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Biomedical subjects

E A Korneva

Publications and source records attributed to E A Korneva.

At least 19 recordsLinked to original sources

Interleukin-2 concentration in hypothalamic structures of rats receiving peptides during mild stress.

The number of hypothalamic IL-2-containing cells changed in rats receiving Vilon and Epithalon during mild stress (handling). The number of IL-2-positive cells in hypothalamic structures decreased 24 h after intramuscular injection of Epithalon and 2 h after intranasal administration of the test peptides. Adaptation of animals to experimental conditions prevented the decrease in the number of IL-2-positive cells in the supraoptic nucleus after intranasal administration of Epithalon.

Animals↗

Expression of the c-Fos gene in hypothalamic cells and cytotoxic activity of natural killer cells in the spleen of rats after treatment with Cytoxan.

In experiments on rats we studied the effect of cyclophosphamide-containing drug Cytoxan on activation of neurons in hypothalamic structures involved in the regulation of natural killer cell activity in the spleen and changes in cytotoxicity of these cells. Administration of Cytoxan in a dose of 60 mg/kg increased the number of c-Fos-positive cells in the ventromedial hypothalamus and lateral hypothalamic area and reduced interferon-alpha-induced cytotoxic activity of natural killer cells. Our findings attest to the involvement of central mechanisms of regulation of splenic natural killer cells into side effects of Cytoxan.

Animals↗

[Structure and functions of the brain orexin-containing neurons].

The results of investigations of the new discovered brain orexin neurons, their chemical structure, localization and functions are reviewed. The following data are described: the specifics of orexins mRNA, orexins A and B and their receptors; connections between orexin neurons and neurons from different structures of the brain and spinal cord and the participation of the orexin neuron system in the functional regulation.

Animals↗

[Interleukin-1 signal transduction in interaction between the nervous and immune systems].

Ligand-receptor interactions of the cytokine Interleukin-1 (IL-1) with its target cells, and further intercellular signal transduction play the key role in manifestation of its biological effects. Peculiarities of IL-1 signaling are determined by its unique structure and the composition of its receptors. The sphingomyelin pathway of IL-1beta signal transduction is one of the principle signal mechanisms providing realization of most, if not all, biological effects of cytokine. This signaling pathway is initiated by activation of the membrane enzyme neutral sphingomyelinase (nSMase), which catalyses the hydrolysis of membrane shingomyelin to the secondary cellular messenger ceramide. It has been established that IL-1beta operation in the CNS involves mechanisms mediated by IL-1 type beta1 receptor and the shingomyeline pathway of cytokine signal transduction into the cell. Type 1 IL-1 receptor is necessary for IL-1-induced activation of nSMase, the key enzyme of the sphingomyelin cascade. Change in nSMase activity in membranes of nerve and immunocompetent cells is the common link in the stress reaction of neuroendocrinal and immune system cells. nSMase activity seems to be a potential target for testing effects of various pharmaceuticals and interventions, while planning strategy of correction of immune system dysfunctions and neuro-immune interaction disturbances.

Animals↗

Immunoprotective effects of prolactin during stress-induced immune dysfunction.

We showed for the first time that prolactin stimulates the synthesis and release of immunomodulating cytokines and lymphocyte-activating factors (e.g., interleukin-1) by peritoneal macrophages. Prolactin abolished the stress-induced inhibition of proliferation of peripheral blood lymphocytes and increased cell sensitivity to regulatory effects of interleukin-1 in the reaction of lymphocyte blast transformation. These data illustrate the mechanism of immunoprotective activity of prolactin during stress.

Animals↗

Expression of the c-fos gene in spinal cord and brain cells in rats subjected to stress in conditions of exposure to various types of halothane anesthesia.

The influences of different treatments on the expression of the c-fos gene in the spinal cord and brain (hypothalamus) was studied in rats using various types of anesthesia. Synthesis of c-Fos-like proteins occurred only in the spinal cord in conditions of constant 1.5% halothane anesthesia. Use of induction anesthesia with 1.5% halothane allowed detection of c-Fos-like protein expression in cells of the rat spinal cord (lumbar segments) and brain, both when animals were placed in a hammock and when mechanical pain stimulation or electromagnetic irradiation of the skin with UHF currents were applied. The pattern of brain structures reacting to mechanical pain stimulation with expression of c-Fos-like protein was identified. This type of stimulation was shown to induce increases in the quantity of c-Fos-positive cells in the lateral hypothalamic area (LHA), the ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei, and in the ventral hypothalamic area (AHA) by 116%, 167%, 101%, and 157% respectively as compared with controls. Skin irradiation with UHF currents decreased the intensity of mechanical pain stimulation-induced synthesis of c-Fos-like protein in most structures (LHA, VMH, DMN, and AHA by 32.8%, 29%, 15%, and 33% respectively). Only induction halothane anesthesia allowed identification of hypothalamic structures reacting to mechanical pain stimulation and the modifying effects of irradiating the skin with UHF currents on the intensity of these reactions.

