Viliuisk encephalomyelitis (VE) is a neurodegenerative disorder that afflicts the aboriginal people of Yakutia in Siberia. The disease is characterized by a progressive duration and aseptic inflammatory episodes, with intrathecal synthesis of oligoclonal IgG (OCBs) in some patients. The aim of this study was to evaluate the role of soluble ligands and receptors of the tumour necrosis factor (TNF) superfamily as potential participants in VE pathogenesis. To achieve this goal, we measured the levels of sTNF-α, sFas-L, sTRAIL, sCD40L ligands, and sCD40 receptor by ELISA in the plasma of VE patients compared with healthy individuals of the same population and patients with demyelinating diseases, including multiple sclerosis (MS) and neuromyelitis optica (NMO), as examples of disorders involving immune pathology. In addition, the same markers were analyzed in the CSF of VE patients and patients with demyelinating diseases. The results obtained showed that the increased level of plasma sTNF-α in VE patients was associated with the detection of OCBs (p = 0.01; two-tailed Student’s t-test). The sCD40L level in plasma was significantly increased in VE patients, regardless of the presence of an inflammatory component (p = 0.001; Student's t-test), and their healthy relatives (p = 0.004; Student's t-test). Our results suggested that increased blood sCD40L levels are associated with the chronic form of VE and may participate in the predisposition to the disease. Increased blood sCD40L levels may lead to pathology of the vascular endothelium in the brain and the development of VE pathology.
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Deciphering the cellular and molecular mechanisms of the development and remodeling of blood vessels is one of the topical areas of modern (patho)physiology and cell biology. Initially, interest in these processes was mainly associated with the need to find the mechanisms of tissues and organ developments, as well as the vascularization of tumors. In recent years, mechanisms of (neo)angiogenesis in physiological conditions and pathologies have attracted the increasing attention of researchers. In the context of the central nervous system physiology, this issue is quite new; however, there is accumulating experimental and clinical evidence that brain plasticity includes not only phenomenon of neurogenesis, synaptic transmission, dynamic changes in the number and activity of synapses, various intercellular interactions, secretion of a wide range of neurotransmitters, gliotransmitters, cytokines and growth factors, but also specific changes in local microcirculation, establishment and regression of microvessels, and altered permeability of the blood-brain barrier in active brain regions. Until now, mechanisms underlying the development and involution of blood vessels in the brain tissue are very scattered; however, some signaling pathways have been identified, in particular, those associated with the response of cells to hypoxia. Obviously, identification of such mechanisms is important for a better understanding of brain development and plasticity, searching for new marker molecules and target molecules used for the accurate diagnostics, effective treatment and reliable prognosis of brain pathologies associated with insufficient or excessive tissue vasculariza-tion and aberrant vessel remodeling, as well as for adequate reproduction of cerebral vascular networks within the in vitro microphysiological systems.
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Prenatal hypoxia remains the leading cause of infant mortality and severe disability in newborns. Disturbances in the development of fetal brain structures and functions due to hypoxic damage are the main trigger for the development of severe neurological disorders and accelerated neurodegeneration processes and can also be the cause of epileptiform activity in the postnatal period. Herein, the role of chronic prenatal hypoxia on the functional state of C3H+C57Bl6 hybrid mice during the first three weeks of postnatal development and the risks of developing epileptiform activity when provoking audiogenic seizures were assessed. Exposure to chronic prenatal hypoxia was found to increase the risk of neonatal mortality and developmental delay in the surviving individuals in the first two weeks of the postnatal period. It was shown that one of the causes of the failure of adaptation might be the disruption of the functional activity of the mitochondrial apparatus of brain cells mediated by the disruption of the first and second respiratory chain complexes. Exposure to chronic prenatal hypoxia has no significant effect on the increased risk of seizure activity in mice during audiogenic stimulation in late postnatal development, does not activate the development of persistent neurological deficit, and does not significantly affect the cognitive functions and learning ability of animals.
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The study was performed at the Gomel Regional Clinic of Sports Medicine (Belarus). Two hundred thirty-six healthy athletes (134 men and 102 women) were examined. The mean age of the examined athletes was 20 years. Features of blood biochemical parameters in athletes of cyclic sports, strength sports, and team game sports have been evaluated.
