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[PMID]:22535688
[Au] Autor:Ahmad S; Hughes MA; Yeh LA; Scott JE
[Ad] Endereço:Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, NC, USA.
[Ti] Título:Potential repurposing of known drugs as potent bacterial ß-glucuronidase inhibitors.
[So] Source:J Biomol Screen;17(7):957-65, 2012 Aug.
[Is] ISSN:1552-454X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The active metabolite of the chemotherapeutic irinotecan, SN-38, is detoxified through glucuronidation and then excreted into the gastrointestinal tract. Intestinal bacteria convert the glucuronidated metabolite back to the toxic SN-38 using ß-glucuronidase (GUS), resulting in debilitating diarrhea. Inhibiting GUS activity may relieve this side effect of irinotecan. In this study, we sought to determine whether any known drugs have GUS inhibitory activity. We screened a library of Food and Drug Administration-approved drugs with a cell-free biochemical enzyme assay using purified bacterial GUS. After triage, five drugs were confirmed to inhibit purified bacterial GUS. Three of these were the monoamine oxidase inhibitors nialamide, isocarboxazid, and phenelzine with average IC(50) values for inhibiting GUS of 71, 128, and 2300 nM, respectively. The tricyclic antidepressant amoxapine (IC(50) = 388 nM) and the antimalarial mefloquine (IC(50) = 1.2 µM) also had activity. Nialamide, isocarboxazid, and amoxapine had no significant activity against purified mammalian GUS but showed potent activity for inhibiting endogenous GUS activity in a cell-based assay using living intact Escherichia coli with average IC(50) values of 17, 336, and 119 nM, respectively. Thus, nialamide, isocarboxazid, and amoxapine have potential to be repurposed as therapeutics to reduce diarrhea associated with irinotecan chemotherapy and warrant further investigation for this use.
[Mh] Termos MeSH primário: Camptotecina/análogos & derivados
Avaliação Pré-Clínica de Medicamentos
Inibidores Enzimáticos/farmacologia
Escherichia coli/enzimologia
Glucuronidase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Amoxapina/farmacologia
Antineoplásicos Fitogênicos/metabolismo
Camptotecina/metabolismo
Descoberta de Drogas
Escherichia coli/metabolismo
Proteínas de Escherichia coli/antagonistas & inibidores
Isocarboxazida/farmacologia
Mefloquina/farmacologia
Inibidores da Monoaminoxidase/farmacologia
Nialamida/farmacologia
Fenelzina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Enzyme Inhibitors); 0 (Escherichia coli Proteins); 0 (Monoamine Oxidase Inhibitors); 34237V843T (Isocarboxazid); 7673326042 (irinotecan); EC 3.2.1.31 (Glucuronidase); O408N561GF (Phenelzine); R63VQ857OT (Amoxapine); T2Q0RYM725 (Nialamide); TML814419R (Mefloquine); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1301
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120427
[St] Status:MEDLINE
[do] DOI:10.1177/1087057112444927


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[PMID]:22106172
[Au] Autor:Meehan CF; Grondahl L; Nielsen JB; Hultborn H
[Ad] Endereço:University of Copenhagen, Department of Neuroscience and Pharmacology, Panum Institute, Bldg 18.5, Blegdamsvej 3, 200 Copenhagen N, Denmark. claire@sund.ku.dk
[Ti] Título:Fictive locomotion in the adult decerebrate and spinal mouse in vivo.
[So] Source:J Physiol;590(2):289-300, 2012 Jan 15.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recently, transgenic mice have been created with mutations affecting the components of the mammalian spinal central pattern generator (CPG) for locomotion; however, it has currently only been possible to evoke fictive locomotion in mice, using neonatal in vitro preparations. Here, we demonstrate that it is possible to evoke fictive locomotion in the adult decerebrate mouse in vivo using l-3,4-dihydroxyphenylalanine methyl ester hydrochloride (l-DOPA) and 5-hydroxytryptophan (5HTP) following injection of the monoaminoxiadase inhibitor Nialamide. We investigate the effects of afferent stimulation and spinalization as well as demonstrate the possibility of simultaneous intracellular recording of rhythmically active motoneurones. Our results demonstrate that several features of the mouse locomotor CPG are similar to those that have been observed in rat, cat, rabbit and monkey suggesting a fairly conserved organisation and allowing for future results in transgenic mice to be extrapolated to existing knowledge of CPG components and circuitry obtained in larger species.
