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[PMID]:29277794
[Au] Autor:Nakuz TS; Berger E; El-Rabadi K; Wadsak W; Haug A; Hacker M; Karanikas G
[Ad] Endereço:Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Clinical Value of F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma.
[So] Source:Anticancer Res;38(1):353-358, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:AIM: We evaluated the clinical usefulness of 6-[ F]fluoro-3,4-dihydroxy-L-phenylalanine( F-FDOPA)-positron-emission tomography (PET)/computed tomography (CT) in insulinoma detection with contrast enhancement, early acquisition time, and no carbidopa premedication. PATIENTS AND METHODS: Twenty-six patients diagnosed with hyperinsulinemic hypoglycemia underwent an F-FDOPA PET/CT examination. Patients without carbidopa premedication and contrast-enhanced CT were included. Imaging findings were compared to the overall final diagnosis (histological findings). RESULTS: In 10 of 26 patients (eight women, two men; mean age=53 years; age range=30-94 years), a detected lesion was confirmed histologically as an insulinoma. F-FDOPA PET detected the tumor in five out of ten patients. Contrast-enhanced CT also detected the tumor in five out of ten. Overall, F-FDOPA PET/CT, with contrast enhancement and without carbidopa premedication, was able to detect the insulinoma in seven out of ten patients (70%). CONCLUSION: Based on our data, F-DOPA PET/CT, with contrast enhancement and without carbidopa premedication, as a 'one-stop' diagnostic modality is a viable option for insulinoma detection.
[Mh] Termos MeSH primário: Inibidores das Descarboxilases de Aminoácidos Aromáticos/farmacologia
Carbidopa/farmacologia
Di-Hidroxifenilalanina/análogos & derivados
Insulinoma/diagnóstico por imagem
Insulinoma/diagnóstico
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Di-Hidroxifenilalanina/farmacologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Pré-Medicação
Compostos Radiofarmacêuticos/farmacologia
Estudos Retrospectivos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aromatic Amino Acid Decarboxylase Inhibitors); 0 (Radiopharmaceuticals); 2C598205QX (fluorodopa F 18); 63-84-3 (Dihydroxyphenylalanine); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


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[PMID]:28937983
[Au] Autor:Dadone-Montaudié B; Ambrosetti D; Dufour M; Darcourt J; Almairac F; Coyne J; Virolle T; Humbert O; Burel-Vandenbos F
[Ad] Endereço:Department of Pathology, University Hospital, Nice, France.
[Ti] Título:[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression.
[So] Source:PLoS One;12(9):e0184625, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:[18F]-FDOPA is a labeled amino acid (AA) analog used for positron emission tomography (PET) which is gaining increasing interest in the evaluation of brain tumors (BT). The AA-transporter LAT1 has been shown to be involved in [18F]-FDOPA uptake. The aim of this study was to determine whether the [18F]-FDOPA uptake was correlated with level of LAT1 expression in BT. Twenty-eight BT (including 19 gliomas and 9 metastases) were investigated by [18F]-FDOPA-PET prior to surgery and by anti-LAT1 immunohistochemistry on surgical specimens. The quantitative [18F]-FDOPA measured parameters were SUVmax, SUVmean and SUVpeak. LAT1 expression was quantified using a score (0 to 400). A significant [18F]-FDOPA uptake was associated with a LAT1 score ≥ 100 (p = 0.02) but there was no linear correlation between intensity of [18F]-FDOPA uptake and score of LAT1 expression whatever the parameters considered. LAT1 expression alone is not sufficient to explain variation of intensity of [18F]-FDOPA uptake in BT.