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The study of mitochondrial DNA (mtDNA), particularly the hypervariable segment (HVS1) region, is widely used to reconstruct a population's history, structure, and origin. The origin of the Sakha people living in the north-east of Russia has been discussed for more than 300 years, but up to the present time many aspects of their ethnogenesis remain unclear. In order to clarify the migration routes of the ancient ancestors of the Sakha, we analyzed the mitotypes of 69 unrelated representatives of this ethnic group, whose belonging to the ethnic group was traced to the third generation. In the studied Sakha group, we identified 33 mitotypes, the distribution of which by haplogroups approximately coincides with the data of other studies. The results of a comparative study of Sakha mitotypes according to EMPOP data and literature sources revealed a wide distribution of the identified mtDNA HVS1 haplotypes in many populations of Eurasia. A comparison of the obtained mitotypes with the results of mtDNA sequencing of ancient samples shows that most of the mtDNA lines of modern Sakha have long been located on the territory of Yakutia. West Eurasian and East Asian mtDNA lines were incorporated into the Sakha genome at different times in different ways. The results obtained contribute to a better understanding of the routes of ancient migrations of the ancestors of the Sakha population.
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The energy shortage, as well as the lack of antioxidant micronutrients that occur with severe thermal lesions, lead to poor clinical outcomes. It is important to carry out timely and effective therapy that helps maintain the redox and energy balance of the burned body. The aim of this work was to evaluate the energy status of red blood cells in severely burned patients with the use of antioxidant therapy and hyperbaric oxygenation on different days of therapy. The study involved 60 practically healthy people (norm) and patients with burns of I-II-III degree with different localization over 25% of the body surface. The age of patients is from 20 to 87 years. The data obtained suggested the effectiveness of the use of antioxidant therapy in burn patients due to the activation of oxidoreductases that support energy metabolism. The combined use of HBO and antioxidant nutrients in addition to standard therapy presumably contributed to maintaining the energy and redox balance of the body in patients with burns.
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The aim of the work was established as to study the effect of low-intensity laser therapy (LILT) on the morphology of neutrophils by the method of interference microscopy in correlation with metabolic parameters in the use of modulators which permits to assess the contribution of various structures of neutrophils to the realization of LILT effect. There was in vitro research. The neutrophils of rats served as the object of research. The neutrophils were incubated with adrenalin, cortisol, and β-blockers of adrenoreceptors. The effect of LILT in combination with a preliminary incubation of these substances was studied. Autonomous laser shower MarsiK (R&D company “Petrolaizer,” Saint Petersbourg), a laser therapeutic complex for animals, was used as a laser irradiation source. The wavelength of the irradiation was 830 nm, and the total power was 90 MW. The phasometry of neutrophils was studied by the laser modulation interference microscopy method, the processes of lipid peroxidation were analyzed by the malondialdehyde concentration, and the ATP concentration was defined by spectrophotometry. LILT provoked unidirectional changes in indices in the groups where the neutrophils were incubated with adrenalin, cortisol, and adrenoreceptor blockers. It manifested in the intensification of lipid peroxidation, increase in ATP concentration, and on the other hand, an increase in phase diameter of neutrophils regarding indicators without the impact of LILT. It is shown that the LILT effect intensity may be modified depending on stress realizing hormones (adrenalin and cortisol), β-blocker of adrenoreceptors. It permits us to suppose that the LILT effects may be realized in different ways depending on the state of the cells.
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The methods of scanning microscopy were used to study blood cells (neutrophil granulocytes, lymphocytes, and erythrocytes) morphology and rigidity. Differences between morphology and adhesion properties of fixed and living cells were shown. The Young’s modulus in various lymphocytes and erythrocytes populations was obtained. Scanning ion-conductance microscopy was compared to the most widespread biological scanning probe methods: atomic force microscopy and scanning electron microscopy. It was established that scanning ion-conductance microscopy is capable of obtaining the morphology and stiffness of living cells at one scan.
