No 4 (2019)
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НОВЫЕ БИОМЕДИЦИНСКИЕ ИТЕХНОЛОГИИ
E. M. Koloskova,
V. N. Karkischenko,
V. A. Yezersky,
N. V. Petrova,
S. V. Maksimenko,
E. L. Matveyenko
12-33 1292
Abstract
With the advent of endonuclease methods of genome editing, particularly CRISPR/Cas9, it has become possible to obtain genetically modified rabbits by microinjection of zygotes. These highly effective human disease models can be used for various purposes. The present review aims to consider modern achievements in the creation of rabbit biomodels of human diseases using the technologies of genetic editing. It is concluded that Russian laboratories should intensify research in the development of genetically modified rabbits that can be used for various biomedical studies and biomodelling.
NEW BIOMEDICAL TECHNOLOGIES
34-45 635
Abstract
For the first time, a liposomal form of a new original drug based on the Siberian musk deer preputial gland extract was obtained and characterized. An effective and scalable method of high-pressure homogenization was used for preparative extraction of liposomes from musk extracts. For the obtained liposomal product, such indicators as the quality of size distribution, homogeneity and the degree of inclusion of biologically active components were characterized using the methods of dynamic light scattering, transmission microscopy, preparative and analytical chromatography and chromatography-mass spectrometry. A homogeneous dispersion of musk liposomes with a uniform size distribution was obtained, with the maximum distribution values being achieved at 50 and 240 nm. The ζ-potential of the obtained nanoparticles of –35...–47 mV confirmed a high physicochemical stability of the developed liposomal dispersion. According to the gel filtration chromatography and mass spectrometry results, the degree of inclusion of the target musk extract components in the liposomes was 55–75% in terms of steroid and total protein values. The obtained quality indicators indicate that the developed liposomal composition of musk deer extracts can be used as a high-effective natural adaptogen.
NEW REGULATORY PEPTIDES
46-57 411
Abstract
This study was aimed at investigating the concentration of urinary catecholamines in female rats both in the normal state and during the development of age-dependent changes associated with estrous cycle disorders at early menopause stages. In addition, we set out to assess possible corrective and delayed effects of a combination of peptide extracts from reindeer endocrine glands (Rangifer tarandus) on both phase changes in the estrous cycle and age-related disorders in the functioning of the hypothalamus — adenohypophysis — gonadal system in experimental animals.
58-66 535
Abstract
In this study, experimental data on the biological action of glyproline peptides — Pro-Gly-Pro, Pro-ArgPro, Arg-Pro-Gly-Pro and Pro-Gly-Pro-Leu — on the processes of blood coagulation and lipid metabolism were obtained using animal models of metabolic syndrome. Under the conditions of increased blood clotting and hypercholesterolemia, the regulatory peptides under study were administered intranasally for 7 days once every 24 hours. 20 hours after the last peptide administration, thromboelastogram parameters confi rmed the restoration of the functional state of the coagulating and anticoagulant systems. In addition, a simultaneous positive shift in the parameters of lipid metabolism was observed. These changes lasted for 7 days following the withdrawal of the drugs. It is found that the biological action of the peptides under study consists in their simultaneous regulatory impact on the processes of hemostasis and lipid metabolism.
METHODS OF BIOMEDICAL RESEARCHES
67-81 3073
Abstract
Research laboratories in various countries are constantly endeavouring to improve the existing and to create new biological objects to simulate various human diseases. Immunodefi cient mice with transplanted human functional cells and tissues, as well as transgenic animals with the relevant human genes integrated in their genome — i. e. humanized mice — are increasingly used as test systems in biomedical studies. Humanized mouse models are constantly being improved to fi nd application in studies investigating human biological reactions and identifying the pathogenetic mechanisms behind a wide range of diseases, or as preclinical tools for medicine testing. In particular, such animals play an increasingly important role both in studies of human-specifi c infectious agents, cancer biology research and in the development of new antitumour agents. In addition, humanized mice are increasingly used as translational models in many areas of clinical research, including transplantology, immunology and oncology. Ultimately, the use of humanized animals can lead to the introduction of a truly personalized medicine into clinical practice. In this review, we discuss modern advances in the creation and use of humanized mice, emphasizing their usefulness for the pathogenesis study, as well as the development of new methods for human cancer treatment.