[Mh] Termos MeSH primário: Sistemas de Transporte de Aminoácidos Básicos/metabolismo
Neoplasias Encefálicas/metabolismo
Di-Hidroxifenilalanina/farmacocinética
Radioisótopos de Flúor/farmacocinética
Tomografia por Emissão de Pósitrons
Compostos Radiofarmacêuticos/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Idoso
Encéfalo/diagnóstico por imagem
Encéfalo/metabolismo
Encéfalo/patologia
Encéfalo/cirurgia
Neoplasias Encefálicas/diagnóstico por imagem
Neoplasias Encefálicas/patologia
Neoplasias Encefálicas/cirurgia
Feminino
Glioma/diagnóstico por imagem
Glioma/metabolismo
Glioma/patologia
Glioma/cirurgia
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport Systems, Basic); 0 (Fluorine Radioisotopes); 0 (Radiopharmaceuticals); 0 (SLC7A6 protein, human); 63-84-3 (Dihydroxyphenylalanine)
[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:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184625


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[PMID]:28902505
[Au] Autor:Matoba Y; Kihara S; Muraki Y; Bando N; Yoshitsu H; Kuroda T; Sakaguchi M; Kayama K; Tai H; Hirota S; Ogura T; Sugiyama M
[Ad] Endereço:Graduate School of Biomedical & Health Sciences, Hiroshima University , Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.
[Ti] Título:Activation Mechanism of the Streptomyces Tyrosinase Assisted by the Caddie Protein.
[So] Source:Biochemistry;56(41):5593-5603, 2017 Oct 17.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tyrosinase (EC 1.14.18.1), which possesses two copper ions at the active center, catalyzes a rate-limiting reaction of melanogenesis, that is, the conversion of a phenol to the corresponding ortho-quinone. The enzyme from the genus Streptomyces is generated as a complex with a "caddie" protein that assists the transport of two copper ions into the active center. In this complex, the Tyr residue in the caddie protein was found to be accommodated in the pocket of the active center of tyrosinase, probably in a manner similar to that of l-tyrosine as a genuine substrate of tyrosinase. Under physiological conditions, the addition of the copper ion to the complex releases tyrosinase from the complex, in accordance with the aggregation of the caddie protein. The release of the copper-bound tyrosinase was found to be accelerated by adding reducing agents under aerobic conditions. Mass spectroscopic analysis indicated that the Tyr residue was converted to a reactive quinone, and resonance Raman spectroscopic analysis indicated that the conversion occurred through the formations of µ-η :η -peroxo-dicopper(II) and Cu(II)-semiquinone. Electron paramagnetic resonance analysis under anaerobic conditions and Fourier transform infrared spectroscopic analysis using CO as a structural probe under anaerobic conditions indicated that the copper transportation process to the active center is a reversible event in the tyrosinase/caddie complex. Aggregation of the caddie protein, which is triggered by the conversion of the Tyr residue to dopaquinone, may ensure the generation of fully activated tyrosinase.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Proteínas de Transporte/metabolismo
Cobre/metabolismo
Modelos Moleculares
Monofenol Mono-Oxigenase/metabolismo
Streptomyces/enzimologia
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Apoenzimas/química
Apoenzimas/genética
Apoenzimas/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Benzoquinonas/química
Benzoquinonas/metabolismo
Sítios de Ligação
Proteínas de Transporte/química
Proteínas de Transporte/genética
Domínio Catalítico
Cobre/química
Di-Hidroxifenilalanina/análogos & derivados
Di-Hidroxifenilalanina/química
Di-Hidroxifenilalanina/metabolismo
Ativação Enzimática/efeitos dos fármacos
Monofenol Mono-Oxigenase/química
Monofenol Mono-Oxigenase/genética
Mutação
Oxirredução
Agregados Proteicos/efeitos dos fármacos
Multimerização Proteica/efeitos dos fármacos
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Substâncias Redutoras/química
Solubilidade
Tirosina/química
Tirosina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoenzymes); 0 (Bacterial Proteins); 0 (Benzoquinones); 0 (Carrier Proteins); 0 (Protein Aggregates); 0 (Recombinant Proteins); 0 (Reducing Agents); 42HK56048U (Tyrosine); 63-84-3 (Dihydroxyphenylalanine); 789U1901C5 (Copper); 8F09Y50AX6 (dopaquinone); EC 1.14.18.1 (Monophenol Monooxygenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00635


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[PMID]:28684245
[Au] Autor:Stokholm MG; Iranzo A; Østergaard K; Serradell M; Otto M; Svendsen KB; Garrido A; Vilas D; Borghammer P; Santamaria J; Møller A; Gaig C; Brooks DJ; Tolosa E; Pavese N
[Ad] Endereço:Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
[Ti] Título:Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study.