[Mh] Termos MeSH primário: Estado de Descerebração/fisiopatologia
Locomoção/fisiologia
Neurônios Motores/fisiologia
Plasticidade Neuronal/fisiologia
Medula Espinal/fisiopatologia
[Mh] Termos MeSH secundário: 5-Hidroxitriptofano/farmacologia
Animais
Gatos
Estimulação Elétrica
Feminino
Haplorrinos
Levodopa/farmacologia
Locomoção/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Modelos Animais
Inibidores da Monoaminoxidase/farmacologia
Neurônios Motores/efeitos dos fármacos
Nialamida/farmacologia
Nervos Periféricos/efeitos dos fármacos
Coelhos
Ratos
Tempo de Reação/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Monoamine Oxidase Inhibitors); 46627O600J (Levodopa); C1LJO185Q9 (5-Hydroxytryptophan); T2Q0RYM725 (Nialamide)
[Em] Mês de entrada:1206
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111123
[St] Status:MEDLINE
[do] DOI:10.1113/jphysiol.2011.214643


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[PMID]:19112051
[Au] Autor:Huang L; Marzan F; Jayewardene AL; Lizak PS; Li X; Aweeka FT
[Ad] Endereço:Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94110, USA.
[Ti] Título:Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for determination of isoniazid in human plasma.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;877(3):285-90, 2009 Jan 15.
[Is] ISSN:1570-0232
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:An LC-MS/MS method for the determination of isoniazid in human plasma was developed and validated. Human plasma aliquots of 100 microL were used for analysis. The assay used nialamide as the internal standard. The calibration curve concentration range was 50-10,000 ng/mL. Sample preparation utilized protein precipitation, and the supernatant was directly injected onto silica column without reconstitution. The recovery was over 90% and matrix effect was negligible. The method is simple and fast, which is advantageous in respect to instability of isoniazid in human plasma and loss on reconstitution due to its low molecular weight.
[Mh] Termos MeSH primário: Antituberculosos/sangue
Cromatografia Líquida/métodos
Isoniazida/sangue
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Calibragem
Fenômenos Químicos
Estabilidade de Medicamentos
Seres Humanos
Modelos Lineares
Nialamida/análise
Padrões de Referência
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antitubercular Agents); T2Q0RYM725 (Nialamide); V83O1VOZ8L (Isoniazid)
[Em] Mês de entrada:0904
[Cu] Atualização por classe:161124
[Lr] Data última revisão:
161124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:081230
[St] Status:MEDLINE
[do] DOI:10.1016/j.jchromb.2008.12.024


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[PMID]:18416142
[Au] Autor:Koval'chuk VV
[Ti] Título:[Pharmacologic correction of psycho-emotive disorders in the rehabilitation of patients after removal of brain tumors].
[So] Source:Vopr Onkol;53(6):704-10, 2007.
[Is] ISSN:0507-3758
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Mh] Termos MeSH primário: Ansiolíticos/uso terapêutico
Antidepressivos/uso terapêutico
Neoplasias Encefálicas/cirurgia
Emoções
Transtornos do Humor/tratamento farmacológico
Transtornos do Humor/etiologia
Procedimentos Neurocirúrgicos/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Alprazolam/uso terapêutico
Amitriptilina/uso terapêutico
Ansiolíticos/administração & dosagem
Antidepressivos/administração & dosagem
Ansiedade/tratamento farmacológico
Ansiedade/etiologia
Depressão/tratamento farmacológico
Depressão/etiologia
Doxepina/uso terapêutico
Feminino
Seres Humanos
Masculino
Maprotilina/uso terapêutico
Meia-Idade
Moclobemida/uso terapêutico
Nialamida/uso terapêutico
Sertralina/uso terapêutico
Tiazepinas/uso terapêutico
Trazodona/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (Thiazepines); 0T493YFU8O (tianeptine); 1668-19-5 (Doxepin); 1806D8D52K (Amitriptyline); 2U1W68TROF (Maprotiline); PJ0Y7AZB63 (Moclobemide); QUC7NX6WMB (Sertraline); T2Q0RYM725 (Nialamide); YBK48BXK30 (Trazodone); YU55MQ3IZY (Alprazolam)
[Em] Mês de entrada:0805
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:080418
[St] Status:MEDLINE


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[PMID]:17375141
[Au] Autor:Bilkei-Gorzo A; Michel K; Noble F; Roques BP; Zimmer A
[Ad] Endereço:Department of Molecular Psychiatry, University of Bonn, Bonn, Germany. abilkei@uni-bonn.de
[Ti] Título:Preproenkephalin knockout mice show no depression-related phenotype.
