Efficient Sensitized Luminescence of Binuclear Ln(III) Complexes Based on a Chelating Bis-Carbacylamidophosphate.

Binuclear rare earth complexes Ln2L3phen2 (LnIII = NdIII, SmIII, EuIII, TbIII, DyIII, YbIII and YIII) with bis-CAPh type ligand - tetramethyl N,N'-(2,2,3,3,4,4-hexafluoro-1,5-dioxopentane-1,5-diyl)bis(phosphoramidate) (H2L) and 1,10-phenanthroline (phen) were synthesized and characterized by elemental analysis, IR, NMR, absorption and luminescence spectroscopy. Luminescence measurements were performed for all the complexes in solid state and for the EuIII, TbIII and YIII complexes - in solution in DMSO as well. The effective energy transfer from organic ligands to LnIII ions strongly sensitizes the LnIII ions emission and under excitation by UV light, the complexes exhibited bright characteristic emission of lanthanide metal centers. It was found that the energy level of the ligands lowest triplet state in the complexes matches better to resonance level of EuIII rather than TbIII ion. Depending on temperature the emission decay times of solid europium and terbium complexes were in the range of 1.5-2.0 ms. In solid state at room temperature the EuIII complex possess intense luminescence with very high intrinsic quantum yield 91% and decay time equal 1.88 ms.

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro.

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene.According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 µM concentration at 72 h of cells treatment was shown. Under combined action of 16 µM C60 fullerene and HL, the value of IC50 was detected at lower 5 µM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 µM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation.Application of C60 fullerene in combination with 2.5 µM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.

Influence of iatrogenic hypercorticoidism induced by long-term application of dexamethasone on power of muscular contraction of white rats.

Research objective consisted in detection of nature of the changes of the myothermiс and the ergometric parameters of the contraction of the forward tibial muscle of rats in the course of performing of the tiring work at the saturation of an organism by therapeutic doses of dexamethasone. Method: The experiments were performed on sexually mature rats-females (200-220 g), divided into control (n = 10) and experimental (n = 60) groups. The animals of experimental group received dexamethasone (D, KRKA, Slovenia) in a dose of 0,25 mg/kg (intraperitoneal, 1 time in 2 days) during from 10 to 60 days. On anesthetized animals (sodium thiopental, 100 mg/kg) with the use of myothermia and ergographia the nature of change of power of the muscle's contraction in the course of the performance of the tiring work (3 six-second tetanus with external loading of 80 g) was studied. Restults: At the initial stage of the development of iatrogenic hypercorticoidism (after 5-20 injections of D) the initial value of the external work of the muscle in comparison with the control is significantly lower (for 30-52%) and the temperature cost of the unit of the work (TCMW), on the contrary, - is higher (for 26-82%). On the end of the 2-month period of application of D the initial values of the power parameters of the muscle came back to control level. During the performance of the tiring tetanus in animal experimental groups the decline of the external work of the muscle is greater (69-73%) compared with the control (55%). This effect does not depend of the number of injections of D, which indicates about a high pathophysiological activity of glucocorticoid concerning working capacity of the muscle. At expressed fatigue the TCMW always increases from 104% (5 injections of D) to 230% (20 injections); at control animals the effect of the tiring work on TCMW is significantly weaker (28%). At long-term application of D (2 months) the described effect of the preparation is weakened, though remains accurately expressed. Conclusion: The obtained data are considered from the point of view of formation at the hypercorticoidizm of the pathophysiological mechanism - the increase of power cost of muscular work. The revealed effect of D can be the cornerstone of the formation of the number of the pathophysiological mechanisms in neuromuscular system including causing the development of the myopathy at the hypercorticoidizm.

[AMPLITUDE-FREQUENCY'S DEPENDENCE OF M-RESPONSE OF THE SKELETAL MUSCLE OF RATS WITH EXPERIMENTAL HYPERCORTICOIDIZM].