[So] Source:Lancet Neurol;16(10):789-796, 2017 Oct.
[Is] ISSN:1474-4465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Findings from longitudinal follow-up studies in patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) have shown that most patients will eventually develop the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Neuroinflammation in the form of microglial activation is present in synucleinopathies and is a potential therapeutic target to halt or delay the neurodegenerative process. We aimed to investigate whether neuroinflammation is present in patients with IRBD and its possible relation to nigrostriatal dopamine function. METHODS: In this prospective, case-control, PET study, patients with IRBD and no clinical evidence of parkinsonism and cognitive impairment were recruited from tertiary sleep centres in Spain (Barcelona) and Denmark (Aarhus). We included patients with polysomnography-confirmed IRBD according to established criteria. Healthy controls were recruited through newspaper advertisements. Controls had no motor or cognitive complaints, a normal neurological examination, and a mean group age similar to the IRBD group. In patients with IRBD, we assessed microglial activation in the substantia nigra, putamen, and caudate with C-PK11195 PET, and dopaminergic axon terminal function in the putamen and caudate with F-DOPA PET. Controls underwent either C-PK11195 PET or F-DOPA PET. We compared F-DOPA uptake and C-PK11195 binding potential between groups with an unpaired, two-tailed Student's t test. FINDINGS: Between March 23, 2015, and Oct 19, 2016, we recruited 20 consecutive patients with IRBD and 19 healthy controls. C-PK11195 binding was increased on the left side of the substantia nigra in patients with IRBD compared with controls (Student's t test, mean difference 0·153 [95% CI 0·055 to 0·250], p=0·003), but not on the right side (0·121 [-0·007 to 0·250], p=0·064). C-PK11195 binding was not significantly increased in the putamen and caudate of patients with IRBD. F-DOPA uptake was reduced in IRBD in the left putamen (-0·0032 [-0·0044 to -0·0021], p<0·0001) and right putamen (-0·0032 [-0·0044 to -0·0020], p<0·0001), but not in the caudate. INTERPRETATION: In patients with IRBD, increased microglial activation was detected by PET in the substantia nigra along with reduced dopaminergic function in the putamen. Further studies, including more participants than were in this study and longitudinal follow-up, are needed to support our findings and evaluate whether the presence of activated microglia in patients with IRBD represents a marker of short-term conversion to a clinically defined synucleinopathy in the near future. FUNDING: Danish Council for Independent Research, Instituto de Salud Carlos III (Spain).
[Mh] Termos MeSH primário: Núcleo Caudado/metabolismo
Neurônios Dopaminérgicos/metabolismo
Microglia/metabolismo
Tomografia por Emissão de Pósitrons/métodos
Putamen/metabolismo
Transtorno do Comportamento do Sono REM
Substância Negra/metabolismo
[Mh] Termos MeSH secundário: Idoso
Amidas
Axônios/metabolismo
Estudos de Casos e Controles
Núcleo Caudado/diagnóstico por imagem
Dinamarca
Di-Hidroxifenilalanina/análogos & derivados
Feminino
Seres Humanos
Inflamação/metabolismo
Isoquinolinas
Masculino
Meia-Idade
Estudos Prospectivos
Putamen/diagnóstico por imagem
Transtorno do Comportamento do Sono REM/diagnóstico por imagem
Transtorno do Comportamento do Sono REM/imunologia
Transtorno do Comportamento do Sono REM/metabolismo
Espanha
Substância Negra/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 ((R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide); 0 (Amides); 0 (Isoquinolines); 2C598205QX (fluorodopa F 18); 63-84-3 (Dihydroxyphenylalanine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE


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[PMID]:28650092
[Au] Autor:Hauf M; Richter F; Schneider T; Faidt T; Martins BM; Baumann T; Durkin P; Dobbek H; Jacobs K; Möglich A; Budisa N
[Ad] Endereço:Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Strasse 10, 10623, Berlin, Germany.
