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[PMID]:29258821
[Au] Autor:Masuda K; Tsutsuki H; Kasamatsu S; Ida T; Takata T; Sugiura K; Nishida M; Watanabe Y; Sawa T; Akaike T; Ihara H
[Ad] Endereço:Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka, Japan; Project Management Department, SHIONOGI & CO., LTD., Osaka, Japan.
[Ti] Título:Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons.
[So] Source:Biochem Biophys Res Commun;495(3):2165-2170, 2018 01 15.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To investigate the role of nitric oxide (NO)/reactive oxygen species (ROS) redox signaling in Parkinson's disease-like neurotoxicity, we used 1-methyl-4-phenylpyridinium (MPP ) treatment (a model of Parkinson's disease). We show that MPP -induced neurotoxicity was dependent on ROS from neuronal NO synthase (nNOS) in nNOS-expressing PC12 cells (NPC12 cells) and rat cerebellar granule neurons (CGNs). Following MPP treatment, we found production of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a second messenger in the NO/ROS redox signaling pathway, in NPC12 cells and rat CGNs, that subsequently induced S-guanylation and activation of H-Ras. Additionally, following MPP treatment, extracellular signal-related kinase (ERK) phosphorylation was enhanced. Treatment with a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor attenuated MPP -induced ERK phosphorylation and neurotoxicity. In conclusion, we demonstrate for the first time that NO/ROS redox signaling via 8-nitro-cGMP is involved in MPP -induced neurotoxicity and that 8-nitro-cGMP activates H-Ras/ERK signaling. Our results indicate a novel mechanism underlying MPP -induced neurotoxicity, and therefore contribute novel insights to the mechanisms underlying Parkinson's disease.
[Mh] Termos MeSH primário: 1-Metil-4-fenilpiridínio
Cerebelo/metabolismo
GMP Cíclico/análogos & derivados
Neurônios/metabolismo
Óxido Nítrico/metabolismo
Transtornos Parkinsonianos/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Cerebelo/efeitos dos fármacos
Cerebelo/patologia
GMP Cíclico/metabolismo
Relação Dose-Resposta a Droga
Neurônios/efeitos dos fármacos
Neurônios/patologia
Neurotoxinas
Células PC12
Transtornos Parkinsonianos/induzido quimicamente
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (8-nitroguanosine 3',5'-cyclic monophosphate); 0 (Neurotoxins); 0 (Reactive Oxygen Species); 31C4KY9ESH (Nitric Oxide); H2D2X058MU (Cyclic GMP); R865A5OY8J (1-Methyl-4-phenylpyridinium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE


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[PMID]:29304113
[Au] Autor:Shao YM; Ma X; Paira P; Tan A; Herr DR; Lim KL; Ng CH; Venkatesan G; Klotz KN; Federico S; Spalluto G; Cheong SL; Chen YZ; Pastorin G
[Ad] Endereço:Department of Pharmacy, National University of Singapore, Singapore.
[Ti] Título:Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment.
[So] Source:PLoS One;13(1):e0188212, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 µM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 µM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 µM), hepatotoxicity (up to 30 µM) or cardiotoxicity (up to 30 µM).
