13C NMR of DIPAC and DIPAB organic ferroelectrics.

The diisopropylammonium chloride (C6H16ClN, DIPAC) and diisopropylammonium bromide (C6H16BrN, DIPAB) molecular crystals are recently discovered ferroelectrics with sufficiently high spontaneous polarization and Curie temperature. We performed first studies of these crystals by 13C NMR. CP MAS spectra were collected within large temperature ranges covering the Curie points. The reconstructive phase transition from the initial orthorhombic P212121 structure of DIPAB to the monoclinic ferroelectric P21 structure leads to an abrupt alteration in the 13C spectrum. The 13C spectra for DIPAC and DIPAB in the ferroelectric P21 phase are quite similar with four lines at lower frequencies, which correspond to the CH3 groups, and two lines with close chemical shifts, which correspond to two CH groups. The transition into the paraphase leads to gradual reduction of the interline distances in the low-frequency quadruplet and in the doublet. The step-like changes in the interline frequency shifts at this transition indicating its first order. The analysis of the spectrum evolution in the paraphase shows that only a CH group lays in the reflection plane above the P21 → P21/m transition, while the second CH group only moves closer to the reflection plane upon further heating.

Studies of the mechanism of the anticonvulsant effect of delta-sleep-inducing peptide in conditions of increased oxygen tension.

Studies of the protective actions of three doses of delta-sleep-inducing peptide (DSIP) given at different times before barochamber compression of animals to an oxygen tension of 0.7 MPa showed that the optimum DSIP dose is 12 micrograms/100 g. Intraperitoneal administration of this dose of DSIP delayed the onset of generalized convulsive activity by a factor of 2-2.5 in animals exposed to an oxygen tension of 0.7 MPa and promoted normalization of the sleep-walking cycle within 24 h after exposure to hyperbaric oxygen (HBO), by creating an optimal balance between excitatory and inhibitory amino acid neuromediators.

[Comparative investigation of anticonvulsive effects of putrescine and structural analogues of delta-sleep-inducing peptide]. / Sravnitel'noe izuchenie protivosudorozhnykh effektov putrestsina i strukturnykh analogov indutsiruiushchego delta-son peptida.

Intracysternal putrescine before a session of hyperbaric oxygenation (0.7 MPa) was shown to be more effective in prolonging the latent period of onset of generalized convulsive activity than intraperitoneal delta-sleep-inducing peptide or its structural analogues ID-1 or ID-3. Biochemical studies indicated that putrescine was also more effective in preventing hyperbaric oxygenation-induced decreases in the levels of GABA and homocarnosine in the brain and the accumulation of lipid peroxidation products in the brain and serum.

[Intensity of label incorporation from [1,4-14C]putrescine into homocarnosine in the brain of rats of various ages]. / Intensivnost' vkliucheniia metki iz [1,4-14C]putrestsina v gomokarnozin v mozgu krys razlichnogo vozrasta.

Intensity of 14C incorporation from the [1.4-14C]-putrescine to the homocarnosine and homocarnosine content in the brain of 1-, 7-, 14-, 21-day and adult rat were investigated. It is shown that dynamics of 14C incorporation from 1.4-14C-putrescine to the homocarnosine in the brain of rats of different age does not correlate with dynamics of homocarnosine content increase. The most significant activity of label incorporation from 14C-putrescine to the homocarnosine takes place in the brain of 1-, 21-day animals and adult rats.

[Antistressor effect of delta-sleep-inducing peptide in hypokinetic stress]. / Antistressornyi éffekt del'ta-son-indutsiruiushchego peptida pri gipokineticheskom stresse.

The influence of DSIP injection on the levels of neurotransmitters during hypokinetic stress was studied. It was shown that hypokinesia produced considerable changes in the levels of GABA glutamate, aspartate and homocarnosine. The injection of DSIP normalized the level of neurotransmitter amino acids. Administration of DSIP also reduced stress-induced changes in the activity of enzymes of GABA metabolism. Stress protective effect of DSIP was also demonstrated by normalising of the POL of lipids in brain.

[Homocarnosinase activity in the rat brain areas kidneys under different states of hyperbarooxygenation]. / Gomokarnozinaznaia aktivnost' v otdelakh golovnogo mozga i pochkakh krys pri raznykh rezhimakh giperbarooksigenatsii.

