[The role of mitochondrial dysfunction in the stabilization of the glaucomatous process]. / Znachenie mitokhondrial'noi disfunktsii v stabilizatsii glaukomnogo protsessa.

Many key aspects of retinal ganglion cell (RGC) neurodegeneration in glaucoma are associated with mitochondrial dysfunction. Understanding the mechanisms and relationships between structural and functional changes in mitochondria would be beneficial for developing mitochondria-targeted therapeutic strategies to protect RGCs from glaucomatous neurodegeneration. PURPOSE: This study determines the extent of mitochondrial dysfunction in patients with primary open-angle glaucoma (POAG) and evaluates the potential for stabilizing the glaucomatous process by improving mitochondrial functional activity and energy production by therapy with Mexidol and Mexidol FORTE 250. MATERIAL AND METHODS: The study included 80 patients with moderate POAG with compensated intraocular pressure and 20 healthy volunteers. The extent of mitochondrial dysfunction was assessed by measuring the activity levels of mitochondrial enzymes: succinate dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (α-GPDH) in peripheral blood lymphocytes using cytochemical analysis and cytometric morphology and density analysis (cytomorphodensitometry). Patients in the main group received sequential therapy with Mexidol as follows: Mexidol solution for intravenous and intramuscular administration at 50 mg/ml, 300 mg daily intramuscularly for 14 days, followed by Mexidol FORTE 250 tablets, one tablet three times daily for 56 days. Stabilization of glaucomatous optic neuropathy during treatment was evaluated using a comprehensive set of perimetric, electrophysiological, and structural-topographical methods at 14, 56, and 90 days. RESULTS: Sequential therapy in the main group resulted in a significant increase in mitochondrial enzyme activity at 14 and 56 days compared to baseline, with a gradual regression by the end of the observation period (90 days). This was accompanied by an increase in the number of mitochondria and an increase in their optical density as measured by cytomorphodensitometry. The improvement in mitochondrial enzyme activity at 14 and 56 days was associated with positive changes in the structural and functional parameters of the retina, as evidenced by static perimetry, optical coherence tomography, and a series of electrophysiological tests. CONCLUSION: The obtained data can be used to optimize POAG therapy by reducing mitochondrial dysfunction and stabilizing glaucomatous optic neuropathy.

The Influence of Metabolites of Microorganisms of the Genus Bacillus from Permafrost Rocks on T Lymphocyte Differentiation.

We studied the influence of metabolites of permafrost microorganisms obtained at different temperature incubation conditions on activity of differentiation of regulatory (Treg) and effector T lymphocytes. It was found that the effect of metabolites is largely regulated by their type that depends on the temperature of production ("cold" at 5°C, "medium temperature" at 22°C, and "warm" at 37°C). The studied metabolites influenced the differentiation of Tregs (CD4+CD25hiCD127-) and the expression of markers of early (CD69), middle (CD25), and late (HLA DR) activation of CD4+ and CD8+ T lymphocytes. In the case of "cold" metabolites, the increase in Treg levels was associated with a decrease in the intensity of CD4+ T lymphocyte differentiation, and under the influence of "warm" metabolites - with a decrease in the activity of CD8+ T lymphocyte differentiation. Under the influence of "medium-temperature" metabolites, Tregs had approximately the same effect on the intensity of CD4+ and CD8+ T lymphocyte differentiation.

The Influence of Permafrost Microorganisms on Monocytes Differentiation In Vitro.