[Mh] Termos MeSH primário: Antagonistas do Receptor A2 de Adenosina/farmacologia
Antiparkinsonianos/farmacologia
Agonistas de Dopamina/farmacologia
Doença de Parkinson/tratamento farmacológico
Doença de Parkinson/metabolismo
Receptor A2A de Adenosina/metabolismo
Receptores de Dopamina D2/agonistas
Receptores de Dopamina D2/metabolismo
[Mh] Termos MeSH secundário: Antagonistas do Receptor A2 de Adenosina/química
Antagonistas do Receptor A2 de Adenosina/farmacocinética
Inibidores de Adenilil Ciclase/química
Inibidores de Adenilil Ciclase/farmacocinética
Inibidores de Adenilil Ciclase/farmacologia
Animais
Animais Geneticamente Modificados
Antiparkinsonianos/química
Antiparkinsonianos/farmacocinética
Células CHO
Cricetulus
Agonistas de Dopamina/química
Agonistas de Dopamina/farmacocinética
Drosophila/genética
Drosophila/metabolismo
Descoberta de Drogas
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Transtornos Parkinsonianos/tratamento farmacológico
Transtornos Parkinsonianos/genética
Transtornos Parkinsonianos/metabolismo
Piperazinas/química
Piperazinas/farmacocinética
Piperazinas/farmacologia
Pirimidinas/química
Pirimidinas/farmacocinética
Pirimidinas/farmacologia
Ensaio Radioligante
Máquina de Vetores de Suporte
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adenosine A2 Receptor Antagonists); 0 (Adenylyl Cyclase Inhibitors); 0 (Antiparkinson Agents); 0 (DRD2 protein, human); 0 (Dopamine Agonists); 0 (Piperazines); 0 (Pyrimidines); 0 (Receptor, Adenosine A2A); 0 (Receptors, Dopamine D2)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188212


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[PMID]:29287113
[Au] Autor:Bajaj S; Krismer F; Palma JA; Wenning GK; Kaufmann H; Poewe W; Seppi K
[Ad] Endereço:Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
[Ti] Título:Diffusion-weighted MRI distinguishes Parkinson disease from the parkinsonian variant of multiple system atrophy: A systematic review and meta-analysis.
[So] Source:PLoS One;12(12):e0189897, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Putaminal diffusivity in brain magnetic resonance diffusion-weighted imaging (DWI) is increased in patients with the parkinsonian variant of multiple system atrophy (MSA-P) compared to Parkinson disease (PD) patients. PURPOSE: We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of DWI to distinguish MSA-P from PD. METHODS: Studies on DWI were identified through a systematic PubMed and Clarivate Analytics® Web of Science® Core Collection search. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of MSA-P and PD patients and documented true positive, true negative, false positive and false negative rates or overall sample size and reported sensitivity and specificity. Meta-analysis was performed using the hierarchical summary receiver operating characteristics curve approach. RESULTS: The database search yielded 1678 results of which 9 studies were deemed relevant. Diagnostic accuracy of putaminal diffusivity measurements were reported in all of these 9 studies, whereas results of other regions of interest were only reported irregularly. Therefore, a meta-analysis could only be performed for putaminal diffusivity measurements: 127 patients with MSA-P, 262 patients with PD and 70 healthy controls were included in the quantitative synthesis. The meta-analysis showed an overall sensitivity of 90% (95% confidence interval (CI): 76.7%-95.8%) and an overall specificity of 93% (95% CI: 80.0%-97.7%) to distinguish MSA-P from PD based on putaminal diffusivity. CONCLUSION: Putaminal diffusivity yields high sensitivity and specificity to distinguish clinically diagnosed patients with MSA-P from PD. The confidence intervals indicate substantial variability. Further multicenter studies with harmonized protocols are warranted particularly in early disease stages when clinical diagnosis is less certain.
[Mh] Termos MeSH primário: Imagem de Difusão por Ressonância Magnética/métodos
Doença de Parkinson/diagnóstico
Transtornos Parkinsonianos/diagnóstico
[Mh] Termos MeSH secundário: Idoso
Diagnóstico Diferencial
Feminino
Seres Humanos
Masculino
Doença de Parkinson/diagnóstico por imagem
Transtornos Parkinsonianos/diagnóstico por imagem
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189897


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[PMID]:29245280
[Au] Autor:Pu J; Si X; Ye R; Zhang B
[Ad] Endereço:Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
[Ti] Título:Straight sinus dural arteriovenous fistula presenting with reversible parkinsonism: A case report and literature review.