In experiments over the mature white female rats the influence of the hypercorticoidizm (simulated by daily parenteral injection of hydrocortisone in a dose of 3 mg/kg/days for 30 days) on some parameters of the M-response of the forward tibial muscle with a different frequency of stimulation of the low-tibial nerve is studied. It is established that the hypercorticoidizm is followed by lengthening of the chronaxia of the forward tibial muscle at its indirect irritation (by 69 per cent), deterioration of stability of M-response's generation, lengthening of the latent period (by 30 per cent) and to reduction of amplitude (by 29 per cent) of single M-responses against increase in frequency of polyphase potentials (to 35 per cent). At animals with hypercorticoidizm in the range of low frequencies of nerve's stimulation (10-30 imp/s) periodic generation of higher-amplitude M-responses, than at control, against their low initial amplitude was observed, which can testify in a favor of an initial partial blocking of synapses. The hypercorticoidizm was followed more expressed, in comparison with control, decreasing of M-responses' amplitude in the process of increasing in frequency of low-tibial nerve's stimulation, decreasing in frequency of nerve's stimulation on achievement which inverse relationship between M-responses' amplitude and frequency of nerve's irritation was established.

INHIBITORY POTENTIAL OF POLYHYDROXYLATED FULLERENES AGAINST PROTEIN TYROSINE PHOSPHATASE 1B.

Inhibition of PTP1B by polyhydroxylated fullerenes was studied in silico and in vitro. The enzyme kinetics in the presence of polyhydroxy small gap fullerenes showed that reciprocal value of maximum velocity non-linearly increases with increasing the inhibitor concentration. Analysis of the dose-dependent curve of PTP1B inhibition suggests an apparent positive cooperativity with involvement of at least two binding sites for the hydroxylated fullerene cages. Molecular docking calculations indicated that highly hydroxylated fullerene C60 may occupy the active site and additional allosteric binding site with similar affinity. In silico analysis of a number of fullerenols with 6, 12, 18, 24, 30, and 36 hydroxyl groups showed that the inhibitory activity may depend on the degree of hydroxylation of the nanoparticles surface. These data provide some understanding of the mechanisms of inhibitory action of fullerenols on activity of protein tyrosine phosphatases.

[Thyroxine caused modulation of dexamethasone effects on the skeletal muscle of white rats].

Experiments in situ on mature white female rats performed with the use of electrophysiological methods allowed to investigate the modulatory influence of thyroxin at the dose which does not cause the signs of hyperthyroidism (10 mkg/ kg), upon the manifestation of the dexamethasone effects on the functional state of the anterior tibial muscle. It has been established that the chronic isolated application of dexamethasone was accompanied by reduction of the amplitude ofmuscle contraction (by 29.7-59.3 per cent after 10-50 days of the drug injection) and the weight of anterior tibial muscle (by 22.4-12.7 per cent after 10-60 days of the drug injection). Combination of thyroxin with dexamethasone smoothed the negative effects of the synthetic glucocorticoid upon the muscle contraction amplitude and even caused its increase (by 41.2-62.1 per cent after 20-60 days of injection of the pair of preparations), as well as prevented the reduction of the muscle weight. The isolated application ofdexamethasone after the first 20 days of injections caused the decrease of the muscle speed that was confirmed through a lengthened control of the muscle active state duration (by 20.5 per cent) and the reduction of its single contraction development speed (by 45.3 per cent), as well as the decrease of frequency of muscle tetanization (to 12-20 imp/s against 26-28 imp/s in control). The application of thyroxine with dexamethasone shortened the active state of the muscle (by 19.3 per cent) and increased the speed of single contraction development (by 72.4), which remained throughout whole further period the preparations were injected. These observations favor for improvement of high-speed characteristics of the muscle under the influence of thyroxine. At the same time, during chronic injection of dexamethasone either alone or in combination with thyroxin, an increased muscle fatigue during the first 10-20 days has been observed.

[Modulation of the effects of dexamethasone in rat skeletal muscle by testosterone].

In experiments on young females white rats by means of methods of electromyography and ergography we investigated the efficiency of a testosterone-propionate for smoothing of negative effects of dexamethasone on skeletal muscle. It has been established that the chronic injection of dexamethasone causes the decreasing of amplitude of contraction of forward tibial muscle on 29.7-59.3% (after 5-25 injections) and the lengthening of the latent period of muscle's excitation on 18.5-16.5% (after 15-25 injections), whereas the complex application of testosterone and dexamethasone prevents the changing of these parameters. At the same time testosterone didn't provide the smoothing of negative influence of dexamethasone on muscle's resistance to fatigue development.