[So] Source:Neuropsychopharmacology;32(11):2330-7, 2007 Nov.
[Is] ISSN:0893-133X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Clinical, preclinical, and pharmacological studies have suggested that decreased enkephalin tone is associated with depression-like symptoms and increase in enkephalin signaling could have a therapeutic value in the treatment of depression. In this study we demonstrate that, surprisingly, animals lacking enkephalin (preproenkephalin, Penk1(-/-)) showed no depression-related phenotype in the Porsolt forced swimming or tail suspension tests. Moreover, Penk1(-/-) mice had a lower frequency of depression-related behavior in stress-induced hypoactivity and ultrasonic vocalization models of depression, similar to animals treated with antidepressant drugs, although this effect was specific to the genetic background. In addition, there was no significant difference in the efficacy of antidepressant reference compounds in wild-type and knockout animals. Nialamide and amitriptyline were even slightly more effective in animals with genetic deletion of Penk1, whereas the minimal effective dose of imipramine and fluoxetine was the same in the two genotypes. The dual peptidase inhibitor RB-101 was also effective in Penk1(-/-) as well as in Penk1(-/-)/Pdyn(-/-) animals, although its efficacy was somewhat reduced compared with wild-type animals. This result was also surprising because the antidepressant effects of RB-101 were thought to be due to the elevation of enkephalin levels.
[Mh] Termos MeSH primário: Depressão/genética
Encefalinas/deficiência
Camundongos Knockout/fisiologia
Fenótipo
Precursores de Proteínas/deficiência
[Mh] Termos MeSH secundário: Animais
Antidepressivos/uso terapêutico
Comportamento Animal/efeitos dos fármacos
Comportamento Animal/fisiologia
Depressão/tratamento farmacológico
Modelos Animais de Doenças
Dissulfetos/uso terapêutico
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/uso terapêutico
Elevação dos Membros Posteriores/fisiologia
Resposta de Imobilidade Tônica/efeitos dos fármacos
Resposta de Imobilidade Tônica/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos DBA
Atividade Motora/fisiologia
Nialamida/uso terapêutico
Fenilalanina/análogos & derivados
Fenilalanina/uso terapêutico
Natação
Vocalização Animal/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Disulfides); 0 (Enkephalins); 0 (Enzyme Inhibitors); 0 (Protein Precursors); 135949-60-9 (RB 101); 47E5O17Y3R (Phenylalanine); 93443-35-7 (preproenkephalin); T2Q0RYM725 (Nialamide)
[Em] Mês de entrada:0801
[Cu] Atualização por classe:150311
[Lr] Data última revisão:
150311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:070322
[St] Status:MEDLINE


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[PMID]:11600693
[Au] Autor:Schomburg ED; Steffens H; Wada N
[Ad] Endereço:Institute of Physiology, University of Göttingen, D-37073 Göttingen, Germany. eds@neuro-physiol.med.uni-goettingen.de
[Ti] Título:Parallel nociceptive reflex pathways with negative and positive feedback functions to foot extensors in the cat.
[So] Source:J Physiol;536(Pt 2):605-13, 2001 Oct 15.
