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[PMID]:28457510
[Au] Autor:Kanawaku Y; Hirakawa K; Koike K; Kanetake J; Ohno Y
[Ad] Endereço:Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan. Electronic address: ykanawaku@nifty.com.
[Ti] Título:Pattern recognition analysis of proton nuclear magnetic resonance spectra of postmortem cerebrospinal fluid from rats with drug-induced seizure or coma.
[So] Source:Leg Med (Tokyo);25:52-58, 2017 Mar.
[Is] ISSN:1873-4162
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Cerebrospinal fluid (CSF) is routinely subjected to gross evaluation in postmortem investigations; however, its use in chemical evaluations has not been fully realized. Analysis of nuclear magnetic resonance (NMR) spectra with pattern recognition methods was applied to CSF samples. Rats were treated with pentylenetetrazol (PTZ) to induce seizure or pentobarbital (PB) to induce coma, and postmortem CSF was collected after CO gas euthanization. Pattern recognition analysis of the NMR data was performed on individual postmortem CSF samples. The aim of this study was to determine if pattern recognition analysis of NMR data could be used to classify the rats according to their drug treatment. The applicability of NMR data with pattern recognition analysis using postmortem CSF was also assessed. Partial Least Squares-Discriminant Analysis (PLS-DA) score plots indicated that the PTZ, PB, and NS (control) groups were clustered and clearly separated. PLS-DA correlation loading plots showed respective spectral and category variances of 41% and 42% for factor 1, and 17% and 27% for factor 2. Thus, factors 1 and 2 together described 58% (41%+17%) and 69% (42%+27%) of the variation, respectively. NMR study of postmortem CSF has the potential to be utilized as both a novel forensic neurochemistry method and in the clinical setting.
[Mh] Termos MeSH primário: Líquido Cefalorraquidiano/efeitos dos fármacos
Coma/induzido quimicamente
Espectroscopia de Ressonância Magnética
Mudanças Depois da Morte
Convulsões/induzido quimicamente
[Mh] Termos MeSH secundário: Animais
Convulsivantes/toxicidade
Análise Discriminante
Hipnóticos e Sedativos/toxicidade
Metabolômica
Pentobarbital/toxicidade
Pentilenotetrazol/toxicidade
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Convulsants); 0 (Hypnotics and Sedatives); I4744080IR (Pentobarbital); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28486854
[Au] Autor:Lei CW; Yang ZQ; Zeng YP; Zhou Y; Huang Y; He XS; Li GY; Yuan XH
[Ad] Endereço:a School of Life Science and Engineering , Southwest University of Science and Technology , Mianyang , P.R. China.
[Ti] Título:Xylastriasan A, a new cytochalasan from the fungus Xylaria striata.
[So] Source:Nat Prod Res;32(1):7-13, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Xylastriasan A (1), a new cytochalasan alkaloid with a rare 5/6/6/5/6 pentacyclic skeleton, and ergosterol (2) were isolated from the ethanol extract of fruiting bodies of the fungus Xylaria striata. Their structures were determined by analysis of their spectroscopic data. Compound 1 exhibited weak cytotoxic activity against HEPG2, B16 and A549 cell lines with IC values of 93.61, 85.61 and 91.58 µM, respectively. Ergosterol (2) potentiated pentobarbital-induced sleep by not only increasing the number of falling asleep and prolonging sleeping time but also reducing sleep latency at a dosage of 5 mg/kg.
[Mh] Termos MeSH primário: Alcaloides/farmacologia
Citocalasinas/farmacologia
Ergosterol/farmacologia
Hipnóticos e Sedativos/farmacologia
Sono/efeitos dos fármacos
Xylariales/química
[Mh] Termos MeSH secundário: Alcaloides/química
Alcaloides/isolamento & purificação
Animais
Linhagem Celular
Citocalasinas/química
Citocalasinas/isolamento & purificação
Ergosterol/química
Ergosterol/isolamento & purificação
Células Hep G2
Seres Humanos
Hipnóticos e Sedativos/química
Espectroscopia de Ressonância Magnética
Camundongos Endogâmicos ICR
Estrutura Molecular
Pentobarbital/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Cytochalasins); 0 (Hypnotics and Sedatives); I4744080IR (Pentobarbital); Z30RAY509F (Ergosterol)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1324959