[Influence of thyroxine on display of dexamethasone's effects on M-response's parameters of skeletal muscle of white rats].

In the studies on white rats-females it was studied the dynamics of the change of some parameters of the M-response of a forward tibial muscle in the process of dexamethasone injection (in a dose of 0.25 mg/kg), applied separately and combined with injection of thyroxine (in a dose of 10 mkg/kg). It was established that the application of thyroxine in a complex with dexamethasone prevented the lengthening of the latent period, the decrease of amplitude and the shortening of the duration of the M-responses, taking place at the isolated injection of dexamethasone and also caused an essential decrease of frequency of polyphase potentials of the muscle. Besides, thyroxine prevented the development of the essential decrement of the amplitude and the lengthening of the latent period of M-responses in the process of indirect electric stimulation of the muscle with a frequency of 4 imp/s, typical of the isolated application of dexamethasone.

[Alpha-rhythm of the EEG in directed attention]. / Al'fa-diapazon EEG pri napravlennom vnimanii.

Degree of manifestation and synchronization of rhythmic alpha-range components in various cortical areas was studied in healthy adult subjects in conditions of controlled computer experiment by spectral-correlation method of EEG analysis during directed attention previous to discrimination of tactile, auditory and visual stimuli. The obtained results show that in preparation for discrimination of heteromodal stimuli, specific reconstructions take place of alpha-range electrical activity determined by signal modality. These changes are expressed in a local increase of the degree of synchronization of alpha oscillations in those projection and associative brain areas which are connected with the analysis of the given stimuli. Functional significance of these reconstructions is seen in the fact that they are significantly more expressed at correct recognition. A hypothesis is suggested about participation of the alpha-range in neurophysiological mechanisms of directed attention.

[Electrophysiologic analysis of the process of recognizing target and non-target stimuli in healthy and oligophrenic children]. / Elektrofiziologicheskii analiz protsessa poznaniia tselevykh i netselevykh stimulov u detei v norme i pri oligofrenii.

In an automatized experiment, with a computer on line, amplitude-temporal parameters of evoked potentials (EPs) to purposive and non-purposive stimuli (digits), were analyzed in normal and mental retarded children. At unilateral stimuli presentation to the left or right visual half-fields EPs were recorded simultaneously in projection, TPO, parietal and central areas of the left and right hemispheres. It has been shown that in normal children, differential involvement of projection and associative structures in the analysis of sensory information takes place in both hemispheres. The amplitudes of most EP components in the range of 100-400 ms to the purposive stimuli are higher than to the non-purposive ones. Considerable similarity of EPs developing in response to ipsi- and contralateral stimulations of visual fields ("direct" and "transmitted" EP) is observed. In mental retarded children significant changes are revealed in intra- and interhemisphere organization of the process of perception of purposive and non-purposive stimuli. In the right hemisphere structures there are no differential EP reactions to the two types of stimuli. Significant, in comparison with the norm, prolongation of the latencies of most EP components is noted, especially in the structures of the left hemisphere, to the purposive stimuli. In the process of perception, changes are seen of the integration of functions of both hemispheres. The totality of disturbances of systemic brain organization at perceptive activity in mental retarded children may reflect neurophysiological mechanisms of mental deficiency.

[Electrophysiological analysis of the perceptive activities of children with normal and retarded mental development]. / Elektrofiziologicheskii analiz pertseptivnoi deiatel'nosti detei s normal'nym i zaderzhannym psikhicheskim razvitiem.

Visual EPs of the occipital, parieto-temporal-occipital, parietal and central areas of the left and right hemispheres in response to unilaterally presented stimuli (figures) were analyzed in normal and developmentally backward children. In tasks of detection and recognition of the signal, developmentally backward children manifested a lowered reactivity of associative cerebral structures, especially of the left hemisphere, during perceptive activity, and a changed, in comparison with normal, interhemispheric interaction in processing of sensory information. It is suggested that properties of brain system organization during perceptive activity reflect to a certain extent neurophysiological mechanisms of disturbance of cognitive processes in developmentally backward children.