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At present, it can be noted that COVID-19 is the most serious challenge to the international health care system in its recent history. Extremely high rates of morbidity and mortality dictate the need for a more detailed study of the pathogenetic aspects of the developing infectious catastrophe. Besides respiratory distress syndrome, systemic inflammatory response syndrome, COVID-19 is characterized by polyvalent disorders of the mechanisms of systemic hemostasis, which has reflected in an increase in the number of venous thromboembolic complications in the overall structure of morbidity and mortality. The given literature summarizes the information on COVID-associated coagulopathy and its effect on changes in the clinical and epidemiological characteristics of venous thromboembolic complications.
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Cisplatin, as an antineoplastic drug belonging to the platinum family, has severely nephrotoxic and neurotoxic side effects. L-carnitine (LC) is an antioxidant-rich natural substance. The notion that LC may play a protective function in Cisplatin-induced nephropathy and neuropathy was investigated in this study. Nephropathy was created by a single intraperitoneal injection of Cisplatin at 20 mg/kg body weight, while neuropathy was induced by daily intraperitoneal injections of Cisplatin at 2.3 mg/kg body weight over two rounds of five days, with five days break in between. The rats were subsequently given LC at a dose of 250 mg/kg body weight, followed by estimation of serum urea and creatinine with histological examination of renal tissue for the nephropathy group and evaluation of nerve conduction velocity for the neuropathy group. In comparison to the nephropathy group, blood urea and creatinine levels were significantly lower after treatment with LC. Furthermore, LC therapy improved the physiological characteristics of the sciatic nerve significantly. In conclusion, the significant impairment of renal function and the decrease in sciatic nerve conduction velocity induced by Cisplatin may be avoided if L-carnitine is administered as a preventative medication.
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Conditions were determined for the identification of cholesterol in erythrocyte membranes by the fluorescent method using amphotericin B as a probe. We performed a comparative analysis of electronic absorption and fluorescence spectra of cholesterol, amphotericin B, and the products of their interaction, and determined the optimal wavelengths for excitation (328 nm) and recording (468 nm) of fluorescence. Amphotericin B stained cholesterol in membranes was visualized by fluorescence microscopy. It was shown that the registration of emission band at 468 nm on fluorescence spectra of free and membrane-bound cholesterol can serve as a marker of the presence of this lipid in the samples.
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The search for new molecular targets to protect brain cells from ischemic damage has remained one of the most urgent tasks of neurobiology and medicine over the past decades. The modern concept of the glucose-lactate shuttle, the main mechanism for providing energy support to neurons under conditions of increased physiological activity, implies a functional fusion of neuron and astrocyte metabolism, which becomes particularly important under energy or oxygen starvation conditions. The transfer of energy substrates in response to increased glutamate release by the presynaptic terminal occurs through monocarboxylate transporters (MCTs) and depends on a large number of endogenous mechanisms of homeostasis. Our work examined the role of MCTs in the implementation of the neuroprotective effect of glial cell-derived neurotrophic factor (GDNF), one of the key participants in the regulatory system capable of maintaining the viability and functional activity of neurons under conditions of energy starvation. It has been shown that the application of the MCT1 transporter inhibitor, even under normal conditions, significantly affects the parameters of spontaneous bioelectrical activity of neural networks and cell viability of primary dissociated hippocampal cultures. However, the authors’ data on the role of this type of transporters in glucose deprivation and the effect of MCT blockade on the neuroprotective effects of GDNF are of the greatest interest.
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Pseudomonas syringae is a widely distributed bacterial epiphyte of plants. When the temperature of the environment drops below zero, P. syringae can serve as biological ice nuclei due to the presence of specialized ice-nucleating proteins. This property has found application in various fields, but despite its evident importance, the molecular mechanisms behind protein-induced freezing have remained largely elusive. One of the problems in the study of the ice-nucleating process is the difficulty of carrying out experiments with freezing/melting solutions at near-zero temperatures. The experimental design implies special requirements for the equipment used and measurement technique. In this work, we used an experimental setup assembled from a dry thermostat that maintains a constant temperature and an accurate digital thermometer. We experimentally tested the possible sources of errors of the setup. As a result, we have shown that the accuracy of determining the freezing temperature of liquids and the coexistence of ice and water is mainly determined by the accuracy of the thermometer. The accuracy of determining the melting point of ice depends on the volume of the sample and is systematically underestimated in our setup. Using the proposed experimental technique, we performed a comparative study of P. syringae and E. coli cells, which revealed that P. syringae cells affect not only the freezing point of the solution but also the temperature of the coexistence of ice and water. The observed effect can be explained by the binding of P. syringae cells to the ice surface.
