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1.
Bull Exp Biol Med ; 173(2): 246-251, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35737153

RESUMO

Differential diagnosis of thyroid gland neoplasms is an urgent problem in modern oncothyroidology. This is especially true for the diagnosis of follicular thyroid cancer and follicular thyroid adenoma at the preoperative stage. In this study, in silico methods were used to search for potential markers that are microRNA target genes. A list of 19 microRNAs was compiled, the expression of which varies depending on the type of thyroid neoplasms. For these microRNAs, the target genes were selected considering tissue specificity and association with thyroid diseases. We selected 9 target genes (MCM2, RASSF2, SPAG9, SSTR2, TP53BP1, INPP4B, CCDC80, GNAS, and PLK1), which can be considered as promising markers according to published data. Also, 6 new potential markers (CDK4, FGFR1, ERBB3, EGR1, MYLK, and SRC) were found, which make it possible to distinguish between follicular thyroid cancer and follicular thyroid adenoma. The proposed algorithm using various bioinformatics tools allows us to identify potential markers for the differential diagnosis of thyroid neoplasms.


Assuntos
Adenoma , MicroRNAs , Neoplasias da Glândula Tireoide , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma Folicular , Adenoma/diagnóstico , Adenoma/genética , Adenoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Humanos , MicroRNAs/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
2.
Bull Exp Biol Med ; 168(4): 453-456, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32146626

RESUMO

It was shown that finasteride, a 5α-reductase inhibitor (50 mg/kg, intraperitoneally) produced analgesic and antiexudative effects in experimental peritonitis induced by intraperitoneal injection of 1% acetic acid. These results agree with published data on its anti-inflammatory properties and ability to potentiate the analgesic effect of morphine in rodents. New pyrazolo[C] pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1H-pyrazolo[4,3-C]pyridine-3-on, chloral hydrate) injected intraperitoneally in doses of 20-80 mg/kg produced dose-dependent antiexudative effects, but exhibited no analgesic properties.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Anti-Inflamatórios/farmacologia , Finasterida/farmacologia , Peritonite/tratamento farmacológico , Pirazóis/farmacologia , Piridinas/farmacologia , Ácido Acético/administração & dosagem , Animais , Animais não Endogâmicos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Peritonite/induzido quimicamente , Peritonite/patologia
3.
Bull Exp Biol Med ; 168(4): 449-452, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32146634

RESUMO

We studied the influence of intraperitoneal injection of ATP-sensitive potassium channels inhibitor glibenclamide in doses of 0.01, 0.1, 1, and 10 mg/kg on the effects of a new pyrazolo[C]pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1Hpyrazolo[ 4,3-C]pyridine-3-on, chloral hydrate; 20 mg/kg, intraperitoneally) in the marble burying and open-field tests in mice. It was found that glibenclamide produced an anxiolytic effect in the open-field test (in a dose of 0.01 mg/kg) and anticompulsive effect in the marble burying test (in doses of 1 and 10 mg/kg). The observed behavioral effects of glibenclamide did not depend on blood glucose level. At the same time, glibenclamide in subeffective (0.01 and 0.1 mg/kg) and effective (1 and 10 mg/kg) doses potentiated the psychotropic effects of GIZh-72 in these tests. It can be assumed that the psychotropic effects of GIZh-72 depend on functional activity of ATP-sensitive potassium channels.


Assuntos
Ansiolíticos/farmacologia , Glibureto/farmacologia , Canais KATP/metabolismo , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Psicotrópicos/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transtorno Obsessivo-Compulsivo/metabolismo , Transtorno Obsessivo-Compulsivo/fisiopatologia
4.
Bull Exp Biol Med ; 168(3): 341-344, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31940131

RESUMO

Standard water-reinforced drug discrimination model was employed to train Wistar rats to discriminate the intraperitoneal injections of tricyclic antidepressant amitriptyline (5.4 mg/kg) and physiological saline. To examine the role of GABAA receptors in psychotropic action of amitriptyline, the substitution tests were performed with muscimol (0.1-1.0 mg/kg) and pregnenolone (30-50 mg/kg). Similar tests were carried out with amitriptyline interoceptive antagonists bicuculline (1 mg/kg), flumazenil (15 mg/kg), finasteride (5 mg/kg), and indomethacin (7.5 mg/kg). The study showed that interoceptive effects of amitriptyline depend on functional activity of GABAA receptors but not on the neurosteroid site of GABAA receptor complex.


