34 research outputs found
ΠΡΠΎΡΠΈΠ²ΠΎΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 4-Π±Π΅Π½Π·ΠΎΠΈΠ»-ΠΏΠΈΡΠΈΠ΄ΠΈΠ½Π° (ΠΠΠ-298) Π½Π° ΠΏΠ°ΡΠΎΠΊΡΠΈΠ·ΠΌΠ°Π»ΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π² ΡΡΡΡΠΊΡΡΡΠ°Ρ ΠΌΠΎΠ·Π³Π° ΠΊΡΡΡ Ρ ΠΊΠΎΠ±Π°Π»ΡΡ-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΎΡΠ°Π³ΠΎΠ²ΠΎΠΉ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΠ΅ΠΉ Π½Π° ΠΏΠ΅ΡΠ²ΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ
He aim of the study was to investigate the influence of a derivative of 4-benzoyl pyridine connection, GIZ-298 on electroencephalographic manifestations ranvulsive activity in the brain structures of rats with cobalt-induced focal epilepsy in the first stage of the formation of epileptic system. Methodology of the study. We used the technique of creation (by an application of cobalt to the brain of rats) chronic epileptogenic focus, generating paroxysmal activity in different brain structures: the ipsi- and contralateral cortex, hippocampus and hypothalamus. The results of the study. Established that injection ofGIZ-298 at a dose of 60 mg/kg (intraperitoneally, once) on the first stage of development of the system eliminates epileptic EEG manifestations of seizure activity in all the investigated structures of the brain, with the greatest efficiency in the ipsilateral cortex and the hypothalamus, significantly reducing both the number and duration of seizure discharges.Π¦Π΅Π»ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²ΠΈΠ»ΠΎΡΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 4-Π±Π΅Π½Π·ΠΎΠΈΠ» ΠΏΠΈΡΠΈΠ΄ΠΈΠ½Π° - ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-298 Π½Π° ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½ΡΠ΅ΡΠ°Π»ΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡ ΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π² ΡΡΡΡΠΊΡΡΡΠ°Ρ
ΠΌΠΎΠ·Π³Π° ΠΊΡΡΡ Ρ ΠΊΠΎΠ±Π°Π»ΡΡ-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΎΡΠ°Π³ΠΎΠ²ΠΎΠΉ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΠ΅ΠΉ Π½Π° ΠΏΠ΅ΡΠ²ΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ. ΠΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»Π°ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΡΠΎΠ·Π΄Π°Π½ΠΈΡ (ΠΏΡΡΡΠΌ Π°ΠΏΠΏΠ»ΠΈΠΊΠ°ΡΠΈΠΈ ΠΊΠΎΠ±Π°Π»ΡΡΠ° Π½Π° ΠΊΠΎΡΡ ΠΌΠΎΠ·Π³Π° ΠΊΡΡΡ) Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΎΠ³Π΅Π½Π½ΠΎΠ³ΠΎ ΠΎΡΠ°Π³Π°, Π³Π΅Π½Π΅ΡΠΈΡΡΡΡΠ΅Π³ΠΎ ΠΏΠ°ΡΠΎΠΊΡΠΈΠ·ΠΌΠ°Π»ΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΡΡΡΠΊΡΡΡΠ°Ρ
ΠΌΠΎΠ·Π³Π°: ΠΈΠΏΡΠΈ- ΠΈ ΠΊΠΎΠ½ΡΡΠ»Π°ΡΠ΅ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠΎΡΠ΅, Π³ΠΈΠΏΠΏΠΎΠΊΠ°ΠΌΠΏΠ΅ ΠΈ Π³ΠΈΠΏΠΎΡΠ°Π»Π°ΠΌΡΡΠ΅. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-298 Π² Π΄ΠΎΠ·Π΅ 60 ΠΌΠ³/ΠΊΠ³ (Π²Π½ΡΡΡΠΈΠ±ΡΡΡΠΈΠ½Π½ΠΎ, ΠΎΠ΄Π½ΠΎΠΊΡΠ°ΡΠ½ΠΎ) Π½Π° ΠΏΠ΅ΡΠ²ΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΡΡΡΡΠ°Π½ΡΠ΅Ρ ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½ΡΠ΅ΡΠ°Π»ΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡ ΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²ΠΎ Π²ΡΠ΅Ρ
ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
ΡΡΡΡΠΊΡΡΡΠ°Ρ
ΠΌΠΎΠ·Π³Π°, Ρ Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ Π² ΠΈΠΏΡΠΈΠ»Π°ΡΠ΅ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠΎΡΠ΅ ΠΈ Π³ΠΈΠΏΠΎΡΠ°Π»Π°ΠΌΡΡΠ΅, ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ ΡΠΌΠ΅Π½ΡΡΠ°Ρ ΠΊΠ°ΠΊ ΡΠΈΡΠ»ΠΎ, ΡΠ°ΠΊ ΠΈ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΡΡ
ΡΠ°Π·ΡΡΠ΄ΠΎΠ²