[Ti] Título:Photoactivatable Mussel-Based Underwater Adhesive Proteins by an Expanded Genetic Code.
[So] Source:Chembiochem;18(18):1819-1823, 2017 Sep 19.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Marine mussels exhibit potent underwater adhesion abilities under hostile conditions by employing 3,4-dihydroxyphenylalanine (DOPA)-rich mussel adhesive proteins (MAPs). However, their recombinant production is a major biotechnological challenge. Herein, a novel strategy based on genetic code expansion has been developed by engineering efficient aminoacyl-transfer RNA synthetases (aaRSs) for the photocaged noncanonical amino acid ortho-nitrobenzyl DOPA (ONB-DOPA). The engineered ONB-DOPARS enables in vivo production of MAP type 5 site-specifically equipped with multiple instances of ONB-DOPA to yield photocaged, spatiotemporally controlled underwater adhesives. Upon exposure to UV light, these proteins feature elevated wet adhesion properties. This concept offers new perspectives for the production of recombinant bioadhesives.
[Mh] Termos MeSH primário: Bivalves/metabolismo
Código Genético/genética
Proteínas/metabolismo
[Mh] Termos MeSH secundário: Adesivos/efeitos da radiação
Aminoacil-tRNA Sintetases/metabolismo
Animais
Materiais Biomiméticos/metabolismo
Bivalves/genética
Di-Hidroxifenilalanina/metabolismo
Microscopia de Força Atômica
Microscopia de Varredura por Sonda
Mutagênese Sítio-Dirigida
Proteínas/genética
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/química
Proteínas Recombinantes/isolamento & purificação
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adhesives); 0 (Proteins); 0 (Recombinant Proteins); 0 (adhesive protein, mussel); 63-84-3 (Dihydroxyphenylalanine); EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700327


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[PMID]:28490115
[Au] Autor:Isaschar-Ovdat S; Fishman A
[Ad] Endereço:Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
[Ti] Título:Mechanistic insights into tyrosinase-mediated crosslinking of soy glycinin derived peptides.
[So] Source:Food Chem;232:587-594, 2017 Oct 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tyrosinase from Bacillus megaterium (TyrBm) was previously used to modulate soy glycinin-based emulsions and gels. To study the crosslinking mechanism, TyrBm oxidation of three tyrosine-containing octapeptides derived from glycinin was analyzed by oxygen consumption measurements, absorbance and mass spectrometry. A significant lag period and lower activity were measured when tyrosine was located in the middle of the peptide chain. Mass spectrometry analysis showed that these peptides are crosslinked via the oxidative quinone ring of the tyrosine residue by aryl-alkylamine addition or aryloxy radical coupling to form di-DOPA (3,4-dihydroxyphenylalanine). In contrast, peptides containing tyrosine in the N- or C-terminus, were rapidly oxidized forming multimer units within thirty minutes. When small amino acids were adjacent to the terminus tyrosine, formation of di-tyrosine was observed. This work confirms that protein crosslinking by TyrBm occurs by several chemical mechanisms and may assist in designing peptide-based inhibitors for the food and cosmetic applications.