Assuntos
Amitriptilina/farmacologia , Psicotrópicos/farmacologia , Receptores de GABA-A/metabolismo , Animais , Bicuculina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Muscimol/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Pregnenolona/farmacologia , Ratos , Ratos Wistar
5.
Biochemistry (Mosc) ; 84(10): 1197-1203, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694515

RESUMO

Here, we suggested that the epigenetic mechanism of benzo(a)pyrene (BP) action might be based on the aryl hydrocarbon receptor (AhR)-mediated transcription of the target genes, including miRNAs, that have the dioxin response element (DRE) in their promoters. The effect of BP on the expression of the oncogenic miR-483-3p, its host gene IGF2, and target gene IGF1 in primary hepatocytes and in the liver of Wistar female rats was investigated. The activation of AhR was confirmed using selective AhR inhibitor CH-223191 and by evaluating expression of the target CYP1A1 gene. The lack of coordination between the expression of miR-483-3p and its host gene IGF2 was revealed, which may be due to the presence of the binding site for the estrogen receptor alpha (ERα), which is a negative expression regulator. Our results confirm the existence of the AhR-mediated pathway in the regulation of expression of miR-483-3p, IGF1, and IGF2 under BP exposure, which is of considerable interest for understanding the epigenetic mechanisms of the carcinogenic effect of BP.


Assuntos
Benzo(a)pireno/farmacologia , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Animais , Células Cultivadas , Biologia Computacional , Feminino , Hepatócitos/metabolismo , Fígado/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Ratos Wistar
6.
Bull Exp Biol Med ; 168(1): 48-51, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31745682

RESUMO

We studied antidepressant and antiparkinsonian properties of N-(5-hydroxynicotinoyl)-Lglutamic acid calcium salt (Ampasse) in rodents. It was found that Ampasse in a dose of 30 mg/kg exhibited antidepressant activity in the forced swimming test in mice and in a dose of 0.1 mg/kg maximally alleviates the symptoms of parkinsonian syndrome induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57Bl/6 mice, and haloperidol-induced catalepsy in rats.


Assuntos
Antidepressivos/uso terapêutico , Cálcio/química , Depressão/tratamento farmacológico , Ácido Glutâmico/química , Ácido Glutâmico/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Catalepsia/induzido quimicamente , Haloperidol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
7.
Cell Mol Neurobiol ; 38(1): 281-288, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28861774

RESUMO

Doxycycline (Dox)-inducible transgenic approach is used to examine the neural mechanisms of anxiety and depression; however, its own effects on related behaviors are not clear. To address this, in the present study, we tested the anxiety- and depression-like behaviors in rats treated with Dox in drinking water (2 mg/ml) in the elevated plus-maze (EPM; on day 5) and forced swim (FST; on day 8) tests, respectively. In addition, the levels of mRNAs and proteins of brain-derived neurotrophic factor (BDNF) and anti-apoptotic protein Bcl-xL in the hippocampus (HIPP) and frontal cortex (FC) were also analyzed. Consumption of Dox for 4 days induced an anxiogenic-like phenotype that was manifested by the decreased percentages of open arm entries and time spent on the open arms of the EPM. After Dox for 7 days, animals demonstrated more active behavior in the FST than control rats as evidenced by the increase in climbing time. When assessed after the FST, expression of Bcl-xL was increased in the hippocampus of Dox-treated animals. Furthermore, hippocampal Bcl-xL content correlated positively with the duration of climbing in the test. This study is the first to find that Dox in treatment regime used to control transgene expression can affect anxiety- and depression-like behaviors in rats. Dox-induced increase in Bcl-xL expression in the hippocampus may be involved in the moderate activation of FST behavior.


Assuntos
Ansiedade/metabolismo , Depressão/metabolismo , Doxiciclina/farmacologia , Hipocampo/metabolismo , Transgenes/fisiologia , Proteína bcl-X/biossíntese , Animais , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Ansiedade/induzido quimicamente , Ansiedade/genética , Depressão/induzido quimicamente , Depressão/genética , Doxiciclina/toxicidade , Expressão Gênica , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Natação/fisiologia , Transgenes/efeitos dos fármacos , Proteína bcl-X/genética
8.
Org Biomol Chem ; 16(7): 1163-1166, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29369320

RESUMO

An efficient, convenient short synthetic procedure for the synthesis of the intricate 5A5B6C-ring fusion topologies of tricyclic spiranoid ß-hydroxybutyrolactones through lactonization of the key intermediate trans-α-hydroxyindenones with malonates is described. All the compounds synthesized exhibited environmentally benign characteristics, moderate fungicidal, nematocidal, and anti-TMV activities.

