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[PMID]:28843542
[Au] Autor:Xiao J; Song M; Li F; Liu X; Anwar A; Zhao H
[Ad] Endereço:Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
[Ti] Título:Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice.
[So] Source:Exp Neurol;298(Pt A):23-30, 2017 Dec.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The dorsal raphe nucleus (DRN) is a key site for 5-hydroxytryptamine (5-HT) synthesis and release. DRN dysfunction has been implicated in several stress-related disorders, including depression and anxiety. The lateral habenular nucleus (LHb) has been shown to inhibit the activity of DRN 5-HT neurons, and thus the LHb-DRN pathway plays an important role in the pathogenesis of depression. Although it is known that the LHb also receives the projection from the 5-HT neuron in the DRN, whether 5-HT neurons in the DRN can influence activity of the LHb in vivo and whether this effect is related to the induced behavioral changes have not been investigated. In the current study, we determined how injecting γ-aminobutyric acid (GABA) into the DRN to inhibit 5-HT neurons affected behavior and the changes in the activity of LHb neurons in mice. We found that GABA injection into the DRN induced depression-like behavior in mice, as indicated by increased immobility time, and decreased climbing time in the forced swimming test and the tail suspension test, decreased time spent in the center and total distance moved in the open field test. Using extracellular single unit recording, we showed that the firing rate of LHb neurons decreased after GABA microinjection into the DRN. Further, c-Fos expression in LHb neurons was inhibited. Together our results indicate that inhibition of DRN 5-HT neurons can cause decreased LHb activity and depression-like behavior in mice, however this depression-like behavior could be independent of the LHb activity. The observed decrease in LHb activity is probably due to the presence of a negative feedback loop between the DRN and the LHb, which may play a role in maintaining emotional homeostasis.
[Mh] Termos MeSH primário: Depressão/induzido quimicamente
Núcleo Dorsal da Rafe/efeitos dos fármacos
Habênula/efeitos dos fármacos
Microinjeções
Neurônios/efeitos dos fármacos
Ácido gama-Aminobutírico/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Depressão/metabolismo
Depressão/psicologia
Núcleo Dorsal da Rafe/metabolismo
Habênula/metabolismo
Ácido Hidroxi-Indolacético/metabolismo
Locomoção/efeitos dos fármacos
Locomoção/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Microinjeções/métodos
Neurônios/metabolismo
Serotonina/metabolismo
Ácido gama-Aminobutírico/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
333DO1RDJY (Serotonin); 54-16-0 (Hydroxyindoleacetic Acid); 56-12-2 (gamma-Aminobutyric Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170828
[St] Status:MEDLINE


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[PMID]:28427516
[Au] Autor:Chan DL; Clarke SJ; Diakos CI; Roach PJ; Bailey DL; Singh S; Pavlakis N
[Ad] Endereço:Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia; Sydney Medical School, University of Sydney, Australia; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.
[Ti] Título:Prognostic and predictive biomarkers in neuroendocrine tumours.
[So] Source:Crit Rev Oncol Hematol;113:268-282, 2017 May.
[Is] ISSN:1879-0461
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Neuroendocrine tumours are extremely heterogeneous malignancies. Despite marked heterogeneity in clinical course and prognosis, few biomarkers exist to help predict prognosis and guide treatment. Many tumour-based biomarkers (Ki-67, mitotic count, genetic/epigenetic changes and microRNAs) exist, but only Ki-67 and mitotic count have strong evidence to support their routine use. Blood-based markers are easily repeatable, but currently established biomarkers (chromogranin A and urinary 5-HIAA) are difficult to measure accurately in practice. Structural imaging is used routinely via the TNM system. Functional imaging such as Ga-based and FDG PET may become valuable biomarkers with their increasing availability, aided by ongoing quantitative research. Multiple nomograms have been proposed to integrate the above factors, but most have not been prospectively validated and are difficult to use in practice. Further research should aim to establish robust new biomarkers and integrate existing ones to help optimise NET treatment.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Tumores Neuroendócrinos/diagnóstico
[Mh] Termos MeSH secundário: Cromogranina A/análise
Epigênese Genética
Seres Humanos
Ácido Hidroxi-Indolacético/urina
Antígeno Ki-67/análise
MicroRNAs/análise
Mutação
Estadiamento de Neoplasias
Tumores Neuroendócrinos/genética
Tumores Neuroendócrinos/patologia
Tomografia por Emissão de Pósitrons
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Chromogranin A); 0 (Ki-67 Antigen); 0 (MicroRNAs); 54-16-0 (Hydroxyindoleacetic Acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE


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[PMID]:28407315
[Au] Autor:Eskelund A; Li Y; Budac DP; Müller HK; Gulinello M; Sanchez C; Wegener G
[Ad] Endereço:Translational Neuropsychiatry Unit, Risskov, Denmark.
