[Effect of taurine and thioctacide on carbohydrate metabolism and the antioxydant system in rats with experimental diabetes].

Peroral administration of taurine and thioctacide in rats with alloxan-induced diabetes (i) decreased the levels of glucose, fructosamine and MDA, (ii) increased the levels of glycogen, insulin, and C-peptide in the liver, and (iii) increased the levels of enzymes of the antioxidant system of catalase and paraoxonase as compared to the control group of animals. These effects show that taurine and thioctacide possess hypoglycemic and antioxidant properties.

[Effect of some imidazole-4,5-dicarboxylic acid derivatives on the activity of N-methyl-D-aspartate (NMDA) receptors].

The results of experiments on mice showed that some imidazole-4,5-dicarboxylic acid derivatives injected into lateral cerebral ventricles produce a dose-dependent convulsant or anticonvulsant effects, that is, possess the properties of partial NMDA receptor agonists. The most promising partial NMDA receptor agonist selected for further investigation is 2-propylimidazole-4,5-dicarboxylic acid.

[The embryo-protective action of antifein derivatives in chloridin-induced teratogenesis]. / Embrioprotektivnoe deistvie proizvodnykh antifeina pri khoridinindutsiruemom teratogeneze.

We studied the effect of propyl- and ethylnorantifein on chloridine-induced abnormalities of extremities in rat embryos. Chloridine (50 and 25 mg/kg, given through the gastric tube) was administered to rats on day 14 of pregnancy, and its embryotoxic effect was estimated from the state of fetuses and implantation sites on day 20 of prenatal development. Propylnorantifein had fetoprotective properties both after intraperitoneal (10 mg/kg) and after intraamniotic (6 and 0.06 micrograms) administration. Ethylnorantifein under similar conditions does not change the action of chloridine, and it prevents the appearance of developmental abnormalities only at the concentration of 0.06 microgram/embryo. These data are discussed in connection with different effects of antifein derivatives on chromatin proteinkinase, which phosphorylates HMG nonhistone proteins.

[The participation of RNA synthesis in the process of the acquisition and retention of conditioned reflexes (a study using antifeins)]. / Uchastie sinteza RNK v protsesse vyrabotki i sokhraneniia uslovnykh refleksov (issledovanie s ispol'zovaniem antifeinov).

RNA-synthesizing activity of neuronal nuclei in the neocortex of rats increases after the termination of conditioning depending on the degree of learning. RNA synthesis shifts induced by propylnorantifein and the demethylated derivatives of ethylnorantifein are correlated only with the influence of the drugs on the retention but not the learning. Participation of RNA synthesis by the neurons of the neocortex in the mechanisms of long-term memory is discussed.

[Effect of ethymisole on long-term memory]. / O vliianii étimizola na dolgovremennuiu pamiat'.

Influence of ethymisol (bismethylamid of 1-ethylimidasol-4,5-dicarbonic acid) on learning and retention of habit was studied in experiments on rats by the method of active conditioned avoidance of electrical stimulation. At the same time optimal conformation form of the drug was determined by the method of proton magnetic resonance and by means of infrared spectra and theoretical conformation analysis. A single administration of ethymisol in the dose of 3 mg/kg reduced the deficit of the avoidance habit, when tested in 30 and 60 days following learning. A stable conformation of the ethymisol molecule with a planar arrangement of atoms of its heterocycle and amide groups was found in which the interaction of this substance with biological macromolecules was most active. The ethymisol effect on the long-term memory apparently results from a stable facilitation of synaptic transmission based on stabilization of spatial structure of biological macromolecules in the given conformation.

[N-butylaspartic acid--a partial agonist of NMDA receptors?]. / N-butilasparaginovaia kislota--chastichnyi agonist NMDA retseptorov?

The convulsive and anticonvulsive properties of the N-alkyl-substituted DL-aspartic acids derivatives were studied after intracerebroventricular injections in mice. It was found that N-butyl-DL-aspartic acid shows some properties of the partial agonist of NMDA receptors.

[Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis]. / Opyt primeneniia vysokodoznoi immunosuppressivnoi terapii s posleduiushchei transplantatsiei autologichnykh stvolovykh krovetvornykh kletok u bol'nykh rasseiannym sklerozom.

AIM: To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. MATERIAL AND METHODS: The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). RESULTS: In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. CONCLUSION: Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

[The efficacy of high-dose chemotherapy and the transplantation of autologous hemopoietic cells in lymphogranulomatosis]. / Effektivnost' vysokodoznoi khimioterapii i transplantatsii autologichnykh gemopoéticheskikh kletok pri limfogranulematoze.

