[Study of neuroprotective, antihypoxic and antiamnesic effects of new mixture of tripeptides].

A new mixture of tripeptides (NMT: H-Lys-Asp-Glu-OH, H-Asp-Glu-Pro-OH, H-Asp-Glu-Arg-OH) in doses of 150 and 300 mg/kg per day produces clearly pronounced neuroprotective effect in rats with brain ischemia and decreases neurologic deficiency 1.1 times more effectively than reference drug semax. NMT (10, 50 and 150 mg/kg) had marked antihypoxic effect on mice in hermetic and altitude chamber. NMT in doses of 10 and 50 mg/kg was more effective than semax in hermetic chamber (1.3 and 1.5 times, respectively) and in a dose of 150 mg/kg in altitude chamber (1.9 times). NMT (50 and 150 mg/kg) had also marked antiamnesic effect on model amnesia caused by scopolamine in rats and was more effective (1.5 and 1.4 times, respectively) than semax in equal doses. NMT (50 and 150 mg/kg) also had marked antiamnesic effect on model amnesia caused by maximal electroshock and complex extreme factors in mice and in both doses was 4 times more effective than semax on the first model and in a dose of 150 mg/kg was 2.9 times more effective on the second model. NMT (50 mg/kg) increased the amplitude of transcallosal evoked potential in rat brain by 69% and was more effective than semax in equal dose. Thus, NMT is a promising neurotropic drug with neuroprotective, antihypoxic and antiamnesic activity.

[Confocal laser endomicroscopy in the diagnosis of diseases of biliary ducts].

Are clinical observations of various diseases of the bile ducts, including cholangiocarcinoma, developed with chronic diseases pancreato-biliary zone. Reflected the complexity of instrumental diagnostics at an early stage of the disease. For the first time at the given pathology diagnostic purposes was applied the method of probe confocal laser endomicroscopy allowed in all cases to clarify and verify the diagnosis. Describes the technique of the research, its results are compared with other diagnostic methods. The authors suggest that in the diagnosis of pancreatic and biliary zone method probe confocal laser endomicroscopy can be crucial in inefficiency or uninformative other methods.

[Study of some pharmacological properties of a new adenine derivative].

It is established that the new compound, 9-[2-(4-isopropylphenoxy)ethyl]adenine (9-IPE-adenine) in a dose of 10 mg/kg per day produces neuroprotective effect in rats with brain ischemia model. 9-IPE-adenine decreased the neurologic deficiency 1.2 times more effectively (p < 0.05) than the reference drug mexidol in analogous dose, and had equal effect with this drug at 25 mg/kg per day on the neurologic deficiency and survival of animals. Electrophysiological studies in hippocampal slices in rats showed that 9-IPE-adenine depressed orthodromic population spikes in CA1 area by 42 ± 4%. Non-competitive antagonist of NMDA receptor complex MK-801, in contrast to D-AP5 (competitive NMDA receptor antagonist) and CNQX (competitive AMPA receptor antagonist), enhanced the depressive effect of the new drug more than two times. These ese results are indicative of the ability of 9-IPE-adenine to modulate the ion channel of NMDA receptor complex.

[Investigation into the vestibular protective properties of melatoninergic agents].

Experiments with rats showed that melatonin (2.5 mg/kg) produces a distinct vestibular protective effect excelling promethazine (50 mg/kg) as a reference agent, and also antidepressant agomelatine (5 mg/kg) as another melatoninergic agent. Lusindol, a blocker of MT1/MT2-receptors (2.5 mg/kg), and bicuculline (1.5 mg/kg), a specific GABA-receptors antagonist, weakened the melatonin effect significantly. The results testify mediation of the melatonin action by these receptors. Whole-cell patch clamp in an experiment with convoluted oblongata sections from white nonlinear infant male rats (14-d old) disclosed that melatonin (2 mM) inhibited drastically (29 +/- 3%) the excitatory postsynaptic current caused by depolarization step in neurons of the medial vestibular nucleus. Lusindol (0.1 mM) inhibited the effect of melatonin (2 mM) significantly (71 +/- 6%) which suggests involvement of melatonin MT1/MT2-receptors.