9.
Bull Exp Biol Med ; 165(1): 27-30, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29797131

RESUMO

The study examined the effect of calcium salt of N-(5-hydroxynicotinoil)-L-glutamic acid (Ampasse preparation) on neuronal activity in hippocampal CA1 area evoked by stimulation of Schaffer collaterals at a rate of 1 Hz (30 impulses during 30 sec) in the surviving hippocampal slices of Wistar rats. The records of 1st and 30th orthodromic population spikes showed that Ampasse in concentrations of 500 µM, 1, 2, and 10 mM facilitated the synaptic transmission in Schaffer collaterals - hippocampal CA1 pyramidal neurons axis; the maximum effect was observed at 2 mM Ampasse. When used in a concentration of 10 mM, Ampasse provoked epileptiform activity, which could be prevented by MK-801, a specific noncompetitive antagonist of the NMDA-receptor complex.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Ácido Glutâmico/farmacologia , Células Piramidais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Ácido Glutâmico/química , Masculino , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo
10.
Dokl Biochem Biophys ; 479(1): 108-110, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29779110

RESUMO

Irradiation of a mixture of oligonucleotides with dextran resulted in the formation of a complex that is detected by a decelerated migration of an irradiated sample in electrophoretic gel compared to a non-irradiated one. When injected into the brain of neonatal rats, the formed complex penetrated into the cells 3 times easier compared to the original oligonucleotide, thus indicating that the use of radiation crosslinking of oligonucleotides with oligosaccharides is promising to enhance the efficiency of delivery of gene-targeted oligonucleotide drugs into cells.


Assuntos
Encéfalo/metabolismo , Oligonucleotídeos/metabolismo , Oligossacarídeos/metabolismo , Animais , Transporte Biológico , Ratos
11.
Biochemistry (Mosc) ; 82(10): 1118-1128, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29037132

RESUMO

The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic xenobiotic compound able to exert estrogen-like effects resulting in activation of estrogen receptor-α (ERα) followed by changed expression of its downstream target genes. In addition, studies performed over recent years suggest that DDT may also influence expression of microRNAs. However, an impact of DDT on expression of ER, microRNAs, and related target genes has not been fully elucidated. Here, using real-time PCR, we assessed changes in expression of key genes involved in hormonal carcinogenesis as well as potentially related regulatory oncogenic/tumor suppressor microRNAs and their target genes in the uterus and ovaries of female Wistar rats during single and chronic multiple-dose DDT exposure. We found that applying DDT results in altered expression of microRNAs-221, -222, -205, -126a, and -429, their target genes (Pten, Dicer1), as well as genes involved in hormonal carcinogenesis (Esr1, Pgr, Ccnd1, Cyp19a1). Notably, Cyp19a1 expression seems to be also regulated by microRNAs-221, -222, and -205. The data suggest that epigenetic effects induced by DDT as a potential carcinogen may be based on at least two mechanisms: (i) activation of ERα followed by altered expression of the target genes encoding receptor Pgr and Ccnd1 as well as impaired expression of Cyp19a1, affecting, thereby, cell hormone balance; and (ii) changed expression of microRNAs resulting in impaired expression of related target genes including reduced level of Cyp19a1 mRNA.


Assuntos
Carcinogênese/genética , DDT/toxicidade , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Ovário/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Aromatase/genética , Aromatase/metabolismo , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Ovário/metabolismo , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Ribonuclease III/antagonistas & inibidores , Ribonuclease III/genética , Ribonuclease III/metabolismo , Útero/metabolismo
12.
Biochemistry (Mosc) ; 82(3): 345-350, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28320276

RESUMO

The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.


