Senescence — cellular aging — is a special form of cell death, characterized by the cell’s irreversible loss of its proliferation potential and the development of resistance to apoptosis. Senescence is based on the attrition (shortening) of telomeres that occurs with each subsequent cell division, which ultimately leads to sustained DNA damage and subsequent activation of the cellular aging program. Senescent cells have a unique so-called senescence-associated secretory phenotype (SASP), i.e. the ability of aging cells to secrete into the extracellular environment a large number of pathogenic factors that act paracrine on undamaged cells and transfer them to a state of senescence. The literature review examines the known mechanisms responsible for the formation of various types of senescence, describes the features of senescence-related cardiac damage, and provides a detailed description of biologically active compounds and drugs with senolytic (apoptosis activators) and/or senostatic (SASP inhibitors) activity.

Relevance. Despite the fact that the pharmacological effect of drugs is well known and studied, unfortunately, it is impossible to predict the development of drug allergies, since the individual characteristics of the body's reactivity are of great importance in its development. The goal is to analyze the clinical situation of the development of drug allergies to illustrate the importance of the role of biotransformation and the chemical structure of drugs in its diagnosis.

Methods. The study was carried out on the patient after signing informed consent and included anamnesis, physical examination, skin prick tests with inhalant allergens, installation of a peripheral venous catheter, and provocative testing.

Results. prick tests with: 0.9 % NaCl solution (negative control), histamine solution (10 mg/ml) (positive control), amoxicillin + clavulanic acid (100 mg + 20 mg), ampicillin (100 mg/ml), cephalexin (50 mg/ml) — positive results, ceftazidime (20 mg/ml), clarithromycin (20 mg/ml) — negative results; intravenous tests with: 0.9 % NaCl solution (negative control), ceftazidime (2 mg/ml), clarithromycin (0.01 mg/ml) — negative results; oral PDT with cefuroxime (cumulative dose — 250 mg), josamycin (cumulative dose — 1000 mg) — negative results. As a result of skin testing, LA for the amino group of beta-lactams was confirmed; No data have been obtained for LA on the beta-lactam ring, clavulanic acid, or macrolides.

Previously, based on the β-turn of the fourth loop of the brain-derived neurotrophic factor, we obtained GSB-106 (bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide), that has pronounced neuroprotective and antidepressant activities in doses of 0.1–10 mg/kg with intraperitoneal and oral administration. For identifying the stereospecificity of the antidepressant-like effect of GSB-106, in this work its enantiomer (GSB-106DD) was synthesized and its antidepressant-like properties were studied. It was shown that GSB-106DD has no antidepressant-like effect when administered intraperitoneally in doses of 0.1 and 1.0 mg/kg. It can be assumed that the stereospecificity of the antidepressant-like activity of GSB-106 dependence on the configuration of amino acid moieties.

Relevance. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive and behavioral disorders. The drugs currently used in clinical practice can slow drug development but are usually associated with lifelong use because of the complexity of pathogenesis. Therefore, to correct AD, a similar approach is needed, which can be CAPAH (2-chloroethoxy-para-N-dimethylaminophenylphosphorylacetohydrazide), a potential drug with a multitarget mechanism of action.

Objective. Investigate the effects of CAPAH, memantine, and rivastigmine on the behavior and cognitive functions of rats.

Materials and methods. This study identified CAPAH as a potential drug with a multitarget mechanism of action. The comparator drugs were memantine (10 mg/kg) and rivastigmine (2 mg/kg). Animals were divided into 4 groups (control, CAPAH, memantine, rivastigmine), 8 males and 9 females each receiving subcutaneous injections of the respective agents for 30 days. Subsequently, their cognitive functions and behavior were studied on the «Morris Water Maze» (MWM) and «Extrapolation deliverance» (EPI) ("Open Science", Russia) with the help of the "EthovisionXT" program (Noldus, the Netherlands). Statistical processing was performed using one-way ANOVA in the GraphPadPrism 8.0.1 program.

Results. In case “MWM” CAPAH increased the swimming time in the platform zone by 1.8 and 1.5 times (p < 0.05) compared with the control in the male and female groups, respectively, exceeding the parameters of the comparison drug. In case "EPI" test, the administration of CAPAH to males reduced the number of jumps by 4.4 times (p < 0.05) and increased the latent period of motor activity by 2.3 times (p < 0.05) compared with the control group, but did not affect these aspects in females.

Conclusion. Administration of CAPAH improves cognitive function and memory in healthy male and female rats and reduces anxiety in male rats, whereas it outperforms the effects of memantine and rivastigmine.

The aim of this study was to evaluate the effect of original tyrosine kinase TrkA antagonist GK-1 on tumor growth, median lifespan and hematological parameters in experiment on female mice C57Bl/6 with mammary gland adenocarcinoma Ca755. 14-day intraperitoneal administration of GK-1 at a dose of 10 mg/kg resulted in a significant tumor growth inhibition (TGI) on the 9th, 15th, and 21st day of adenocarcinoma Ca755 development. TGI on the 21st day was 60 %. Administration of GK-1 at doses of 1 mg/kg and 10 mg/kg significantly increased median lifespan of experimental animals by 53 % and 47% respectively. Median lifespan was calculated using the Kaplan-Meier survival analysis. Median lifespan of active control group was 18 days, in groups that received GK-1 at doses of 1 mg/kg and 10 mg/kg median lifespan was 30 days. Hematological parameters of experimental animals were not altered by administration of GK-1. Double injection of the doxorubicin on the 2nd and the 4th day of tumor development at dose of 4 mg/kg resulted in TGI by 73% on the 21st day of experiment, increase in lifespan was 58% and median lifespan was 31 days. Our data show that further investigation of the antitumor activity of GK-1 may bring promising results.

Relevance. Cyclo-L-prolylglycine (CPG), discovered as an endogenous compound in the central nervous system, is involved in the formation of a reaction to emotional stress in rodents with a pronounced fear reaction and has an analgesic effect in vivo. However, data on the dependence of the antinociceptive effect of CPG on genotype are currently unavailable.

Objective. To evaluate the effect of exogenous CPG on the thresholds of acute pain response and morphine–induced analgesia in mice with an opposite reaction to emotional stress.

Methods. The experiments were performed on inbred male mice BALB/c (n = 207) and C57Bl/6 (n = 204). To assess the analgesic effect of CPG, the "writhing test" (0.75 % acetic acid solution, i.p.) and the "hot plate" (55 ± 0.5 °C).

Results. CPG at doses of 1, 2, and 4 mg/kg, i.p., significantly reduced the number of writhings in BALB/c and C57Bl/6 mice, whereas the effect of CPG was comparable to that of diclofenac at a dose of 10 mg/kg per os. During thermal stimulation, interline differences in the antinociceptive effect of CPG were revealed, which was more pronounced at a maximum effective dose of 2 mg/kg in "stress-non-resistant" BALB/c mice compared with C57Bl/6 mice. CPG at a dose of 2 mg/kg weakened morphine-induced analgesia during thermal stimulation in BALB/c and C57Bl/6 mice for 30, 60, and 90 minutes of observation.

Conclusion. The established dependence of the central antinociceptive effect of CPGs on genotype is important in the context of biomedical research on pain detection and control using pharmacological correctors.

(13.02.1931 — 22.09.2024)