[On the mechanism of ikaron-1 anti-naupathia action].

Pneumomicroinjection of vestibuloprotector ikaron-1 (Russia) in specific neurons of the medial vestibular nucleus (MVN) was studied in cats immobilized by muscle relaxants using microelectrode devices. The original preparation had a direct effect on the majority of MVN neurons (95 %). Thirty four neurons of 37 cells (92 %) developed an inhibitory response, only one cell (3 %) was activated and 2 neurons (5 %) were areactive. Therefore, the inhibitory reaction to the preparation was 34 times more often than excitatory. An investigation of the MVN neurons activity evoked by adequate stimulation of the vestibular apparatus showed that ikaron-1 attenuates the evoked response in 92 % cells. This phenomenon could be behind the ikaron-lantinaupathia action.

[Development of Scotch pine seedlings and functioning of antioxidant systems under the chronic action of lead ions].

This study has shown that the effect of Pb2+ ions (10-150 microM) on Scotch pine seedlings is manifested by a biomass decrease and a delay in development of the root system, including shortening of the main root, reduction of the lateral root formation zone, and reduction of the number of lateral roots. The ability of the root system to deposit Pb2+ ions and to perform a barrier function, preventing Pb2+ uptake into assimilating organs, has been revealed. This ability is blocked if the Pb2+ concentration in the nutrient medium exceeds 80 microM. In the case of heightened Pb2+ concentrations, the content of photosynthetic pigments in pine needles decreases, whereas that in cotyledons increases. Analysis of the proline content and the functioning of the antioxidant enzyme system (superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase) shows that the presence of Pb2+ ions in a wide concentration range does not induce intensive oxidative stress in pine seedlings.

[Genetic diversity and molecular evolution of the influenza A viruses in Russia during 2006-2012].

The results of molecular genetic analysis of more than 280 strains of influenza A virus subtypes H1N1 and H3N2 circulating in Russia in 2006-2012 are presented. The genetic changes underlying the evolution of the virus strains and sensitivity to antiviral drugs were analyzed. Significant changes in the genetic structure of influenza A viruses circulating in the Russian Federation and their phylogenetic affiliation are shown to occur within the studied period. The studies identifying codons under the positive selection in silico in the genes encoding surface proteins of the influenza virus were demonstrated to be efficient for the analysis of the antigenic drift and direction of evolutionary variability of the influenza viruses.

[Effects of different neuromediators and regulatory peptides on the impulse activity of neurons in the superior vestibular nucleus].

The microelectrode technique and microiontophoresis of physiologically active substances in experiments with cats immobilized with the muscle relaxants made it clear that different classical neuromediators (acetylcholine, norepinephrine, gamma-aminobutyric acid (GABA) and others), as well as regulatory peptides (enkephalins, thyrotropin-releasing hormone (TRH), vasoactive interstitial peptide (VIP), somatostatin (SS) and others) can exert a direct effect on the majority (61 to 100%) of neurons in the superior vestibular nucleus (SVN). The inhibiting effect of enkephalins, VIP and SS on the neurons impulse activity remained essentially unchanged by L-glutamate. Also, enkephalins, VIP and SS were found to amplify the inhibiting action of GABA and glycine. Consequently, these substances can fulfill the role of SVN neuromediators and/or neuromodulators.

[Investigation of anti-hypoxic action of 3-hydroxypyridine derivatives in animals with some types of experimental pathology].