Metabolites of fossil microorganisms of dispersed watered rocks that have passed into a frozen state (Bacillus sp. strains 2/09 and 9/08, Bacillus megaterium 8-75) can modulate the differentiation activity of human peripheral blood monocytes into phenotypically different subpopulations when cultured in vitro for 7 days. This effect is largely determined by the type of metabolites that depends on the temperature of their production: cold (collected after bacterium culturing at 5°C), medium (at 22°C), and warm temperature (at 37°C). All three types of metabolites had a weak negative influence on the level of classical (CD14hiCD16-) monocytes and stimulated the differentiation of intermediate (CD14+CD16+) and non-classical (CD14loCD16+) monocytes. The monocytes differentiation into the subpopulation of intermediate (CD14+CD16+) was stimulated to a greater extent by medium-temperature metabolites of the strain 8/75 and into the subpopulation of non-classical (CD14loCD16+) monocytes by warm metabolites of the strains 8/75 and 2/09 throughout culturing of mononuclear cells (days 1, 3, 7). Bearing in mind the anti-infection activity of intermediate and non-classical monocytes, we can consider strains 8/75 Bacillus megaterium and 2/09 Bacillus sp. promising for their in-depth testing.

[Assessment of reserves of mineral water's geothermal sources in the south of Tyumen region]. / Otsenka zapasov geotermal'nykh istochnikov mineral'nykh vod yuga Tyumenskoi oblasti.

There are rich reserves of underground mineral waters in the south of Tyumen region, which are generally deep located, in the so-called difficult exchange water zone (on average at a depth of 1311.29±34.53 m). Currently, there is a lack of assessment of prognostic resources of underground mineral waters in the south of Tyumen region. The article provides an assessment of underground mineral (therapeutic) waters' reserves (2011-2019 yrs.) in the considered territory. It was shown that the number of deposits, their sites and underground mineral waters' well bores is 76, of which less than half are in operation, as at date of 01.07.2021. Moreover, the number of deposits is remained almost constant since 2011 yr. Meanwhile, underground mineral (therapeutic) waters' reserves are gradually decreasing. Thus, there is a necessity to intensify not only the stocktaking and identification of mineral waters' well bores, but also to develop the new medical technologies to use geothermal waters in rehabilitation and prevention. Monitoring for underground waters' condition should be continued with the use of modern research tools and techniques. The above mentioned will give a new impetus to the development of health resort sphere in the tourism industry, in addition to increasing the therapeutic effects of mineral waters.

Influence of Paleobacteria on the Proliferative Activity of Human Lymphocytes In Vitro.

When testing the proliferative activity of 14 strains of permafrost microorganisms in the reaction of blast transformation of human lymphocytes in vitro, a strain (Alcaligenes sp.) with mitogen properties was isolated (20-fold increase in the rate of lymphocyte proliferation in comparison with the control). Four strains activated lymphocyte proliferation by 3-9 times in comparison with the control. Three strains produced substances with cytostatic properties and reduced proliferation activity by 33-43% and one strain (Bacillus sp.) almost completely suppressed phytohemagglutinin-induced lymphocyte proliferation. These data indicate that strains with a unique immunobiological potential are concentrated in the population of permafrost microorganisms that have undergone rigorous evolutionary selection.

[Therapeutic possibilities of stimulating reparative neurogenesis in patients with glaucoma who have recovered from a coronavirus infection]. / Terapevticheskie vozmozhnosti stimulyatsii reparativnogo neirogeneza u patsientov s glaukomoi, perenesshikh koronavirusnuyu infektsiyu.

