Genomic characterization of MDR/XDR-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94-32 central Asian/Russian clusters.

BACKGROUND: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. METHODS: A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay. RESULTS: Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were "modern" Beijing and (2) most of these belonged to the previously described 94-32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. CONCLUSIONS: For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.

[Membrane-modifying effect of taurine].

The effect of taurine on the membrane-bound processes in rat erythrocytes and peritoneal mast cells was studied. By EPR method using spin probe 5-DS a significant decrease in the order parameter S of erythrocyte membrane phospholipid acyl chains in in vitro experiments after incubation with taurine (10 mM, 1 h) was shown. The increase of erythrocyte membrane response to peroxide hemolysis was also observed, that was apparently induced by decrease of membrane viscosity as a result of lessening the solidity of the erythrocyte membrane phospholipid packing. The different effects of taurine on ionophore A23187 and compound 48/80-stimulated functional activity of the peritoneal rat mast cells by various modes of administration (peroral, intraperitoneal, intramuscular) were shown. This makes it possible to conclude that the mechanism of taurine activity at the organism level seems to be a mediated process and systemic by nature.

[Studies of the blood antioxidant system and oxygen-transporting properties of human erythrocytes during 105-day isolation].

Effects of strict 105-d isolation on blood antioxidant status, erythrocyte membrane processes and oxygen-binding properties of hemoglobin were studied in 6 male volunteers (25 to 40 y.o.) in ground-based simulation of a mission to Mars (experiment Mars-105). The parameters were measured using venous blood samples collected during BDC, on days 35, 70 and 105 of the experiment and on days 7 and 14-15 after its completion. Methods of biochemistry (determination of enzyme activity and thin-layer chromatography) and biophysical (laser interference microscopy, Raman spectroscopy) showed changes in relative content of lipid and phospholipid fractions suggesting growth of membrane microviscosity and increase in TBA-AP (active products of lipids peroxidation interacting with thiobarbituric acid). A significant increase in glucose-6-phosphate dehydrogenase and superoxide dismutase activities against reduction of catalase activity points to both reparative processes in erythrocytes and disbalance between the number of evolving active forms of oxygen and antioxidant protection mechanisms in cells. Hemoglobin sensitivity of oxygen and blood level of oxyhemoglobin were found to increase, too. It is presumed that adaptation of organism to stresses experienced during and after the experiment may destroy balance of the antioxidant protection systems which is conducive to oxidation of membrane phospholipids, alteration of their content, increase of membrane microviscosity and eventual failure of the gas-exchange function of erythrocytes.

Tissue-specific changes in heme oxygenase activity and level of nonprotein thiols in C57Bl/6 mice after whole-body gamma-irradiation.

Heme oxygenase catalyzes heme degradation and is an important component of the antioxidant defense. Nonprotein thiols participate in redox regulation of heme oxygenase gene expression. Changes in heme oxygenase activity and levels of nonprotein thiols in the liver, lungs, and brain of C57Bl/6 mice were studied on days 1-7 after whole-body gamma-irradiation in a dose of 10 Gy. The maximum increase in heme oxygenase activity was observed in the liver (to 196% in females and to 250% in males) and was associated with an 8-fold increase in the level of heme oxygenase-1 (inducible form of the enzyme) mRNA. The increase in heme oxygenase activity was less pronounced in the lungs, while in the brain this parameter slightly decreased. Changes in the levels of nonprotein thiols were sex-dependent: in the liver and lungs this parameter increased in females and decreased in males.

[An ACTH-like peptide immunocortin: effect on the activity of cells from the rat adrenal cortex]. / Vliianie AKTG-podobnogo peptida immunokortina na aktivnost' kletok kory nadpochechnikov krysy.

The effect of immunocortin, an ACTH-like decapeptide VKKPGSSVKV corresponding to the 11-20 sequence of the variable part of the human IgG1 heavy chain on the content of 11-hydroxycorticosteroids (CS) in rat adrenal glands and blood serum in vivo was studied. An intramuscular injection of immunocortin at a dose of 10 microg/kg was found in an hour to induce a twofold decrease in CS content in the adrenal glands and a 1.8-fold increase in the blood serum CS content. At the same time, an immunocortin dose of 100 microg/kg exerted practically no effect on the CS content and its dose of 1000 microg/kg increased the CS content both in adrenal glands and in blood serum by 1.6 and 2.2 times, respectively. Four hours after the injection of any of the three doses of immunocortin, the CS content in adrenal glands did not differ from the control value, and after 24 h the content decreased threefold. Immunocortin was shown to be bound by the ACTH receptors in the membranes of the rat adrenal cortex with a high affinity and specificity (inhibiting the specific binding of 125I-labeled ACTH-(11-24) peptide with Ki of 1.2 nM).

