Vol 162, No 6 (2017)

The whole-cell voltage clamp technique was employed to record the total ionic currents in rat cerebellar Purkinje neurons. When intrapipette solution contained 120 mM KCl, replacement of the standard external physiological saline with Na-free solution resulted in appearance of inward tail current after the end of the depolarizing pulse. When intrapipette potassium ions were replaced for cesium ones, the tail currents were observed even in the presence of normal Na⁺ concentration (140 mM) in the external solution. Tail currents were not observed when external solution contained no Cl^– and/or Ca²⁺ ions. Niflumic acid (25-100 μM) blocked these currents by 80-100%. Complete replacement of external Na⁺ for Tris ions pronouncedly augmented the amplitude and duration of the tail currents. These findings suggest that the tail transients in rat cerebellar Purkinje neurons are calcium-activated chloride currents whose amplitude and kinetics depend on ionic composition of the extracellular and intracellular solutions.

The study focuses on induction of autoantibodies directed against neurotransmitter norepinephrine during neuropathic pain syndrome and on the effect of immunization with norepinephrine-protein conjugated antigen on the development of this syndrome. The formation of anti-norepinephrine antibodies aggravated and prolonged neuropathic pain.

Coagulation and optical (based on chromogenic substrate) methods were employed to examine antithrombin activity of erythrocytes and erythrocyte-derived microvesicles isolated days 7, 14, 21, and 28 on erythrocyte storage. The erythrocyte-derived microvesicles decelerated fibrin clot formation from fibrinogen in the presence of exogenous thrombin both with and without heparin. Microvesicles reduced optical density of chromogenic substrate. These data suggest that erythrocyte-derived microvesicles display a prominent antithrombin activity, which significantly increases during erythrocyte storage.

We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1β). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

Effects of prenatal hyperhomocysteinemia on hypothalamic regulation of estrous cycles were studied in female rats. In mature rats exposed to prenatal hyperhomocysteinemia, changes in the catecholamine content in hypothalamic areas responsible for the formation of the preovulatory surge of gonadotropin-releasing hormone were revealed: the level of norepinephrine in the medial preoptic area decreased and concentration of dopamine in the median eminence with arcuate nuclei increased. Administration of melatonin attenuated the observed changes, which can be related to neuroprotective effects of this hormone determined by its antioxidant properties.

Experiments on random-bred albino mice showed that M1 muscarinic acetylcholine receptor agonist (TBPB) and α7n-acetylcholine receptor agonist (GTS-21) significantly reduced mortality of mice with experimental sepsis (intraperitoneally administration of E. coli) in 4 and 24 h after modeling by reducing blood concentration of proinflammatory cytokines TNF-α, IL-1β, and IL-6. Combined treatment with TBPB and GTS-21 determined their additive effect.

We investigated the effect of a new indole derivative Sbt-828 with antiaggregant properties on prostacyclin-generating activity of the vascular wall and thromboxane A₂ level in platelets of intact rats. The substance under study did not affect prostacyclin production by the vascular wall and significantly reduced thromboxane A₂ level, being superior to the reference drug acetylsalicylic acid by 1.6 times, as seen from reduced malonic dialdehyde level in the thrombin-induced rat platelets.

We studied combined effects of antimicrobial peptide arenicin-1 from lugworm Arenicola marina and some conventional antibiotics. A number of drug combinations with pronounced synergistic effects were revealed. The influence of antibacterial activity assessment conditions was determined and the methodology excluding false-positive test results was developed.

Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin. The obtained Fc-PEG-AMogP3 conjugate effectively interact with autoreactive antibodies, which attests to their high therapeutic potential.

We studied the profile of miRNA secreted into culture medium by DU145 prostate cancer cells and identified a subset of miRNAs characterized by the absence of correlation of their content in the cell and medium, which is likely a result of specific secretion. Three of these miRNA, hsa-miR-4417, hsa-miR-3175, and hsa-miR-6782-5p, exhibit the highest expression and are candidate circulating biomarkers for metastatic activity of prostate cancer. Two of these miRNA are coded by introns of genes linked with genome stability maintenance and chromatin remodeling regulation.

We studied the effects of some aniline and dioxaborininopyridine derivatives on the rate of oxidative deamination of putrescine and polyamines in a tissue with high mitotic index. These effects were evaluated quantitatively by measuring diamine oxidase and polyamine oxidase activities in a model cell-free test system of regenerating rat liver tissue. Aniline derivatives exhibited mainly antiproliferative effects and promoted oxidative degradation of putrescine, spermidine, and spermine. Dioxaborininopyridine derivatives inhibited this process, thus exhibiting carcinogenic properties.

