The lack of adequate methods for identifying the psychotropic properties of various chemical compounds has dramatically hindered the search for new psychoactive substances. The role of β- and γ-rhythms of brain electrograms in the elucidation of mental processes is poorly investigated. On the other hand, even the isolation of the main acting components of psychotropic substances in animal studies for extrapolating to humans presents a challenge. This article is devoted to the aforementioned issues. This research was performed on cats with electrodes that had been stereotactically implanted in different parts of the brain. Since commercial electroencephalographs were not suitable for our purposes, specialized microchip devices were designed at the Scientific Centre for Biomedical Technologies (SCBMT), Russia. As a mathematical instrument, the fast Fourier transform (FFT) algorithm with a window discrete Fourier transform based on Hamming functions was implemented.

Normalization of the FFT-transformed brain electrograms recorded under the influence of doxylamine, xylazine, caffeine, sertraline, phenotropyl was carried out. The suitability of the proposed approach for assessing the pharmacodynamics of the studied substances, which are characterized by a phase character coinciding with the main pharmacokinetic points, is demonstrated. The β- and γ- rhythms are shown to be the most important indicators of the effects of psychotropic substances. 

The Siberian musk deer (Moschus Moschiferus) is a deer-like animal. The substance that is secreted by sexually mature males is highly valued worldwide for its perceived pharmaceutical and perfumery properties. However, there is a lack of comprehensive information regarding the component composition of the musk and tissues of this species. A complex study of the protein composition of biologically active components in the preputial gland secretion of the Siberian musk deer was performed using the methods of size-exclusion chromatography and peptide mapping. The latter method was realized using high-performance liquid chromatography tandem mass-spectrometric detection following fermentation by trypsin. These are effective methods for generating vast amounts of data that can facilitate research on the Siberian musk deer. A molecular weight distribution characteristic of the investigated extracts was established. Optimal conditions for the extraction, chromatographic separation and relative quantitative determination of the main musk components were determined. Detailed information on the most significant (major and minor) protein components in the studied samples is presented in accordance with the algorithm of the Spectrum Mill MS Proteomics Workbench search program and the UniProt protein database. Protein profiling data was clustered according to their molecular and biological functions. The identified proteins were assessed in terms of possible mechanisms of biological action and targets, which can be affected by the protein components of the objects under the study. A conclusion is made about a multicomponent composition of the Siberian musk deer preputial gland secretion. Marker protein components in the studied extracts are suggested. Possible links between the identified proteins and biological effects are outlined.

Type 2 diabetes is a major metabolic disorder that leads over time to serious complications. Tight glycemic control is considered to be an essential strategy for preventing diabetes-related complications. However, randomized clinical trials accrued over last decades have demonstrated no significant benefit of glycemic control in terms of decreasing micro- and macrovascular complications, except for a 15% reduction in the risk of nonfatal myocardial infarction. Emerging evidence suggests that vascular complications of diabetes correlate with a dysregulation of the angiogenic response governed by hypoxia-inducible transcription factor 1 (HIF-1) and succinate receptor 1 (SUCNR1). Type 2 diabetes affects HIF-1 activity at several levels, including HIF-1α subunit transcription, mRNA translation into the HIF-1α protein, degradation of the HIF-1α protein and binding of the HIF-1α protein to co-activators, which eventually results in a dysregulation of the adaptive angiogenic response to hypoxia. Both hyperglycemia and insulin resistance are involved in these impairments. Diabetes affects SUCNR1 signaling in a tissue-specific manner. A cross-talk between HIF-1 and SUCNR1 signaling explains, at least partially, paradoxical tissue-specific changes in the angiogenesis in diabetic microvascular complications, an excessive formation of blood vessels in the retina and a deficiency in small blood vessels in peripheral tissues, such as the skin. As a conclusion, targeting HIF-1 and SUCNR1 signaling seems to represent a novel promising approach for the prevention and treatment of diabetes-related vascular complications.