[Is] ISSN:0022-3751
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:1. Nociceptive reflex pathways to foot extensors were investigated with particular attention given to those not following a flexor reflex (FRA) or withdrawal pattern. 2. In anaemically decapitated, high spinal paralysed cats nociceptive afferents of the foot pad were activated by noxious radiant heat (48-60 degrees C), while for comparison non-nociceptive afferents were activated by weak mechanical stimulation of the skin or graded electrical nerve stimulation. The reflex action of the afferents on hindlimb motoneurones, innervating plantaris and intrinsic foot extensors (tibial nerve), was investigated by intracellular recording, by monosynaptic reflex testing and by recording of neurograms during fictive locomotion. A possible descending control of the nociceptive and non-nociceptive pathways was tested by application of opioidergic and monoaminergic compounds. 3. Beside the typical FRA pattern evoked in the majority of hindlimb motoneurone pools by nociceptive afferents from different skin areas of the foot, the results revealed parallel excitatory and inhibitory nociceptive reflex pathways from the central pad and partly from the toe pads to foot extensors. The excitatory pathways, which did not follow the FRA pattern, were predominantly to plantaris and intrinsic foot extensors. They were distinctly less depressed by opioids and monoaminergic compounds than FRA pathways. 4. While the nociceptive FRA pathways have a general nocifensive withdrawal function, the nociceptive excitatory non-FRA pathway to the foot extensors causes a movement of the affected area towards the stimulus or at least a resistance against the stimulus, i.e. it mediates a positive feedback.
[Mh] Termos MeSH primário: Encefalina Leucina/análogos & derivados
/inervação
/fisiologia
Nociceptores/fisiologia
Reflexo/fisiologia
[Mh] Termos MeSH secundário: Analgésicos/farmacologia
Analgésicos Opioides/farmacologia
Animais
Benzomorfanos/farmacologia
Gatos
Dopaminérgicos/farmacologia
Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia
Encefalina Leucina/farmacologia
Encefalinas/fisiologia
Retroalimentação Fisiológica/fisiologia
Levodopa/farmacologia
Locomoção/efeitos dos fármacos
Locomoção/fisiologia
Mecanorreceptores/fisiologia
Inibidores da Monoaminoxidase/farmacologia
Músculo Esquelético/inervação
Músculo Esquelético/fisiologia
Inibição Neural/fisiologia
Nialamida/farmacologia
Estimulação Física
Medula Espinal/fisiologia
Nervo Tibial/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Analgesics); 0 (Analgesics, Opioid); 0 (Benzomorphans); 0 (Dopamine Agents); 0 (Enkephalins); 0 (Monoamine Oxidase Inhibitors); 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-); 46627O600J (Levodopa); 57236-85-8 (MR 2034); 58822-25-6 (Enkephalin, Leucine); 75644-90-5 (enkephalin, Ser(2), Leu(5), Thr(6)-); T2Q0RYM725 (Nialamide)
[Em] Mês de entrada:0112
[Cu] Atualização por classe:170219
[Lr] Data última revisão:
170219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:011016
[St] Status:MEDLINE


  7 / 997 MEDLINE  
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[PMID]:10811739
[Au] Autor:Leblond H; Menard A; Gossard JP
[Ad] Endereço:Centre de Recherche en Sciences Neurologiques, Departement de Physiologie, Faculte de Medecine, Universite de Montreal, CP 6128, Succursale Centre-ville, Montreal, Quebec, Canada H3C 3J7.
[Ti] Título:Bulbospinal control of spinal cord pathways generating locomotor extensor activities in the cat.
[So] Source:J Physiol;525 Pt 1:225-40, 2000 May 15.
[Is] ISSN:0022-3751
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Intracellular recording of lumbosacral motoneurones in the decerebrate and partially spinalized cat injected with nialamide and L-dihydroxyphenylalanine (l-DOPA) was used to investigate the interneuronal convergence of two bulbospinal pathways and of the segmental pathways involved with the generation of extensor activities during locomotion. Deiter's nucleus (DN) or the medial longitudinal fasciculus (MLF) was stimulated in alternation with, and in combination with, stimulation of group I afferents from extensor muscles or of contralateral flexor reflex afferents (coFRA). The evoked polysynaptic EPSPs were recorded in extensor motoneurones when long-latency, long-lasting discharges were evoked by the stimulation of coFRA and when the group I autogenetic inhibition in extensors was reversed to polysynaptic excitation. Spatial facilitation was inferred when the amplitude of the EPSPs evoked by the combined stimuli was notably larger than the algebraic sum of the EPSPs evoked by individual stimulation. Both DN (16 motoneurones) and MLF inputs (8 motoneurones) showed spatial facilitation when preceded by coFRA stimuli and both could reset the rhythm of fictive stepping by triggering a precocious extensor phase. MLF showed spatial facilitation with extensor group I inputs in 69% of trials but DN failed to show spatial facilitation in any cells. These results indicate that DN and MLF project to the coFRA pathways of the extensor half-centre for locomotion and MLF, but not DN, converge on segmental interneurones of the extensor group I pathways. The implications of such convergence patterns on the functional organization of the extensor half-centre are discussed.
