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[PMID]:28793772
[Au] Autor:López-Moreno J; García-Carpintero S; Jimenez-Lucena R; Haro C; Rangel-Zúñiga OA; Blanco-Rojo R; Yubero-Serrano EM; Tinahones FJ; Delgado-Lista J; Pérez-Martínez P; Roche HM; López-Miranda J; Camargo A
[Ad] Endereço:Lipids and Atherosclerosis Research Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba , 14004 Cordoba, Spain.
[Ti] Título:Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response.
[So] Source:J Agric Food Chem;65(35):7756-7763, 2017 Sep 06.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes one to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 weeks each. We administered a fat challenge reflecting the fatty acid composition of the diets at postintervention. We determined the plasma lipoproteins and glucose and gene expression in peripheral blood mononuclear cells (PBMC) and adipose tissue. LPS and LPS binding protein (LBP) plasma levels were determined by ELISA, at fasting and postprandial (4 h after a fat challenge) states. We observed a postprandial increase in LPS levels after the intake of the HSFA meal, whereas we did not find any postprandial changes after the intake of the other three diets. Moreover, we found a positive relationship between the LPS plasma levels and the gene expression of IkBa and MIF1 in PBMC. No statistically significant differences in the LBP plasma levels at fasting or postprandial states were observed. Our results suggest that the consumption of HSFA diet increases the intestinal absorption of LPS which, in turn, increases postprandial endotoxemia levels and the postprandial inflammatory response.
[Mh] Termos MeSH primário: Gorduras na Dieta/metabolismo
Endotoxemia/dietoterapia
Síndrome Metabólica/dietoterapia
Período Pós-Prandial/imunologia
[Mh] Termos MeSH secundário: Gorduras na Dieta/análise
Endotoxemia/imunologia
Endotoxemia/metabolismo
Feminino
Seres Humanos
Leucócitos Mononucleares/imunologia
Hormônio Inibidor da Liberação de MSH/genética
Hormônio Inibidor da Liberação de MSH/imunologia
Masculino
Síndrome Metabólica/imunologia
Síndrome Metabólica/metabolismo
Meia-Idade
Estresse Oxidativo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Dietary Fats); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b01909


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[PMID]:26111490
[Au] Autor:Pan W
[Ad] Endereço:Biopotentials Sleep Center, Baton Rouge, LA 70809, USA. Electronic address: sleep@biopotentials.org.
[Ti] Título:From blood to brain through BBB and astrocytic signaling.
[So] Source:Peptides;72:121-7, 2015 Oct.
[Is] ISSN:1873-5169
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this Festschrift, I discuss the career and guiding principles to which Abba J. Kastin has adhered during the last 20 years we worked together. I briefly describe the history of our joint laboratory group, the context of studies of peptide permeation across the blood-brain barrier (BBB), and newer developments in the BBB Group as Abba steps down after serving 35 years as the founding Editor-in-Chief for Peptides. Abba's BBB studies on peptides have contributed to concepts in the neuroendocrinology of feeding and developed information on molecular trafficking across BBB cells. The astroglial leptin signaling studies and the interactions of sleep and BBB are two major directions, whereas the long-term MIF-1 project demarcates a tortuous road on translational research.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Barreira Hematoencefálica/metabolismo
Leptina/metabolismo
Hormônio Inibidor da Liberação de MSH/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
História do Século XX
História do Século XXI
Seres Humanos
Leptina/história
Hormônio Inibidor da Liberação de MSH/história
Publicações Periódicas como Assunto/história
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Leptin); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150627
[St] Status:MEDLINE