Anesthetics, Inhalation↗

[The role of glucocorticoid hormones in interleukin-1 signal transduction via the sphingomyelin pathway].

Interleukin-1 and glucocorticoid hormones are the key transmitters of interaction between the neuroendocrine and immune systems. To study the molecular mechanisms of immunomodulatory effects of Interleukin-1 and glucocorticoid hormones, a search for changes in activity of neutral sphingomyelinase: the main marker of initiation of Interleukin-1beta signal transduction via the sphingomyelin pathway in target cells, was accomplished. The Interleukin-1beta was found to activate neutral sphingomyelinase both in P2 fraction of murine brain cortex and membranes of immune-competent cells. Experimental modifications of endogenous glucocorticoid level in the mouse blood were for the first time shown to induce changes in neutral sphingomyelinase activity in membranes of the cells of the immune and nervous systems. It appears that the sphingomyelinase pathway of Interleukin-1beta signaling might be a possible target for glucocorticoid hormones' immune-modulating effects.

Adrenalectomy↗

Effects of short peptides on thymocyte blast transformation and signal transduction along the sphingomyelin pathway.

Immunomodulating effects of synthetic peptides Vilon (Lys-Glu), Epithalon (Ala-Glu-Asp-Gly), and Cortagen (Ala-Glu-Asp-Pro) and possible involvement of the sphingomyelin signal transduction pathway in their effects in mouse thymocytes were studied. Vilon produced the most potent comitogenic effect on thymocyte proliferation and modulated comitogenic activity of interleukin-1b. Epithalon was less potent, while Cortagen produced no such effects. Vilon produced a more pronounced stimulatory effect on sphingomyelinase activity in mouse thymocyte membranes compared to Epithalon and Cortagen.

Animals↗

In vitro effect of short peptides on expression of interleukin-2 gene in splenocytes.

Synthetic peptides Vilon (Lys-Glu), Epithalon (Ala-Glu-Asp-Gly), and Cortagen (Ala-Glu-Asp-Pro) in vitro activated interleukin-2 mRNA synthesis in splenocytes from CBA mice in the absence of specific inductors. The intensity of interleukin-2 mRNA synthesis in splenocytes depended on the type, concentration, and duration of treatment with the peptides. Vilon and Epithalon were most potent, while Cortagen produced a less pronounced effect on interleukin-2 mRNA synthesis.

Animals↗

[C-fos gene expression in the rat spinal cord and brain cells during stress and the use of different types of halothane anesthesia].

C-fos gene expression was studied as a marker of nervous cells activation in the rat spinal cord and brain cells under different conditions (different kinds of narcosis). Using of 1.5% light halothane narcosis allowed the detection of c-Fos-like proteins expression in the spinal cord cells only. Under initial 1.5% halothane narcosis, c-Fos-like proteins expression in the rat spinal cord (lumbar segments) and the brain cells was observed after placing the rats into the hammock, noxious mechanical stimulation (NMS) or high frequency electromagnetic irradiation of the skin (EHF). The pattern of the brain structures reacting on the NMS by c-Fos proteins expression, was determined. It was shown that NMS increases the c-Fos positive cell quantity in the lateral hypothalamic area (LHA), ventro-medial (VMH), dorso-medial (DMH) hypothalamic nuclei and anterior hypothalamic area (AHN) by 116, 199, 101 and 157% resp., in comparison with the c-Fos immunoreactive cell quantity in intact animals. EHF irradiation of the skin decreased the intensity of c-Fos-like proteins synthesis induced by NMS in the most of the investigated structures (LHA, VMH, DMH and AHA by 32.8, 29, 15 and 33%, resp.). It was shown that only initial halothane narcosis allowed to determine the hypothalamic structures which realized the responses to the NMS, and modification effects of EHF skin irradiation on the intensity of these responses.

Anesthesia, Inhalation↗

[Achievements and problems in studies of antibiotic peptides of an organic origin].

The paper contains the original data of the authors and literature survey in the field of studies of the structure and functions of antibiotic peptides. Physical-and-chemical as well as structural properties of a new subfamily of defensins, i.e. minidefensins (theta-defensins), are described in detail. Mechanisms of the antibiotic action of defensins and bactenecins as well as their role in regulating the body immune reactions are discussed.

Anti-Bacterial Agents↗

[Cell activation in the hypothalamus after exposure to an antigen (based on c-fos gene expression)].

Increase of the c-fos mRNA positive cells number was insignificant in 30 min. following activation of the rat hypothalamic structures with the tetanus toxoid (TT). Elevation of the c-fos mRNA positive cells number occurred in the hypothalamic' posterior (PHA), lateral (LHA), anterior (AHA), areas dorsomedial (DMH), and ventromedial (VMH) nuclei within 2 hours of the TT administration. In 6 hours the c-fos mRNA positive cells number decreased in PHA, LHA, DMH. The c-fos mRNA expression was stable in arquate and supraoptic hypothalamic nuclei following either the TT or saline administration.