[Mh] Termos MeSH primário: Locomoção/fisiologia
Região Lombossacral/fisiologia
Medula Espinal/fisiologia
[Mh] Termos MeSH secundário: Animais
Tronco Encefálico/fisiologia
Gatos
Estado de Descerebração
Estimulação Elétrica
Potenciais Evocados
Feminino
Membro Posterior/inervação
Levodopa/farmacologia
Masculino
Inibidores da Monoaminoxidase/farmacologia
Neurônios Motores/efeitos dos fármacos
Neurônios Motores/fisiologia
Nialamida/farmacologia
Núcleo Vestibular Lateral/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Monoamine Oxidase Inhibitors); 46627O600J (Levodopa); T2Q0RYM725 (Nialamide)
[Em] Mês de entrada:0007
[Cu] Atualização por classe:140615
[Lr] Data última revisão:
140615
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:000516
[St] Status:MEDLINE


  8 / 997 MEDLINE  
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[PMID]:10449982
[Au] Autor:Lambert HW; Lauder JM
[Ad] Endereço:Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA.
[Ti] Título:Serotonin receptor agonists that increase cyclic AMP positively regulate IGF-I in mouse mandibular mesenchymal cells.
[So] Source:Dev Neurosci;21(2):105-12, 1999.
[Is] ISSN:0378-5866
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Evidence from the present study suggests that activation of both 5-HT(1A) and 5-HT(4) (5-hydroxytryptamine) receptor subtypes stimulates cyclic adenosine monophosphate (cAMP) synthesis in cultured embryonic mouse mandibular mesenchymal cells (micromass cultures). When these cells were grown in serum-free medium and treated with 10(-8) M agonist selective for either the 5-HT(1A) or 5-HT(4) receptor subtype (8-OH-DPAT and SC53116, respectively), this significantly stimulated cAMP synthesis and increased insulin-like growth factor I (IGF-I), but not IGF-II, protein levels compared to vehicle-treated controls, as measured by semi-quantitative immunobinding assays. Consistent with these results, IGF-I was significantly decreased when mandibular mesenchymal cells were grown in serum-containing medium (which contains micromolar amounts of 5-HT from fetal calf serum) and treated with 10(-8) M antagonist selective for the 5-HT(1A) or 5-HT(4) receptor subtype (NAN-190 on SDZ-205,557). Forskolin also stimulated cAMP and IGF-I (but not IGF-II) in both serum-containing and serum-free cultures. These results indicate that activation of 5-HT receptors that increase cAMP promotes synthesis of IGF-I. This may occur by activation of the cAMP response element sequence present in the IGF-I promoter region. Stimulation of the adenylyl cyclase pathway by activation of 5-HT(1A) or 5-HT(4) receptors may be one mechanism by which serotonin regulates IGF-I synthesis in developing craniofacial mesenchymal cells.