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[PMID]:25817911
[Au] Autor:Ehrensing RH
[Ad] Endereço:Department of Psychiatry, Ochsner Medical Center, New Orleans, LA, USA. Electronic address: rudyehren@aol.com.
[Ti] Título:An extraordinary relationship involving MIF-1 and other peptides.
[So] Source:Peptides;72:73-4, 2015 Oct.
[Is] ISSN:1873-5169
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In commemoration of Abba J. Kastin's exceptional service as the founding editor for the international journal Peptides, I review our collaborative work on how neuropeptides are involved in depression and other neuropsychiatric behavior. A special focus is on MIF-1 (prolyl-leucyl-glycinamide) that was discovered in the Kastin laboratory and shown effective to treat human depression with greater efficacy and faster onset of action than traditional antidepressants at the time of clinical trial. My personal reflection of the evolving changes of translational research on neuropeptides will hopefully provide some insight to young investigators.
[Mh] Termos MeSH primário: Antidepressivos
Depressão
Hormônio Inibidor da Liberação de MSH
[Mh] Termos MeSH secundário: Animais
Antidepressivos/química
Antidepressivos/uso terapêutico
Depressão/tratamento farmacológico
Depressão/metabolismo
Seres Humanos
Hormônio Inibidor da Liberação de MSH/química
Hormônio Inibidor da Liberação de MSH/metabolismo
Hormônio Inibidor da Liberação de MSH/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antidepressive Agents); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151110
[Lr] Data última revisão:
151110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150331
[St] Status:MEDLINE


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[PMID]:25033398
[Au] Autor:Mohammed YH; Yamada M; Lin LL; Grice JE; Roberts MS; Raphael AP; Benson HA; Prow TW
[Ad] Endereço:Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia; School of Pharmacy, CHIRI-Biosciences, Curtin University, Perth, Western Australia, Australia; Therapeutics Research Centre, The University of Queensland,
[Ti] Título:Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin.
[So] Source:PLoS One;9(7):e101956, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides.
[Mh] Termos MeSH primário: Técnicas Cosméticas
Microinjeções/métodos
Peptídeos/administração & dosagem
Fenômenos Fisiológicos da Pele
Cirurgia Plástica/métodos
[Mh] Termos MeSH secundário: Abdominoplastia
Administração Cutânea
Sistemas de Liberação de Medicamentos/métodos
Seres Humanos
Hormônio Inibidor da Liberação de MSH/administração & dosagem
Microscopia Confocal
Oligopeptídeos/administração & dosagem
Imagem Óptica
Peptídeos/uso terapêutico
Pele
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oligopeptides); 0 (Peptides); 9083-38-9 (MSH Release-Inhibiting Hormone); KK181SM5JG (palmitoyl-lysyl-threonyl-threonyl-lysyl-serine); X519T00027 (rigin)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140718
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0101956


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[PMID]:22780223
[Au] Autor:Ishiguro H; Hall FS; Horiuchi Y; Sakurai T; Hishimoto A; Grumet M; Uhl GR; Onaivi ES; Arinami T
[Ad] Endereço:Department of Neuropsychiatry and Clinical Ethics, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi, Japan; Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
[Ti] Título:NrCAM-regulating neural systems and addiction-related behaviors.
[So] Source:Addict Biol;19(3):343-53, 2014 May.
[Is] ISSN:1369-1600
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral phenotypes in Nrcam knockout mice. Consistent with a potential general reduction in motivational function, Nrcam knockout mice demonstrated less curiosity for novel objects and for an unfamiliar conspecific, showed also less anxiety in the zero maze. Nrcam heterozygote knockout mice reduced alcohol preference and buried fewer marbles in home cage. These observations provide further support for a role of NrCAM in substance abuse including alcoholism vulnerability, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety-provoking stimuli. Additionally, in order to prove glutamate homeostasis hypothesis of addiction, we analyzed glutamatergic molecules regulated by NRCAM expression. Glutaminase appears to be involved in NrCAM-related molecular pathway in two different tissues from human and mouse. An inhibitor of the enzyme, prolyl-leucyl-glycinamide, treatment produced, at least, some of the phenotypes of mice shown in alcohol preference and in anxiety-like behavior. Thus, NrCAM could affect addiction-related behaviors via at least partially modulation of some glutamatergic pathways and neural function in brain.
[Mh] Termos MeSH primário: Comportamento Aditivo/fisiopatologia
Moléculas de Adesão Celular/fisiologia
[Mh] Termos MeSH secundário: Adaptação Psicológica/efeitos dos fármacos
Consumo de Bebidas Alcoólicas/fisiopatologia
Analgésicos Opioides/farmacologia
Animais
Ansiedade/fisiopatologia
Depressores do Sistema Nervoso Central/farmacologia
Condicionamento (Psicologia)/efeitos dos fármacos
Etanol/farmacologia
Comportamento Exploratório/efeitos dos fármacos
Hormônio Inibidor da Liberação de MSH/farmacologia
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Morfina/farmacologia
Tempo de Reação/efeitos dos fármacos
Comportamento Social
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Cell Adhesion Molecules); 0 (Central Nervous System Depressants); 0 (Nrcam protein, mouse); 3K9958V90M (Ethanol); 76I7G6D29C (Morphine); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:170721
[Lr] Data última revisão:
170721
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120712
[St] Status:MEDLINE
[do] DOI:10.1111/j.1369-1600.2012.00469.x


