[No Effect of the p.Arg230His Variant Of The VCL Protein on the Course of the Hypertrophic Cardiomyopathy In Russian Family Carrying The p.Gln1233Ter Pathogenic Variant In The MYBPC3 Gene].

Aim      To determine specific clinical characteristics caused by a combination of the rs397516037 pathogenic variant in the myosin-binding protein C (MTBPC3) and the rs749628307 polymorphic variant in the vinculin (VCL) gene in a Russian family of carriers and to evaluate the contribution of the rs749628307 polymorphic variant in the VCL gene to the development of hypertrophic cardiomyopathy (HCMP).Material and methods  The family under study included one healthy person and 3 patients with HCMP. A targeted analysis of proband's exome was performed. A structural alignment for both forms of the VCL protein, the canonical form and the form with p.Arg230His substitution, was performed.Results The pathogenic rs397516037 variant and the potentially pathogenic rs749628307 variant were detected in the proband and several family members. A possibly damaging variant rs749628307 was detected in the proband and several family members evaluated in this study. The structural alignment confirmed that the rs749628307 variant did not alter the protein structure significantly and could not cause an impairment or loss of the protein function.Conclusion      This study demonstrated that apparently the rs749628307 variant in the VCL gene does not affect the protein structure in a pathogenetically significant way, neither does it affect the severity and form of the clinical manifestations of HCMP; therefore, it cannot be considered as pathogenic.

[The organization of pre-clinical studies of bactericidal and wound healing effects of the impulse photoherapy device "Zarya"].

The purpose of the study is to determine therapeutic effectiveness of the pulsed high intensity optical irradiation device "Zarya" exemplified by treatment of model wounds in laboratory animals and to compare with traditional methods of wound treatment. The prototype of "Zarya" device was used whose operating principle was based on pulsed irradiation of affected areas with high intensity optical radiation in continuous spectrum generated by pulsed xenon lamp. The therapeutic effect of the "Zarya" device was compared with effectiveness of the certified medical ultraviolet irradiator based on low-pressure mercury lamp and also with known wound-healing and antibacterial medication Levomekol ointment. The mature male rats of Wistar line were used in the study. The animals were distributed to 4 groups: group 1 was irradiated by "Zarya" device, group 2 was irradiated by low-pressure mercury lamp, group 3 was treated with Levomekol ointment and group 4 was exposed to no exposure. The linear wound was modeled according to the standard method under ether anesthesia. The therapeutic procedures were applied daily during 7 days. The bactericidal effect was studied on the basis of smears from wound onto flora on the 2nd, 5th and 7th day. On the 8th day the animals were subjected to euthanasia. It was established that "Zarya" device application permits to reduce considerably both duration of therapeutic procedures and therapy course in general and also to achieve more pronounced bactericidal effect. The obtained data is supposed to be used for development of program of clinical trials.

Effect of Chronic Administration of Obestatin and Its Fragment FNAP-NH2 on Behavioral Activity and Nociceptive Threshold in Rats with Normal and Excess Body Weight.

The effects of chronic intranasal administration of 300 nmol/kg obestatin and its fragment FNAP-NH2 on behavioral activity and nociceptive threshold were examined in male Wistar rats with normal body weight or alimentary obesity. In normal rats, obestatin produced no effect on behavior and nociception, whereas FNAP-NH2 fragment enhanced risk-taking behavior. Rats with excess body weight demonstrated less pronounced risk-taking behavior and elevated nociceptive threshold in comparison with normal animals, but these differences were abolished by chronic administration of FNAP-NH2.

Effect of spatial coherence of light on the photoregulation processes in cells.

The effect of the statistical properties of light on the value of the photoinduced reaction of the biological objects, which differ in the morphological and physiological characteristics, the optical properties, and the size of cells, was studied. The fruit of apple trees, the pollen of cherries, the microcuttings of blackberries in vitro, and the spores and the mycelium of fungi were irradiated by quasimonochromatic light fluxes with identical energy parameters but different values of coherence length and radius of correlation. In all cases, the greatest stimulation effect occurred when the cells completely fit in the volume of the coherence of the field, while both temporal and spatial coherence have a significant and mathematically certain impact on the physiological activity of cells. It was concluded that not only the spectral, but also the statistical (coherent) properties of the acting light play an important role in the photoregulation process.