[Ti] Título:Drugs with antidepressant properties affect tryptophan metabolites differently in rodent models with depression-like behavior.
[So] Source:J Neurochem;142(1):118-131, 2017 Jul.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression, and its controls: Flinders Sensitive Line and Sprague-Dawley rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains. Furthermore, effects of vortioxetine on tryptophan metabolites were assessed in the cortical regions of lupus mice (MRL/MpJ-Fas ), a murine model of increased depression-like behavior associated with inflammation. Sustained vortioxetine or fluoxetine (at doses aimed to fully occupy serotonin transporter via food or drinking water for at least 14 days) reduced levels of the excitotoxin quinolinic acid (QUIN) in various brain regions in all rats. Furthermore, chronic vortioxetine reduced levels of QUIN in MRL/MpJ-Fas mice. Acute i.p. administration of fluoxetine (10 mg/kg) or vortioxetine (10 mg/kg) led to reduced brain 5-hydroxyindoleacetic acid in Sprague-Dawley rats (2, 4, 6, and 8 h) and a similar trend was evident in Flinders Sensitive Line and Flinders Sensitive Line rats after 4 h. In contrast, single or repeated administration of ketamine (15 mg/kg i.p.) did not induce significant changes in metabolite levels. In conclusion, sustained vortioxetine and fluoxetine administration decreased QUIN independent of species, while ketamine was ineffective. These results support the hypothesis that modulating tryptophan metabolism may be part of the mechanism of action for some antidepressants.
[Mh] Termos MeSH primário: Antidepressivos/farmacologia
Depressão/metabolismo
Depressão/psicologia
Triptofano/metabolismo
[Mh] Termos MeSH secundário: Animais
Química Encefálica/efeitos dos fármacos
Fluoxetina/farmacologia
Lobo Frontal/efeitos dos fármacos
Lobo Frontal/metabolismo
Ácido Hidroxi-Indolacético/metabolismo
Ketamina/farmacologia
Cinurenina/metabolismo
Lúpus Eritematoso Sistêmico/metabolismo
Masculino
Camundongos
Piperazinas/farmacologia
Ácido Quinolínico/metabolismo
Ratos
Ratos Sprague-Dawley
Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
Inibidores da Captação de Serotonina/farmacologia
Sulfetos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Piperazines); 0 (Serotonin Plasma Membrane Transport Proteins); 0 (Serotonin Uptake Inhibitors); 0 (Sulfides); 01K63SUP8D (Fluoxetine); 343-65-7 (Kynurenine); 3O2K1S3WQV (vortioxetine); 54-16-0 (Hydroxyindoleacetic Acid); 690G0D6V8H (Ketamine); 8DUH1N11BX (Tryptophan); F6F0HK1URN (Quinolinic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14043


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[PMID]:28342863
[Au] Autor:Cheng J; Jin H; Hou X; Lv J; Gao X; Zheng G
[Ad] Endereço:Department of Medical Instrument, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai 201318, China.
[Ti] Título:Disturbed tryptophan metabolism correlating to progression and metastasis of esophageal squamous cell carcinoma.