The homocarnosinase activity in different brain areas and kidneys of the normal rats and under different conditions of hyperbarooxygenation are determined. The highest activity of this enzyme is observed in cerebellum. The high homocarnosinase activity is typical of kidneys as well. The action of oxygen in a dose of 0.425 MPa for 60 min (in the absence of convulsions) increases the homocarnosinase activity in the cerebral hemispheres by 18.6%, in the midbrain by 18.6%, in midbrain and diencephalon--by 56.5%, and in the medulla oblongata--by 40.6%. The homocarnosinase activity in the cerebellum decreases by 16.7%, in kidneys--by 18.5%. At the convulsive stage of oxygen intoxication caused by the effect of 0.7 MPa dose of oxygen the homocarnosinase activity in cerebral hemispheres rises by 158.5%, in the midbrain and diencephalon--by 141.5%, in the medulla oblongata by--161.1%. Under the same conditions homocarnosinase activity in the cerebellum is unchanged as compared with the control.

[The effect of naloxone and delta-sleep inducing peptide on the homocarnosine content of brain tissue]. / Vliianie naloksona i del'ta-son-inutsiruiushchego peptida na soderzhaniie gomokarnozina v tkani golovnogo mozga.

The intraventricular and intravenous administration of naloxone was studied for its effect on the homocarnosine amount in cerebral hemispheres, striatum, hippocamp, hypothalamus, thalamus, cerebellum, medulla oblongata as well as in the spinal cord of rabbits. The intracysternal administration of naloxone decreases the homocarnosine amount in the striatum, hypothalamus, cerebellum and medulla oblongata. The intravenous administration of peptide exerts no statistically reliable effect on the homocarnosine content in the rabbit brain. The intraperitoneal administration of delta-sleep-inducing peptide increases sharply the homocarnosine content in the rat brain.

[The neuromediator mechanism of the additive action of the delta sleep-inducing peptide in experimental audiogenic epilepsy caused by hypokinesia]. / Neiromediatornyi mekhanizm adaptivnogo deistviia del'ta-son indutsiruiushchego peptida pri éksperimental'noi audiogennoi épilepsii, vyzvannoi gipokineziei.

The DSIP influence on the rat cortex, thalamic and hypothalamic adrenaline, noradrenaline, DOPA, dopamine and serotonin level under normal, hypokinetic stress condition (1 h in duration) and experimental audiogenic epilepsy was studied. It was found, that a single intraperitoneal DSIP injection (12 microns/100 g body weigh, 1 h before placing the animals into the stress condition) prevented spontaneous epileptic activity development due to creation of optimal ratio between monoamines in brain structures.

[Dipeptide nootropic agent GVS-111 prevents accumulation of the lipid peroxidation products during immobilization]. / Dipeptidnyi nootrop GVS-111 predotvrashchaet nakoplenie produktov perekisnogo okisleniia lipidov pri immobilizatsii.

Immobilization of rats in a narrow plastic chamber for 24 h caused a sharp increase in the level of diene conjugates and the content of schiff bases in the synaptosomes of the brain cortex as well as accumulation of extraerythrocytic hemoglobin in blood serum. The dipeptide nootropic agent GVS-111 (ethyl ether of phenylacetylprolylglycine), when administered 15 and particularly 60 min before immobilization reduced the accumulation of these products of lipid peroxidation in the brain and blood. GVS-111 demonstrated these signs of its antioxidant effect after a single i.p. injection in doses of 0.12 and 0.5 mg/kg. Pyracetam produced a similar effect on the listed parameters in injection in a dose of 300 mg/kg for three successive days. The protective effect of the new pyracetam dipeptide analog GVS-111 in relation to activation of free-radical processes induced by immobilization is additional proof of the antistress action of this dipeptide.

[Ratio of neuromediator amino acids in a comparative analysis of the stress protective effects of delta-sleep inducing peptide and piracetam]. / Sootnoshenie neiromediatornykh aminokislot pri sravnitel'nom analize stressprotektornykh éffektov delta-sonindutsiruiushchego peptida i piratsetama.