[Mh] Termos MeSH primário: Monofenol Mono-Oxigenase
[Mh] Termos MeSH secundário: Di-Hidroxifenilalanina
Globulinas
Oxirredução
Peptídeos
Proteínas de Soja
Feijão de Soja
Tirosina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Globulins); 0 (Peptides); 0 (Soybean Proteins); 42HK56048U (Tyrosine); 63-84-3 (Dihydroxyphenylalanine); 9007-93-6 (glycinin); EC 1.14.18.1 (Monophenol Monooxygenase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE


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[PMID]:28349331
[Au] Autor:Kroiss AS; Uprimny C; Shulkin BL; Frech A; Tilg H; Gasser RW; Sprinzl GM; Gruber L; Thomé C; Plangger C; Url C; Fraedrich G; Virgolini IJ
[Ad] Endereço:Department of Nuclear Medicine, Medical University Innsbruck, Anichstrasse 35 A-6020, Innsbruck, Austria. alexander.kroiss@i-med.ac.at.
[Ti] Título:Compared to I-MIBG SPECT/CT, F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma.
[So] Source:Ann Nucl Med;31(5):357-365, 2017 Jun.
[Is] ISSN:1864-6433
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:AIM: The aim of this study was to compare the accuracy of I-MIBG SPECT/CT with that of F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards. METHODS: Three men and seven women (age range 26-73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with F-DOPA PET, and I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis. RESULTS: On a per-patient basis, F-DOPA PET's detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar I-MIBG imaging alone was 10.0% and that of I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, F-DOPA PET showed a sensitivity of 69.2% (McNemar p < 0.001) compared with anatomical imaging. Sensitivity of planar I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p < 0.0001). Overall, F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions. CONCLUSION: F-DOPA PET is more sensitive than is I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.
[Mh] Termos MeSH primário: 3-Iodobenzilguanidina
Di-Hidroxifenilalanina/análogos & derivados
Paraganglioma Extrassuprarrenal/diagnóstico por imagem
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Estadiamento de Neoplasias
Paraganglioma Extrassuprarrenal/patologia
Estudos Retrospectivos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
2C598205QX (fluorodopa F 18); 35MRW7B4AD (3-Iodobenzylguanidine); 63-84-3 (Dihydroxyphenylalanine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1007/s12149-017-1162-7


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[PMID]:28336296
[Au] Autor:Wile DJ; Agarwal PA; Schulzer M; Mak E; Dinelle K; Shahinfard E; Vafai N; Hasegawa K; Zhang J; McKenzie J; Neilson N; Strongosky A; Uitti RJ; Guttman M; Zabetian CP; Ding YS; Adam M; Aasly J; Wszolek ZK; Farrer M; Sossi V; Stoessl AJ
[Ad] Endereço:University of British Columbia, Department of Medicine, Vancouver, BC, Canada. Electronic address: dwile@mail.ubc.ca.
[Ti] Título:Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.
[So] Source:Lancet Neurol;16(5):351-359, 2017 May.