[Synthetic peptides -- analogs of biologically active fragment of the differentiation factor from HL-60 cells show radioprotective and adaptogenic activities]. / Sinteticheskie peptidy -- analogi biologicheski aktivnogo fragmenta faktora differentsirovki kletok HL-60 proiavliaiut radioprotektornuiu i adaptogennuiu aktivnost'.

It was shown that the addition of synthetic six-membered peptide (HLDF-6) and its Tyr-analog (HLDF-Y) to cultural medium significantly increased the survival of cells HL-60, treated by cold shock. The prophylactic administration of HDLF-Y (1 mg/kg, 4 hours prior to applied actions) decreased the response of hypothalamushypophysis-adrenal glands system and sympathicoadrenal system of rat males on supercooling and also increased the resistance of mouse males to supercooling and X-irradiation. In the experiences with females HDLF-Y did not show the similar biological activity.

[Effect of natural radioprotector carnosine on histamine-diamine oxidase system of rat's myocardium after action of various extreme factors]. / Vliianie prirodnogo radioprotektora karnozina na sistemu gistamin-diaminoksidaza miokarda krys posle deistviia razlichnykh ékstremal'nykh faktorov.

The unbalance in system histamine-diaminooxydase in myocardium of rats subjected to various stress actions (intensive cold influence, hyperthermia and hypoxia) was found. The preventive application of a natural radioprotector carnosine prevented apparent changes, that gives the basis to assume about carnosine ability to enlarge a nonspecific resistance of an organism.

[Effect of small doses of ionizing radiation on the level of catecholamines and corticosteroids in mouse adrenals]. / Vliianie malykh doz ioniziruiushchei radiatsii na uroven' soderzhaniiakatekholaminov i kortikosteroidov v nadpochechnikakh myshei.

Effects of 137Cs gamma-radiation (0.06-0.54 cGy, 0.06 cGy/day) on the levels of catecholamines and corticosteroids in mouse adrenals were investigated. There were observed increase of these parameters after mice irradiation during 1-2 days and their decrease after mice irradiation during 9 days.

[Protective effects of MIGI-K during UV irradiation of animals]. / Zashchitnye éffekty MIGI-K pri UF-obluchenii zhivotnykh.

Prophylactic peroral use of MIGI-K preparation (products of acid hydrolysis of mussels meat) largely or completely prevented intensification of lipoperoxidation and depression of antioxidative systems (superoxide dismutase, glutathione peroxidase, nonprotein thiols, lipoantioxidants) in skin and liver of UV-irradiated rats.

[The action of sublethal doses of ionizing radiation on the endogenous radioresistance background]. / Issledovanie deistviia subletal'nykh doz ioniziruiushchego izlucheniia na éndogennyi fon radiorezistentnosti.

Sublethal doses of X radiation (0.5 Gy and 1 Gy) caused the alterations in levels of main components of endogenous radioresistance background in rat tissues. There were demonstrated the decrease of serotonin content in stomach mucosa and spleen, adrenalin, noradrenalin and corticosteroid contents in adrenal glands, nonprotein thiols content in spleen, and the increase of lipid peroxide level in serum on the 3-14 days after irradiation. The recovery of the investigated parameters was occurred to the 21 day after exposure.

[The effect of x-ray irradiation on the cytochrome P-450-dependent mono-oxygenase system of the liver in different animal species]. / Vliianie rentgenovskogo oblucheniia na tsitokhrom P-450-zavisimuiu monooksigenaznuiu sistemu pecheni u razlichnykh vidov zhivotnykh.