In patients with glaucoma, the neuroplasticity of retinal cells, their axons and neuroglial elements is pathogenetically reduced, including due to a decrease in the concentration of neurotrophic factors. Coronavirus infections contribute to the damage processes, causing apoptosis of retinal and optic nerve cells. In this regard, the possibility of pharmacological stimulation of the production of these peptides through energy potentiation of the cell mitochondria function, reduction of oxidative stress severity and activation of interneuronal transduction system becomes relevant. PURPOSE: This study aimed to conduct a comprehensive diagnosis of the severity of oxidative stress, identify changes in the neuroplasticity and reparative ability of the retina in patients with primary open-angle glaucoma (POAG) who have recovered after a coronavirus infection, and are undergoing therapy with the complex drug Cytoflavin. MATERIAL AND METHODS: The study included 40 patients (mean age 57.2±3.6 years) with advanced POAG compensated by hypotensive agents; all of them recovered from moderate Covid-19 30 to 90 days prior to inclusion in the study. Twenty patients of the main group received therapy with the complex drug Cytoflavin, 20 other patients comprised the control group. In the comparison groups, the concentration of BDNF and CNTF in blood serum (SC) was determined by enzyme-linked immunosorbent assay (ELISA). Overall assessment of oxidative stress was done by high performance liquid chromatography. Studies of the functional activity of the retina were performed using the Tomey EP 1000 electroretinograph according to the standard method. RESULTS AND DISCUSSION: Retinal photosensitivity significantly improved in patients of the main group taking the complex drug Cytoflavin (mD mean after treatment increased from -7.34±0.62 dB to -4.52±0.12 dB (p>0.001), PSD mean decreased from 6.23±0.21dB to 4.27±0.13 dB (p>0.001)); the neural activity of the retina improved according to PERG (the amplitudes of the P50 and N95 components increased from 0.92±0.04 µv to 1.65±0.01 µv and from 1.83±0.06 µv to 2.68±0.01 µv, respectively (p>0.001), the latency of the P50 and N95 components decreased from 53.40±2.51 ms to 49.37±2.22 ms and from 112.40±5.23 ms to 107.4±8.11ms, respectively (p>0.001); the concentration of BDNF increased (from 18.65±5.32 ng/ml to 20.23±4.05 ng/ml (p>0.001)) and the concentration of CNTF in the blood serum decreased (from 3.99±0.37 pg/ml to 1.85±0.02pg/ml (p>0.001)), the severity of oxidative stress decreased (the indicator of oxidative stress decreased by 1.4 times after treatment p>0.001) and the content of antioxidant protection indicators increased: the indicator of antioxidant protection of blood serum increased by 1.4 times, the concentration of superoxide dismutase - by 1.9 times (p>0.001), glutathione peroxidase - by 1.4 times (p>0.001), coenzyme Q10 - by 4.5 times (p>0.001). CONCLUSION: The obtained data can be used to determine the risk of progression of glaucomatous optic neuropathy in patients with glaucoma who have had a coronavirus infection.

[Enzymatic activity of paraoxonase depending on polymorphism Q192R of the PON1 gene in patients with primary open-angle glaucoma]. / Fermentativnaya aktivnost' paraoksonazy v zavisimosti ot polimorfizma Q192R gena PON1 u patsientov s pervichnoi otkrytougol'noi glaukomoi.

It is believed that one of the main blood enzymes that hydrolyzes oxidized lipids incorporated in lipoproteins is the calcium-dependent hydrolase of paraoxonase 1, which has a significant antioxidant effect depending on the polymorphism of the PON1 gene. PURPOSE: To genotype patients with primary open-angle glaucoma (POAG) by the Q192R polymorphism of the PON1 gene in order to identify their genetic predisposition to dyslipidemia and atherosclerosis, as well as to determe the possibility of correcting the reduced activity of the PON1 enzyme in the examined individuals by the complex drug Cytoflavin. MATERIAL AND METHODS: The study included 25 men with advanced POAG, IOP compensated by hypotonic agents, and 20 volunteers without POAG (mean age 63.0±5.4 years). All subjects underwent genotyping by the Q192R polymorphism of the PON1 gene using an analyzer. PON1 activity was assessed by the rate of nitrophenol formation when paraoxone diluted in acetone was added to the blood plasma. At the second stage, patients (of different phenotypes) were prescribed the complex drug Cytoflavin. RESULTS: Homozygous carriers of the 192R allele were found to have significantly lower levels of PON1 activity than homozygous carriers of the Q192 allele. Carriage of the 192R allele may determine an increased risk of atherosclerotic injury in patients with POAG, especially in cases with high levels of atherogenic blood lipoproteins, low levels of high-density lipoproteins, or high levels of peroxidized lipids in the blood. The drug Cytoflavin showed a positive therapeutic effect on oxidative stress and hypercholesterinemia in POAG patients. CONCLUSION: These findings can be used to determine the atherogenicity of lipoproteins and the progression of glaucomatous optic neuropathy and to optimize the therapy of PAHO.

