Xenon Antiaggregant Effects.

In in vitro model of short-term therapeutic inhalation of Xe/O mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.

The Role of JNK and p53 in the Regulation of Secretory Function of Neuroglial Cells of Various Types in β-Amyloid-Induced Neurodegeneration.

We studied the effect of JNK and p53 inhibitors on the production of neurotrophic factors stimulating the realization of the growth potential of neural stem cells by neuroglial cells of various types under conditions of simulation of induced β-amyloid neurodegeneration in vitro. It was shown that β-amyloid stimulates the production of neurotrophins by astrocytes and microglial cells, but does not affect the functioning of oligodendrocytes. JNK and p53 were not involved in the secretion of neurotrophins by intact astrocytes.

The Role of cAMP-Dependent Intracellular Signaling Pathways in the Regulation of the Functions of Neural Stem Cells and Neuroglial Cells in Amyloid-β-Induced Neurodegeneration.

Under conditions of neurodegeneration modeled in vitro by the β-amyloid peptide-(25-35) fragment (Aβ), we studied the role of individual links of cAMP-dependent intracellular signaling pathways in determining the proliferation and differentiation status of neural stem cells (NSCs) and colony-stimulating activity of supernatants from neuroglial cells. The important role of intracellular cAMP and PKA in the inhibition of the progression of the NSC cell cycle and stimulation of the process of their specialization induced by Aβ was found. The selective ability of PKA to block the production of factors constituting colony-stimulating activity by neuroglial cells under conditions of their cultivation in vitro with a neurotoxic agent was revealed.

Effect of Paclitaxel on the Hemostatic Potential of the Blood in the Experiment.

The duration and severity of prothrombotic effects of the maximum tolerated dose of paclitaxel (40 mg/kg) were evaluated in intact outbred mice. Hemostasis was assessed before and on days 1, 2, 5, 7, 10, 15, 20, and 30 after a single injection of paclitaxel using standard coagulation tests (activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin III) and a "global" method, low-frequency piezothromboelastography. A pronounced prothrombotic effect of paclitaxel was revealed starting from the first day postinjection that consisted in intensification of fibrinogenesis up to the 7th day in parallel with activation of the anticoagulant mechanisms.

Functional State of Various Types of Regenerative-Competent Neural Tissue Cells in β-Amyloid-Induced Neurodegeneration.

We analyzed the content and functional activity of various types of regenerative-competent cells of the subventricular zone of the cerebral hemispheres in experimental mice under conditions of in vitro modeling of β-amyloid-induced neurodegeneration. Fundamentally different (opposite) effects of β-amyloid on functional activity of multipotent neural stem cells (NSC) and neuronal committed progenitors (NCP) were revealed. β-Amyloid suppressed proliferation of NSC and stimulated their differentiation.

The Role of MARK ERK1/2 and p38 in Regulation of Functions of Neural Stem Cells and Neuroglia under Conditions of β-Amyloid-Induced Neurodegeneration.

The role of ERK1/2 and p38 in the realization of the growth potential of neural stem cells and secretion of neurotrophic growth factors by glial cells was studied using in vitro model of β-amyloid-induced neurodegeneration. It was shown that amyloid-β fragment 25-35 significantly inhibits the cell cycle progression of neural stem cells against the background of stimulation of their differentiation and reduced production of growth factors by neuroglia. The inhibitory role of ERK1/2 and p38 in relation to the proliferative activity of neural stem cells and the secretory activity of glial elements was revealed.

The Role of JAKs and STAT3 in Regulation of Regenerative-Competent Cells of the Nervous Tissue in β-Amyloid-Induced Neurodegeneration.

We studied the role of JAKs and STAT3 in the growth potential of neural stem cells and the humoral neurotrophic function of neuroglia in modeling β-amyloid-induced neurodegeneration in vitro. It was found that these signaling molecules do not participate in the neural stem cell functioning, and JAKs plays an inhibitory role (realized, however, without STAT3) in the secretion of neurotrophins by glial cells under conditions of their optimal vital activity. The effect of β-amyloid on progenitor cells is accompanied by the appearance of a "negative" effect of STAT3 signaling pathway on their proliferative activity.

Nf-κb: A Target for Synchronizing the Functioning Nervous Tissue Progenitors of Different Types in Alzheimer's Disease.

Background: The efficacy of Alzheimer's disease (AD) treatment can be enhanced by developing neurogenesis regulation approaches by synchronizing regenerative-competent cell (RCCs) activity. As part of the implementation of this direction, the search for drug targets among intracellular signaling molecules is promising.

Objective: This study aims to test the hypothesis that NF-кB inhibitors are able to synchronize the activities of different types RCCs in AD.

Changes in Hemostasis System in Outbred Female Mice with Cisplatin-Induced Procoagulant Status.

Procoagulant status was modeled in outbred female mice by single injection of cisplatin in a maximum tolerated dose and hemostasis parameters monitored over 30 days by methods of coagulogram and low-frequency piezothromboelastography (global test). Monitoring revealed waveform changes in the hemostatic potential: the structural and chronometric hypercoagulation recorded starting from the first day and attaining its maximum on days 5-7 was followed by hypocoagulation and returned to normocoagulation on day 30. This pattern reflects prolonged effect of cisplatin: formation of severe dysfunction of the endothelium providing the main anticoagulant pool of hemostasis (day 1) aggravated by disturbances of the plastic functions of the liver (days 15-20), and recovery (days 20-30).

Features of Pharmacodynamics of the Anticoagulant Dabigatran in Secondary Thrombophilia.

One of the crucial risk factors for development of severe postthrombotic disease (PTD) is the recurrence of deep vein thrombosis (DVT). New opportunities for pharmacological thromboprophylaxis of secondary thrombophilia were associated with the direct thrombin inhibitor-Dabigatran (Pradaxa; Boehringer Ingelheim, Germany). We aimed to investigate the daily pharmacodynamics of dabigatran in healthy volunteers and patients with PTD.