patients included in the study had their thyroid status assessed.

Results. SHT was detected in 8 (21.6 %) patients with loss of lumen in the stent area and in 26 (19.1 %) patients without loss of lumen, p = 0.73. STT was detected in 2 (5.4 %) and 3 (2.2 %) patients, respectively, p = 0.30. A prognostic analysis performed by logistic regression with forced inclusion as predictors of lumen loss identified the parameters Syntax Score I, stent diameter, and the number of affected coronary arteries. No effect of thyroid status on lumen loss was found. In patients with subclinical hypothyroidism, OCT data revealed insufficient endothelialization of everolimus-eluting stents 6 months after stenting for NSTE-ACS. The percentage of uncovered stent struts depended on TSH levels (r = 0.42, p = 0.007). The higher the TSH level, the higher the healing index and the worse the stent endothelialization (r = 0.37, p = 0.016). Conclusion. Thus, routine determination of thyroid status indicators in patients with NSTE-ACS in order to identify subclinical thyroid dysfunction does not provide significant prognostic information regarding the risk of lumen loss of implanted stents. Considering the potential risk of thrombotic complications associated with insufficient endothelialization of everolimus-eluting stents in the presence of subclinical hypothyroidism, it seems advisable to identify it when deciding on de-escalation of antithrombotic therapy. The question remains open about the need to correct the parameters of subclinical thyroid dysfunction in order to modify the prognosis.

Background. An urgent problem of creating a domestic production of modern medicines under the conditions of sanctions pressure is the molecular design and development of rational methods for the synthesis of active pharmaceutical ingredients of original drugs and young generics.

Objective. In this work, a computer prediction of the biological activity of β-(2R,3S,5R)-2-(hydroxymethyl)-6-(5-phenyl-2H-tetrazole-2-yl) tetrahydro-2H- piran-3,4,5-triol 1 — compounds, in the molecule of which there are two promising pharmacophore fragments, was performed: tetrazolyl and galactopyranosyl. Both fragments of the studied molecule are actively used by leading scientific centers for the molecular design and synthesis of promising active pharmaceutical ingredients (API) of modern medicines.

Design and methods. For this purpose, the latest versions of the PASS computer complex were used in combination with molecular docking and scoring in the AutoDoc Vina program.

Results. Based on computer prediction data, it is shown that this compound may have multi-target biological activity.

Conclusion. A rational, scalable method for the synthesis of compound 1, which is recommended for testing in vitro, in vivo activity, is proposed.

One of the most promising areas for the use of fullerenes and their derivatives is biology and medicine. This is due to the fact that fullerenes are highly reactive due to the presence of double bonds capable of attaching various radicals, and demonstrate high antioxidant activity, the ability to penetrate through the lipid bilayer, and modulate transmembrane ion transport. The review considers the main biological properties of water-soluble derivatives of light fullerenes, which determine their application in biomedicine.

Background. Administration of certain drugs causes undesirable effects associated with the systemic effect of the active substance on the entire body. Selective targeting of the drug to the affected tissue promotes a selective increase in the concentration of the substance in the area of interest, thereby reducing the systemic effect and enhancing the local therapeutic effect.

Objective. Development of a targeted delivery system for theranostic agents using recombinant human vascular endothelial growth factor type A (rhVEGF-A121) as a targeting ligand.

Design and method. To create the theranostic complex, commercially available reagents were used: the recombinant protein rhVEGF-A121 (cat.#: PSG140-10, LLC CyStorLab, Skolkovo, Russia) and fumed silica Aerosil (A-200, Degussa AG, Germany). The tosyl spacer that interconnects both components was synthesized in the laboratory. Protein conjugation with fluorophores was also carried out in-house. Indocyanine green (ICG; Sigma-Aldrich, USA) and rhodamine B (JSC Lenreaktiv, St. Petersburg, Russia) were taken for immobilization.

Results. In the course of the work, functionalization of silica nanoparticles (SiNPs) with a tosyl spacer was carried out, conjugates of SiNPs with rhVEGF-A121 were synthesized, and theranostic constructs based on SiNPs were obtained, including rhVEGF-A121 as a targeting ligand, and ICG/Rhodamine B as a visualizing label.

Conclusion. In the presented study, a prototype of a complex for targeted delivery of a theranostic agent to tissues with an active angiogenesis process, for example, to tumor and ischemic tissues, was developed. To solve the problem, we immobilized on the surface of SiNP a recombinant protein of human vascular endothelial growth factor (rhVEGF) to use as a guide ligand. Such a synthetic construct will help to deliver diagnostic and/ or medicinal substances packed in SiNP directly to cells that overexpress extracellular specific receptors of the VEGFR family. In subsequent in vivo experiments, delivery efficiency will be assessed by tissue accumulation of the fluorophores ICG and rhodamine B, which have been conjugated to the targeting ligand protein. The physicochemical characteristics of the obtained samples were studied by the methods of spectrophotometry and dynamic light scattering.

Relevance. Osteoporosis is a clinical and economic problem on a global scale. A significant contribution to solving the problem of effective treatment of osteoporosis can be the creation of drugs based on unique biologically active compounds.

The aim of the study was the morphological substantiation of the experimental model of osteoporosis and a comprehensive (multifactorial) assessment of the effectiveness of its drug therapy.