Reparative and Immunomodulatory Potential of Low-Molecular-Weight Fractions of Secondary Metabolites of Bacillus sp.

The experiment was performed on male BALB/c mice with modeled skin wound. Two chromatographic fractions of secondary metabolites of permafrost bacteria Bacillus sp., that represent a mixture of polyethylene-polypropylene glycols oligomers with a molecular weight from 900 to 1350 Da were used as therapeutic agents. Application of the test substances on the wound surface and their parenteral administration significantly accelerated wound epithelialization in comparison with untreated control, activated metabolic processes, and improved humoral immunity. In in vitro experiments, the fractions activated the synthesis of IFNγ and IL-4 by human peripheral blood mononuclear cells. We conclude that polyethylene-polypropylene glycol oligomers can be a part of effector molecules that determine the repair and immunomodulatory potential of secondary metabolites of permafrost microorganisms Bacillus sp.

Influence of the Microbiota of the Cryolithozone Paleoecosystems on the Behavioral Functions of the Nervous System of Chickens Gallus gallus.

We studied the influence of microorganisms isolated from permafrost on the psychophysiological parameters of birds. Significant effect of the microbiota of the paleoecosystems of the cryolithozone on locomotor activity, psycho-emotional state, and psychophysiological lateralization of brain function of Gallus gallus chickens. The involvement of both the autonomic and the higher central nervous systems in this regulatory process via synthesis of neuropeptides by symbionts is discussed.

Dose-Dependent Effect of Bacillus sp. Metabolites from Permafrost on Lymphocyte Differentiation in the Thymus.

We studied the effect of a single intraperitoneal injection of metabolites from Bacillus sp. M3 strain isolated from permafrost (from 5×103 to 50×103 microbial bodies) on differentiation of T cells in the thymus of F1(CBA/Black-6) mice. On day 21 after the injection of metabolites, a dose-dependent decrease in the level of CD34+CD44+ and an increase in the number of CD34+CD44-, CD25-TCR+, CD25+TCR+max, CD4+CD8-, CD4-CD8+, and CD44+TCR+ lymphocytes were observed in the thymus. The increase in thymus level of mature (CD25+TCR+max) and migration-ready (CD44+TCR+) T cells in combination with a moderate decrease in the level of T cell precursors entering the thymus from the bone marrow (CD34+CD44+) can indicate a modulating influence of Bacillus sp. metabolites on functional activity of the thymus aimed at maintenance of the T cell balance in the body.

[Dynamics of the emotional state and physiological parameters of the organism during long-term aqua-thermal impact]. / Dinamika émotsional'nogo sostoianiia i fiziologicheskikh parametrov organizma pri dlitel'nom akvatermal'nom vozdeistvii.

The data presented in this article illustrate the dynamics of the affective sphere of the mental processes associated with the higher nervous activity and the characteristics of the neuroendocrine system (including the vegetative index of Kerdo, cortisol and serotonin levels) in the participants of the marathon swimming competition covering the distance of 101.4 km. We investigated the relationship between the levels of the above hormones and the functional activity of the vegetative nervous system. AIM: The objectives of the present study were (1) to determine the dynamics of the changes in the psychophysiological characteristics of the participants in the marathon swimming competition during which the world record for the covering of the 101,4 km distance in the ice water was set and (2) to follow up the development of the stress response at different levels of the life support system. MATERIAL AND METHODS: A total of 22 participants in the competition were available for the examination designed to evaluate their psychological status and hemodynamic parameters as well as to determine the cortisol and serotonin levels in the blood sera of these subjects. RESULTS: The data obtained in this study give evidence that before the start and during the marathon distance swimming, only positive emotions prevailed among the participants whereas the setting of the world record was followed by the progressive development of the state of indifference. The dynamics of the Kerdo vegetative index suggests the balance between the functioning of the sympathetic and parasympathetic parts of the autonomous nervous system at the start of the competition and the prevalence of sympathetic activity in the autonomic nervous system at its finish. The dynamics of the level of cortisol in the serum indicates the presence of a stress. CONCLUSIONS: Despite the lack of the proper sports training, the participants in the marathon distance swimming competition proved capable of overcoming a variety of physical and psychological workloads which made it possible to set the world record. On the one hand, this confirms that the experience with winter swimming gained during a few years is sufficient to enable the swimmers to participate in such events. On the other hand, the results of the study give the idea of the 'price' to be paid by the physiological and psychological components of the life support system of the participants in the marathon distance swimming competitions seeking to set a world record.