Experiments with occlusion of the common carotid artery in mice demonstrated that, unlike mexidol and SK-170, single injection of new derivatives of 3-hydroxypyridine (3-HP) SK-100 and IBKhF-2, and semax have an anti-hypoxic action on the model of acute normobaric hypoxia with hypercapnia. In analogous experiments with rats the distinct anti-hypoxic action was produced by 4 new 3-HP derivatives (SK-100, SK-170, IBKhF-22 at the dose of 100 mg/kg and IBKhF-2 at the doses of 10 and 30 mg/kg--extension of life span by 25-39%), mexidol (100 mg/kg) and reference-class antihypoxant amtisol (30 mg/kg, life span expansion by 19 and 27%, respectively). A series of experiments with rats with acute pancreatitis, a distinct anti-hypoxic action was shown by SK-100, SK-170 at 100 mg/kg and IBKhF at 10 and 30 mg/kg (life span extension by 26-40%), mexidol (100 mg/kg) and amtisol (30 mg/kg) which extended life span by 17 and 22%, respectively. Therefore, SK-100 and IBKhF-2 are potent to prolong life span of equally mice and rats; SK-170 and mexidol were effective only in experiments with rats.

[Effects of different neuromediators and regulatory peptides on the impulse activity of neurons in vestibular zone-I of the cerebral cortex].

Microelectrodes and micro-iontophoresis of physiologically active substances in experiments with cats immobilized by muscle relaxants made it apparent that different classical neuromediators (acetylcholine, norepinephrine, GABA and others) and regulatory peptides (enkephalins, thyrotropin-releasing hormone, vasoactive intestinal peptide (VIP), somatostatin (SS) and others) are capable to influence directly 68 to 100% of neurons in vestibular zone-I of the cerebral cortex. In the presence of L-glutamate, the inhibiting effect of enkephalins, VIP and SS on the neurons impulse activity was essentially unaltered. Also it was shown that enkephalins, VIP and SS are potent to augment the inhibiting effect of GABA and glycine. Therefore, these substances may have the neuromediator and/or neuromodulator role in this cortical zone.

[Effects of various neuromediators and regulatory peptides on the impulse activity of neurons in the lateral vestibular nucleus].

The myoelectrode technique and microiontophoresis of physiologically active substances were applied to cats immobilized with neuromuscular relaxant to show that the classic neuromediators (acetylcholine, norepinephrine, GABA etc.) and regulatory peptides (enkephalins, TRHs, vasoactive intestinal peptide (VIP), somatostatin (SS) and others) can influence directly most neurons (58 to 100%) in the lateral vestibular nucleus (LVN). Enkephalins, VIP and SS retained largely their inhibitory effect on the neuron impulse activity in the presence of L-glutamate. Also, enkephalins, VIP and SS are able to stimulate or suppress the inhibitory effect of GABA and glycine. Consequently, the substances under study may act as LVN neuromediators and/or neuromodulators.

[Evaluation of antihypoxic and antiamnemonic effects of mexicor in animals].

In experiments with mice closed in airtight and altitude chambers mexicor effectiveness against hypoxia was evident only at the dose of 100 mg/kg; effect was nil against acute hemic and histotoxic hypoxia. The reference antihypoxic substance (amtisol succinate, 25-100 mg/kg) excelled mexicor in all models of acute hypoxia. In the model of cerebral infarct in rats, the mexicor neuroprotective effect at the doses from 12.5 to 100 mg/kg was dose-dependent with a nearly linear trend and significantly stronger as compared to amtisol succinate. In amnesia models in mice the antimnemonic effect of the drug at the dose of 50-100 mg/kg was much stronger than of amtisol succinate and comparable to commonly used pyracetam and oxiracetam. Mexicor (5 mM per 53 +/- 4%, 10 mM per 94 +/- 6%) inhibited the orthodromic population response in survival sections of hippocampal CA1 in rats. Stimulation of respiration of isolated mitochondria from rat's cerebral cells showed linear dose dependence in the range from 1 mM to 5 mM. It can be concluded that the antihypoxic, neuroprotective and antiamnemonic action is achievable with high mexicor dosage.

[Modification by various neuromediators and regulatory peptides of the impulsation activity of neurons in the medial vestibular nucleus].