Changes in Behavior and Blood Corticosterone Level in Male and Female Rats after Single Administration of Obestatin Fragment 1-4.

Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.

Antioxidant Defense System after Single and Chronic Administration of Obestatin and Its Fragment (1-4) to Normal and Overweight Male Rats.

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.

Profiles of mRNA expression for genes involved in implantation, early and middle phases of secretion stage in human endometrium.

The expression of mRNA of 36 genes involved in implantation was studied by reverse transcription and real-time PCR. Significant differences in mRNA expression during the early and middle stages of the secretion phase were detected for genes mmp7, vegf, il2m, il1ß, il8, il18, tnfα, il10, tgfß, igfbp2, etc.

Efficacy of green tea extract in two exercise models.

Oral administration of green tea extract in a dose of 6 mg/kg twice a day (before and after exercise) over 2 weeks significantly increased swimming times on week 1 and 2 in comparison with control animals receiving water. The 7-day and final exhaustive running in rats was accompanied by a significant decrease in spleen weight and iron serum levels associated with developed reticulocytosis. Administration of green tea extract in a dose of 12 mg/kg once a day (before exercise) for 2 weeks did not affect the duration of the running, but prevented the decrease in serum iron and spleen weight, that, along with a significantly increased concentration of reduced glutathione in erythrocytes, can indicate a normalizing effect of green tea extract on hemopoiesis and stimulating effect on the antioxidant system of erythrocytes.

[Repeated action of hyperbaria on rat blood system].

There are considered reactions of male Wistar rat blood system to repeated action of nitrogen-oxygen hyperbaria (pressure 0.5 MPa, density of gas medium 6 g/l, pO2 = 0.02-0.03 MPa). Rats were placed into a barochamber for 5 h 24, 72, and 120 h after the first exposition (control in air without the increased pressure). Parameters of red blood were studied and the general state of the animals was estimated. It has been established that after the first hyperbaria séance the stress-reaction develops in rats with all objective stress parameters (level of corticosteroids and content of ascorbic acid in adrenals). At repeated exposure after 24 h the almost complete normalization of all stress parameters was observed, except for the increased hemoglobin content in plasma as a result of impair of permeability of erythrocytic membranes. After repeated actions 72 and 120 h later, the stress parameters manifested again. After exposure 120 h later, the general state of animals was sharply deteriorated they did not move in the "open" field, could not be hold on a horizontal bar, and mainly were lying. The performed control with the immobilization stress showed that after the initial stress-reaction the rats were recovered completely and at repeated exposures no changes were observed in the blood system and in the general state of the animals. We belive that the hyperbaria-produced stress is connected with difficult breathing under pressure. Thereby, the repeated action of hyperbaria is a harmful factor and habituation to it does not occur.

Effect of anorexigenic peptide obestatin on platelet aggregation and osmotic resistance of erythrocytes.

We studied the effects of the anorexigenic peptide obestatin on the coagulation system and blood rheology (by the parameters of platelet aggregation and osmotic resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro platelet aggregation in the entire dose range and reduced osmotic resistance of erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg had no effect on this parameter). Similar to the results of in vitro experiments, intranasal, intraperitoneal, and subcutaneous administration of obestatin in a dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the osmotic resistance of erythrocytes.

[The effect of antioxidants on erythrocytes in rats during an exhaustive run].

The run of trained rats until exhaustion affected changes of red-ox balance in red blood cells (RBC) and deteriorated the acid stability of RBC. The oral administration of quercetin, 20 mg/kg, caused expansion of oxidative stress in RBC and a significant decrease in RBC acid stability. Pro-oxidant activity of quercetin could contribute accelerated intravascular hemolysis. It was accompanied by a significant reticulocytosis compared with a control group of rats no fed on antioxidant but exposed to run. Green tea extract (GTE) oral administration, 12 mg/kg, resulted in preventing oxidative stress in RBC, increasing in acid stability of RBC and reducing reticulocytosis. Thus, prooxidant activity of quercetin and the high antioxidant efficacy of GTE are indicative of the advantages of the complex preparations containing several antioxidant compounds. Such complex preparations may counteract an oxidative stress and save mechanical stability of erythrocytes under exhausted run.

Effects of GSM-Frequency Electromagnetic Radiation on Some Physiological and Biochemical Parameters in Rats.