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[PMID]:28902674
[Au] Autor:Kuo MC; Leung LS
[Ad] Endereço:From the Department of Physiology and Pharmacology (M.-C.K.) and the Department of Physiology and Pharmacology and Program in Neuroscience (L.S.L.), The University of Western Ontario, London, Ontario, Canada.
[Ti] Título:Disruption of Hippocampal Multisynaptic Networks by General Anesthetics.
[So] Source:Anesthesiology;127(5):838-851, 2017 Nov.
[Is] ISSN:1528-1175
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function. METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal). RESULTS: Monosynaptic population excitatory postsynaptic potentials at the basal and apical dendrites of CA1 were significantly decreased at greater than or equal to 0.25% (n = 4) and greater than or equal to 1.0% (n = 6) isoflurane, respectively. The perforant path evoked multisynaptic response at CA1 was decreased by ~50% at greater than or equal to 0.25% isoflurane (n = 5). A decreased population excitatory postsynaptic potential was accompanied by increased paired-pulse facilitation. Population spike amplitude in relation to apical dendritic population excitatory postsynaptic potential was not significantly altered by isoflurane. Spontaneous hippocampal local field potential at 0.8 to 300 Hz was dose-dependently suppressed by isoflurane (n = 6), with local field potential power in the 50- to 150-Hz band showing the highest decrease with isoflurane dose, commensurate with the decrease in trisynaptic CA1 response. Low-dose pentobarbital (n = 7) administration decreased the perforant path evoked trisynaptic CA1 response and hippocampal local field potentials at 78 to 125 Hz. CONCLUSIONS: Hippocampal networks are sensitive to low doses of isoflurane and pentobarbital, possibly through both glutamatergic and γ-aminobutyric acid-mediated transmission. Network disruption could help explain the impairment of hippocampal-dependent cognitive functions with low-dose anesthetic.
[Mh] Termos MeSH primário: Anestésicos Gerais/toxicidade
Hipocampo/efeitos dos fármacos
Rede Nervosa/efeitos dos fármacos
Sinapses/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Eletrodos Implantados
Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos
Potenciais Pós-Sinápticos Excitadores/fisiologia
Hipocampo/fisiologia
Isoflurano/toxicidade
Masculino
Rede Nervosa/fisiologia
Pentobarbital/toxicidade
Ratos
Ratos Long-Evans
Sinapses/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, General); CYS9AKD70P (Isoflurane); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1097/ALN.0000000000001861


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[PMID]:28717108
[Au] Autor:Nakatsu N; Igarashi Y; Aoshi T; Hamaguchi I; Saito M; Mizukami T; Momose H; Ishii KJ; Yamada H
[Ad] Endereço:Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, Health and Nutrition.
[Ti] Título:Isoflurane is a suitable alternative to ether for anesthetizing rats prior to euthanasia for gene expression analysis.
[So] Source:J Toxicol Sci;42(4):491-497, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Diethyl ether (ether) had been widely used in Japan for anesthesia, despite its explosive properties and toxicity to both humans and animals. We also had used ether as an anesthetic for euthanizing rats for research in the Toxicogenomics Project (TGP). Because the use of ether for these purposes will likely cease, it is required to select an alternative anesthetic which is validated for consistency with existing TGP data acquired under ether anesthesia. We therefore compared two alternative anesthetic candidates, isoflurane and pentobarbital, with ether in terms of hematological findings, serum biochemical parameters, and gene expressions. As a result, few differences among the three agents were observed. In hematological and serum biochemistry analysis, no significant changes were found. In gene expression analysis, four known genes were extracted as differentially expressed genes in the liver of rats anesthetized with ether, isoflurane, or pentobarbital. However, no significant relationships were detected using gene ontology, pathway, or gene enrichment analyses by DAVID and TargetMine. Surprisingly, although it was expected that the lung would be affected by administration via inhalation, only one differentially expressed gene was extracted in the lung. Taken together, our data indicate that there are no significant differences among ether, isoflurane, and pentobarbital with respect to effects on hematological parameters, serum biochemistry parameters, and gene expression. Based on its smallest affect to existing data and its safety profile for humans and animals, we suggest isoflurane as a suitable alternative anesthetic for use in rat euthanasia in toxicogenomics analysis.
[Mh] Termos MeSH primário: Anestesia
Anestésicos Inalatórios
Éter
Eutanásia Animal
Isoflurano
Ratos Sprague-Dawley/sangue
Ratos Sprague-Dawley/genética
Transcriptoma
[Mh] Termos MeSH secundário: Anestésicos Inalatórios/toxicidade
Animais
Éter/toxicidade
Fígado
Pulmão
Masculino
Pentobarbital
Toxicogenética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Inhalation); 0F5N573A2Y (Ether); CYS9AKD70P (Isoflurane); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.491


