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.

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.

[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.

[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.

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.

[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.

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.

[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.

Retrospective luminescence dosimetry: development of approaches to application in populated areas downwind of the Chernobyl NPP.

The cumulative absorbed dose in fired-clay bricks collected from ten buildings in the populated contaminated settlement (137Cs, 1,470 kBq m(-2)) of Stary Vishkov, located 175 km downwind of the Chernobyl Nuclear Power Plant (NPP) in the Bryansk administrative region of Russia, was determined using luminescence techniques by five laboratories. At each location, the cumulative dose, after subtraction of the natural background dose, was translated to absorbed dose in air using conversion factors derived from Monte Carlo simulations. The simulations employed source distributions inferred from contemporary soil contamination data and also took into account heterogeneity of fallout deposition. At four locations the cumulative dose at a reference location was calculated, enabling the luminescence determinations to be compared directly with values of cumulative absorbed dose in air obtained using deterministic models. A "local" conversion factor was also derived from the Monte Carlo simulations for locations where the disturbance of soil was significant. Values of the "local" cumulative dose in air calculated using this factor were compared with those predicted using the deterministic models at each sampled location, allowing location factors to be calculated. The methodology developed is generally applicable to populated areas contaminated by radioactive fallout in which brick buildings are found. The sensitivity of the luminescence techniques for bricks from this region of Russia was sufficient to evaluate cumulative absorbed dose in brick due to fallout of less than 20 mGy.

[Initial morphological manifestations in experimental neuroleukemia]. / Nachal'nye morfologicheskie proiavleniia éksperimental'nogo neiroleikoza.

The results of the study of primary morphological manifestation of neuroleukemia (MMN) by mice with transplanting leukemia strains L 1210, P-388, L 5178Y, and are presented. It is determined that the MMN development degree depends on the leukemia cells dissemination amplitude after their transplantation and, in particular, on the degree of the bone-marrow affection, from which the leukemia cells grow into the dura mater encephali and epidural fat of the vertebral canal from the side of skull bones and vertebral canal. The analogous dependence is assumed to be present in a man and, therefore, there appears the possibility of using it for the neuroleukemia development frequency prognosing.

Comparison of retrospective luminescence dosimetry with computational modeling in two highly contaminated settlements downwind of the Chernobyl NPP.

The cumulative absorbed dose in bricks collected from six buildings in two heavily contaminated settlements (137Cs > 2,000 kBq m(-2)) located downwind of the Chernobyl Nuclear Power Plant was determined using luminescence techniques by six laboratories. The settlements, Vesnianoje in Ukraine and Zaborie in Russia, are located in, respectively, proximal and distal locations relative to the Chernobyl Nuclear Power Plant. The luminescence determinations of cumulative dose in brick, after subtraction of the natural background dose, were translated to absorbed dose in air at a Reference Location using conversion factors derived from Monte Carlo simulations of photon transport. The simulations employed source distributions inferred from contemporary soil contamination data and also took into account heterogeneity of fallout deposition. This translation enables the luminescence determinations to be compared directly with values of cumulative absorbed dose obtained by computational modeling and also other dose reconstruction methods. For each sampled location the cumulative dose was calculated using three deterministic models, two of which are based on the attenuation of dose-rate with migration of radionuclides in soil and the third on historic instrumental gamma dose-rate data. The results of the comparison of the two methods indicate overall agreement within margins of +/-25%. The methodology developed is generally applicable and adaptable to areas contaminated by much lower levels of radioactive fallout in which brick buildings are found.

[Characteristics of the gene pool of Russian Old Believers in Siberia based on polymorphism of blood groups, isoenzymes, and blood proteins]. / Osobennosti genofonda Russkikh staroverov Sibiri na osnove izucheniia polimorfizma grupp krovi, izofermentov i syvorotochnykh belkov.

The frequency distributions of A1A2B0, Rhesus, MNSs, P, Duffy, Kell, Hp, Tf, AcP, PGM1 alleles, and haplotypes were studied in Siberian populations of Old Believers (Burnyi village, Krasnoyarskii krai, and Isetskii raion, Tyumenskaya oblast) and in ethnic Russians from Tyumenskaya oblast. Features characteristic of the genetic structure of these groups were revealed. The Siberian groups of Russians were shown to be genetically removed from European Russian populations (Tverskaya and Vologodskaya oblasts). The Burnyi population of Old Believers was significantly removed from the other groups of Russians due to peculiarities in the sample.

[The antiviral properties of 4-iodoantipyrine in an experimental enterovirus infection]. / Issledovanie protivovirusnykh svoistv 4-iodantipirina pri éksperimental'noi énterovirusnoi infektsii.

The studies of the therapeutic and prophylactic action of a compound from the group of nonsteroid antiinflammatory substances, iodantipyrine-4, in newborn white mice infected with Coxsackie B3 virus showed the drug to possess both therapeutic and prophylactic activity in the acute period of infection.

[Morphogenesis of experimental neuroleukemia]. / Morfogenez éksperimental'nogo neiroleikoza.

22 mice with L-1210 leukemia treated with quinoline dibromide were studied histologically. Two ways of the development of leptomeningeal infiltrates in the brain are established. The first is due to the growth of uninhibited by treatment bone-marrow leukemic infiltrates (LI) of the skull, while the second-when the above infiltrates are suppressed-due to the proliferation of leukemic cells penetrating from the dura mater to the leptomeninges protected by the hematoencephalic barrier from the effect of anticancer drugs. when the recurrence of leukemia occurs the growth of bone-marrow LI continues resulting in the additional migration of leukemic cells to the leptomeninges. These ways of the leptomeninx LI formation should be taken into consideration in the leukemia treatment.

[Morphogenesis of neuroleukemia]. / Morfogenez neiroleikoza.

A comparative study of neuroleukemia in children with acute leukemia and in mice with experimental leukemia was carried out. Spontaneous leukemia in AKR mice and transplantation leukemia (LIO-I, La, P388, L-5178Y) were shown to be adequate models for investigations on the pathogenesis of neuroleukemia. The initial morphological manifestations of neuroleukemia consisted in infiltration of dura mater of the brain and epidural space, particularly of the lumbar region of the spine. The leukemic cell infiltrates originating from the bone marrow spread along the walls of vascular anastomoses between the venous system of the skull and vertebrae on the one hand, and dura mater of the brain and epidural space of the spinal cord, on the other.

[Thiochrome inhibition of alcohol dehydrogenase]. / Ingibirovanie alkogol'degidrogenazy tiokhromom.

It is shown that thiochrome inhibits alcohol dehydrogenase. Thiochrome is able to be bound with alcohol dehydrogenase more quickly than other thiamine metabolites. This process is specific and has common features with the process of NAD binding by this enzyme. The inhibition of alcohol dehydrogenase by thiochrome is concurrent to NAD. The constant of alcohol dehydrogenase inhibition by thiochrome is 3.9 x 10(-5) M.