[The role of polypeptide compounds in mechanism of CNS plasticity in patients with hereditary pathology of peripheral motor neuron]. / Rol' rostovykh polipeptidnykh soedinenii v mekhanizme plastichnosti TsNS u bol'nykh nasledstvennoi patologiei perifericheskogo dvigatel'nogo neirona.

Synaptic pruning is a physiological mechanism of neuroplasticity, which is regulated through synthesis of growth polypeptides, neurotrophins. The role of neurotrophins in the mechanism of synaptic pruning in patients with hereditary pathology of peripheral motor neuron was studied in a clinical experimental trial. It was found that patients had elevated levels of regulatory growth polypeptides, which led to the axon growth inhibition effect in organotypic tissue cultures. Thus, neurotrophin overexpression can be considered as a factor preventing synaptic pruning and contributing to further process of neurological degeneration in nerve tissue in patients with hereditary pathology of peripheral motor neuron.

[Remodeling of Cardiovascular System: Causes and Consequences].

Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, ß-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension.

[INVOLVEMENT OF р38 МАРК OF SENSORY NEURONS IN OUABAIN-ACTIVATED SIGNALING CASCADE].

Recent investigations of the new transducting function of Na+,K+-АTPase is of great interest. Na+,K+-АTPase might be a target (receptor) for cardiotonic steroids. This membrane protein switches on intracellular signaling mechanisms due to its ligand-receptor interactions with the steroids that, in turn, result in activation of intracellular cascade processes. р38 belongs to mito-gen-activated protein kinase family (MAPK). The kinase transduces signals of wide range intra-cellular signaling cascades that control proliferation, differentiation, and survival. Using embryonic organotypic tissue culture method the present work shows that р38 МАРК is involved in the signal transducting process in series with Na+,K+-АTPase.

[THE USING OF THE METHOD OF RECONSTRUCTION OF OPTICAL CROSS SECTIONS FOR INVESTIGATION OF THE TROPHOTROPIC EFFECTS OF ADRENALINE AND ATENOLOL].

The trophotropic effects of epinephrine and atenolol were investigated by using the organotypic culture method combined with the method of the reconstruction of optical cross sections. For the best possible image contrast was experimentally established the correction for Petri dish bottom thickness equal to 1 mm (objective lens Carl Zeiss). It was shown by method of the reconstruction of optical cross sections that growth zone in organotypic culture forms a multidimensional structure. In the presence of atenolol (10(-4) M) the thickness of the growth zone of the cardiac tissue explants was above the reference value 212%. The thickness of the growth zone in the presence of epinephrine (10(-9)-10(-13) M) did not differ from the control values. Experimentally was proved that atenolol mimics the trophotropic effects of epinephrine and these effects of epinephrine is realized primarily through ß1-adrenergic receptors.

The effect of marinobufagenin on the growth and proliferation of cells in the organotypic culture.

In recent years, a substantial interest has been aroused in investigating Na(+),K(+) ATPase as a membrane structure which not only performs its direct function in maintaining the gradients of Na(+) and K(+) concentrations, but also may participate in the intracellular signal transduction processes in response to various physiological stimuli. The effect of marinobufagenin, a digitalislike factor, on the growth and proliferation of sensory ganglia, cardiac, retina, skin, and liver tissue explants of 10-12day old chicken embryos was investigated by the organotypic culture method in a wide range of concentrations (10(-10) to 10(-4) M). It was first demonstrated that marinobufagenin inhibited the growth of the investigated tissue explants in the dosedependent but not tissuespecific manner. The experimental data obtained allow us to suggest that the mechanism of regulation of tissue growth by marinobufagenin during the embryonic period of ontogenesis is associated with the modulation of the pump function of Na(+),K(+) ATPase but not its transducing function.

Organotypic tissue culture investigation of homocysteine thiolactone cardiotoxic effect.

