In the course of improving the pilot-scale technology for manufacturing a liposomal substance of biologically active substances (BAS) isolated from the gland secretion of musk deer, the authors established operations and modes to ensure the production of liposomes with the specified stability parameters (shape, hydrodynamic diameter, charge, and polydispersity index) in full compliance with GMP requirements and the maximum inclusion of BAS from deer musk into liposomes with the preservation of the initial biological activity of its most important components. The established modes provide for a two-fold reduction in the technological cycle duration with the substance yield of more than 90%. The improved technology ensures the production of at least 80% of liposomes with the main liposome fraction in experimental samples in the range of 200+50 nm and 250+100 nm for the final substance (before lyophilization) and after its recovery (rehydration), respectively, which is considered optimal for transmucosal drug administration. The polydispersity index was less than 0.3, and the zeta (Z)-potential was less than -35 mV. The quality indicators characterizing the dispersity of the resulting liposomal substance were studied by conventional analytical methods (dynamic light scattering, electron microscopy). On the basis of the obtained results, a draft specification for a liposomal substance (powder) containing a complex of BAS isolated from deer musk was finalized.

In this study, we investigated the heart rate variability (HRV) of awake male and female Wistar rats using a non-invasive technique of electrocardiosignal recording. We established significant differences in the value of HRV indicators in groups of animals differing in spectral parameters (total power of the spectrum (TP), high-(HF) and low-frequency (LF) components of the spectrum). The following HRV indicators were shown to be highly informative: statistical (SDNN — the standard deviation of the complete array of RR intervals, RMSSD — the square root of the standard deviations of successive RR intervals, CV — the coefficient of variation) and spectral (TP, HF, LF, VLF is a very low–frequency component of the HRV spectrum, LF/HF is the vagosympathetic interaction index, IC — centralization index). The data obtained should be taken into account when advancing the existing methodology for studying the pathogenetic mechanisms of HRV changes and determining the prognostic value of these HRV parameters.

Behavioral phenotyping of rodents using neurodegeneration models has received much research attention over the past three decades. However, some difficulties still exist in understanding the variability of behavior caused by genetic, environmental, and biological factors, human intervention and poorly standardized experimental protocols, which can negatively affect the interpretation of the results obtained. In this article, we discuss factors that have a negative impact on the performance of behavioral testing of laboratory animals, modern approaches to overcome them, as well as new technologies, such as visualization of neuronal activity using ion-dependent fluorescent indicators (optogenetics), which expand the boundaries of the study of neuronal networks responsible for behavior by evaluating neuronal function at both the cellular and population levels. Ultimately, this will increase the reliability of the results obtained and provide an opportunity to take a fresh look at the ethological paradigms of a particular transgenic mouse model.

This work presents research studies into the comparability of Tigerase® (inhalation solution, manufactured by JSC «GENERIUM», Russia) to the reference drug Pulmozim® (inhalation solution, manufactured by Hoffmann-La Roche Ltd., Switzerland). Both drugs contain human recombinant deoxyribonuclease I – dornase alpha as an active substance and are intended for the treatment of cystic fibrosis with pulmonary manifestations (cystic fibrosis). The specific enzymatic activity of dornase alpha was studied in vitro and ex vivo using samples of patients’ purulent sputum. The pharmacokinetic parameters of the drugs were studied in the blood serum, bronchi and lungs. The main physiological parameters (body weight and temperature, the state of the cardiovascular, respiratory, excretory systems, hematological and biochemical blood parameters, pathomorphological changes in the internal organs, including the state of the cornea of the eyes, mortality rates) were assessed in comparative studies of subchronic toxicity in juvenile and sexually mature rats using 28-day inhalation in doses of 0.2 mg/kg to sexually mature and 0.26 mg/kg to juvenile animals (the dose was 6 times higher than the recommended dose for clinical use). It was concluded that the drugs were comparable in terms of their enzymatic, mucolytic (secretolytic) DNase activity, safety profile, and basic pharmacokinetic parameters.

In this work, we studied the pharmacological activity of a newly-synthesized compound 4-(3,4- dibromothiophenylcarbonyl)-10-(2-ethoxyacetyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,0,03,11,05,9]dodecane (M3) using somatogenic pain models of various genesis (thermal and visceral pain, mechanical compression of a paw). The compound showed a high antinociceptive efficacy, comparable to or exceeding that of tramadol. It was shown that the new molecule from the class of hexaazaisowurtzitane effectively blocks nociceptive reactions at the supraspinal and peripheral levels of pain sensitivity organization. The results obtained confirm the possibility of creating new pharmacologically active molecules based on the high-energy substance of hexaazaisowurtzitane, which is a priority in domestic pharmaceutical production.

We studied the pharmacokinetics, tissue availability and metabolism of fluorothiazinon, a novel antivirulence drug, in mouse blood, liver, kidneys and lungs by administering the substance intragastrically at dose of 400 mg/kg. Fluorothiazinon was established to exhibit good tissue availability and long residential time. This drug is metabolized mainly by glucuronidation.

The adrenal gland is one of the first organs to respond to external influences. Cortisol, with its important properties affecting the immune system, proliferation and apoptosis in various tissues, is a significant indicator of such a pathological process as malignant growth. Selenium is a powerful antioxidant having an immunomodulatory action and exhibiting anticarcinogenic effects. In this paper, we investigate adrenal morphofunctional changes under experimental carcinogenesis against the background of urethane and selenium administration by determining blood cortisol concentrations and studying the aggregate morphometric index of adrenal glands. The study revealed that carcinogen introduction imitates the adaptation syndrome stages in the organism and is accompanied by changes in the cortisol level and aggregate morphometric index. Maximal values of the studied parameters were detected after 1 month of exposure to carcinogen, which indicated the development of the alarm phase. A further decrease in the indices after 2 and 3 months down to the intact level indicates the development of the resistance stage. A sharp decrease in the indices after 6 months shows the exhaustion stage. An isolated course introduction of selenium leads to a reliable decrease in the aggregate morphometric index practically in all terms that indicates the stress-relieving influence of the microelement. The combined effects of selenium and carcinogen revealed a dropout of the alarm stage, but rapid elimination of the micronutrient from the body could not prevent the development of the exhaustion phase after 6 months.