Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova最新文献

The article reviews the literature regarding the role of c-Jun-N-terminal kinases (JNK) and its inhibitors in brain damage in the settings of ischemia and reperfusion injury. The implication of JNK in signaling mechanisms involved in ischemia-reperfusion-induced cerebral injury are discussed. Described effects associated with JNK inhibition using synthetic and natural substances in experimental models of ischemic and reperfusion injury of the brain. Results of experimental studies demonstrated that JNK represent promising therapeutic targets for brain protection against ischemic stroke. However, multiple physiologic functions of various JNK family members do not allow for the systemic use of non-specific JNK inhibitors for therapeutic purposes. The authors conclude that the continuous search for selective inhibitors of JNK3 remains an important task.

IEM-2062 [1-(6-aminohexylamino)-1-phenylcyclohexyl dihydrochloride], causing a combined block NMDA and AMPA receptors, after chronic oral administration in doses, respectively, 0.3 and 3 mg/kg, induce maximal anticonvulsant effect in the pentylenetetrazol kindling rats because decrease the number of completely kindling rats by 100 %, and also decrease in 2.5-3.3 times the average severity of clonic-tonic kindling seizures. IEM-2062 causes significant anticon- 299 vulsant effects in the widest range of doses, 1-48 mg/kg, which is 24-22 times more than that of memantine (12-20 mg/kg) and sodium valproate (100-200 mg/kg). Sodium valproate and memantine cause significant disturbances of locomotor activity in the «open field» test in doses causing maximal anticonvulsant effect in the kindling rats. At the same time IEM-2062 cause disturbance of locomotor activity only in very high dose of 92 mg/kg, which exceeds in 30.7 times the dose causing the maximum anticonvulsive effect in the kindling rats. Thus, IEM-2062 reduces the severity of kindling seizures in 1.7-1.9 times stronger than sodium valproate and memantine and also by 30.7 times is safer than sodium valproate and memantine.

The review represents a modern concept about cells-molecular basis of mechanisms of neuro-immune interactions, the data on the effects of destabilizing factors (electric pain stimulation, rotation, cold and psychoemotional stress) on the functioning of neurons and immune cells. It must be underlined, that under the stress conditions take place the alterations of ligand-receptors interactions on the membrane of lymphocyte. In particular the reaction of these cells to regulating signal - application of Interleikin-1 grow up after mild stress, but it falls down after an influence of severe stress factors. Special attention is paid to the role of the orexinergic system in mechanism of realization of CNS reactions to application of antigens. In the present work the possible methods of correction of imbalance in functional interactions between nervous and immune systems, caused by different destabilizing factors, are reviewed.

Changes of the alpha1 and alpha2 rhythms during convergent (addition in the mind) and divergent (heuristic task solving) thinking due to rational and irrational cognitive styles were studied. It is shown that the functional activity of the cerebral cortex during convergent thinking was associated with rational style and presented in parietal low-frequency alpha1 biopotentials whereas during divergent thinking - with the irrational, and this effect was produced by widespread regional and frequency differences of alpha1 and alpha2 oscillations in posterior cortex. The originality of ideas correlated with the alpha desynchronization in the posterior cortex in the persons with high intuition, whereas the persons with low intuition characterized by the alpha synchronization.

Unlike prosthetic hearing, which develops technology for more than 30 years, the problem of the vestibular prosthesis developed a little more than one and half decades. Meanwhile, the involvement of the vestibular system in ensuring the normal functioning of the visual, motor and other systems of the body determines its decisive contribution to the spatial orientation of humans and animals. In case of damage of the vestibular apparatus (the labyrinth), there are serious violations of posture control, stabilization of sight, spatial orientation, psychological status, that is, in the aggregate quality of human life deteriorates. At present, on the animals developed technology of prosthetic semicircular canals, sensing angular acceleration, and control eye movements in dynamic situations. New approaches based on the replacement of the lost natural vestibular afferent impulses by electrical stimulation through multichannel vestibular prosthesis, are successfully introducing into the clinic.

The frequency of cells with abnormal nuclear morphology (micronuclei, perinuclear vacuo-les, notches, protrusions, such as «tongue» and «broken egg») in the buccal epithelium of wrestlers on different days of the competition period was identified. The largest number of violations observed on the 3rd day after the competition. It was conducted psychological testing of athletes and it was determined 16 psychological characteristics associated with the aggressiveness of athletes. It was revealed the effect of psychoemotional state on the cytogenetic apparatus athletes. It was found associations of the dynamics of reactive anxiety athletes and frequency of nuclear aber- 327 rations. The hypothetical scheme of influence human aggression and related psychological characteristics of its genetic apparatus by neurohumoral system was constructed.

The effects of the Nothrombel on the formation of platelet-leukocyte complexes (PLCs) induced by thrombin was studied. It was shown, that Nothrombel dose-dependently inhibited the formation of PLCs. Its activity is higher than the activity of the comparison compounds Aspirin. The half maximal effective concentration (EC50) for Nothrombel is 1.75 mMol/mL, for Aspirin is much more than 2.5 mMol/mL. The inhibition mechanism of the PLCs formation by Nothrombel caused by the ability of this drug to inhibit the P-selectin translocation on the platelet membrane, the expression of membrane complex GPIb-IX-V, the mobilization of cytoplasmic calcium in platelets, as well as, apparently, its inhibitory effect on platelet P2Y12 purine receptors.

We study the dependence of the mitogen-induced cytokine secretion by splenocytes from the character of the behavior of F1 (C57BL/6XDBA/2) mice in environments with different degrees of spatial complexity: simple in the form of home box, enriched box and maze. Suppression of in-terleukins IL-2, IL-4, IL-6 and IL-10 expression, regardless of their structural and functional properties, was observed only in an enriched environment when aggressive and neurotic manifestations were increased. The opposite effect in the form of significant increase of the productions in all studied cytokines was observed in the case of the stereotypical goal-directed behavior in a maze. It was supposed that cytokines of the splenocytes are involved in the realization of highly 307 differentiated adaptive response of the organism due to the influence of social and cognitive factors, the expression of which depends on the specific physiological and biochemical systems.

Activation of m-, d1-, d2- and k1-opioid receptors increases cardiac resistance to ischemia-reperfusion. The cardioprotective effect of opioids in many cases appears to be associated with the activation of the peripheral OR. However, when it comes to non-peptide agonists OR able to cross the blood-brain barrier, we cannot exclude the involvement of central opioid receptors in cardioprotection. Endogenous opioids are not involved in the regulation of cardiac tolerance to ischemia- reperfusion in non-adapted animals. Stimulation of k1- and d1-OP may exert delayed cardioprotective effect. Activation d- and k1-OP reduces the intensity of cardiomyocyte apoptosis after reperfusion. The results of studies related to the inotropic effect of opioids during reperfusion of the heart remain highly controversial.

Reduced insulin sensitivity plays an important role in the pathogenesis of type II diabetes. Est-radiol increases sensitivity to insulin. Effect of estradiol may be due to the influence on gene expression, level of proteins or activity of insulin signaling pathway components and insulin target proteins. Effect of estradiol also may be due to the influence on GLUT4 translocation in the cell membrane. Effects of estradiol on insulin receptor substrate, phosphatidylinositol-3-kinase, protein kinase B, glucose transporter type 4, glucose-6-phosphatase most often examined. In this paper, data on the influence of estradiol on insulin sensitivity in liver, adipose and muscle tissues systematized in order to identify promising areas of research and new targets for pharmacological correction of insulin resistance.