[So] Source:Biochem Biophys Res Commun;486(3):781-787, 2017 May 06.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. Lymph node metastasis is the leading cause of death in ESCC patients. To identify early diagnostic and prognostic biomarkers of ESCC and elucidate underlying pathogenesis of the disease, a targeted metabolomics strategy based on liquid chromatography combined with tandem mass spectrometry was applied to explore tryptophan metabolism between ESCC patients, metastatic ESCC patients (mESCC), and healthy controls. Statistical analysis on metabolite expression abundance and compound concentration ratio was conducted to discriminate patients from healthy controls. The concentration ratio of kynurenine, 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, 5-hydroxytryptamine to their precursor tryptophan were identified as potential biomarkers, presenting high diagnostic capacity for distinguishing ESCC and mESCC patients from healthy controls. Moreover, a prognostic prediction model was also built on these ratios to distinguish metastasis patients from non-metastasis patients successfully. The high performance of ESCC prediction models suggest that concentration ratios of compounds may be used as biomarkers for early diagnosis and prognosis of the disease. In addition, concentration ratios of compounds show a progressively increased trend from non-metastasis to metastasis patients compared with healthy controls, which is in accordance with process of malignant transformation of ESCC. This interested finding suggests that disturbed tryptophan metabolism is correlated to progression and metastasis of ESCC since concentration ratios of compounds reflect activity of enzymes involved in tryptophan metabolism. This study reveals the impact of tryptophan metabolism to tumorigenesis and metastasis of ESCC, which help biologists investigate mechanism of the disease.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Carcinoma de Células Escamosas/sangue
Carcinoma de Células Escamosas/diagnóstico
Neoplasias Esofágicas/sangue
Neoplasias Esofágicas/diagnóstico
Metaboloma
Triptofano/sangue
[Mh] Termos MeSH secundário: 5-Hidroxitriptofano/sangue
Idoso
Carcinoma de Células Escamosas/patologia
Estudos de Casos e Controles
Progressão da Doença
Diagnóstico Precoce
Neoplasias Esofágicas/patologia
Feminino
Seres Humanos
Ácido Hidroxi-Indolacético/sangue
Cinurenina/sangue
Metástase Linfática
Masculino
Meia-Idade
Prognóstico
Serotonina/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 333DO1RDJY (Serotonin); 343-65-7 (Kynurenine); 54-16-0 (Hydroxyindoleacetic Acid); 8DUH1N11BX (Tryptophan); C1LJO185Q9 (5-Hydroxytryptophan)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170602
[Lr] Data última revisão:
170602
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170327
[St] Status:MEDLINE


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[PMID]:28289088
[Au] Autor:Tirosh A; Papadakis GZ; Millo C; Sadowski SM; Herscovitch P; Pacak K; Marx SJ; Yang L; Nockel P; Shell J; Green P; Keutgen XM; Patel D; Nilubol N; Kebebew E
[Ad] Endereço:Section on Medical NeuroendocrinologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
[Ti] Título:Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total Ga-DOTATATE-Avid tumor volume measurements.
[So] Source:Eur J Endocrinol;176(5):575-582, 2017 May.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by Ga DOTATATE PET/CT imaging. DESIGN: A retrospective analysis of a prospective database of patients with NETs. METHODS: Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total Ga-DOTATATE-avid tumor volume (TV) was analyzed. RESULTS: The analysis included 232 patients. In patients with pancreatic NETs ( = 112), Ga-DOTATATE TV correlated with CgA ( = 0.6, = 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 ( = 39), Ga-DOTATATE TV correlated with glucagon ( = 0.5, = 0.01) and PP levels ( = 0.5, = 0.049). In patients with von Hippel-Lindau ( = 24), plasma VIP ( = 0.5, = 0.02) and PP levels ( = 0.7, < 0.001) correlated with Ga-DOTATATE TV. In patients with small intestine NET (SINET, = 74), Ga-DOTATATE TV correlated with CgA ( = 0.5, = 0.02) and 5-HIAA levels ( = 0.7, < 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values ( = 0.001). Ga-DOTATATE TV in patients with NET of unknown primary ( = 16) and those with NET of other primary location ( = 30) correlated with 5-HIAA levels ( = 0.8, = 0.002 and = 0.7, = 0.02 respectively). CONCLUSIONS: Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Tumores Neuroendócrinos/diagnóstico por imagem
Tumores Neuroendócrinos/metabolismo
[Mh] Termos MeSH secundário: Adulto
Biomarcadores Tumorais/análise
Estudos de Coortes
Bases de Dados Factuais
Feminino
Seres Humanos
Ácido Hidroxi-Indolacético/urina
Imagem por Ressonância Magnética
Masculino
Imagem Multimodal
Neoplasia Endócrina Múltipla/diagnóstico por imagem
Neoplasia Endócrina Múltipla/metabolismo
Metástase Neoplásica
Compostos Organometálicos
Neoplasias Pancreáticas/diagnóstico por imagem
Neoplasias Pancreáticas/metabolismo
Tomografia por Emissão de Pósitrons
Compostos Radiofarmacêuticos
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Organometallic Compounds); 0 (Radiopharmaceuticals); 54-16-0 (Hydroxyindoleacetic Acid); 9L17Y0H71P (dotatate gallium ga-68)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-16-1079


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[PMID]:28267211
[Au] Autor:Shi DD; Yuppa DP; Dutton T; Brais LK; Minden SL; Braun IM; Kulke MH; Chan JA; Meyer FL
[Ad] Endereço:Harvard Medical School, Boston, Massachusetts.
