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Vol 16, No 1 (2020)
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NEW BIOMEDICAL TECHNOLOGIES

12-27 601
Abstract

The pharmacological modulation and analysis of psychopathological processes in animals is a research method providing a possibility to study similar processes in humans. Methods and approaches based on the principles of the pharmacological modulation of systemic behaviour and normalization of FFT-transformed functions of the brain electrograms allow identification of the quantitative parameters of intracentral relations, cognitive functions and fundamental mechanisms for evaluating the effects of neuropsychoactive drugs in the whole brain in vivo.

The work was carried out on cats with stereotactically implanted electrodes in the brain. Subtherapeutic doses of ketamine, amphetamine and nakom were used to model obsessive-compulsive disorders and cognitive changes. The pharmacological modulation of the animals’ behaviour was evaluated by the effect on the frontal brain and hippocampus. The activation of γ-rhythms (from 35 to 60 Hz) was considered as an improvement in cognitive functions. Ketamine exhibited a more pronounced depressing effect on the proreal gyrus, with its activating effects being close to amphetamine across the frequency ranges of 11–15 and 32–35 Hz. Ketamine had a pronounced activating effect on the gyrus suprasilvium anterior and the hippocampus. Ketamin and nakom demonstrated similar effects in the area of the proreal gyrus, most clearly manifested at frequencies of about 9–15 and 35–36 Hz. The action of nakom was characterized by the episodes of activation in a higher frequency range of 40–55 Hz as well. In the area of the gyrus suprasilvium anterior, the effects of nakom were similar to those of ketamine; however, these substances exhibited different effects in the range of 9–11 Hz. Compared to amphetamine, nakom showed no depressing episodes over the high-frequency range of 55–65 Hz. In the hippocampus, nakom demonstrated an activating effect exceeding that of ketamine by 100–150%. It was shown that neuroimaging of the normalized functions of electrograms during the pharmacological modulation of obsessive-compulsive and cognitive disorders reflects the most striking transformations in high-frequency brain rhythms, primarily related to the γ-range.

Comparison of the results of pharmacomodulation with the pharmacodynamic and pharmacokinetic parameters of drugs when modelling psychopathologies in animals helps researchers in their search for approaches to modifying animal behaviour and extrapolating them to humans.

28-41 680
Abstract

The development of new methods for the conservation of biological raw materials, which can be used in the production of active pharmaceutical substances, is increasingly attracting research attention. This article presents the results of comparative studies into the effectiveness of biological conservation using cryopreservation, electron beam treatment and the lactoperoxidase system. Electron beam technologies demonstrated a pronounced antimicrobial effect in the treatment of musk deer extract and other biologically active substances. A recommendation was formulated to treat musk extract with electron-beam radiation at an absorbed dose of 6 kGy (9.5 MeV) following cryopreservation at –25°C over the period of 1 year. The data obtained using the method of accelerated testing allows an extended shelf life of up to 48 months to be predicted.

For the first time, the main indicators of the quality and safety of musk deer extract as a potential raw material for the production of active pharmaceutical substances and medicinal animal raw materials were determined. A standard for the quality of musk deer extract as a raw material, as well as an experimental-industrial regulation for its preparation and preservation, were developed.