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[PMID]:23416534
[Au] Autor:Tan ML; Basu D; Kwiecien JM; Johnson RL; Mishra RK
[Ad] Endereço:Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
[Ti] Título:Preclinical pharmacokinetic and toxicological evaluation of MIF-1 peptidomimetic, PAOPA: examining the pharmacology of a selective dopamine D2 receptor allosteric modulator for the treatment of schizophrenia.
[So] Source:Peptides;42:89-96, 2013 Apr.
[Is] ISSN:1873-5169
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Schizophrenia is a mental illness characterized by a breakdown in cognition and emotion. Over the years, drug treatment for this disorder has mainly been compromised of orthosteric ligands that antagonize the active site of the dopamine D2 receptor. However, these drugs are limited in their use and often lead to the development of adverse movement and metabolic side effects. Allosteric modulators are an emerging class of therapeutics with significant advantages over orthosteric ligands, including an improved therapeutic and safety profile. This study investigates our newly developed allosteric modulator, PAOPA, which is a specific modulator of the dopamine D2 receptor. Previous studies have shown PAOPA to attenuate schizophrenia-like behavioral abnormalities in preclinical models. To advance this newly developed allosteric drug from the preclinical to clinical stage, this study examines the pharmacokinetic behavior and toxicological profile of PAOPA. Results from this study prove the effectiveness of PAOPA in reaching the implicated regions of the brain for therapeutic action, particularly the striatum. Pharmacokinetic parameters of PAOPA were found to be comparable to current market antipsychotic drugs. Necropsy and histopathological analyses showed no abnormalities in all examined organs. Acute and chronic treatment of PAOPA indicated no movement abnormalities commonly found with the use of current typical antipsychotic drugs. Moreover, acute and chronic PAOPA treatment revealed no hematological or metabolic abnormalities classically found with the use of atypical antipsychotic drugs. Findings from this study demonstrate a better safety profile of PAOPA, and necessitates the progression of this newly developed therapeutic for the treatment of schizophrenia.
[Mh] Termos MeSH primário: Peptidomiméticos/farmacocinética
Pirrolidinonas/farmacocinética
Pirrolidinonas/toxicidade
[Mh] Termos MeSH secundário: Administração Intravenosa
Administração Oral
Animais
Antipsicóticos/farmacocinética
Antipsicóticos/farmacologia
Antipsicóticos/toxicidade
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Avaliação Pré-Clínica de Medicamentos/métodos
Seres Humanos
Hormônio Inibidor da Liberação de MSH/química
Masculino
Terapia de Alvo Molecular/métodos
Peptidomiméticos/farmacologia
Peptidomiméticos/toxicidade
Pirrolidinonas/sangue
Pirrolidinonas/farmacologia
Ratos
Ratos Sprague-Dawley
Receptores de Dopamina D2/efeitos dos fármacos
Esquizofrenia/tratamento farmacológico
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (DRD2 protein, human); 0 (Peptidomimetics); 0 (Pyrrolidinones); 0 (Receptors, Dopamine D2); 106732-52-9 (3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130219
[St] Status:MEDLINE