S. V. Okovitiy,
N. V. Petrova,
E. B. Shustov,
M. A. Belykh,
N. V. Kirillova,
O. M. Spasenkova,
A. G. Ivanov,
A. V. Karavaeva,
D. Yu. Ivkin,
Yu. V. Fokin,
E. L. Matveyenko,
O. V. Alimkina
82-97 807
Abstract
This article sets out to analyze possible approaches to assessing the joint effect of simultaneously occurring and mutually aggravating pathological processes. In medicine of extreme environments, such examples include the joint effect of hypoxia and hyperthermia (desert mountain environments); hypoxia and low temperatures (high altitude locations, mountain stations in Antarctica); intense physical exertion and endogenous or combined hyperthermia (work in insulating protective equipment or in humid tropics); respiration using specialized hypoxic helium-oxygen gas mixtures under the conditions of hyperbaria and deep-sea dives; exposure to weightlessness and vestibular loads during spacefl ight; etc. In clinical practice, such conditions may be referred either to the phenomenon of comorbidity, when the pathological processes have common pathogenesis links, or to the phenomenon of polymorbidity, when there is no clear pathogenetic link between the processes. This research shows that clinical methods currently used for assessing comorbidity cannot be directly applied in preclinical studies performed with the participation of laboratory animals. A methodology for assessing the interaction of two experimentally simulated pathological processes in one group of animals based on a two-factorial experiment is presented. It is shown that the phenomenon of mutual aggravation is manifested through a signifi cant interaction between the controlled factors, thus requiring an additive or supra-additive effect according to the key parameters of the experimental model. The feasibility of the proposed approach was tested experimentally by evaluating the interaction of two independent simulated processes, i.e. chronic periodic moderate normobaric hypoxia (typical of sleep apnea) and non-alcoholic fatty liver disease. It was established that the simulated processes are mainly realized as independent factors. High-calorie lipid-carbohydrate nutrition causes a predominant rearrangement of carbohydrate metabolism in the tissues and has a partial antagonistic effect on the metabolic manifestations of chronic hypoxic effects.
98-106 416
Abstract
Effects of cryopreservation of male Wistar rat brain slices with different duration (4, 8, 10, 23, and 90 days) on changes in their electrical activity was investigated. The amplitudes of AMPA- and NMDA-dependent glutamatergic ionotropic mechanisms were measured, as well as the action potential of the lateral olfactory tract (AP LOT) at a temperature of –20°C and subsequent warming to +37°C. After cryopreservation, these mechanisms were preserved and restored. We used the method of electrophysiological registration of the AMPA and NMDA potentials and the total AP LOT. After cryopreservation, the AMPA-dependent mechanisms and the activity of conductive LOT fi bers were restored to normothermal values. On the contrary, the recovery of NMDA-dependent mechanisms was incomplete and averaged 34% compared with the normothermal values. The results indicate that, after cryopreservation, the activity of basic ionotropic glutamatergic mechanisms in rat brain slices is restored.
107-120 750
Abstract
A series of amplitude and spectral studies was performed to investigate brain cortical activity in rats with traumatized brain (open penetrating traumatic brain injury (TBI)). Electrocorticograms (ECoG) were recorded on the 3rd and the 7th day following the trauma. An amplitude analysis comprised an estimation of the mean signal amplitude and the degree of Lempel — Ziv compression. A spectral analysis involved a calculation of the mean amplitude and δ-, θ-, α- and β-rhythm indices. Characteristic changes in the ECoG amplitude and spectral parameters were revealed in TBI rats. Traumatized animals demonstrated decreased values of both the mean signal amplitude, as well as the amplitudes and indices of θ-, α- and β-rhythms. At the same time, the mean amplitude and the index of delta-frequency were increased. Similar changes were observed not only near the traumatized area but also in the other brain cortex regions on the 3rd and 7th day following the trauma. The obtained results demonstrate that the investigated TBI model has numerous electro physiological similarities with traumas in clinical practice, thus being applicable for neurophysiological and pharmacological studies.
ISSN 2074-5982 (Print)
ISSN 2713-0428 (Online)
ISSN 2713-0428 (Online)