AIM: To determine clinical effectiveness of high-dose polychemotherapy (PCT) and transplantation of autologous hemopoietic cells (TAHC) in patients with lymphogranulomatosis (LGM). MATERIAL AND METHODS: 27 LGM patients aged 16-42 years who have undergone TAHC after high-dose PCT (BEAM--17 patients or CBV--10 patients). 4 patients given high-dose PCT were in the first-second complete remission (CR), 7 patients--in the first partial remission (PR). Prior to TAHC, 8 patients had one, two and more relapses of LGM, and 8 patients had no remission at all. Bone marrow, hemopoietic blood cells and both were transplanted to 17, 2 and 8 patients, respectively. Mobilization of hemopoietic blood cells and stimulation of hemopoiesis after TAHC were achieved using colony-stimulating factors. RESULTS: The treatment resulted in CR or PR (from 6 to 95 months) in 70.4% of patients. The remission duration varied depending on the disease phase at transplantation. Four patients who underwent TAHC in PR maintained it for 13-95 months (median 47.5 months). Lasting remissions (29-59 months) were achieved in 42.9 and 37.5% of patients who underwent TAHC in the first PR or in recurrent LGM. None of the patients was in remission longer than 2 years after TAHC if high-dose PCT was conducted in advanced tumor process due to resistant LGM or inadequate previous treatment. Infectious complications lethality early after the transplantation reached 7.4%(2 patients). CONCLUSION: High-dose PCT followed by TAHC is effective in LGM if the tumor is chemosensitive.

[Antiamnestic properties of pyrazole dicarboxylic acid derivatives in rats]. / Izuchenie antiamnesticheskikh svoistv proizvodnykh pirazoldikarbonovoi kisloty u krys.

Eight derivatives of pyrazole dicarboxylic acid (IEM-565, IEM-476, IEM-1332, IEM-474, IEM-373, IEM-440, IEM-1333, IEM-439) have been studied in rats for the ability to abolish the amnesia of passive avoidance behavior induced by electroconvulsive shock IEM-476, IEM-373 and IEM-439 have proved to be the most efficacious.

[Selective anticonvulsive action of N-substituted imidazole-4,5-dicarboxylic acids against quinolinic acid]. / Izbiratel'noe protivosudorozhnoe deistvie N-zameshchennykh imidazol-4,5-dikarbonovykh kislot protiv khinolinovoi kisloty.

Selective antagonists of quinolinic acid (2,3-pyridine dicarboxylic acid, QUIN)--an endogenous convulsant tryptophan metabolite, administered intracerebroventricular to mice, were identified during comparison with the following intracerebroventricular convulsants: l-kynurenine, aspartic, glutamic, N-methyl-DL-aspartic and kainic acids. It is suggested that the antagonism arises due to a common fragment of the structure which consists of two carboxylic groups at two nearest carbon atoms of the ring and of one nitrogen atom in the alpha-position. The selective action of the compounds found against QUIN supports the suggestion that QUIN produces seizures via N-methyl-D-aspartate binding sites.

[A new class of N-methyl-D-aspartic acid receptor agonists and antagonists--derivatives of imidazole-4,5- and pyrazole-3,4-dicarboxylic acids]. / Novyi klass agonistov i antagonistov retseptorov N-metil-D-asparaginovoi kisloty--proizvodnye imidazol-4,5- i pirazol-3,4-dikarbonovykh kislot.

New agonists and antagonists of the N-methyl-D-aspartic acid (NMDA) receptors were found among the derivatives of 1- or 2-alkyl-substituted imidazole-4,5- and pyrazole-3,4-dicarboxylic acids. Lipophilic surrounding of the nitrogen atom in these compounds was found to determine their ability to be either agonists or antagonists, while the distance between the terminal acidic functions was the same. An increase in the lipophilicity can also cause loss of selective action upon the NMDA receptors and occurrence of non- NMDA antagonistic activity.

[State of the "protein kinase CK2-HMG14" system in age-dependent amnesia in rats]. / Sostoianie sistemy "proteinkinaza CK2-HMG14" pri vozrastnoi amnezii u krys.

It has been shown that a decrease in HMGs transcription factors phosphorylation by protein kinase CK2 may be the cause of a gene expression decline in cognitive disorders. Passive avoidance amnesia in old rats (24 month) was accompanied by a decrease in synaptosomal protein synthesis and transcription in isolated nuclei of cortex, hippocampus, and striatum. A decrease in chromatin protein kinase CK2 activity and a significant decrease in HMG14 phosphorylation by CK2 was found in old rats. CK2 selective activators, a 4-carbamoyl-5-N-methylcarbamoyl-1-ethyl-imidazole and 4,5-dicaramoyl-1-ethyl-imidazole, produced the HMG14 phosphorylation and transcription activation in old rats. At the same time, synaptosomal protein synthesis activation and passive avoidance amnesia reduction were observed in old rats. Thus, activation of CK2-HMG14 was accompanied by synaptic plasticity optimisation. The data show a high therapeutic potential of activators of CK2-HMG14.