卷 49, 编号 1 (2023)

Many different receptors and ion channels regulating ion currents are involved in the regulation of the cardiovascular system (CVS). The functioning of the CVS occurs via mechanisms of both nervous and humoral regulation, and in both cases, acetylcholine receptors of different families and subtypes with different localization participate in the regulation processes. It has been shown that acetylcholine receptors are located on the cell membranes directly of the heart and blood vessels; and this review examines the mechanisms of regulation of the functions of the CVS with the participation of only those cholinergic receptors that are located in the tissue of the heart and blood vessels. In general, both muscarinic and nicotinic cholinergic receptors are widely represented in the tissues of the CVS. While muscarinic acetylcholine receptors are generally involved in the regulation of vascular tonus and contractility of the heart, the nicotinic acetylcholine receptors are mainly involved in the regulation of a number of important pathophysiological processes directly affecting the functioning of the CVS. Regulation of the functioning of cholinergic receptors can be considered as an addition to existing methods for the treatment of diseases of the CVS, including such diseases as atherosclerosis and heart failure. The use of blockers and activators of cholinergic receptors for the study and/or treatment of pathological conditions of the CVS is discussed.

It is known that antibacterial drugs with prolonged use cause antibiotic resistance in bacteria. Fast formation of resistance of microorganisms to modern antibacterial drugs requires the search for new methods of treatment. An alternative direction is the use of metal nanoparticles and their oxides as a basis for the creation of antimicrobial agents of a new generation, therefore, the study of methods for the synthesis of metal nanoparticles, their physico-chemical and pharmacological properties seems promising. The review examines the mechanisms of antibiotic resistance formation in biofilm and possible ways to overcome them for nanoscale metal particles, describes the synthesis and mechanism of action of nanoparticles containing silver, copper and zinc cations, presents the results of studies evaluating the effect of metal nanoparticles on antibiotic sensitivity in gram-positive and gram-negative bacteria, as well as fungi in comparison with the action of known dosage forms. Cu²⁺ and Zn²⁺ cations have a pronounced antibacterial effect in cultures Staphylococcus aureus and Pseudomonas aeruginosa. Ag⁺ cations showed the greatest efficacy against S. aureus, Escherichia coli, Klebsiella pneumoniae and Candida albicans.

Potential nonameric epitopes of CD8⁺ T lymphocytes were selected from the composition of structural, accessory, and non-structural proteins of SARS-CoV-2 virus (13 peptides) and a 15-mer epitope of CD4⁺ T lymphocytes, from the S-protein, based on the analysis of publications on genome-wide immunoinformatic analysis of T-cell epitopes of the virus (Wuhan strain), as well as a number of clinical studies of immunodominant epitopes among patients recovering from COVID-19 disease. The peptides were synthesized and five compositions of 6–7 peptides were included in liposomes from egg phosphatidylcholine and cholesterol (~200 nm size) obtained by extrusion. After double subcutaneous immunization of conventional mice, activation of cellular immunity was assessed by the level of cytokine synthesis by splenocytes in vitro in response to stimulation with relevant peptide compositions. Liposomal formulation exhibiting the best result in terms of the formation of specific cellular immunity in response to vaccination was selected for further experiments. Evaluation of the protective efficacy of this formulation in an infectious mouse model showed a positive trend in the frequency of occurrence of hyaline-like membranes in the lumen of the alveoli, as well as a somewhat lower severity of microcirculatory disorders. The latter circumstance can potentially help reduce the severity of the disease and prevent its adverse outcomes. A method to produce liposome preparations with peptide compositions for long-term storage is under development.

5-α-Reductase (5-AR) inhibitors are considered the most effective drugs in the treatment of proliferative processes in prostate adenoma. These include two synthetic azasteroids – finasteride and dutasteride, which cause side effects in conditions of long-term course therapy which form the disorders of sexual function in men. We propose 3-meta-pyridine-1,2,4-oxadiazole derivative of deoxycholic acid as prototype of low-toxic 5-AR inhibitors. It has been shown that the new agent is able to penetrate the 5-AR binding site through the formation of covalent adducts with NADP-H, like finasteride. At the same time, both ligands have comparable with the target binding energy values (–20 and –15 kcal/mol, respectively, for finasteride and target compound). In experiments on testosterone and sulpiride models of BPH, we have found that intragastric administration of DCA derivative at a dose of 20 mg/kg and finasteride at a dose of 10 mg/kg has a similar prostatoprotective effect by reducing proliferative processes in the glandular epithelium and prostate stroma of rats. The new agent is less toxic than finasteride: the LD₅₀ value in mice is >1500 mg/kg versus 1060 mg/kg in finasteride. Based on the results obtained, the 3-meta-pyridine-1,2,4-oxadiazole derivative of deoxycholic acid can be considered as a promising candidate for preclinical testing.