Homocysteine thiolactone was demonstrated to inhibit the growth of 10-12-day-old chicken embryo cardiac tissue explants at 7 × 10⁻9 -1 × 10⁻³ M concentrations in a dose-dependent manner. The maximal cardiotoxic effect of homocysteine thiolactone was detected at 1 × 10⁻³ M, which corresponds to severe hyperhomocysteinemia. The results of experiments on culturing of cardiac tissue explants in the medium containing homocysteine thiolactone (1 × 10⁻³ M) and ouabain at concentrations regulating the signal-transducing (1 × 10⁻¹° M) and pumping (1 × 10⁻8 M) functions of Na⁺,K⁺ -ATPase indicate that the cardiotoxic effect of homocysteine thiolactone is supposed to result from inhibition of the Na⁺,K⁺ -ATPase pumping function.

[The influence of ouabagenin on the growth and proliferation of cells in the organotypical culture].

The aim of the present work was to investigate the effect of ouabagenin on the growth and proliferation of cells in organotypic culture. The objects of study were explants of nerve, cardiac, retina and liver tissue of 10-12 day old chicken embryos. Inhibitor of Na+,K(+)-ATPase ouabagenin was investigated in a wide range of concentrations (0.1 nM-1 mM). It has been found that the ouabagenin controls cell growth and proliferation in a dose-dependent manner and tissue-unspecific. The data obtained show that ouabagenin regulates only the pumping function of Na+,K(+)-ATPase.

Effect of ouabain on growth of skin explants in organotypic culture.

Organotypic culture was used to study the effects of glycoside ouabain and its aglycone ouaba-genin on the growth of skin explants from 10-12-day chicken embryos. The tested agents demonstrated dose-dependent inhibition of skin growth. The effective concentrations imply that ouabain and ouabagenin mediate their inhibitory effect on the skin growth via interaction with α1-isoform of Na(+),K(+)-ATPase that plays mostly the role of ionic pump.

Effect of anoceptin on detoxifying function of the liver.

The absence of negative effects of anoceptin on the liver tissue and detoxifying function was proven experimentally in vitro and in vivo. It was proven for the first time that comenic acid (anoceptin active substance) in concentrations of 10(-4)-10(-12) does not modulate the growth of liver explants from 10-12-day chicken embryos. The effect of anoceptin on the detoxifying function of the liver was studied on Wistar rats under conditions of hexenal-induced sleep. The drug was injected into the caudal vein for 90 days in a daily dose of 5, 100, or 300 mg/kg. The duration of hexenal-induced sleep was evaluated before and on days 30 and 90 of the study. Anoceptin did not modify the duration of hexenal-induced sleep and the status and detoxifying function of the liver.

[Application of polyguanidine solution for fixation of biological and anatomical specimens].

A new method for fixation of biological material is described, and its effectiveness is compared to that one of formalin fixation. As an embalming agent, polyhexamethylenguanidine (PHMG) hydrochloride was used. Using the proposed method of fixation, the anatomical and histological preparations of human organs and of chick embryos at developmental 12 days, were produced. The anatomical preparations obtained show the appearance, similar to that of the recently removed organs. Histological preparations were free from significant distortions of the microscopic characteristics of the specimens, which are typical to the material fixed with formalin. The results of the study suggest the possibility of PHMG application in the morphological studies.

[Role of oubain in regulation of growth of different tissues].

Using the method of organotypical cell culture, experimental data was obtained supporting the hypothesis that chelate complex ouabain-Ca2+ modulates the transducer function of Na+, K+- ATPase. Quantum-chemical calculations helped to elucidate two principally distinct modes for chelation of Ca2+ ions by ouabain molecule. It is predicted that ligang-receptor complex of ouabain-Ca2+--Na+,K+-ATPase is formed due to ion-ionic bonds. The forming of this complex switches on the transducer function of the sodium pump. Our data also show that removal of free Ca2+ ions from the cell culture media using EGTA has no effect on binding of ouabain with pumping control site of Na+K+-ATPase.