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[PMID]:28642232
[Au] Autor:Kumar M; Kumar M; Freund JM; Dillon GH
[Ad] Endereço:Department of Physiology and Pharmacology, Center for Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia (Mo.K., Mi.K., J.M.F., G.H.D.); and Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science
[Ti] Título:A Single Amino Acid Residue at Transmembrane Domain 4 of the Subunit Influences Carisoprodol Direct Gating Efficacy at GABA Receptors.
[So] Source:J Pharmacol Exp Ther;362(3):395-404, 2017 Sep.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The muscle relaxant carisoprodol has recently been controlled at the federal level as a Schedule IV drug due to its high abuse potential and consequences of misuse, such as withdrawal syndrome, delusions, seizures, and even death. Recent work has shown that carisoprodol can directly gate and allosterically modulate the type A GABA (GABA ) receptor. These actions are subunit-dependent; compared with other GABA receptors, carisoprodol has nominal direct gating effects in 3 2 2 receptors. Here, using site-directed mutagenesis and whole-cell patch-clamp electrophysiology in transiently transfected human embryonic kidney 293 cells, we examined the role of GABA receptor subunit transmembrane domain 4 (TM4) amino acids in direct gating and allosteric modulatory actions of carisoprodol. Mutation of 3 valine at position 440 to leucine (present in the equivalent position in the 1 subunit) significantly increased the direct gating effects of carisoprodol without affecting its allosteric modulatory effects. The corresponding reverse mutation, 1(L415V), decreased carisoprodol direct gating potency and efficacy. Analysis of a series of amino acid mutations at the 415 position demonstrated that amino acid volume correlated positively with carisoprodol efficacy, whereas polarity inversely correlated with carisoprodol efficacy. We conclude that 1(415) of TM4 is involved in the direct gating, but not allosteric modulatory, actions of carisoprodol. In addition, the orientation of alkyl or hydroxyl groups at this position influences direct gating effects. These findings support the likelihood that the direct gating and allosteric modulatory effects of carisoprodol are mediated via distinct binding sites.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Carisoprodol/farmacologia
Relaxantes Musculares Centrais/farmacologia
Transporte Proteico/efeitos dos fármacos
Receptores de GABA-A/efeitos dos fármacos
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Sítios de Ligação/efeitos dos fármacos
Agonistas GABAérgicos/farmacologia
Células HEK293
Seres Humanos
Ativação do Canal Iônico/efeitos dos fármacos
Mutagênese Sítio-Dirigida
Técnicas de Patch-Clamp
Pentobarbital/farmacologia
Receptores de GABA-A/genética
Esteroides/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (GABA Agonists); 0 (Muscle Relaxants, Central); 0 (Receptors, GABA-A); 0 (Steroids); 21925K482H (Carisoprodol); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170902
[Lr] Data última revisão:
170902
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.117.242156


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[PMID]:28535865
[Au] Autor:de Souza Dyer C; Brice AK; Marx JO
[Ad] Endereço:University Laboratory Animal Resources, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
[Ti] Título:Intraperitoneal Administration of Ethanol as a Means of Euthanasia for Neonatal Mice ( ).
[So] Source:J Am Assoc Lab Anim Sci;56(3):299-306, 2017 May 01.
[Is] ISSN:1559-6109
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of ethanol as "acceptable with conditions," and recent work confirmed that this method is appropriate for euthanizing adult mice, but neonatal mice have not been tested. To explore this method in neonatal mice, mouse pups (C57BL/6 and CD1, 162 total) were injected with 100% ethanol, a pentobarbital-phenytoin combination, or saline at 7, 14, 21, 28, or 35 d of age. Electrocardiograms, respiratory rates, and times to loss of righting reflex and death were recorded. Time to death (TTD) differed significantly between ethanol and pentobarbital-phenytoin at 7, 14, and 21 d and between ethanol groups at 7, 14, and 21 d compared with 35 d. The average TTD (± 1 SD) for ethanol-injected mice were: 7 d, 70.3 ± 39.8 min; 14 d, 51.7 ± 30.5 min; 21 d, 32.3 ± 20.8 min, 28 d, 14.0 ± 15.2; and 35 d, 4.9 ± 1.4. Mean TTD in pentobarbital-phenytoin-injected mice were: 7 d, 2.8 ± 0.4 min; 14 d, 2.9 ± 0.5 min; 21 d, 3.9 ± 1.2 min; 28 d, 3.9 ± 0.7 min; and 35 d, 4.4 ± 0.5. Although TTD did not differ between ethanol and pentobarbital-phenytoin at 28 d of age, the TTD in 3 of 12 mice was longer than 15 min after ethanol administration at this age. Therefore, ethanol should not be used as a method of euthanasia for mice younger than 35 d, because the criteria for humane euthanasia were met only in mice 35 d or older.
[Mh] Termos MeSH primário: Animais Recém-Nascidos
Etanol/administração & dosagem
Eutanásia Animal/métodos
Camundongos
[Mh] Termos MeSH secundário: Bem-Estar do Animal
Animais
Injeções Intraperitoneais
Camundongos Endogâmicos C57BL
Pentobarbital/administração & dosagem
Fenitoína/administração & dosagem
Inconsciência/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
3K9958V90M (Ethanol); 6158TKW0C5 (Phenytoin); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE


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[PMID]:28222732
[Au] Autor:Zatroch KK; Knight CG; Reimer JN; Pang DS
[Ad] Endereço:Cornell University College of Veterinary Medicine, Ithaca, NY, USA.
[Ti] Título:Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus).
[So] Source:BMC Vet Res;13(1):60, 2017 Feb 21.
[Is] ISSN:1746-6148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia. In a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability in CHB was assessed by calculating the coefficient of variation (CV). RESULTS: The fastest euthanasia method (CHB) was HH (283.7 ± 38.0 s), compared with LL (485.8 ± 140.7 s, p = 0.002) and LH (347.7 ± 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 ± 29.6 s), compared with HH (111.6 ± 19.7 s, p = 0.046) and LH (104.2 ± 19.3 s, p = 0.01). Misinjections occurred in 17.0% (7/41) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (4/11, LL) to 46% (5/11, HH). CONCLUSIONS: These data illustrate refinement of the IP pentobarbital euthanasia technique. Both dose and volume contribute to speed of death, with a dose of 800 mg/kg (HH) being the most effective method. An increase in volume alone does not significantly reduce variability. The proportion of misinjections was similar to that of previous studies.
[Mh] Termos MeSH primário: Eutanásia Animal/métodos
Pentobarbital/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Feminino
Injeções Intraperitoneais
Pentobarbital/farmacologia
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
I4744080IR (Pentobarbital)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170306
[Lr] Data última revisão:
170306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE
[do] DOI:10.1186/s12917-017-0982-y


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[PMID]:28177696
[Au] Autor:Edge D; Shortt CM; Johns EJ; Gobbo OL; Markos F; Abdulla MH; Barry EF
[Ad] Endereço:a Department of Physiology, University College Cork, Cork, Ireland.
[Ti] Título:Assessment of renal function in the anaesthetised rat following injection of superparamagnetic iron oxide nanoparticles.
[So] Source:Can J Physiol Pharmacol;95(4):443-446, 2017 Apr.
[Is] ISSN:1205-7541
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:A recent study showed that a significant fall in mean arterial pressure (MAP) occurred following intravenous injection of two novel superparamagnetic iron oxide nanoparticles (SPIONs), MF66 and OD15. To assess if this was caused by excessive glomerular clearance, the effect of both particles on renal function was studied. Experiments were performed on sodium pentobarbital anaesthetised male Wistar rats (250-350 g). Twenty-minute urine clearances were taken followed by an i.v. bolus of MF66, OD15 (2 mg·kg ), or dH O (0.4 mL·kg ). MF6 or OD15 injection resulted in a significant transient drop in MAP and renal blood flow by approximately 33% and 50% (P < 0.05). The absolute excretion of sodium was significantly increased (P < 0.05) by almost 80% and 70% following OD15 and MF66, respectively. Similarly, fractional excretion of sodium was increased by almost 80% and 60% following OD15 and MF66, respectively. The glomerular filtration rate was not significantly affected, but urine flow increased nonsignificantly by approximately 50% and 66% following i.v. injection of OD15 and MF66, respectively. SPIONs produce a decrease in blood pressure and a natriuresis; however, the rate of fluid filtration in the kidney was not significantly affected.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos/efeitos adversos
Compostos Férricos/efeitos adversos
Taxa de Filtração Glomerular/efeitos dos fármacos
Hipotensão/induzido quimicamente
Nanopartículas de Magnetita/efeitos adversos
Natriurese/efeitos dos fármacos
Circulação Renal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anestesia Intravenosa
Animais
Diurese/efeitos dos fármacos
Compostos Férricos/administração & dosagem
Compostos Férricos/farmacocinética
Injeções Intravenosas
Imagem por Ressonância Magnética/métodos
Nanopartículas de Magnetita/administração & dosagem
Nanopartículas de Magnetita/química
Masculino
Taxa de Depuração Metabólica
Modelos Animais
Pentobarbital/administração & dosagem
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ferric Compounds); 0 (Magnetite Nanoparticles); 1K09F3G675 (ferric oxide); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1139/cjpp-2016-0405