Computer-assisted video biomicroscopy of bulbar conjunctiva was employed to examine the sequelae of endothelial dysfunction manifested by microcirculatory bed abnormalities and microcirculation disturbances. The signs of endothelial dysfunction provoked by tobacco smoking in young adults disappeared after cessation of smoking, which resulted in pronounced widening of arterioles and capillaries as well as moderation of intravascular erythrocyte aggregation.

The effect of mitochondria-targeted antioxidant 10-(6’-plastoquinonyl) decyltriphenylphosphonium bromide (SkQ1) and its fragment dodecyltriphenylphosphonium (C12TPP), weak uncouplers of respiration and oxidative phosphorylation, was studied using a mouse model of carrageenan-induced acute inflammation in the subcutaneous air pouch. In our model, SkQ1 demonstrated a strong anti-inflammatory effect that manifested in a decrease in the absolute number of inflammatory cells, mainly neutrophils, and their relative number in parallel with an increase in macrophages and mast cell content in the inflammatory exudate. The concentration of proinflammatory cytokine IL-6 in the exudate also tended to decrease. C12TPP produced no significant effect on the inflammation process.

We studied activation of macrophages with humic acids extracted from peat of large deposits in the Tomsk region by two extraction methods: by hydroxide or sodium pyrophosphate. Humic acid of lowland peat types containing large amounts of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and ethers, irrespectively of the extraction methods contained LPS admixture that probably determines their activating properties. Humic acid of upland peat types characterized by high content of carbonyl, carboxyl, and ester groups enhance NO production and reduce arginase expression, but these effects were minimized when sodium hydroxide was used as an extraction solvent. Pyrophosphate samples of the upland peat types were characterized by aromaticity and diversity of functional groups and have a significant advantage because of they induce specific endotoxin-independent stimulating action on antigen presenting cells.

Mechanisms of thioredoxin peroxidase secretion by Opisthorchis felineus were studied in vivo and in vitro. Specific antibodies were obtained and used for western blotting and immunohistochemical detection in Syrian hamster model of opisthorchiasis. Secreted thioredoxin peroxidase protein was accumulated in the worm incubation medium under conditions of oxidative stress and in bile duct cells of hamsters with chronic opisthorchiasis.

Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal damage predominantly in the CA3 and CA1 fields. These lesions can be significantly reduced by simultaneous administration of MPEP, a negative allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal death in the hippocampus during pharmacological modulation was paralleled by adaptive changes in gene expression. In the hippocampus, gene expression of type 5 postsynaptic metabotropic glutamate receptor was close to the control level, and in the frontal cortex expression of the gene of α₁-subunit of the GABAA receptor returned to normal. In the frontal cortex, a reciprocal relationship was observed for type 2 metabotropic glutamate receptor: expression of the corresponding gene decreased in response to pharmacological activation.

Sex-related systemic status of pituitary and thyroid hormones and cortisol was studied in rats on days 7 and 14 after transplantation of sarcoma C-45 cells into the lung. Females demonstrated slower development of the tumor process (49.0±10.7 vs. 32.0±3.9 days in males). Injection of tumor cells causes similar disorders in the levels of ACTH, thyrotropic hormone, and prolactin in males and females and opposite disorders in the thyroid and glucocorticoid homeostasis associated in males (in contrast to females) with reduction of cortisol level (by 1.9 times) and increase in the concentrations of total thyroxine forms (by 1.4 times) and triiodothyronine (by 2.9 times) by day 14. Early sex-related shifts in the status of hormone that are a component of the adaptive system attest to their possible relationship with different course of the malignant process in male and female rats.

We studied the influence of the characteristics of oxide porous coatings on osteogenesis and integration of new bone tissue and titanium implant surface in the ectopic osteogenesis test. Implants with coating with pore size 2-20 μ exhibit better osteogenic and osteoconductive characteristics than implants with homogenous surface and smooth relief (pore size 0.5-5.0 μ). Physical characteristics of the surface of the material along with chemical composition of the coating are essential for the formation of bone tissue and its integration with the implant.

Studies of the dynamics of thyroid hormone concentrations in the blood revealed a 3-day rhythm that significantly manifested in male Wistar rats and Chinchilla rabbits during intensive growth and in common starlings (Sturnus vulgaris) during moult. Synphasic 3-day biorhythms of thyroid hormonal activities were found in these animals, which attested to an external synchronizer of this biorhythm common for mammals and birds. The maximum level of thyroid hormones coincided with the extrema of daily fluctuations of the Earth rotation velocity, as a result of which this external factor or another factor closely related to it seemed to be involved in synchronization of the 3-day infradian biorhythm of thyroid hormones in mammals and birds.

The device for cell encapsulation makes it possible to fabricate microcapsules of a preset size with even smooth surface, without defects or adhesion to each other, with viable cells inside the capsule. The cells were derived from newborn piglet pancreases.