Single exposure of white outbred rats to electromagnetic radiation with a frequency 905 MHz (GSM frequency) for 2 h increased anxiety, reduced locomotor, orientation, and exploration activities in females and orientation and exploration activities in males. Glucocorticoid levels and antioxidant system activity increased in both males and females. In addition to acute effects, delayed effects of radiation were observed in both males and females 1 day after the exposure. These results demonstrated significant effect of GSM-range radiation on the behavior and activity of stress-realizing and stress-limiting systems of the body.

[Transgenerational effects of prenatal stress of different etiology].

This paper considers the transgenerational effects of prenatal stress of different etiology. The impacts of stress factors on the biochemical and morphofunctional parameters of life of the mother, fetus, and offspring in the first and subsequent generations (F1-F4) are estimated. Particular attention is paid to assessing changes in the parameters of physical development, the state of the hypothalamic-pituitary-adrenal axis, proinflammatory status, behavioral indicators, cognitive performance, and vegetative balance in the post-stress period. Contemporary concepts of possible mechanisms of transgenerational transmission of the effects of prenatal stress are considered.

[Hyperbaria and stress].

Causes of the appearance of stress-reaction at action of hyperbaira on the organism were studied on rats. It has been established that at the 5-h action of gas mixtures (oxygen-nitrogen and oxygen-argon) under pressure 0.35 and 0.5 MPa and partial pressure of oxygen 0.02-0.03 MPa in the chamber of the volume of 300 1 there is obviously manifested stress confirmed by the corresponding markers. The appearance of stress was connected with the gas mixture density that amounts to 6 g/l, which interferes with respiration mechanically. Use of helium at the same pressure of the gas mixture did not cause stress, as its pressure did not exceed the normal air density. On the other hand, use for respiratory mixtures of elegas (SF6) with density of 6 g/l at the normal pressure produced obvious stress. No difference was revealed in action of nitrogen, argon or elegas at equal density. Thus, use of high pressures needs light gases (helium, hydrogen, neon) that have low density.

[Transgenerational consequences of acute antenatal stress in pregnant rats].

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.

Comparative analysis of the effects of various stress factors at the stage of early organogenesis on heart rate variability in pregnant female rats and their offspring.

We studied changes in the autonomic balance of heart regulation (by the parameters of heart rate variability) in non-pregnant female rats and rats on the days 10-11 of pregnancy on the next day after stress provoked by acute hypobaric hypoxia, intermittent normobaric hypoxia, or immobilization. The same parameters were assessed in 36-day-old offspring. In non-pregnant rats, the intermittent hypoxia resulted in a shift of the autonomic balance of heart regulation towards activation of the parasympathetic nervous system; in pregnant females, immobilization led to a shift of the autonomic balance towards the sympathetic nervous system. In the offspring, the changes also depended on the type of stress.

Behavioral impact of the regulation of the brain 2-oxoglutarate dehydrogenase complex by synthetic phosphonate analog of 2-oxoglutarate: implications into the role of the complex in neurodegenerative diseases.

Decreased activity of the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) in brain accompanies neurodegenerative diseases. To reveal molecular mechanisms of this association, we treated rats with a specific inhibitor of OGDHC, succinyl phosphonate, or exposed them to hypoxic stress. In males treated with succinyl phosphonate and in pregnancy-sensitized females experiencing acute hypobaric hypoxia, we revealed upregulation of brain OGDHC (within 24 hours), with the activity increase presumably representing the compensatory response of brain to the OGDHC inhibition. This up-regulation of brain OGDHC was accompanied by an increase in exploratory activity and a decrease in anxiety of the experimental animals. Remarkably, the hypoxia-induced elevation of brain OGDHC and most of the associated behavioral changes were abrogated by succinyl phosphonate. The antagonistic action of hypoxia and succinyl phosphonate demonstrates potential therapeutic significance of the OGDHC regulation by the phosphonate analogs of 2-oxoglutarate.

[Postnatal behavioral consequences of antenatal intermittent hypoxia experienced during early organogenesis in mature rats].

This study analyses the spontaneous behavior and anxiety-phobic status of mature rats that were subjected to antenatal intermittent hypoxia during the early stages of organogenesis. Antenatal intermittent hypoxia caused a decrease of motor activity as well as an enhanced anxiety level in rats of both sexes, while males appeared to be more sensitive to hypoxic influence. The effects of single antenatal intermittent hypoxia were more expressed than those of double exposure.