METHODS OF BIOMEDICAL RESEARCHES

42-55 636
Abstract
This article sets out to evaluate the expression of the NFE2L2 gene (Nuclear Factor, Erythroid 2 Like 2) when adapting to physical loads (achieving oxidative stress) in mini pigs. The conducted experiment reproduced natural conditions of oxidative stress in laboratory animals (16 mini pigs). Sports training is the most optimal and natural model of enhanced dissimilation as a cause of oxidative stress. The results of the study indicate that the NFE2L2 gene encoding the Nrf2 transcription factor is actively expressed in response to oxidative stress in animal cells. The NFE2L2 gene can serve as an evaluation criterion for molecular genetic studies of performance and endurance for individual selection by groups. Such evaluation can be recommended for studies aimed at revealing the effects of pharmacological drugs on the regenerative properties of the body, with the possible choice of pharmaceutical ingredients and extrapolation from animal studies to humans. An important practical result and an indicator of adaptation is increased performance. The possibility of affecting the expression of the NFE2L2 gene paves the way to enhancing the body’s ability to adapt to oxygen starvation.
56-64 638
Abstract
Acute experiments on anesthetized adult rats breathing atmospheric air of constant gas composition were performed in order to assess changes in the parameters of the spirogram and the bioelectric activity of the diaphragm in response to microinjections of GABAA -agonist muscimol into the retrotrapezoid nucleus/ parafacial respiratory group (RTN/pFRG) region. Microinjections of muscimol into RTN had an inhibitory effect on respiration, which developed sufficiently quickly. The rats demonstrated a decrease in the respiratory minute volume and the inspiratory flow rate, which occurred primarily due to a change in the temporal parameters of respiration, including its reduced frequency. The reactions of external respiration corresponded to а significant increase in the duration of inspiratory bursts and a less pronounced decrease in the amplitude of oscillations on the electromyogram (EMG) of the diaphragm. Microinjections of muscimol into pFRG also caused respiratory depression; however, a decrease in the lung ventilation and inspiratory flow rate was associated predominantly with a decrease in the tidal volume and a slight prolongation of inspiration and expiration. In this case, the diaphragm EMG showed a pronounced decrease in the oscillation amplitude in combination with a slight increase in the duration of inspiratory bursts and interburst intervals. The obtained experimental data indicate that GABAA -receptors contribute to the activity of the RTN/pFRG region and constitute an important link in the central mechanisms of respiratory control in mammals breathing atmospheric air of unchanged gas composition. Thus, GABAA -receptors of RTN make a significant contribution to regulation of the phase structure of the respiratory cycle and the frequency of diaphragmatic inspiratory bursts, while GABAA -receptors of pFRG are more involved in the inhibitory modulation of the volumetric parameters of external respiration and the amplitude of diaphragmatic activity oscillations.

RELEVANT AND ALTERNATIVE BIOMODELLING

65-81 477
Abstract
Use of non-steroidal anti-inflammatory drugs (NSAIDs) is considered to be a factor in the development of gastrointestinal tract (GIT) diseases. Thus, enterocolitis is a frequent complication of NSAIDs. Experimental modelling of GIT diseases in laboratory animals, which describes the origin and mechanism of the corresponding disease in humans with maximal precision, is an urgent problem of modern medicine. This paper presents the results of comparative experimental biomodelling of NSAID-induced enterocolitis in laboratory rats. It was found that the intragastric administration of acetylsalicylic acid resulted mainly in stomach damage. The introduction of dexketoprofen — both orally and intramuscularly — causes erosive and ulcerative lesions of the stomach and intestines. The type of damage showed no correlation with the type of administration. For the first time, the results of enterocolitis biomodelling using dexketoprofen are presented.
82-88 1305
Abstract
This paper presents the results of a comparative analysis of behavioural indicators in rats with modelled genetic dopamine transporter (DAT) deficiency. Two groups of laboratory animals — heterozygous DAT knockout rats (DAT-HET) and Wistar rats — underwent the “Open field”, “Elevated plus maze” and “Extrapolation deliverance” tests. It is established that DAT-HET rats are characterized by an increased locomotor and research activity along with reduced anxiety and cognitive impairment compared to Wistar rats used as control.
89-98 749
Abstract
The state of cognitive functions in cerebrovascular disorders is one of the most urgent healthcare problems. Recently obtained data convincingly indicate the participation of astrocytes in the formation of cognitive functions of the brain. We conducted a study on 88 Wistar rats. Following the results of testing the rats in a Morris water maze, all animals were divided into two subgroups: those with a high (HLA) and low (LLA) level of spatial situational learning abilities in the Morris water maze test. The animals in the experimental group (48 animals) underwent bilateral ligation of both carotid arteries. The animals were removed from the experiment on the 21st, 60th and 90th day after the operation. Glial fibrillar acidic protein (GFAP), a marker of mature astrocytes, was detected using primary polyclonal rabbit antibodies on histological sections of the precentral gyrus of the brain. Data were obtained on a more pronounced decrease in the numerical density of astrocyte bodies and the number of astrocyte main processes in HLA and LLA animals in earlier (on the 21st day) and later (on the 90th day) stages of the experiment, respectively. The growth of the area occupied by the astrocyte processes occurred earlier in HLA animals (on the 60th day after the simulation) compared to LLA animals (on the 90th day after the simulation). The conducted factor analysis confirmed the presence of two factors associated with the dynamics of the studied parameters. The conclusion is made about alternative variants of changes in the studied groups. The HLA subgroup predominantly demonstrated changes of an alterational character in earlier experimental stages, while adaptive changes were observed in the later stages of the experiment. Conversely, in the LLA subgroup, alterations and adaptations occurred in later and earlier experimental stages, respectively.


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ISSN 2074-5982 (Print)
ISSN 2713-0428 (Online)