[Is] ISSN:1474-4465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. METHODS: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson's disease, people with sporadic Parkinson's disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson's disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson's disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage ( F-6-fluoro-L-dopa; F-FDOPA). We compared findings with those in people with sporadic Parkinson's disease and age-matched healthy controls. In the second study, distinct groups of LRRK2 mutation carriers, individuals with sporadic Parkinson's disease, and age-matched healthy controls seen from November, 2012, to May, 2016, were studied with tracers for the serotonin transporter and vesicular monoamine transporter 2 (VMAT2). Striatal dopamine transporter binding, VMAT2 binding, F-FDOPA uptake, and serotonin transporter binding in multiple brain regions were compared by ANCOVA, adjusted for age. FINDINGS: Between January, 1997, and January, 2012, we obtained data for our first study from 40 LRRK2 mutation carriers, 63 individuals with sporadic Parkinson's disease, and 35 healthy controls. We identified significant group differences in striatal dopamine transporter binding (all age ranges in caudate and putamen, p<0·0001) and F-FDOPA uptake (in caudate: age ≤50 years, p=0·0002; all other age ranges, p<0·0001; in putamen: all age ranges, p<0·0001). LRRK2 mutation carriers with manifest Parkinson's disease (n=15) had reduced striatal dopamine transporter binding and F-FDOPA uptake, comparable with amounts seen in individuals with sporadic Parkinson's disease of similar duration. LRRK2 mutation carriers without manifest Parkinson's disease (n=25) had greater F-FDOPA uptake and dopamine transporter binding than did individuals with sporadic Parkinson's disease, with F-FDOPA uptake comparable with controls and dopamine transporter binding lower than in controls. Between November, 2012, and May, 2016, we obtained data for our second study from 16 LRRK2 mutation carriers, 13 individuals with sporadic Parkinson's disease, and nine healthy controls. Nine LRRK2 mutation carriers without manifest Parkinson's disease had significantly elevated serotonin transporter binding in the hypothalamus (compared with controls, individuals with LRRK2 Parkinson's disease, and people with sporadic Parkinson's disease, p<0·0001), striatum (compared with people with sporadic Parkinson's disease, p=0·02), and brainstem (compared with LRRK2 mutation carriers with manifest Parkinson's disease, p=0·01), after adjustment for age. Serotonin transporter binding in the cortex did not differ significantly between groups after age adjustment. Striatal VMAT2 binding was reduced in all individuals with manifest Parkinson's disease and reduced asymmetrically in one LRRK2 mutation carrier without manifest disease. INTERPRETATION: Dopaminergic and serotonergic changes progress in a similar fashion in LRRK2 mutation carriers with manifest Parkinson's disease and individuals with sporadic Parkinson's disease, but LRRK2 mutation carriers without manifest Parkinson's disease show increased serotonin transporter binding in the striatum, brainstem, and hypothalamus, possibly reflecting compensatory changes in serotonergic innervation preceding the motor onset of Parkinson's disease. Increased serotonergic innervation might contribute to clinical differences in LRRK2 Parkinson's disease, including the emergence of non-motor symptoms and, potentially, differences in the long-term response to levodopa. FUNDING: Canada Research Chairs, Michael J Fox Foundation, National Institutes of Health, Pacific Alzheimer Research Foundation, Pacific Parkinson's Research Institute, National Research Council of Canada.
[Mh] Termos MeSH primário: Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo
Doença de Parkinson/metabolismo
Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Encéfalo/metabolismo
Estudos Transversais
Di-Hidroxifenilalanina/análogos & derivados
Feminino
Heterozigoto
Seres Humanos
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética
Masculino
Meia-Idade
Mutação
Doença de Parkinson/genética
Tomografia por Emissão de Pósitrons/métodos
Compostos Radiofarmacêuticos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dopamine Plasma Membrane Transport Proteins); 0 (Radiopharmaceuticals); 0 (Serotonin Plasma Membrane Transport Proteins); 2C598205QX (fluorodopa F 18); 63-84-3 (Dihydroxyphenylalanine); EC 2.7.11.1 (LRRK2 protein, human); EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


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[PMID]:28319498
[Au] Autor:Moreau A; Giraudet AL; Kryza D; Borson-Chazot F; Bournaud-Salinas C; Mognetti T; Lifante JC; Combemale P; Giammarile F; Houzard C
[Ad] Endereço:From the *Service de Médecine Nucléaire, CHU; †Service de Médecine Nucléaire, CLB; ‡Service d'Endocrinologie, Groupement Hospitalier Est, CHU; §Service de Chirurgie Endocrinienne, Groupement Hospitalier Sud, CHU; ∥Unité de Dermatologie, CLB; and ¶EA 3637, Université de Lyon 1, Lyon, France.
[Ti] Título:FDOPA Patterns in Adrenal Glands: A Pictorial Essay.