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[PMID]:23353749
[Au] Autor:Jlalia I; Lensen N; Chaume G; Dzhambazova E; Astasidi L; Hadjiolova R; Bocheva A; Brigaud T
[Ad] Endereço:Laboratoire SOSCO, Université de Cergy-Pontoise, EA 4505, 5 Mail Gay Lussac, Neuville sur Oise, 95000 Cergy-Pontoise Cedex, France.
[Ti] Título:Synthesis of an MIF-1 analogue containing enantiopure (S)-α-trifluoromethyl-proline and biological evaluation on nociception.
[So] Source:Eur J Med Chem;62:122-9, 2013 Apr.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The synthesis and the effect of a novel MIF-1 analogue on nociception during acute pain in rat model are reported. The synthesis of this enantiopure trifluoromethyl group containing tripeptide was performed through a peptide coupling reaction between the HCl. Leu-Gly-NH2 and the (S)-α-Tfm-proline. The analgesic effect of the CF3-(MIF-1) 2 has been evaluated in vivo on rat model by paw pressure (PP) and hot plate (HP) tests and compared to the native peptide MIF-1. Highest analgesic effect was observed with CF3-(MIF-1) 2 only in PP test. In order to study the mechanisms of nociception induced by the studied peptides, the involvement of the opioid and the nitric oxideergic systems was investigated. The results are in favor of a participation of both system since pretreatment, 20 min before injection of the CF3-(MIF-1) 2, with the non-competitive antagonist of opiate receptors naloxone, the nitric oxide synthase (NOS) inhibitor l-N(G)-nitroarginine ester (l-NAME) or the nitric oxide (NO) donor l-arginine (l-Arg) significantly decreased the pain perception in PP and HP tests.
[Mh] Termos MeSH primário: Dor Aguda/tratamento farmacológico
Hormônio Inibidor da Liberação de MSH/farmacologia
Antagonistas de Entorpecentes/farmacologia
Nociceptividade/efeitos dos fármacos
Oligopeptídeos/química
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Hormônio Inibidor da Liberação de MSH/análogos & derivados
Hormônio Inibidor da Liberação de MSH/síntese química
Masculino
Conformação Molecular
Estrutura Molecular
Antagonistas de Entorpecentes/síntese química
Antagonistas de Entorpecentes/química
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Narcotic Antagonists); 0 (Oligopeptides); 0 (alpha-trifluoromethylprolyl-leucyl-glycinamide); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1310
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130129
[St] Status:MEDLINE


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[PMID]:22860194
[Au] Autor:Bhagwanth S; Mishra S; Daya R; Mah J; Mishra RK; Johnson RL
[Ad] Endereço:Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, Minnesota 55455, United States.
[Ti] Título:Transformation of Pro-Leu-Gly-NH2 peptidomimetic positive allosteric modulators of the dopamine D2 receptor into negative modulators.
[So] Source:ACS Chem Neurosci;3(4):274-84, 2012 Apr 18.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The synthesis of dimethyl derivatives of 5.6.5 spiro bicyclic lactam Pro-Leu-Gly-NH(2) peptidomimetics was carried out to test the hypothesis that by placing methyl groups on the ß-methylene carbon of the thiazolidine ring steric bulk would be introduced into the topological space that the ß-methylene carbon is believed to occupy in the negative allosteric modulators of the dopamine D(2) receptor. With such a modification, a positive allosteric modulator would be converted into a negative allosteric modulator. This hypothesis was shown to be correct as 3a and 4a where found to be negative allosteric modulators, whereas their unmethylated derivatives were positive allosteric modulators of the dopamine D(2) receptor.
[Mh] Termos MeSH primário: Antagonistas dos Receptores de Dopamina D2
Hormônio Inibidor da Liberação de MSH/química
Mimetismo Molecular/efeitos dos fármacos
Peptidomiméticos/química
Receptores de Dopamina D2/agonistas
[Mh] Termos MeSH secundário: Regulação Alostérica/efeitos dos fármacos
Regulação Alostérica/fisiologia
Animais
Bovinos
Relação Dose-Resposta a Droga
Hormônio Inibidor da Liberação de MSH/farmacologia
Mimetismo Molecular/fisiologia
Peptidomiméticos/farmacologia
Receptores de Dopamina D2/fisiologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Dopamine D2 Receptor Antagonists); 0 (Peptidomimetics); 0 (Receptors, Dopamine D2); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1308
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120804
[St] Status:MEDLINE
[do] DOI:10.1021/cn200096u