Effect of Contamination with Perennial Permafrost Microorganisms on the Outcome of Closed Brain Neurotrauma.

We studied the effect of contamination with Bacillus genus microorganisms isolated from perennial permafrost samples on the outcome of closed brain neurotrauma in Wistar rats. It was found that contamination with different Bacillus strains produced different effects on the mortality of experimental animals with closed neurotrauma. The complex of metabolites from strain Ch2/9 - Bacillus spp. (pumilus) produced a protective effect in experimental closed brain neurotrauma.

[Extracting and study of biochemical properties of thiamine pyrophosphokinase from non-malignant and tumor tissue of myometrium].

The method of extraction and purification of thiamine pyrophosphokinase from non-malignant and tumor tissue of myometrium has been elaborated. Kinetic characteristics of T-kinase from non-malignant and tumor tissue of women myometrium have been studied. It has been shown, that malignization of myometrium is accompanied by a decrease in affinity of thiamine pyrophosphokinase from tumor to thiamine and by an increase in sensitivity of the enzyme from tumor to thiochrome.

[The effect of a water-soluble vitamins on the activity of some enzymes in diabetes].

Intramuscular injections of the vitamin complex containing: thiamine chloride (B1), riboflavin (B2), lipoic acid (N), calcium pantothenate (B5), pyridoxine hydrochloride (B6), folic acid (B9), ascorbic acid (C) can reduce the blood glucose level in serum of rats with alloxan diabetes, stabilize activity of some enzymes of energy metabolism, lactate dehydrogenase and pyruvate dehydrogenase complex.

[Influence of heavy metal salts on the activity of trypsin-like hydrolases from Drosophila melanogaster].

The influence of salts of heavy metals on trypsin-like peptide hydrolase of drosophila larvae partly refined by methods of salting-out, gel chromatography and electrophoresis has been researched. It is established that cadmium chloride is characterized by the greatest inhibitory effect, while zinc chloride by the lowest one. Since metal chlorides were used in all cases, it is the differentiated effect of metal ions on manifestations of amidase activity of trypsin-like peptide hydrolase of drosophila larvae, which rather may be considered as proved than the effect of chlorine ions. This, as a whole, agrees with the effect of these ions on proteolytic digestion system at the level of live organisms.

[Study of activity of enzymes of antioxidant system of blood at HIV infection].

HIV infection is accompanied by activation of lipid peroxidation, oxidative modification of lipoprotein complexes, and a decrease in activity of antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione peroxidase (GP)) in blood serum. A significant increase of glutathione reductase observed under these conditions is considered as a function of the antioxidant defence. These changes were already seen at early (symptomless) stages of this disease, however, at manifested forms they were more pronounced.

[Correlation of lipid spectrum with red blood cells izoantigene polymorphism and nutritional status of isetski believers].

In genetically homogeneous groups food habits associate with a number of food substances which act with food stuffs, and render essential influence on a lipid spectrum wheys of blood. Thus can influence character of current not only not infectious, but also on infectious inflammatory diseases which associate with secondary immune.

[Features of immune status among native population of Yamal in the conditions of Europeanization of traditional food].

The destruction of nutrition traditional structure and imbalance of food allowance by the basic kinds of plastic and energy materials impose a negative mark on efficiency of immune protection of north Aboriginals.

[Role of carboxypeptidases in carcinogenesis].

The literature and our experimantal data about the role of carboxypeptidases in carcinogenesis have been reviewed. Activity of all groups of the enzymes increases under development of different tumors. In some cases it is possible to suppose existence of protective role of these enzymes which is directed to inhibition of tumor development.