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[PMID]:28160425
[Au] Autor:Brito AF; Fajemiroye JO; Neri HFS; Silva DM; Silva DPB; Sanz G; Vaz BG; de Carvalho FS; Ghedini PC; Lião LM; Menegatti R; Costa EA
[Ad] Endereço:Department of Pharmacology, ICB, Federal University of Goiás, Goiânia, GO, Brazil.
[Ti] Título:Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways.
[So] Source:Chem Biol Drug Des;90(3):432-442, 2017 Sep.
[Is] ISSN:1747-0285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this study, we proposed the design, synthesis of a new compound 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032), and pharmacological evaluation of its anxiolytic-like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital-induced sleep, open-field and wire tests. The anxiolytic-like effect of this compound was evaluated using elevated plus maze and light-dark box tests. In addition, the mnemonic activity was evaluated through step-down test. In sodium pentobarbital-induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open-field test, LQFM032 altered behavioral parameter, that suggested anxiolytic-like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light-dark box test, the LQFM032 showed anxiolytic-like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic-like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic-like activity without altering the mnemonic activity.
[Mh] Termos MeSH primário: Ansiolíticos/metabolismo
Benzodiazepinas/metabolismo
Piperazinas/metabolismo
Pirazóis/metabolismo
Receptores Nicotínicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/síntese química
Ansiolíticos/farmacologia
Comportamento Animal/efeitos dos fármacos
Benzodiazepinas/química
Benzodiazepinas/farmacologia
Espectroscopia de Ressonância Magnética
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Pentobarbital/farmacologia
Piperazinas/síntese química
Piperazinas/farmacologia
Pirazóis/síntese química
Pirazóis/farmacologia
Receptores Nicotínicos/química
Sono/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol); 0 (Anti-Anxiety Agents); 0 (Piperazines); 0 (Pyrazoles); 0 (Receptors, Nicotinic); 12794-10-4 (Benzodiazepines); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170205
[St] Status:MEDLINE
[do] DOI:10.1111/cbdd.12961


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[PMID]:28049349
[Au] Autor:Song Y; Yang CJ; Wang ZB; Zhao N; Feng XS; Meng FH
[Ad] Endereço:a School of Pharmacy , China Medical University , Shenyang , P.R. China.
[Ti] Título:Chemical constituents of Eleutherococcus sessiliflorus extract and its sedative-hypnotic effect.
[So] Source:Nat Prod Res;31(17):1995-2000, 2017 Sep.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The present study was designed to investigate the chemical constituents and bioactivities of the roots of Eleutherococcus sessiliflorus (E. sessiliflorus). The compounds were isolated through various chromatography techniques and elucidated by mass spectrometric (MS), 1D- and 2D-NMR analyses. The sedative-hypnotic effect of E. sessiliflorus ethanol extract and its fractions (acetic ether, n-butanol and water fraction) were also investigated. In the chemical constituent study, one new compound, 3-ethyl-5-hydroxy-3-(hydroxymethyl) pentyl-3-(3,4-dihydroxyphenyl) acrylate and fourteen known compounds were isolated and identified. The chromatographic fingerprint of E. sessiliflorus was established by UPLC-PDA-MS/MS analysis. In bioactivity study, it was found that the water fraction of E. sessiliflorus extract could prolong pentobarbital-induced sleeping time more than that of the other fractions of E. sessiliflorus extract in mice, which provided a basis for future study on sedative-hypnotic effect of the chemical constituents in E. sessiliflorus.
[Mh] Termos MeSH primário: Eleutherococcus/química
Hipnóticos e Sedativos/farmacologia
Extratos Vegetais/química
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: 1-Butanol/química
Animais
Etanol
Hipnóticos e Sedativos/química
Masculino
Camundongos
Pentobarbital/farmacologia
Extratos Vegetais/análise
Raízes de Plantas/química
Sono/efeitos dos fármacos
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (Plant Extracts); 3K9958V90M (Ethanol); 8PJ61P6TS3 (1-Butanol); I4744080IR (Pentobarbital)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2016.1272106



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