[Ti] Título:Retrospective review of serotonergic medication tolerability in patients with neuroendocrine tumors with biochemically proven carcinoid syndrome.
[So] Source:Cancer;123(14):2735-2742, 2017 Jul 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with carcinoid tumors frequently could benefit from the pharmacologic treatment of depression and anxiety. However, many prescribers avoid serotonergic medications due to the theoretical risk of exacerbating carcinoid syndrome. METHODS: The authors conducted a retrospective chart review of patients with carcinoid tumors and elevated serotonin levels (as measured by 24-hour urine 5-hydroxyindoleacetic acid [5-HIAA]) at Dana-Farber/Brigham and Women's Cancer Center who initiated treatment with serotonergic antidepressants after a carcinoid diagnosis from 2003 to 2016. Each medication regimen was categorized based on the presence of adverse interactions as defined by clinical worsening of symptoms of carcinoid syndrome in the absence of progressive disease that temporally correlated with a serotonergic medication trial. RESULTS: A total of 73 serotonergic regimens received by 52 patients were included in the primary analysis. Among these medication trials, 8.2% of the regimens (6 regimens) were categorized as being associated with a likely adverse interaction, 61.6% of the regimens (45 regimens) were categorized as having no adverse reaction, 9.6% of the regimens (7 regimens) were categorized as an unlikely adverse reaction, and 20.6% of the regimens (15 regimens) were categorized as unknown. It is interesting to note that none of the 73 trials resulted in a carcinoid crisis requiring emergency care or hospitalization. Only 3 patients discontinued serotonergic medications due to worsening carcinoid syndrome. CONCLUSIONS: Serotonergic medications appear to be a safe option for the treatment of depressive and anxiety symptoms in the majority of patients with neuroendocrine tumors and carcinoid syndrome. In the current study, <10% of patients developed a combination of flushing, diarrhea, and bloating after the initiation of serotonergic medications. Clinicians can begin with low doses, monitor these symptoms, and reduce the dose or discontinue the medication if necessary. Cancer 2017;123:2735-42. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Ansiedade/tratamento farmacológico
Depressão/tratamento farmacológico
Síndrome do Carcinoide Maligno/metabolismo
Inibidores da Captação de Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Ansiedade/complicações
Tumor Carcinoide/complicações
Tumor Carcinoide/metabolismo
Depressão/complicações
Diarreia/induzido quimicamente
Diarreia/etiologia
Feminino
Rubor/induzido quimicamente
Rubor/etiologia
Seres Humanos
Ácido Hidroxi-Indolacético/urina
Masculino
Síndrome do Carcinoide Maligno/complicações
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Serotonin Uptake Inhibitors); 54-16-0 (Hydroxyindoleacetic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30633


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[PMID]:28213524
[Au] Autor:Wang J; Luo J; Aryal DK; Wetsel WC; Nass R; Benovic JL
[Ad] Endereço:From the Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
[Ti] Título:G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in .