Π ΠΎΠ»Ρ 3-ΠΎΠΊΡΠΈΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ° ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠ° ΠΈ Π»Π΅Π²Π°Π½Ρ Π² ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈΡ Π½Π΅ΠΉΡΠΎΡΡΠΎΠΏΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ
Work is devoted to a comparative analysis of the pharmacological action and integral indicators pharmacokinetics of 1,4- benzodiazepine - phenazepam and levan, as well as their total active 3-oximetabolite formed by different mechanisms. It is shown that in the tests levan antagonism corazolum and thiosemicarbazide inferior phenazepam anticonvulsant activity, but surpasses phenazepam on activity in the maximal electroshock test and has a lower severity miorelaxation action. Comparison effects of phenazepam and levad with effects of 3-oximetabolite indicate greater similarity effects than metabolite with phenazepam. With the use of radiolabeled compounds were established change in the ratio of the areas under the concentration curve 3-oximetabolite in the brain and blood when administered phenazepam (AUCbrain / AUCblood = 0,96 Β± 0,27) or levan (AUCbrain / AUCblood = 1,4 Β± 0,1). This fact is associated with different ways of biotransformation: oxidative hydroxylation of phenazepam CYP450 and nonspecific carboxylesterase hydrolysis of levan, which explains the difference in the pharmacological effect of the test compounds.Π Π°Π±ΠΎΡΠ° ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌΡ Π°Π½Π°Π»ΠΈΠ·Ρ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΈ ΠΈΠ½ΡΠ΅Π³ΡΠ°Π»ΡΠ½ΡΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΊΠΈΠ½Π΅ΡΠΈΠΊΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
1,4-Π±Π΅Π½Π·Π΄ΠΈΠ°Π·Π΅ΠΏΠΈΠ½Π° - ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠ° ΠΈ Π»Π΅Π²Π°Π½Ρ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΡ
ΠΎΠ±ΡΠ΅Π³ΠΎ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ 3-ΠΎΠΊΡΠΈΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ°, ΠΎΠ±ΡΠ°Π·ΡΡΡΠ΅Π³ΠΎΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°ΠΌΠΈ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π»Π΅Π²Π°Π½Π° Π² ΡΠ΅ΡΡΠ°Ρ
Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΠ·ΠΌΠ° Ρ ΠΊΠΎΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΠΈ ΡΠΈΠΎΡΠ΅ΠΌΠΈΠΊΠ°ΡΠ±Π°Π·ΠΈΠ΄ΠΎΠΌ ΡΡΡΡΠΏΠ°Π΅Ρ ΠΏΠΎ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΡ, Π½ΠΎ ΠΏΡΠ΅Π²ΠΎΡΡ
ΠΎΠ΄ΠΈΡ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌ ΠΏΠΎ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π² ΡΠ΅ΡΡΠ΅ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΠΊΠ° ΠΈ ΠΈΠΌΠ΅Π΅Ρ ΠΌΠ΅Π½ΡΡΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΡ ΠΌΠΈΠΎΡΠ΅Π»Π°ΠΊΡΠ°Π½ΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ. Π‘ΠΎΠΏΠΎΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΎΠ² ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠ° ΠΈ Π»Π΅Π²Π°Π΄Ρ Ρ ΡΡΡΠ΅ΠΊΡΠ°ΠΌΠΈ 3-ΠΎΠΊΡΠΈΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ° ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎ Π±ΠΎΠ»ΡΡΠ΅ΠΌ ΡΡ