[So] Source:Clin Nucl Med;42(5):379-382, 2017 May.
[Is] ISSN:1536-0229
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:F-FDOPA is a well-established tool to explore pheochromocytomas. It tends to replace I-MIBG scan in metastatic pheochromocytomas, multiple endocrine neoplasia type 2-related tumors, succinate dehydrogenase [ubiquinone] iron-sulfur subunit-negative tumors, and succinate dehydrogenase[ZERO WIDTH SPACE]-positive lesions. To our knowledge, no study has characterized physiological and pathological adrenal glands with F-FDOPA from a quantitative point of view. We report the features of different normal and pathological adrenal glands with F-FDOPA. Within our series, only pheochromocytomas present a significantly increased uptake reflecting the high specificity of this tracer. Tumors such as adenomas or myelolipomas present no F-FDOPA significant accumulation. Interestingly, adrenal gland hyperplasia and solitary glands do not demonstrate compensatory uptake.
[Mh] Termos MeSH primário: Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem
Glândulas Suprarrenais/diagnóstico por imagem
Di-Hidroxifenilalanina
Radioisótopos de Flúor
Feocromocitoma/diagnóstico por imagem
Compostos Radiofarmacêuticos
[Mh] Termos MeSH secundário: Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Radiopharmaceuticals); 63-84-3 (Dihydroxyphenylalanine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170518
[Lr] Data última revisão:
170518
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE
[do] DOI:10.1097/RLU.0000000000001636


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[PMID]:28294334
[Au] Autor:Becker G; Bahri MA; Michel A; Hustadt F; Garraux G; Luxen A; Lemaire C; Plenevaux A
[Ad] Endereço:GIGA - CRC In vivo Imaging, University of Liège, Liège, Belgium.
[Ti] Título:Comparative assessment of 6-[ F]fluoro-L-m-tyrosine and 6-[ F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model.
[So] Source:J Neurochem;141(4):626-635, 2017 May.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the preclinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [ F]fluoro-3,4-dihydroxyphenyl-L-alanine ([ F]FDOPA) and 6-[ F]fluoro-L-m-tyrosine ([ F]FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [ F]FMT and [ F]FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase inhibitor. A catechol-O-methyl transferase inhibitor was also given before [ F]FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [ F]FMT and [ F]FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant K . However, only [ F]FMT K succeeded to discriminate between the partial and the full 6-OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [ F]FMT could be more sensitive, with respect of [ F]FDOPA, to investigate DA terminals loss in 6-OHDA rats, and open the way to in vivo L-aromatic amino acid decarboxylase activity targeting in future investigations on progressive PD models.
[Mh] Termos MeSH primário: Di-Hidroxifenilalanina/análogos & derivados
Doença de Parkinson Secundária/diagnóstico por imagem
Doença de Parkinson/diagnóstico por imagem
Compostos Radiofarmacêuticos
Receptores Pré-Sinápticos/metabolismo
Tirosina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Apomorfina/farmacologia
Descarboxilases de Aminoácido-L-Aromático/metabolismo
Modelos Animais de Doenças
Dopamina/metabolismo
Radioisótopos de Flúor
Processamento de Imagem Assistida por Computador
Masculino
Neostriado/diagnóstico por imagem
Oxidopamina
Doença de Parkinson Secundária/induzido quimicamente
Tomografia por Emissão de Pósitrons
Ratos
Ratos Sprague-Dawley
Comportamento Estereotipado/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Radiopharmaceuticals); 0 (Receptors, Presynaptic); 148613-12-1 (6-fluoro-3-tyrosine); 2C598205QX (fluorodopa F 18); 42HK56048U (Tyrosine); 63-84-3 (Dihydroxyphenylalanine); 8HW4YBZ748 (Oxidopamine); EC 4.1.1.28 (Aromatic-L-Amino-Acid Decarboxylases); N21FAR7B4S (Apomorphine); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170316
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14016



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