[So] Source:J Biol Chem;292(14):5943-5956, 2017 Apr 07.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Our studies demonstrate that loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). The egg laying defect could be rescued by the expression of wild type but not by catalytically inactive or by the selective expression of in hermaphrodite-specific neurons. The addition of 5-HT or inhibition of 5-HT metabolism also rescued the egg laying defect. Furthermore, we demonstrate that AMX-2 is the primary monoamine oxidase that metabolizes 5-HT in , and we also found that loss-of-function strains have abnormally high levels of AMX-2 compared with wild-type nematodes. Interestingly, GRK-2 was also found to interact with and promote the phosphorylation of AMX-2. Additional studies reveal that 5-HIAA functions to inhibit egg laying in a manner dependent on the 5-HT receptor SER-1 and the G protein GOA-1. These results demonstrate that GRK-2 modulates 5-HT metabolism by regulating AMX-2 function and that 5-HIAA may function in the SER-1 signaling pathway.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/biossíntese
Caenorhabditis elegans/metabolismo
Quinases de Receptores Acoplados a Proteína G/biossíntese
Regulação Enzimológica da Expressão Gênica/fisiologia
Monoaminoxidase/metabolismo
Serotonina/metabolismo
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/metabolismo
Quinases de Receptores Acoplados a Proteína G/genética
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo
Ácido Hidroxi-Indolacético/metabolismo
Monoaminoxidase/genética
Receptores 5-HT2 de Serotonina/genética
Receptores 5-HT2 de Serotonina/metabolismo
Serotonina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (GOA-1 protein, C elegans); 0 (Receptors, Serotonin, 5-HT2); 0 (SER-1 protein, C elegans); 333DO1RDJY (Serotonin); 54-16-0 (Hydroxyindoleacetic Acid); EC 1.4.3.4 (Monoamine Oxidase); EC 2.7.11.16 (G-Protein-Coupled Receptor Kinases); EC 2.7.11.16 (GRK-2 protein, C elegans); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170219
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.760850


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[PMID]:28194570
[Au] Autor:Gasparini CF; Smith RA; Griffiths LR
[Ad] Endereço:Menzies Health Institute Queensland, Griffith University Gold Coast, Parklands Drive, Southport, QLD, 4222, Australia.
[Ti] Título:Genetic and biochemical changes of the serotonergic system in migraine pathobiology.
[So] Source:J Headache Pain;18(1):20, 2017 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Migraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the family in addition to the sufferer, particularly as it affects three times more women than men and is most prevalent between the ages of 25 and 45, the years of child rearing. Migraine typically occurs in individuals with a genetic predisposition and is aggravated by specific environmental triggers. Attempts to study the biochemistry of migraine began as early as the 1960s and were primarily directed at serotonin metabolism after an increase of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin was observed in urine of migraineurs. Genetic and biochemical studies have primarily focused on the neurotransmitter serotonin, considering receptor binding, transport and synthesis of serotonin and have investigated serotonergic mediators including enzymes, receptors as well as intermediary metabolites. These studies have been mainly assayed in blood, CSF and urine as the most accessible fluids. More recently PET imaging technology integrated with a metabolomics and a systems biology platform are being applied to study serotonergic biology. The general trend observed is that migraine patients have alterations of neurotransmitter metabolism detected in biological fluids with different biochemistry from controls, however the interpretation of the biological significance of these peripheral changes is unresolved. In this review we present the biology of the serotonergic system and metabolic routes for serotonin and discuss results of biochemical studies with regard to alterations in serotonin in brain, cerebrospinal fluid, saliva, platelets, plasma and urine of migraine patients.
[Mh] Termos MeSH primário: Encéfalo/citologia
Encéfalo/metabolismo
Transtornos de Enxaqueca/genética
Transtornos de Enxaqueca/fisiopatologia
Neurônios Serotoninérgicos/metabolismo
Serotonina/metabolismo
[Mh] Termos MeSH secundário: Adulto
Feminino
Predisposição Genética para Doença
Seres Humanos
Ácido Hidroxi-Indolacético/metabolismo
Masculino
Transtornos de Enxaqueca/metabolismo
Tomografia por Emissão de Pósitrons
Receptores de Serotonina/metabolismo
Serotonina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Receptors, Serotonin); 333DO1RDJY (Serotonin); 54-16-0 (Hydroxyindoleacetic Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170413
[Lr] Data última revisão:
170413
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170215
[St] Status:MEDLINE
[do] DOI:10.1186/s10194-016-0711-0


  9 / 8339 MEDLINE  
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[PMID]:28189610
[Au] Autor:El Arfani A; Parthoens J; Demuyser T; Servaes S; De Coninck M; De Deyn PP; Van Dam D; Wyckhuys T; Baeken C; Smolders I; Staelens S
[Ad] Endereço:Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: aelarfan@vub.ac.be.
[Ti] Título:Accelerated high-frequency repetitive transcranial magnetic stimulation enhances motor activity in rats.