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In this study, we investigated the toxic properties of synthesized immunomagnetoliposomes of the following composition: phosphatidylcholine - cholesterol - disteroylphosphoethanolamine-polyethylene glycol (2000) - magnetite - antibodies to histone H3. Their dimensional characteristics were studied by the dynamic light scattering method. It was revealed that liposomal nanoparticles have dimensions of 176.4 ± 12.9 nm. Data on the toxicity of the synthesized nanoparticles in relation to human blood cells: liposomes in cells to liposomes ratio from 1/1 to 1/1000 have no toxic effect on lymphocytes; lactate dehydrogenase (LDH) release from human blood erythrocytes has been observed in the case of cells/liposomes ratio 1/100-1/1000 after the incubation with liposomes containing sodium azide (0.03%).
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The widespread occurrence of drug-resistant urogenital mycoplasmas and the high rate of their genetic variability make it possible to consider Mycoplasma hominis as a natural reservoir of antibiotic resistance determinants. Multiple drug resistance of many bacterial types is due to the active elimination of the antibiotic from the cell through various efflux systems. The genome structure of ten clinical isolates Mycoplasma hominis was studied using next-generation sequencing. The molecular genetic characterization family MATE proteins of Russian isolates M. hominis genes using bioinformatics analysis was obtained in the first. It has been established that proteins of the transport systems (ABC-transporters) and MATE play an important role in the formation of antibiotic resistance in urogenital mycoplasmas. The activity and functioning of transport systems are associated with the presence of mutations in the genes encoding regulatory proteins. Efflux systems should be considered as promising potential targets in the creation of new generation antibacterial drugs.
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The methodology of digital psychophysiological mapping was used in a group of 18 stroke patients and a matched group of healthy controls to reveal possible markers of acute cerebrovascular accident. The patients were found to have a number of indicators that were significantly different from the norm and could claim the role of stroke biomarkers. Among them there are lowered values of the power and peak frequency of the EEG alpha rhythm, significantly lowered HRV indices, as well as a significantly higher levels of emotional disadaptation. Stroke patients participated in a treatment session, in which they were exposed to EEG-based bimodal (light-musical) adaptive neurostimulation, in which some EEG characteristics (EEG oscillators) control sound (musical) stimulation, and other EEG characteristics (native EEG) simultaneously control light stimulation. As a result of the treatment, patients demonstrated a normalization of all the described indicators of the functional state: the values of a power and frequency of the EEG alpha rhythm significantly increased and approached the norm, as well as the parameters of the cardiovascular system and the cognitive-emotional sphere of stroke patients. The method of EEG-guided adaptive neurostimulation used in this work demonstrates the possibility of effective cognitive rehabilitation of stroke patients even with a single application.
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Purpose of the study: substantiation of indications and assessment of results X-ray endovascular treatment of "critical" PE in patients with acute hemorrhagic cerebrovascular accident. Material and methods: the study included 47 patients with acute violation of cerebral circulation for hemorrhagic and mixed types complicated by massive pulmonary thromboembolism of high risk, with "critical" manifestations of right ventricular failure. Depending on the method of PE treatment used, the patients were divided into 2 groups: the study group (17 people), in which endovascular mechanical fragmentation of thromboembols was performed, and the control group (30 people), in which only basic intensive therapy was used. Results: patients of the study group underwent thromboembolic fragmentation in order to transfer embolism of the trunk and the main branches into embolism of smaller branches of the pulmonary artery. Technical success of the procedure (destruction of the central thromboembolus) was achieved in 100% of the cases. 14 patients (82.4%) showed positive clinical dynamics in the form of an improvement in the general condition, a decrease in pressure in the pulmonary artery, and a decrease in the volume of the lesion of the pulmonary bed according to CT angiography. Three patients (17.6%) died in the early postoperative period. In the control group of 30 patients, 25 patients died, hospital mortality was 83.3%. Conclusion: the method of catheter endovascular fragmentation of thrombi for the treatment of "critical" pulmonary embolism in patients with acute hemorrhagic cerebrovascular accident leads to a rapid and safe decrease in pulmonary artery pressure.