ΠΎΠ΄ΡΡΠ²Π΅ ΡΡΡΠ΅ΠΊΡΠΎΠ² ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ° Ρ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠΎΠΌ. Π‘ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠ°Π΄ΠΈΠΎΠ°ΠΊΡΠΈΠ²Π½ΠΎ ΠΌΠ΅ΡΠ΅Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΠΏΠ»ΠΎΡΠ°Π΄Π΅ΠΉ ΠΏΠΎΠ΄ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΎΠ½Π½ΡΠΌΠΈ ΠΊΡΠΈΠ²ΡΠΌΠΈ 3-ΠΎΠΊΡΠΈΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ° Π² ΠΌΠΎΠ·Π³Ρ ΠΈ ΠΊΡΠΎΠ²ΠΈ ΠΏΡΠΈ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠ° (AUC /AUC = 0,96 Β± 0,27) ΠΈΠ»ΠΈ Π»Π΅Π²Π°Π½Ρ (AUC /AUC = 1,4 Β± 0,1). ΠΠ°Π½Π½ΡΠΉ ΡΠ°ΠΊΡ ΡΠ²ΡΠ·Π°Π½ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΏΡΡΡΠΌΠΈ Π±ΠΈΠΎΡΡΠ°Π½ΡΡΠΎΡΠΌΠ°ΡΠΈΠΈ: ΠΎΠΊΠΈΡΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠ° P450 ΠΈ Π³ΠΈΠ΄ΡΠΎΠ»ΠΈΠ· Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»ΡΡΡΠ΅ΡΠ°Π·Π°ΠΌΠΈ Π»Π΅Π²Π°Π½Ρ, ΡΡΠΎ ΠΈ ΠΎΠ±ΡΡΠ»Π°Π²Π»ΠΈΠ²Π°Π΅Ρ ΠΎΡΠ»ΠΈΡΠΈΠ΅ Π² ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ
Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease
<p>Abstract</p> <p>Background</p> <p>Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.</p> <p>Methods</p> <p>CCl<sub>4 </sub>was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured.</p> <p>Results</p> <p>High levels of PON1 and MCP-1 expression were observed at 12<sup>th </sup>week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl<sub>4</sub>-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARΞ΄ expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001).</p> <p>Conclusion</p> <p>Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.</p
COMPARATIVE ANTICONVULSANT AND ANTIHYPOXIC EFFECTS OF ASTROKS AND MEXIDOL IN INJECTABLE FORM AND 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE SUCCINATE SUBSTANCE
The purpose of this study was to examine in experiment anticonvulsant and antihypoxic action of 2-ethyl-6-methyl-3-hydroxypyridine succinate medications β Astroks in injectable form (vial of 100 mg in 2 ml) compared with Mexidol injectable form (vial of 100 mg in 2 ml) and the substance 2-ethyl-6- methyl-3-hydroxypyridine succinate (EMHPS). Materials and methods. Simulation of primary generalized eizures was performed using the maximal electroshock (MES) and pentylenetetrazole injection. Antihypoxic effects of drugs was studied on the model of normobaric hypoxia with hypercapnia.Results: it was found that astroks injection at a dose of 200 mg/kg has a similar antihypoxic and anticonvulsant efficacy with EMHPS substance. Compared to injectable form of Meksidol astroks has similar efficacy in the test of antagonism with MES. Astroks exceeds the effect of Mexidol in the test of antagonism with pentylenetetrazole and has more severe antihypoxic action.Conclusion. Πstroks injectable has pronounced antihypoxic and anticonvulsant action in the experiment which have some advantages over injectable Meksidol
ELECTROPHYSIOLOGICAL MECHANISMS OF ANTIEPILEPTIC ACTIONS REALIZATION OF BEPRODON
The purpose of this research was to study electric and physiological mechanisms of the achievement of the antoconvulsant effect of the new original beprodon combination together with determination of determinant brain structures β therapeutic targets.Materials and Methods. Partial (focal) and secondary generalized convulsions were generated using the method of creation of a chronic epileptogenic focus, caused by the cobalt application on ratsβ brain.Results: it was revealed, that at the first stage of the epileptic system (ES) beprodone is targeted to cortical focuses, and at the second stage β to subcortical focuses, generating epileptic activities. Conclusion: the beprodone effect depends on the stage of the epileptic system development and is targeted to determinant focuses