Assuntos
Lobo Frontal/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Cloreto de Lítio/farmacologia , Estresse Psicológico/metabolismo , Proteína bcl-X/biossíntese , Doença Aguda , Animais , Lobo Frontal/patologia , Hipocampo/patologia , Lítio/farmacologia , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/patologia
13.
Mol Biol (Mosk) ; 50(2): 266-71, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27239846

RESUMO

The ratio of the expression levels of the immediate early genes c-jun and c-fos that encode components of the AP-1 transcription complex determines the direction of changes in the expression of genes controlled by the complex, including changes induced by glucocorticoids. The aim of the present work was to assess the levels of mRNA encoded by genes c-jun and c-fos and the ratio of expression levels of these genes in various regions of the neonatal rat brain after the administration of dexamethasone, a selective ligand of the glucocorticoid receptor. The level of mRNA encoded by the immediate early gene c-fos in the hippocampus and prefrontal cortex of 3-day-old rat pups was elevated at 30, 60, and 120 min after dexamethasone administration. The basal level of c-fos gene expression in the brainstem was higher than in the cortex and hippocampus, and administration of the hormone was followed by a reduction in the amount of transcript detectable in the brainstem after 2 h. As a result, the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats was doubled after dexamethasone administration. The dexamethasone-induced shift of the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats towards a predominance of c-jun reported for the first time in the present work may induce the expression of genes that contain AP-1 response elements in the promoters, since the glucocorticoid receptor can be involved in protein-protein interactions with the Jun/Jun homodimer of the AP-1 complex.


Assuntos
Encéfalo/crescimento & desenvolvimento , Dexametasona/administração & dosagem , Proteínas Quinases JNK Ativadas por Mitógeno/biossíntese , Proteínas Proto-Oncogênicas c-fos/biossíntese , Animais , Encéfalo/metabolismo , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Embrião de Mamíferos , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Mapas de Interação de Proteínas/genética , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/biossíntese , Ratos , Fator de Transcrição AP-1/genética
14.
Bull Exp Biol Med ; 160(6): 767-70, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27165079

RESUMO

Experiments on rabbits showed that increasing the dose of intravenously administered cellulose sulfate from wheat straw (dynamic viscosity 3.4 cP, sulfur content 14.1%) increased plasma clotting time in some coagulation tests and plasma anticoagulant activity. When cellulose sulfate was administered in the dose of 1 mg/kg, plasma clotting time in the presence of the anticoagulant (5 min after administration) was ~3-fold higher than after saline administration.


Assuntos
Anticoagulantes/administração & dosagem , Celulose/análogos & derivados , Administração Intravenosa , Animais , Coagulação Sanguínea/efeitos dos fármacos , Celulose/administração & dosagem , Relação Dose-Resposta a Droga , Fator Xa/metabolismo , Heparina/farmacologia , Coelhos
15.
Bull Exp Biol Med ; 161(3): 377-80, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27502699

RESUMO

Anticompulsive activity of a novel compound GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1H-pyrazolo[4,3-C]Pyridine-3-on, chloral hydrate) in a dose of 20 mg/kg (single, subchronic, and chronic administration) in comparison with fluvoxamine (25 mg/kg) was studied in the marble burying test in the model of unpredictable chronic mild stress on BALB/c mice. GIZh-72 produced an anticompulsive effect that increased with increasing treatment duration under stress conditions in contrast to fluvoxamine that induced inversion of this effect after long-term administration. Neuroleptic activity of GIZh-72 in doses of 20 and 40 mg/kg was studied on the model of apomorphine-induced climbing in C57Bl/6 mice. In contrast to haloperidol (0.5 mg/kg), GIZh-72 exhibited no neuroleptic properties. Our results indicate that GIZh-72 holds much promise for pharmacotherapy of obsessive-compulsive disorder.


Assuntos
Ansiolíticos/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Animais , Ansiolíticos/química , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/química
16.
Eksp Klin Farmakol ; 79(10): 3-7, 2016.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-30085476

RESUMO

The anxyolitic effects of diazepam and afobazole on the anxiety model caused by subconvulsive doses of pentylenetetrazole have been studied in the open field test and drug discrimination in rodents. It is found that diazepam (I and 5 mg/kg, i.p.) and afobazole (1 mg/kg, i.p.) reduced the pentylenetetrazole-induced (20 mg/kg, i.p.) anxiety in Wistar rats in the open field test. Only diazepam (1 mg/kg, i.p.) in Balb/c mice and only afobazole (1 mg/kg, i.p.) in C57B11/6 mice decreased anxiety caused by pentylenetetrazole (30 mg/kg, i.p.). Afobazole (20 mg/kg, i.p.) partially inhibited the effect of pentylenetetrazole (20 mg/kg, i.p.) in drug discrimination paradigm in Wistar rats learned in the Skinner box, in contrast to diazepam (5 mg/kg, i.p.) that fully blocked the stimulus properties of non-competitive GABA(A) receptor antagonist. The obtained results suggest that restorative effects of diazepam and afobazole on pentylenetetrazole-induced anxiety depend on the type of emotional stress reaction in rodent species and mice strains, though anxiogenic effects of pentylenetetrazole are not influenced by interstrain differences.


Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Benzimidazóis/farmacologia , Diazepam/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Morfolinas/farmacologia , Receptores de GABA-A/metabolismo , Animais , Ansiedade/metabolismo , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar
17.
Patol Fiziol Eksp Ter ; 60(4): 34-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29244920

RESUMO

Mutant EPO molecules, deprived of erythropoietic activity, but possessing cytoprotective action, were created by the method of genetic engineering. The assessment of the therapeutic effectiveness of the received mutant proteins was carried out by the retention of the conditioned reflex of passive avoidance (PA), developed before the ischemic injury of rat brain prefrontal cortex, and by the MRI-analysis of ischemic damage volume. Antiamnestic and neuroprotective action of mutant molecules - MERO-Fc and MEPO-TR is investigated on model of photothrombosis of rat brain prefrontal cortex at single intranasal introduction in 1 h after cortex ischemic damage. The neuroprotective (MRI) and antiamnestic (PA) effects of mutant molecules of erythropoietin derivatives are shown.


Assuntos
Eritropoetina , Trombose Intracraniana , Mutação , Fármacos Neuroprotetores/farmacologia , Córtex Pré-Frontal , Animais , Modelos Animais de Doenças , Eritropoetina/genética , Eritropoetina/farmacologia , Trombose Intracraniana/induzido quimicamente , Trombose Intracraniana/tratamento farmacológico , Trombose Intracraniana/fisiopatologia , Masculino , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos
18.
Bull Exp Biol Med ; 158(3): 318-21, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25573359

RESUMO

Using the model of bilateral photothrombosis of the blood vessels in the prefrontal cortex we have shown that new hybrid proteins derived from recombinant human erythropoietin, carbamylated EPO-Fc and EPO-TR fusion proteins, injected intraperitoneally 1 h after ischemic injury contribute to restoration of passive avoidance response formed before photothrombotic injury and reduction in the volume of the ischemic focus. These data attest to nootropic and neuroprotective activities of these hybrid proteins. Carbamylated glycopeptide derivative ЕPO-TR exhibited prolonged neuroprotective properties.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Eritropoetina/química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Animais , Humanos , Masculino , Fármacos Neuroprotetores/uso terapêutico , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Acidente Vascular Cerebral/tratamento farmacológico
19.
Eksp Klin Farmakol ; 78(11): 3-7, 2015.
Artigo em Russo | MEDLINE | ID: mdl-27017697

RESUMO

It was studied the anxiolytic properties of 4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-1Í-pyrazolo[4,3-c]pyridin-3-one chloralhydrate (GIZh-72, 20 mg/kg, i.p.) and afobazole (1 mg/kg, i.p.) in comparison to fluoxetine (20 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) in open-field and marble burying tests on male mice of inbred strains BALB/C and C57BL/6. It is established that GIZh-72 administered both 30 min and 24 h before testing produces anxiolytic effect in the open-field test. The open field anxiety response patterns following GIZh-72 administration differed from these in diazepam or afobazole treated BALB/C mice. This drug also decreased the number of buried marbles in both BALB/C and C57BL/6 mice, the effect being comparable to that of afobazole and fluoxetine. In operant drug discrimination liquid-reinforcement paradigm in male Wistar rats, GIZh-72 failed to antagonize or substitute for the interoceptive stimulus cues of pentylenetetrazole evoking the saline-like responses in the latter case, which was evidence for the absence of properties of a ligand bearing positive modulator sites of GABA-A receptor.


Assuntos
Ansiolíticos/química , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Animais , Ansiolíticos/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar
20.
Patol Fiziol Eksp Ter ; (3): 28-33, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26852592

RESUMO

It was stated with model of bilateral photochemically induced thrombosis of the prefrontal cortex by injected intranasally or intraperitoneally in 1h after operation new derivatives of eritropoetine: Epo, Epo-Fc, Epo-Tr provoked neuroprotective and antiamnestic action. Epo-Fc demonstrated more effective action by intranasal injection.


Assuntos
Eritropoetina/farmacologia , Trombose Intracraniana/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Córtex Pré-Frontal/metabolismo , Animais , Trombose Intracraniana/metabolismo , Trombose Intracraniana/patologia , Masculino , Córtex Pré-Frontal/patologia , Ratos
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