[Mh] Termos MeSH primário: AMP Cíclico/metabolismo
Fator de Crescimento Insulin-Like I/biossíntese
Mandíbula/embriologia
Mesoderma/metabolismo
Antagonistas da Serotonina/farmacologia
Agonistas de Receptores de Serotonina/farmacologia
Serotonina/farmacologia
[Mh] Termos MeSH secundário: Ácido 4-Aminobenzoico/farmacologia
Animais
Benzamidas/farmacologia
Células Cultivadas
Meios de Cultura
Meios de Cultura Livres de Soro
Cisteína/farmacologia
Embrião de Mamíferos
Fator de Crescimento Insulin-Like I/análise
Fator de Crescimento Insulin-Like II/análise
Mandíbula/citologia
Mandíbula/metabolismo
Mesoderma/citologia
Mesoderma/efeitos dos fármacos
Camundongos
Nialamida/farmacologia
Piperazinas/farmacologia
Pirróis/farmacologia
Receptores de Serotonina/fisiologia
Receptores 5-HT1 de Serotonina
Receptores 5-HT4 de Serotonina
para-Aminobenzoatos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Benzamides); 0 (Culture Media); 0 (Culture Media, Serum-Free); 0 (Piperazines); 0 (Pyrroles); 0 (Receptors, Serotonin); 0 (Receptors, Serotonin, 5-HT1); 0 (Serotonin Antagonists); 0 (Serotonin Receptor Agonists); 0 (para-Aminobenzoates); 115338-32-4 (1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine); 137196-67-9 (2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester); 141196-99-8 (SC 53116); 158165-40-3 (Receptors, Serotonin, 5-HT4); 333DO1RDJY (Serotonin); 67763-96-6 (Insulin-Like Growth Factor I); 67763-97-7 (Insulin-Like Growth Factor II); E0399OZS9N (Cyclic AMP); K848JZ4886 (Cysteine); T2Q0RYM725 (Nialamide); TL2TJE8QTX (4-Aminobenzoic Acid)
[Em] Mês de entrada:9910
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:990818
[St] Status:MEDLINE


  9 / 997 MEDLINE  
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[PMID]:10079182
[Au] Autor:Boldyrev AA; Carpenter DO; Huentelman MJ; Peters CM; Johnson P
[Ad] Endereço:Department of Biochemistry, International Biotechnological Center of M. V. Lomonosov Moscow State University, Moscow, 119899, Russia.
[Ti] Título:Sources of reactive oxygen species production in excitotoxin- stimulated cerebellar granule cells.
[So] Source:Biochem Biophys Res Commun;256(2):320-4, 1999 Mar 16.
[Is] ISSN:0006-291X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reactive oxygen species (ROS) production in rat cerebellar granule cells in the presence of the excitotoxins N-methyl-d-aspartate (NMDA) and kainic acid (KA) and by the protein kinase C activator phorbol myristate acetate (PMA) was Ca2+-dependent and resulted in decreased cell viability. Exposure of stimulated cells to rotenone (a respiratory chain inhibitor) did not decrease ROS levels and did not affect short-term cell viability. In cells stimulated by NMDA and KA, exposure to indomethacin (a cyclooxygenase inhibitor) and nialamide (a monoamine oxidase inhibitor) caused a decrease in ROS levels and increased cell viability occurred in NMDA-treated cells. In contrast, PMA-stimulated neurons did not show decreased ROS levels when exposed to indomethacin and nialamide. These studies suggest that there is a multiplicity of routes for Ca2+-dependent ROS production in neurons but that ROS generation by cyclooxygenase and monoamine oxidase is not controlled by protein kinase C.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Córtex Cerebelar/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Neurotoxinas/farmacologia
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Córtex Cerebelar/citologia
Córtex Cerebelar/metabolismo
Inibidores de Ciclo-Oxigenase/farmacologia
Transporte de Elétrons/efeitos dos fármacos
Citometria de Fluxo
Fluoresceínas
Indometacina/farmacologia
Ácido Caínico/antagonistas & inibidores
Ácido Caínico/farmacologia
Inibidores da Monoaminoxidase/farmacologia
N-Metilaspartato/antagonistas & inibidores
N-Metilaspartato/farmacologia
Neurônios/metabolismo
Nialamida/farmacologia
Proteína Quinase C/antagonistas & inibidores
Proteína Quinase C/fisiologia
Ratos
Ratos Sprague-Dawley
Rotenona/farmacologia
Acetato de Tetradecanoilforbol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cyclooxygenase Inhibitors); 0 (Fluoresceins); 0 (Monoamine Oxidase Inhibitors); 0 (Neurotoxins); 0 (Reactive Oxygen Species); 03L9OT429T (Rotenone); 56NQM5UZT1 (2',7'-dichlorofluorescein); 6384-92-5 (N-Methylaspartate); EC 2.7.11.13 (Protein Kinase C); NI40JAQ945 (Tetradecanoylphorbol Acetate); SIV03811UC (Kainic Acid); SY7Q814VUP (Calcium); T2Q0RYM725 (Nialamide); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:9904
[Cu] Atualização por classe:161124
[Lr] Data última revisão:
161124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:990318
[St] Status:MEDLINE


  10 / 997 MEDLINE  
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Fotocópia
[PMID]:9310449
[Au] Autor:Whelan PJ; Pearson KG
[Ad] Endereço:Department of Physiology, University of Alberta, Edmonton, Canada.