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Objectives: to evaluate the efficacy and safety of circular radiofrequency ablation of the pulmonary trunk and main pulmonary arteries in patients with severe pulmonary hypertension using a histological study. Materials and methods: for the analysis of autopsy material from non-operated patients, three study groups were identified. Experimental – with chronic pulmonary hypertension with mitral disease and radiofrequency ablation. Comparisons – with severe pulmonary hypertension and without radiofrequency ablation. Control – without pulmonary hypertension and radiofrequency ablation, who died from causes not associated with cardiovascular diseases. Hematoxylin and eosin staining according to Van Gieson was used to visualize the damage to the tissue samples of the vascular wall. The technique of impregnation with silver staining was used to determine the damage to the nerve plexuses and endings. Results: analysis of the results of optical density and the relative average area of argentophilic fibers revealed a decrease in these parameters in the ablation group. In patients of the comparison group, where a high level of pulmonary hypertension was also observed, there was a significant accumulation of argentophilic fibers. Conclusion: histological examination showed an increase in the formation of sympathetic nerves in the adventitia of the pulmonary arteries in severe pulmonary hypertension. The same pulmonary arteries denervation procedure is an effective and safe way of denervation of the sympathetic plexuses located in the adventitia layer of the pulmonary arteries, which is confirmed by histological studies.
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The actuality of the problem of thermal trauma is determined by its high prevalence. Severe disorders of central, regional and peripheral hemodynamics are developing with a predominant violation of microcirculation and metabolic processes in the body during burn disease. Promising NO donors suitable for biomedical use are dinitrosyl iron complexes (DNIC). The aim of the study was to evaluate the effect of DNIC on the state of microcirculation in normal conditions and on the model of combined thermal trauma (CTT). The experiments were carried out on white male rats of the Wistar line. CTT (contact burn on the area of 20% of the body surface and thermal inhalation exposure to hot air and combustion products for 20-30 seconds) was applied under anesthesia. Animals with CTT were treated daily with intraperitoneal injections of a 10% DNIC solution (1 ml; 0.3 micromol/l). Laser Doppler flowmetry was used to assess the dynamics of the microcirculation state. The physiological and biochemical mechanisms of microcirculation disorders in CTT are revealed in the work. There was an increase in the endothelial, neurogenic and respiratory components of microcirculation, microhemodynamics of the border area of the burn, and the index of the microcirculation bypass. It was shown that when using 0.3 micromol/l of DNIC in rats under normal conditions, there is a decrease in the neurogenic and respiratory components, an increase in perfusion and the myogenic component of the microcirculatory channel. The role of 0.3 micromol/l of DNIC in the normalization of microcirculation in CTT was established.
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Currently, we continue to actively develop a high-tech rehabilitation method of microwave therapy using sub- and millimeter-wave radiation sources. However, the question of the feasibility of its use in the rehabilitation of patients with burn injuries is not sufficiently studied. In this connection, the works analyzing the effectiveness of the influence of different micro-wave ranges on the nature and degree of development of adaptive metabolic and vascular reactions in the early period of trauma, which affect the outcome of the burn, become particularly relevant. The study was carried out on male rats of the Wistar line under conditions of experimental contact thermal burn of the IIIА degree on an area of 20% of the dorsal surface of the body. A 7-day course of point non-contact exposure to broadband microwave emitters of various ranges with a radiation power of 10 µW on the occipital protuberance area was started after the rats were released from anesthesia when the contact burn was applied. The vascular status, the state of oxidative stress and energy homeostasis were assessed by the intensity of oxidative processes, antioxidant protection, and the total microcirculation index with a wavelet analysis. The obtained data reliably revealed a more pronounced favorable effect on the level of adaptive reactions in the range of 150,179-150.664 GHz, which contains the frequencies of radiation and absorption of nitric oxide. This should be taken into account when choosing frequency-energy parameters and developing a potential method of rehabilitation in the acute period of burn injury.
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