The whole X-irradiation (7 Gy) of male rat, mouse and guinea-pig caused in general similar alterations in the content of cytochrome P-450 and aminopyrine-N-demethylase activity in liver microsomes. On the 5-7th day after irradiation the parameters were 39-79% of the normal level. The same postradiation changes were observed in females of these animal species but in females of rats and guinea-pigs the effect was less expressed. The depression of activity in liver microsomal cytochrome P-450-dependent monooxygenase system has been concluded to be one of the characteristic features of acute form in radiation damage.

[Treatment of the abdominal cavity with a colloid solution of magnetite during surgery in experimental ichorous peritonitis]. / Obrabotka briushnoi polosti kolloidnym rastvorom magnetita pri operatsiiakh po povodu ikhoroznogo peritonita v éksperimente.

Experimental investigations gave grounds for the possibility of using the solution of colloid magnetite for the treatment of the abdominal cavity during operation for peritonitis. It was established that the substance has good bacteriocidal and bacteriostatic properties, adsorbs toxic substances present in the peritoneal exudate, is absorbed into blood from the abdominal cavity, does not destruct the cytostructure of the cells of formed elements of the blood, and is easily eliminated from the organism with the bile.

[Effect of x-ray irradiation on the activity of key enzymes in heme biosynthesis and breakdown in the rat liver]. / Vliianie rentgenovskogo oblucheniia na aktivnost' kliuchevykh fermentov sinteza i raspada gema v pecheni krys.

The authors studied the effects of the whole-body x-irradiation on the activity of delta-aminolevulinate synthase and heme oxygenase in the liver of Wistar rats. The activity of delta-aminolevulinate synthase decreased to 81-49% of normal by the 1st-3d day after irradiation in a dose of 7 Gy followed by partial normalization of the enzyme activity by the 5th-7th day. The activity of heme oxygenase was over 2 times as increased by the 5th-7th day following irradiation in a dose of 7 Gy. Irradiation in a dose of 5 Gy did not alter the activity of heme oxygenase and caused a negligible reduction in the activity of delta-aminolevulinate synthase. During the most pronounced decrease in the rate of heme synthesis in the liver of irradiated rats, there was an elevation in the level of "free" heme (measured by the degree of tryptophane pyrrolase saturation with heme). This attests to a possible lowering of the rate of heme utilization in the synthesis of heme. A possible role of the effects described in the irradiation-induced decrease in the content of cytochrome P-450 in the animals' liver.

[The effect of x-rays on the level, composition and para-nitroanisole-o-demethylase activity of cytochrome P-450 in the liver microsomes of rats]. / Vliianie rentgenovskogo oblucheniia na soderzhanie, sostav i para-nitroanizol-o-demetilaznuiu aktivnost' tsitokhroma P-450 v mikrosomakh pecheni krys.

A study was made of the effect of X-radiation of different doses on the content of P-450 cytochrome in a microsomal fraction of rat liver. When the haemoprotein level markedly decreased an increase in Km and a decrease in Vmax were noted in the reaction of O-demethylation of para-nitroanisole by microsomes of the irradiated rat liver. It is suggested that one of the cause of the effect observed is the postirradiation change in the composition of cytochrome P-450 pool resulting from a selective decrease in the level of the radiosensitive forms of haemoprotein.

[Relation of changes in the content and activity of rat liver microsomal cytochrome P-450 to the intensification of lipid peroxidation under stress]. / O sviazi izmenenii soderzhaniia i aktivnosti mikrosomal'nogo tsitokhroma P-450 pecheni krys s intensifikatsiei perekisnogo okisleniia lipidov pri stressovykh vozdeistviiakh.

The content of cytochromes and aminopyrine demethylase activity of rat liver microsomes were studied after 3 hours of swimming, adrenaline administration, and immobilization of the animals. Immobilization and swimming resulted in a short-term 19-25% decrease in the content of cytochrome P-450. Administration of adrenaline entailed a more prolonged and appreciable reduction in the content of both cytochrome P-450 and cytochrome b5. These changes were preceded by intensification of lipid peroxidation (LPO) in the liver. After the exposures described the pattern of changes in demethylase activity of microsomes was more complex than the changes in the content of cytochrome P-450. It is assumed that the decreased content of cytochrome P-450 in the endoplasmic liver reticulum is a non-specific body reaction to stress exposures and that this reaction is related to the intensification of LPO in animal tissues.