The accumulation of scientific data in the field of pharmacogenetics requires the creation of adequate biomodels to reflect the immunogenetic characteristics of different population groups. We have obtained the ancestors of a new humanized transgenic mouse line carrying the human HLA-A*02:01:01:01 gene, which is characteristic of the Russian population. The new biomodels was created using the pronuclei microinjection method of a linearized fragment of genetically engineered DNA construct into zygotes, followed by overnight cultivation in CO₂ incubator and transfer of potentially modified embryos at the stage of two 4.0 blastomere to pseudopregnant foster females. A total of 91 living offspring were obtained and analyzed, with 18 pups carrying the target genome modification. The resulting transgenic animals were used to create a new line of mouse biomodels carrying the human HLA-A*02:01:01:01 gene.

The content of biologically active substances in the gland secretion of Siberian musk deer obtained in vivo was studied by gas chromatography-mass spectrometry using derivatization by silylation. The musk chemical composition of animals held under natural conditions and in captivity was compared. The food spectrum of Siberian musk deer was found to affect the content of biologically active components in the musk, primarily of androsteroid substances. The results of evaluating the content of musk components exhibiting the most pronounced biological effects are presented. An increase in the diversity of food spectrum was established to improve the qualitative composition of biologically active substances in the musk obtained from the adult males of Siberian musk deer held in captivity.

Extreme physical exertion (work to failure) was simulated in untrained mini pigs. The results of complete blood tests, lactate measurements and clinical urine analysis revealed variations in the basic parameters of animals similar to those observed in people after extreme exertion.

Liposomal forms of preparations containing biologically active substances extracted from renewable sources of raw materials of plant and animal origin are attracting considerable research and practical interest. Liposomal drugs are efficiently absorbed in the gastrointestinal tract, retaining their structure while passing through the liver and entering the target cell. This allows either smaller amounts of the active substance to be used without losing bioavailability or its effective concentration to be increased.

Deer musk liposomes administered at doses equivalent to 300, 1500 and 3000 mg/person/day were found to exhibit an actoprotective effect, whose intensity at the minimum dose (300 mg) is comparable to that achieved at the maximum dose (3000 mg).

A course daily transpalatal administration of musk deer liposomes for 14 days was established to statistically significantly improve the indices of physical endurance and working capacity of rats in forced swimming tests under load, kineso-hydrodynamic models of swimming and rotarod performance tests. The observed increase in indicators persisted for another seven days after the cessation of administration, which indicates pharmacological cumulation. The tested drug reduces locomotor and orienting-exploratory activity, at the same time as exhibiting no adverse effect on the psycho-emotional and intoxication status of animals. In addition, no local irritant action on the route of administration was noted. The drug is assigned to toxicity class VI (relatively harmless).

The effect of nifedipine, a calcium channel blocker (CCB), at a dose of 7.5 mg/kg on the energy metabolism of rabbit cardiomyocytes was evaluated in a vibration-mediated model of cellular hypoxia (56 sessions of vibration 44 Hz, amplitude 0.5 mm). The energy metabolism of native heart mitochondria in a 30% tissue homogenate was assessed using a polarographic method, by recording the rate of oxygen uptake by mitochondria at 37°C in 1 ml of a saline incubation medium, equilibrated with atmospheric oxygen. In the animals exposed to vibration against the background of CCB, the rate of endogenous respiration (Ve) remained at the level of intact animals, with the amytal sensitivity increasing by 39% (p<0.05) and the malonate sensitivity decreasing by 40% (p<0.05). The malate oxidase activity at rest increased, and hyperactivation of the endogenous succinic acid oxidation system decreased as compared to the indices of the animals exposed to vibration without pharmacological protection. The observed results indicate the cardioprotective effect of nifedipine, which prevented the development of cardiomyocyte necrosis.

Mountain ash (Sorbus aucuparia L.) is a prominent representative of phenolic medicinal plants. A widespread and cultivated plant, it has a sufficient raw material base not only of fruits, but also of other parts of the plant (leaves, flowers); it is a promising source of biologically active complexes for the development of new medical drugs. In the work, the content of the main groups of phenolic compounds in plant extracts from fruits, leaves and flowers of S. aucuparia L. was determined. Extracts were obtained using the original technology with acidified 95% ethanol. The content of the sum of phenolic compounds was determined, as well as the content of anthocyanins, flavonoids, phenolic acids, tannins. The effect of these phenol-containing complexes on the development of transplanted tumors (Lewis lung carcinoma, lung cancer-67) and the effectiveness of cyclophosphane treatment were studied. It was revealed that the use of plant complexes leads to a significant inhibition of the development of metastases in the lungs, as well as an increase in the antitumor and anti-metastatic activity of cyclophosphane in combined treatment. The new data obtained are of interest for further study of these phenol-containing complexes in order to create drugs based on them to increase the effectiveness of chemotherapy for malignant neoplasms.