Animals↗

C-fos and IL-2 gene expression in rat brain cells and splenic lymphocytes after nonantigenic and antigenic stimuli.

Immunostimulatory or immunosuppressive stress models were used: (1) rotation stress (RS) and (2) immobilization (restraint) stress (IS). Intravenous injection of tetanus toxoid (anatoxin) (TT) was chosen as the antigenic stimulus (500 micrograms/kg weight), and intravenous injection of saline solution was used as the control. Splenic lymphocytes (CBA mice) or different brain structures (Wistar and Sprague-Dawley rats) were analyzed. The c-fos and interleukin-2 (IL-2) mRNA expression was measured using a digoxigenin (Dig)-labeled cDNA probe by spot or in situ hybridization. Rotation stress stimulated IL-2 mRNA synthesis in lymphocytes in the presence of ConA and rIL-2 by 40%. IL-2 mRNA synthesis in lymphoid cells obtained from animals after IS and after IS in combination with the administration in vitro of the cytotoxic drug CsA to the splenic lymphocytes was inhibited (30% and 99%), accordingly, as compared with control rats. Induction of c-fos mRNA synthesis in rat brain cells was noted 30 minutes after RS in the hypothalamus (lateralis hypothalamic area, LHA), thalamus, corpus collosum, and sensorimotor zone of the brain cortex. IL-2 mRNA synthesis was shown two hours after RS in the same structures. The increased number of c-fos mRNA-positive cells two hours after TT injection was shown in the posterior hypothalamus area (PHA), LHA, dorsomedial nucleus (DMH), ventromedial nucleus (VMH), and anterior hypothalamus area (AHA) as compared to the effect of i.v. saline injection. Moreover, IL-2 mRNA-positive cell induction was noted in the PHA, DMH, and VMH. Six hours after TT injection, c-fos mRNA expression was decreased in the PHA, LHA, and AHA. Activation of c-fos and IL-2 mRNA was detected in the paraventricularis nucleus 6 hours after TT i.v. injection. Thus, inhibition or stimulation of IL-2 gene expression in lymphoid cells depends on the nature of the stressors. RS or antigenic stimuli induce c-fos and IL-2 gene expression in definite structures of the brain. The dynamics of this process are time dependent. The partial correlation between c-fos and IL-2 mRNA expression in localization in brain structures and time dependence was shown.

Animals↗

[Interleukin-1 in realisation of stress-induced changes in functions of the immune system].

Stress influences of different duration and intensity induce production of a lymphocyte-activating factor (LAF) by murine peritoneal macrophages, and enhancement of Interleukin 1 (IL-1) level in the murine blood, inducing no alterations in the thymocyte reaction to concomitant action of the IL-1 beta which correlates with changes in the value of humoral immune response. The data obtained are in agreement with differently aimed stress-induced alterations in the activity of the membrane neutral sphingomyelinase: the key enzyme of the sphingomyelin cascade, in the membrane P2 fraction of the brain cortex. The IL-1 seems to participate in physiological mechanisms of realisation of stress reactions on the levels of its production and biological action on target cells as well as of the sphingomyelin pathway of its signal transduction in nerve tissue.

Animals↗

[The role of neutral sphingomyelinase in the interleukin-1beta signal transduction in cells of the mouse cerebral cortex].

Involvement of the sphingomyelin cascade in Interleukin 1 beta (IL-1) signal transduction pathway in membrane fraction P2 of the murine brain cortex, was found. A key role of the membrane enzyme neutral sphingomyelinase (nSMase) in triggering the sphingomyelin pathway for IL-1 beta, was confirmed. The IL-1 beta was shown to activate in a dose-dependent manner nSMase in the P2 fraction of the brain cortex. Employment of both brain cortex membranes from the mice deficient in the type I IL-1 receptor and of IL-1 receptor antagonist made it possible to obtain evidence on the necessity of the IL-1 beta binding to the type I IL-1 receptor for the nSMase activation. It appears that the IL-1 beta effects on the CNS are realized via IL-1 receptor type I and activation of the nSMase as an initiating enzyme of the sphingomyelin cascade.

Animals↗

Effect of peptide Lys-Glu on interleukin-2 gene expression in lymphocytes.

Lys-Glu in vitro stimulated interleukin-2 gene expression in mouse spleen lymphocytes. This effect depended on peptide concentration and duration of treatment. It is hypothesized that this peptide is the shortest regulatory fragment promoting the transport of trans-acting factors into the nucleus. It can not be excluded that Lys-Glu is a structural component of trans-acting factor active centers, which are necessary for the activation of interleukin-2 gene transcription in lymphocytes.

Animals↗