Cats were immobilized with myorelaxation agents to apply the microelectrode technique and microlonophoresis of physiologically active substances. As a result it was shown that various classic neuromediators (GABA, taurine and others) and regulatory peptides (vasoactive intestinal peptide (VIP), somatostatine (SS) and others) have effect on the majority (62 to 100%) of neurons in the medial vestibular nucleus. In the presence of L-glutamate VIP and SS CC retained essentially their inhibitory effect on the neurons impulse activity. Both VIP and SS were found to amplify the inhibitory action of GABA and glycine. To sum up, the substances under study can function as neuromediators and/or neuromodulators in the medial vestibular nucleus.

[Destabilization and stabilization of poly(A).poly(U) structure by platinum(II) compounds].

On the basis of molecular biophysics, a methodology for the analysis of intramolecular structural order of the polynucleotide duplex poly(A).poly(U) has been developed. It was shown that the combination of circular dichroism spectroscopy with differential scanning calorimetry is an optimal approach, which ensures the screening of a wide set of substances and interaction conditions and the choice of compound(s) that can stabilize the structure and increase the biological activity of this duplex. The study is aimed at obtaining a new and highly active antiviral remedy.

[Status of mucous membrane of the maxillary sinus in patients with oral-sinus interconnection in different terms after its appearance].

The status of anatomy-morphology of maxillary mucosa depending on the time of interconnection between the maxillary sinus and oral cavity, the size of it and its function were studied. The study was conducted on 25 patients and 20 cadavers. Changes in the mucous membrane of the maxillary sinus in relation to some of factors are discussed.

[Investigation of the anti-motion sickness effect of 3-hydroxypyridine derivatives].

Experiments with rats showed that three out of 12 3-hydroxypyridine derivatives (ethyl-methyl hyd- roxypyrine succinate, SK-132 and IBCP-2 - had an anti-motion sickness effect stronger than of scopolamine, the reference vestiboloprotector. The anti-motion sickness effect of ethyl-methyl hydroxypyrine was also demonstrated in experiments with cats. Apparent anti-motion sickness effect of ethyl-methyl hydroxypyrine (mexydol) was found in 69% of healthy male volunteers which is comparable with the effect of scopolamine (62%). In experiments with immobilized cats (myorelaxation drugs) the microelectrode technique and microontoiphoresis of physiologically active substances revealed that ethylmethyl hydroxypyrine influences the majority of neurons in the medial vestibular nucleus (61%). Suppression of cell spontaneous activities in more than one half of cases can be stopped completely or attenuated significantly by bicucculine, a specific GABA(A)-receptor antagonist. In 42% of neurons ethyl-methyl hydroxypyrine subdues the response to vestibular stimulation which is likely to underlie the anti-motion sickness effect.

[Pharmacological correction of memory impairment caused by a complex extremal action in mice with bilateral ligation of common carotid arteries]. / Farmacologicheskaia korrektsiia mnesticheskikh rasstroistv, vyzvannykh kompleksnym ékstremal'nym vozdeistiem u myshei s pereviazannymi oshchimi sonnymi arteriiami.

Semax and mexidol significantly increase the survival of white mongrel male mice upon bilateral ligation of common carotid arteries. Semax virtually completely prevented retrograde amnesia development in ligated mice under conditions of a complex extremal action (emaciating swim in cold water with simultaneous wheel rotation) and increased the lifetime of these animals in altitude test chamber.

[Effectiveness of mexidol in acute pancreatitis]. / Effektivnost' meksidola pri ostrom pankreatite.

Mexidol effectiveness was tried in acute pancreatitis (AP). It was found that in acute pancreatitis mexidol provides a reliable defence of membrane structures, decreased the rate of lipid peroxidation, enhanced the activity of the antioxidative system. This eventually results in reduced number of AP complications (by 9-13%) and mortality (by 7%). In AP mexidol should be injected intraductally.