[So] Source:Neuroscience;347:103-110, 2017 Apr 07.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is currently accepted as an evidence-based treatment option for treatment-resistant depression (TRD). Additionally, HF-rTMS showed beneficial effects on psychomotor retardation in patients. The classical HF-rTMS paradigms however are unlikely to replace electroconvulsive therapy, a more potent alternative for TRD albeit with important side-effects. Therefore, recent studies have investigated 'accelerated' HF-rTMS protocols demonstrating promising clinical responses in patients with TRD. Since the neuronal effects of accelerated HF-rTMS are underinvestigated, we evaluate here the possible metabolic and neurochemical effects of this treatment alternative. More specifically, we measured the effect on brain glucose metabolism and monoamines/metabolites, as well as on the spontaneous motor activity in rats. We found that brain glucose metabolism and monoamines remained generally unaffected after accelerated HF-rTMS, with the exception of reduced total striatal 5-hydroxyindolacetic acid (a metabolite of serotonin) levels. Interestingly, when compared to sham stimulation, the velocity, the total distance traveled as well as the percentage of movement, as measured by the open-field test, were significantly enhanced after accelerated HF-rTMS showing an increased motor activity. Our current results indicate that the accelerated HF-rTMS-induced increase in motor activity in rats, may be related to the striatal neurochemical effect.
[Mh] Termos MeSH primário: Monoaminas Biogênicas/metabolismo
Encéfalo/metabolismo
Glucose/metabolismo
Atividade Motora
Estimulação Transcraniana por Corrente Contínua
[Mh] Termos MeSH secundário: Ácido 3,4-Di-Hidroxifenilacético/metabolismo
Animais
Química Encefálica
Dopamina/metabolismo
Fluordesoxiglucose F18
Ácido Hidroxi-Indolacético/metabolismo
Masculino
Tomografia por Emissão de Pósitrons
Ratos
Ratos Sprague-Dawley
Serotonina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biogenic Monoamines); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 102-32-9 (3,4-Dihydroxyphenylacetic Acid); 333DO1RDJY (Serotonin); 54-16-0 (Hydroxyindoleacetic Acid); IY9XDZ35W2 (Glucose); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170213
[St] Status:MEDLINE


  10 / 8339 MEDLINE  
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[PMID]:28166276
[Au] Autor:Morimoto S; Takao M; Hatsuta H; Nishina Y; Komiya T; Sengoku R; Nakano Y; Uchino A; Sumikura H; Saito Y; Kanemaru K; Murayama S
[Ad] Endereço:Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
[Ti] Título:Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer's disease: An autopsy-confirmed study.
[So] Source:PLoS One;12(2):e0171524, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aß) 1-42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia. We obtained a total of 3498 CSF samples from patients admitted to our hospital during the period from 1996 to 2015. Of these patients, we were able to carry out a brain autopsy in 94 cases. Finally, 78 neuropathologically diagnosed cases (10 AD, six DLB, five DLB with AD, five controls without neurological diseases, and 52 cases with other neurological diseases) were studied. CSF levels of HVA and 5-HIAA were consistently decreased in pathologically advanced Lewy body disorder (LBD; Braak LB stages >3) compared with pathologically incipient LBD (Braak LB stages <2). These results suggest that if an individual has LB pathology in the central nervous system, CSF levels of HVA and 5-HIAA may decrease after the onset of clinical symptoms. In addition, CSF levels of HVA and 5-HIAA decreased with LB pathology, and were especially low in cases of DLB and DLB with AD. Furthermore, the combination of HVA, 5-HIAA, and brain specific proteins t-tau, p-tau, and Aß 1-42 in CSF were useful for discriminating among DLB, DLB with AD, and AD with high diagnostic accuracy.
[Mh] Termos MeSH primário: Doença de Alzheimer/líquido cefalorraquidiano
Doença de Alzheimer/complicações
Ácido Homovanílico/líquido cefalorraquidiano
Ácido Hidroxi-Indolacético/líquido cefalorraquidiano
Doença por Corpos de Lewy/líquido cefalorraquidiano
Doença por Corpos de Lewy/complicações
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/diagnóstico
Peptídeos beta-Amiloides/líquido cefalorraquidiano
Autopsia
Biomarcadores
Diagnóstico Diferencial
Seres Humanos
Doença por Corpos de Lewy/diagnóstico
Meia-Idade
Proteínas tau/líquido cefalorraquidiano
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Biomarkers); 0 (tau Proteins); 54-16-0 (Hydroxyindoleacetic Acid); X77S6GMS36 (Homovanillic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171524



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