Materials and methods. The study was carried out on 40 mature female Wistar rats, which comprised 6 groups. A model of osteoporosis was formed in animals of four experimental groups (6 animals in each): the first and second groups (respectively) consisted of young rats, the third and fourth — old ones. Animals of the second and fourth groups were injected with a drug tested for its ability to activate the process of osteosynthesis. Rats of the fifth and sixth groups (young and old, 8 animals each), subjected to sham surgery, served as controls. As a result of the use of the histo-morphometric method and atomic absorption spectroscopy in the diaphysis of the femur, the thickness of the layers of the compact substance, the number of bone plates and osteocytes, as well as the amount of collagen, calcium and phosphorus were determined. Using enzyme immunoassay, bone remodeling markers — osteocalcin, sclerostin, osteoprotegerin, fibroblast growth factor-23 and nuclear factor kappa-β activator ligand (RANKL) — were determined in the blood serum. Statistical processing of the data was carried out using the GraphPad PRISM (USA) program to determine the median, upper and lower quartiles. Differences were considered significant at p < 0.01.

Results. Modeling of osteoporosis induces atrophic thinning of the compact substance, a decrease in the number of osteocytes and bone plates in the diaphysis of the femur, a decrease in the content of collagen, calcium and phosphorus in them, a decrease in the concentration of osteocalcin, sclerostin, fibroblast growth factor, osteoprotegerin and an increase in the concentration of RANKL in the blood plasma, more pronounced in old animals. As a result of the use of the drug X3 for the treatment of osteoporosis, the following were revealed: a significant increase in the thickness of the compact substance, the number of osteocytes and bone plates in the diaphysis, the content of collagen, calcium and phosphorus in them, an increase in the concentration of biochemical markers of osteosynthesis, and a mild imbalance of RANKL. The increase in plasma levels of markers of bone remodeling was most pronounced when the drug X3 was combined with vitamin D3.

Conclusion. 1. The used surgical-endocrine method of modeling osteoporosis leads to pronounced degenerative changes in osteocytes and their derivatives in all parts of the compact bone substance, and also causes significant disturbances in the mineral composition and an imbalance of bone remodeling markers, more pronounced in senile rats. 2. The tested drug X3, used for the treatment of osteoporosis, has a high degree of effectiveness, since it stimulates regenerative osteogenesis, restores the damaged structure of bone tissue elements, its organic and mineral components. 3. The restorative effect of the drug is more pronounced in senile rats.

It was evaluated the feasibility of using Zebrafish as a model to study extracellular vesicles (EVs) based on literature. Particularly, it was described experimental models that were used to assess the contribution of the EVs in the regulation of pathological and physiological processes (ischemic, reperfusion, mechanical damage to tissues and organs, development of local and systemic immune response, tumor growth and metastasis, etc.), the bioavailability and the distribution of injected EVs in different tissues and organs, the effects of exogenous EVs as therapeutic agents.

The paper investigates the role of the association of polymorphic variants of the tissue plasminogen activator inhibitor 1 (PAI-1) and angiotensin-converting enzyme (ACE) genes in 244 patients with coronavirus infection with varying degrees of disease severity (mild, moderate, and the group of deaths). The influence of the age factor in conjunction with various genotypes on the course of coronavirus infection is also being studied. An analysis of the frequencies of alleles and genotypes of ACE found statistically significant differences: the D allele is associated with the severity and outcome of COVID-19. The I/D genotype is associated with a milder course of the disease, while the D/D genotype increases the likelihood of death.

Acute cerebrovascular accident is one of the leading causes of disability and death worldwide. Given the significant increase in life expectancy of the population, stroke will remain a serious medical and social problem in the next few decades. Among the various causes of stroke, ischemic brain damage predominates. Ischemic stroke is based on a decrease in the intensity of blood supply to the brain tissues, as a result of which there is a decrease in the delivery to neurons of the required amount of glucose and oxygen, which are required to ensure the normal function of this organ. At the same time, in many cases, spontaneous or medical restoration of blood flow after a period of ischemia is accompanied by a paradoxical increase in damage, and therefore it is advisable to consider the process of damage to brain tissue during circulatory disorders in the context of ischemic-reperfusion injury (IRI). One of the key mechanisms of brain IRP is the inflammatory response. In the process of secondary immune damage to the brain, both mechanisms of innate immunity, manifested by leukocyte infiltration of the damaged brain area, and antigen-dependent reactions of adaptive immunity are involved. One of the most important manifestations of neuroinflammation in cerebral IRI is an increase in transand paracellular permeability of the blood-brain barrier, which underlies the development of vasogenic cerebral edema and hemorrhagic transformation of the focus. This review considers current ideas about the molecular mechanisms that link aseptic inflammation, edema, and hemorrhagic transformation.

The effectiveness of upper cervical sympathectomy in the treatment of patients with neurovascular pathology has been discussed in the researcher’s article for many years. However, the indications for this surgery need still to be clarified. The dynamics of cerebral blood flow during sympathetic blockade could not become the significant criterion for determining indications for surgical treatment. A cerebral perfusion pressure change in neurovascular pathology can activate the neurogenic mechanism of cerebral blood flow regulation. The need to search for new methods for the intensity of the autonomic nervous system impact on the cerebral vessels tone (the neurogenic mechanism of cerebral blood flow regulation) to clarify the indications for upper cervical sympathectomy in patients with neurovascular pathology is justified. The review put forward a hypothesis about the relationship between intracranial B-waves amplitude and the state of the neurogenic mechanism of cerebral blood flow regulation.

The article discusses the contradictions in medical science and practice caused by the discrepancy between the amount of knowledge and the methodology for their development. The proposed methodological approach to the development of the general theory of medicine. The article clarifies the concepts of objects, subject and methods of medicine. Health is defined as the body’s ability to make up indefinitely. Two forms of ill-health have been identified: illness and functional insufficiency. The disease is defined as a set of processes leading to the loss of signs of the organism and its consequences. Disclose the results of the diagnosis of diseases. The direction of detection of diseases and urgent tasks of medical semiotics are provided.