[Ti] Título:Plasticity in reflex pathways controlling stepping in the cat.
[So] Source:J Neurophysiol;78(3):1643-50, 1997 Sep.
[Is] ISSN:0022-3077
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Previous studies have shown that stimulation of group 'I' afferents from ankle extensor muscles can prolong the cycle period in decerebrate walking cats and that the magnitude of these effects can be altered after chronic axotomy of the lateral-gastrocnemius/soleus (LGS) nerve. The effectiveness of LGS group I afferents in prolonging the cycle period decreases after axotomy, whereas the effectiveness of the uncut medial-gastrocnemius (MG) group I afferents is increased. The objectives of this investigation were to establish the time course of these changes in effectiveness and to determine whether these changes persist after transection of the spinal cord. The effects of stimulating the LGS and/or MG group I afferents on the cycle period were examined in 22 walking decerebrate animals in which one LGS nerve had been cut for 2 to 31 days. The effectiveness of LGS group I afferents declined progressively in the postaxotomy period, beginning with significant decreases at 3 days and ending close to zero effectiveness at 31 days. Large increases in the effectiveness of MG group I afferents occurred 5 days after axotomy, but there was no progressive change from 5 to 31 days. To test whether these changes in effectiveness were localized to sites within the spinal cord, the cord was transected in some decerebrate animals and stepping induced by the administration of L-DOPA L-3-4 dihydroxyphenylalanine (L-DOPA) and Nialamide. The effects of stimulating the MG and/or the LGS group I afferents on the cycle period were reexamined. In all four animals tested, stimulating the axotomized LGS group I afferents had a reduced effectiveness during locomotor activity in both the decerebrate and spinal states, whereas the increased effectiveness of the MG group I afferents was retained after transection of the spinal cord in two of five animals. Different mechanisms may be responsible for the changes in strength of the LGS and MG group I afferent pathways that project onto the rhythm generating sites in the spinal cord. This possibility follows from our observations of a linear relationship between the time after axotomy and decreased effectiveness of LGS group I afferents but no significant relationship between time postaxotomy and increased effectiveness of MG group I afferents; no significant relationship between the decreased effectiveness of LGS group I afferents and the increased effectiveness of MG group I afferents; and, after spinalization, consistent (4/4 cases) preservation of decreased LGS effectiveness but frequent (3/5 cases) loss of increased MG effectiveness.
[Mh] Termos MeSH primário: Marcha/fisiologia
Plasticidade Neuronal/fisiologia
Reflexo/fisiologia
[Mh] Termos MeSH secundário: Animais
Antiparkinsonianos/farmacologia
Axônios/efeitos dos fármacos
Axônios/fisiologia
Axotomia
Gatos
Estado de Descerebração/fisiopatologia
Estimulação Elétrica
Eletromiografia
Feminino
Marcha/efeitos dos fármacos
Levodopa/farmacologia
Masculino
Inibidores da Monoaminoxidase/farmacologia
Músculo Esquelético/efeitos dos fármacos
Músculo Esquelético/inervação
Músculo Esquelético/fisiologia
Vias Neurais/efeitos dos fármacos
Vias Neurais/fisiologia
Plasticidade Neuronal/efeitos dos fármacos
Nialamida/farmacologia
Reflexo/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Monoamine Oxidase Inhibitors); 46627O600J (Levodopa); T2Q0RYM725 (Nialamide)
[Em] Mês de entrada:9711
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:971006
[St] Status:MEDLINE



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