In this study, the neuroprotective activity of alpha-2 adrenergic receptor agonist (6-oxo-1-phenyl-2- (phenylamino)-1,6-dihydropyrimidine-4-sodium olate) (mafedine) at the doses of 2.5 and 5 mg/kg was estimated by modelling a traumatic brain injury in rats. The effect of mafedine on rat behaviour and their motor activity was also assessed following such conventional tests as limb placing, open field, elevated plus maze, cylinder, beam walking and staircase. A morphological analysis of the amount of brain damage in the experimental animals was carried out on the 7th day following injury. In addition, the protein composition of the cerebrospinal fluid was investigated. The effects of mafedine were assessed in a comparative perspective with clonidine. The administration of mafedine at a dose of 2.5 mg/kg to rats after brain trauma is shown to lead to an increase in their overall motor activity and an improvement of fore- and hindlimb motor function without any negative behavioural effects. The studied compound is established to have no effect on the protein composition of the cerebrospinal fluid; however, it decreased the overall size of the damaged area by the 7th day after injury. Moreover, mafedine is shown to decrease the intensity of inflammation processes in the damaged area in rats with traumatic brain injuries. In comparison with clonidine, mafedine demonstrated a higher efficacy in most of the tests. Yohimbine abolished most of the beneficial effects of mafedine; therefore, the positive effects of mafedine are likely to be related to its action on alpha-2 adrenergic receptors.

Dabigatran is a relatively new direct and reversible thrombin inhibitor characterized by a low molecular weight. Dabigatran is included in the latest clinical guidelines as part of anticoagulant therapy for patients with non-valvular atrial fibrillation and an involved high risk of bleeding. Dabigatran can be used in the prevention of venous thromboembolic events in patients who have undergone total knee arthroplasty. However, there is a large interindividual variability in the therapeutic effect of dabigatran, which is reflected in its safety profile. Among the most studied genetic determinants of dabigatran safety has so far been CES1 gene SNP rs2244613. However, the racial and ethnic homogeneity among human subjects participating in NOAC clinical trials creates a problem of an adequate extrapolation of their results on the representatives of other ethnic population groups. In this regard, the aim of this study was to investigate the prevalence of the CES1 gene rs2244613 polymorphism among 12 different ethnic groups residing in Russia to provide a basis for future clinical studies concerned with the investigation of the genetic determinants of dabigatran safety.

Wistar rats with monocrotaline-induced pulmonary hypertension were investigated using bioelectrical impedance analysis. Monocrotaline-treated rats compared to sham-treated rats demonstrated significantly lower absolute values of such components of bioelectrical impedance as the reactive resistance (32.9±4.9 Ohm vs. 39.3±5.3 Ohm in the sham control, ρ=0.023) and the phase angle (7.1±0.6º vs. 8.2±0.6º in the sham control, ρ=0.002). The active resistance of the bioelectrical impedance of the lung showed a downward trend in rats having undergone monocrotaline treatment (with a significantly lower value at 150 kHz: 398.9±240.2 Ohm vs. 647.2±270.5 Ohm in the sham control, ρ=0.043). A decrease in the whole-body and pulmonary bioimpedance values under our experimental conditions is shown to result from accumulation of the whole-body or intrathoracic fluid and physiological changes in the tissues during the development of pulmonary arterial hypertension.

This study was aimed at estimating the erythrocyte electrophoretic mobility by investigating the effect of exogenous reactive oxygen species and nitric oxide on the blood specimens and organism of healthy rats. In the first (in vitro) experimental stage, blood specimens taken from 15 healthy people were analyzed. Each specimen was divided into 5 portions (5 ml.). One portion was used a as control (without any manipulations), with the rest being treated with different gas mixtures, including an ozone-oxygen mixture with the ozone dose of 60 mg/l; singlet oxygen and an NO-containing gas mixture with 20 and 100 ppm of NO. The second (in vivo) experimental stage was performed on 40 male Wistar rats divided into 7 groups. The first group (n=10) was considered to be a control group. Animals in the second group (n=5) were given daily inhalations with the ozone-oxygen mixture. Rats in the third and fourth groups (n=5 in each) received inhalations with singlet oxygen (under the power of the generator of 50 and 100%, respectively). Animals in the fifth, sixth and eleventh groups (n=5 in each) were given daily inhalations with nitric oxide (under the NO concentration of 20, 50 and 100 ppm, respectively). Our study has demonstrated the biosystems under study to exhibit identical response patterns both to direct (blood treatment) and indirect (inhalations) action of the investigated substances. Thus, the ozone-oxygen mixture and high doses of nitric oxide (100 ppm) are shown to result in a decrease in the electrophoretic mobility of erythrocytes. Alternatively, both low NO doses (20 ppm) and singlet oxygen stabilize erythrocyte membranes by elevating the antioxidant potential of the biofluid. These effects contribute to the activation of erythrocyte electrokinetic properties in vivo experiments (after a course of inhalations).