This paper studies the acute toxicity of an herbal extract of Astragalus vulpinus Willd. growing in the Astrakhan Oblast. Experiments were carried out on white nonlinear rats. The animals were divided into several groups (n = 6): the control group receiving intragastric distilled water and the experimental groups receiving intragastric extract of the Astragalus vulpinus extract once at doses of 100, 500, 1000, 2000, and 4000 mg/kg. On the first day after extract administration, the animals were under continuous observation. During the entire observation period for 14 days, the animals were monitored in terms of their general condition, body weight, food refusal, and coat appearance, as well as their response to sound, light, and tactile stimuli. The response to sound was evaluated by a sudden sharp knock on the cage and identification of the animal’s flinching. The response to light was assessed by shining light into the eye with a penlight to control eye lid closure. Tactile stimuli were evaluated by compressing the basal part of the tail. After removing the animals from the experiment, macroscopic examination of internal organs (brain, liver, spleen, heart, stomach) and hematological analysis of blood smears were performed. During the research, the LD₅₀ of the Astragalus vulpinus herbal extract under study was established. When the extract was administered at a dose of 4000 mg/kg, animal mortality was recorded (3 individuals died by the third day). In the remaining animals, a decrease in weight and leukocyte count was observed along with changes in the gastric mucosa. In terms of acute toxicity, the extract under study was found to belong to low-toxic substances with an LD₅₀ of 4000 mg/kg. However, its administration at a dose of 4000 mg/kg led to changes in leukocyte count and gastric mucosa. Therefore, the chronic toxicity of Astragalus vulpinus herbal extracts requires additional research.

This paper investigates the state of axodendritic (ADS) and axosomatic (ASS) synapses in orbitofrontal cortex (OFC) layers I-IV of adult white laboratory rats associated with balanced and low-protein food after acute sound exposure. Experiments were performed on 64 white non-linear sexually mature laboratory male rats weighing 180–230 g (eight intact, 56 experimental). After a continuous call with an intensity of 120 db for 120 seconds, 56 rats were divided into two groups: those receiving balanced (control – 28) and low-protein food (basic – 28). Each of these two groups was divided into two subgroups: stress-resistant (12 animals in each) and stress-unstable animals (16 animals in each). Water intake was unlimited. The animals were removed from the experiment on the 10th, 20th, 30th, and 40th day after sound exposure. Along with histological and immunohistochemical analysis, the samples of OFC layers I–IV were studied by transmission electron microscopy. Electron microscopic changes in the structure of ADS and ASS were found in all OFC layers. Violations of the fine structure of both the presynaptic and postsynaptic poles were noted. The maximum severity of ultrastructural changes was observed in the ADS of the surface (I, molecular), outer granular (II), pyramidal (III), and inner granular (IV) OFC layers. ASS disorganization was noted mainly in contacts, the postsynaptic pole of which was formed by the bodies of small pyramidal neurons of layer III, as well as pyramidal and stellate neurons of layer IV of the OFC. During all periods of observation, violations of fine organization were most pronounced in stress-unstable animals of the main experimental group, especially on the 10th and 20th day after exposure. Acute sound exposure initiates disturbances in the fine organization of axodendritic and axosomatic synapses in OFC layers I–IV of white laboratory rats. Focal destruction of a part of the noted synapses in rats with a low-protein diet after acute auditory stress is irreversible.

Paravertebral muscles play an important role in the development of deformities and degenerative diseases of the spine. The impact of posterior arthrodesis of the ileosacral articulation (sacrum-iliac joint) on the morphological characteristics of the m. sacrocaudalis (coccygeus) dorsalis lateralis of mongrel dogs was studied in animal experiments. Titanium cages were used, followed by stabilization with an external fixation device for 30 days. The advantages of posterior arthrodesis include a small incision, minimal blood loss, preservation of the integrity of most ligaments, and a short immobilization period. Nevertheless, when modeling arthrodesis experimentally in animals, fibrosis of the interstitial space and fatty infiltration in the adjacent muscle were revealed at the end of the experiment, which amounted to 240% and 310% of the intact parameters, respectively. In addition, fibrosis of the vessel membranes of the arterial link was observed. When performing surgical interventions on the spine, traumatization of the muscles should be reduced in order to minimize fibrogenesis and fatty involution of the paravertebral muscles.

Disruption of normal epigenetic reprogramming during the prenatal period under the influence of exogenous factors affects fetus development and adult phenotype formation. The mechanisms through which determinants, such as maternal alcohol intake, contribute to the formation of an alcohol-vulnerable phenotype later in life still remain unclear. In this paper, we suggest that alteration in the reinforcing properties of ethanol in prenatally alcohol-exposed subjects may be associated with transcriptional dysregulation of the brain opioid receptor genes. We compared voluntary alcohol intake and levels of mRNA coding for μ- (MOP) and κ-opioid (KOP) receptors in the mesolimbic areas of adult male offspring of the female Wistar rats having received 10% ethanol as the only source of liquid throughout pregnancy or water (control). We found that prenatally alcohol exposed rats had higher alcohol preference on PND60 (free-choice paradigm) and lower mRNA expression for both MOP and KOP in the midbrain compared to the control. This suggests a potential link between prenatal alcohol, dysfunction of the brain opiate system and adult vulnerability for alcohol use disorder.