The GABAergic system was adequate altered after simultaneous use of delta-sleeping peptide and piracetam in intact animals: gamma-butyric acid was accumulated unidirectionally by inhibiting brain glutamate decarboxylase activity. Administration of the peptide caused a slight decrease in the levels of aspartic acid, while piracetam contributed to a marked accumulation of the amino acid. The antistressor and adaptive effects of each drug were augmented if they were given simultaneously before acute emotional stress developed in the animals during one-hour hypokinesia; these effects were expressed as stabilized balance of inhibitory and excitatory neurotransmitter amino acids.

[Use of gamma-aminobutyric acid from various sources in the synthesis of homocarnosine in the brain of animals of various ages]. / Ispol'zovanie razlichnykh istochnikov gamma-aminomaslianoi kisloty v sinteze gomokarnozina v mozga zhivotnykh raznogo vozrasta.

The dynamics and intensity of radiolabelled carbon incorporation from [14C] putrescine into homocarnosine in the brains of rats of various age have been studied. In the brains of 1-, 7-, and 2-day-old rats putrescine is the main GABA source for homocarnosine synthesis. In the brains of 14- and 31-day-old animals the GABA formed from glutamic acid participates in homocarnosine synthesis alongside with putrescine. In the brains of adult rats the rate of [14C] incorporation from glutamic acid into homocarnosine is 7 times as low as that of [14C] incorporation from putrescine.

[Proteolytic processes in the rat brain and serum in hypokinesia and the adaptive effect of delta-sleep inducing peptide]. / Proteoliticheskie protsessy v mozge i syvorotke krovi krys pri gipokinezii i adaptivnom vliianii del'ta-son indutsiruiushchego peptida.

It has been demonstrated for the first time that a single injection of the delta-sleep inducing peptide (DSIP) results in long-term alteration of proteolytic enzyme activity within a broad range of pH. Using Ca(2+)-independent neutral endopeptidases from the synaptosomal fraction of rat brain and blood serum kallikrein as an example, it has been shown that DSIP activates limited proteolysis. This effect may contribute to the alteration of the set and "active" concentration of regulatory peptides and peptide hormones to the induction of the preadaptive state. DSIP also causes the redistribution of activity between Ca(2+)-dependent and Ca(2+)-independent neutral endopeptidases associated with synaptosomal membranes, particularly under hypokinetic conditions. The significant decrease of the Ca(2+)-activated neutral proteinase I activity may be one of the mechanisms whereby the modulating effect of DSIP manifested as regulation of the number of glutamate receptors and limitation of effect of this excitatory neuromediator is realized under stress. Preliminary injection of DSIP prevents disturbances in the permeability of lysosomal membranes under long-term (24 hours) hypokinesia.

[The mechanism of the anticonvulsive effect of the delta sleep-inducing peptide under conditions of elevated oxygen pressure]. / Issledovanie mekhanizma protivosudorozhnogo éffekta del'ta-son indutsiruiushchego peptida v usloviiakh povyshennogo davleniia kisloroda.

Delta-sleep-inducing peptide (DSIP) exerted a protective effect against seizures, the effect depending on the DSIP ability to create an optimal ratio between inhibitory and excitatory amino acid neurotransmitters. Administration of the DSIP dramatically increased the contents of gamma-aminobutyric acid and homocarnosine while decreasing the glutamate and aspartate contents in the rat brain cortex.

Metabolic features of the adaptive effect of delta-sleep inducing peptide and piracetam under hyperoxic conditions.

Adaptive effects of delta-sleep inducing peptide (DSIP, 12 microgram/100 g body weight, single intraperitoneal injection) and piracetam (3 mg/100 g body weight, daily intraperitoneal injection for 3 days) are manifested via differential changes in neurotransmitter amino acids (GABA, glutamate, aspartate), modulation of transport ATPase activity, and decreased accumulation of lipid peroxidation products (conjugated dienes, malonic dialdehyde, Schiff bases) in various fractions of neuronal membranes (myelin, synaptic and mitochondrial membranes) in the sensomotor cortex of rat brain. Under hyperbaric oxygenation (0.3 MPa for 2 h), the combination of DSIP and piracetam enhanced the protective effect of each compound.