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[PMID]:21036015
[Au] Autor:Dyck B; Guest K; Sookram C; Basu D; Johnson R; Mishra RK
[Ad] Endereço:Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
[Ti] Título:PAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: implications for the treatment of negative symptoms in schizophrenia.
[So] Source:Schizophr Res;125(1):88-92, 2011 Jan.
[Is] ISSN:1573-2509
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to investigate whether a potent analogue of the endogenous brain peptide l-prolyl-l-leucyl-glycinamide (PLG), (3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), can prevent the induction of social withdrawal caused by sub-chronic treatment with the non-competitive NMDA (N-methyl-l-aspartate) receptor antagonist, MK-801. Results indicate that MK-801 (0.5 mg/kg) significantly decreased social interaction following sub-chronic treatment (7 days). Treatment with PAOPA (1 mg/kg) blocked the effects of MK-801, and increased the amount of time spent in social interaction in comparison to control animals. These results provide evidence for the development of peptidomimetic compounds for the treatment of social withdrawal and related negative symptoms associated with schizophrenia.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Relações Interpessoais
Hormônio Inibidor da Liberação de MSH/análogos & derivados
Pirrolidinonas/farmacologia
Transtornos do Comportamento Social/prevenção & controle
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Modelos Animais de Doenças
Maleato de Dizocilpina/toxicidade
Esquema de Medicação
Masculino
Pirrolidinonas/administração & dosagem
Pirrolidinonas/química
Ratos
Ratos Sprague-Dawley
Transtornos do Comportamento Social/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Pyrrolidinones); 106732-52-9 (3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide); 6LR8C1B66Q (Dizocilpine Maleate); 9083-38-9 (MSH Release-Inhibiting Hormone)
[Em] Mês de entrada:1104
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:101102
[St] Status:MEDLINE
[do] DOI:10.1016/j.schres.2010.09.025


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[PMID]:20639138
[Au] Autor:Mann A; Verma V; Basu D; Skoblenick KJ; Beyaert MG; Fisher A; Thomas N; Johnson RL; Mishra RK
[Ad] Endereço:Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada.
[Ti] Título:Specific binding of photoaffinity-labeling peptidomimetics of Pro-Leu-Gly-NH2 to the dopamine D2L receptor: evidence for the allosteric modulation of the dopamine receptor.
[So] Source:Eur J Pharmacol;641(2-3):96-101, 2010 Sep 01.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The present study was undertaken to investigate the mechanistic role of l-prolyl-l-leucyl-glycinamide (PLG) in modulating agonist binding to the dopamine D(2L) receptor. Competition and displacement assays indicate that the photoaffinity-labeling peptidomimetics of PLG, 3(R)-[(4(S)-(4-azido-2-hydroxy-benzoyl) amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride (1a) and 3(R)-[(4(S)-(4-azido-2-hydroxy-5-iodo-benzoyl)amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride (1b) bind at the same site as PLG. Autoradiography was used to establish the covalent binding of [(125)I]-1b to an approximately 51kDa protein in bovine striatal membranes. Western blot analysis with a dopamine D(2L)-specific antibody, in combination with autoradiography, following a two-dimensional gel separation, suggested this approximately 51kDa protein to be the dopamine D(2L) receptor. Further evidence for binding of 1b to dopamine D(2L) was provided by samples immunoprecipitated with the D(2L) antibody. These samples were analyzed by western blotting in parallel with autoradiography of [(125)I]-1b labeled protein. Both methods revealed bands at approximately 51kDa. Furthermore, PLG is shown to compete with 1b for binding to the dopamine D(2L) receptor as determined by autoradiography, as well as competition experiments with PLG and 1a. Collectively, these findings suggest the successful development of a photoaffinity-labeling agent, compound 1b, that has been used to elucidate the interaction of PLG specifically with the dopamine D(2L) receptor.
[Mh] Termos MeSH primário: Hormônio Inibidor da Liberação de MSH/metabolismo
Peptidomiméticos/metabolismo
Receptores de Dopamina D2/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica
Animais
Autorradiografia
Ligação Competitiva
Western Blotting
Bovinos
Corpo Estriado/metabolismo
Dopamina/metabolismo
Eletroforese em Gel Bidimensional
Imunoprecipitação
Hormônio Inibidor da Liberação de MSH/química
Estrutura Molecular
Marcadores de Fotoafinidade/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Peptidomimetics); 0 (Photoaffinity Labels); 0 (Receptors, Dopamine D2); 0 (dopamine D2L receptor); 9083-38-9 (MSH Release-Inhibiting Hormone); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1101
[Cu] Atualização por classe:161122
[Lr] Data última revisão:
161122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100720
[St] Status:MEDLINE
[do] DOI:10.1016/j.ejphar.2010.05.018



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