[So] Source:Medicine (Baltimore);96(49):e9005, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: A dural arteriovenous fistula (DAVF) refers to an abnormal direct connection between an intracranial artery and a dural venous sinus. A DAVF presenting with parkinsonism is rare, and is therefore easily misdiagnosed. Therefore, early consideration of DAVF in the differential diagnosis of reversible parkinsonism is necessary. PATIENT CONCERNS: We present the case of a 51-year-old male with progressive parkinsonism. DIAGNOSES: He was diagnosed as straight sinus occlusion. Imaging studies revealed a DAVF associated with cerebral hypoperfusion of the lenticular nuclei and frontal lobe white matter. INTERVENTIONS: Endovascular embolization was performed through his left occipital artery. OUTCOMES: Treatment resulted in marked clinical improvement that a major improvement of parkinsonism was observed concomitant with no evidence of early venous drainage of this patient. LESSONS: DAVF should always be considered as a potential cause of progressive parkinsonism on account of its potential reversibility. Our case suggests a concomitant role of basal ganglia degeneration and frontal white matter hypoperfusion in the pathology of parkinsonism due to DAVF. However, the precise pathophysiology remains to be investigated.
[Mh] Termos MeSH primário: Malformações Vasculares do Sistema Nervoso Central/complicações
Malformações Vasculares do Sistema Nervoso Central/terapia
Transtornos Parkinsonianos/etiologia
[Mh] Termos MeSH secundário: Malformações Vasculares do Sistema Nervoso Central/fisiopatologia
Embolização Terapêutica/métodos
Seres Humanos
Masculino
Meia-Idade
Transtornos Parkinsonianos/fisiopatologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009005


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[PMID]:27771532
[Au] Autor:Han C; Nie S; Chen G; Ma K; Xiong N; Zhang Z; Xu Y; Wang T; Papa SM; Cao X
[Ad] Endereço:Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
[Ti] Título:Intrastriatal injection of ionomycin profoundly changes motor response to l-DOPA and its underlying molecular mechanisms.
[So] Source:Neuroscience;340:23-33, 2017 Jan 06.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long-term l-DOPA treatment of Parkinson's disease is accompanied with fluctuations of motor responses and l-DOPA-induced dyskinesia (LID). Phosphorylation of the dopamine and c-AMP regulated phosphoprotein of 32kDa (DARPP-32) plays a role in the pathogenesis of LID, and thus dephosphorylation of this protein by activated calcineurin may help reduce LID. One important activator of calcineurin is the Ca ionophore ionomycin. Here, we investigated whether intrastriatal injection of ionomycin to hemiparkinsonian rats produced changes in l-DOPA responses including LID. We also analyzed the effects of ionomycin on key molecular mediators of LID. Results confirmed our hypothesis that ionomycin could downregulate the phosphorylation of DARPP32 at Thr-34 and reduce LID. Besides, ionomycin decreased two established molecular markers of LID, FosB/ΔFosB and phosphorylated ERK1/2. Ionomycin also decreased the phosphorylation of three main subunits of the NMDA receptor, NR1 phosphorylated at ser896, NR2A phosphorylated at Tyr-1325, and NR2B phosphorylated at Tyr-1472. Furthermore, the anti-LID effect of striatally injected ionomycin was not accompanied by reduction of the antiparkinsonian action of l-DOPA. These data indicate that ionomycin largely interacts with striatal mechanisms that are critical to the l-DOPA motor response highlighting the role of protein dephosphorylation by calcineurin.
[Mh] Termos MeSH primário: Antiparkinsonianos/farmacologia
Ionóforos de Cálcio/farmacologia
Discinesia Induzida por Medicamentos/tratamento farmacológico
Ionomicina/farmacologia
Levodopa/efeitos adversos
Transtornos Parkinsonianos/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antiparkinsonianos/efeitos adversos
Calcineurina/metabolismo
Corpo Estriado/efeitos dos fármacos
Corpo Estriado/metabolismo
Dopamina/metabolismo
Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo
Discinesia Induzida por Medicamentos/metabolismo
Ácido Glutâmico/metabolismo
Levodopa/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Sistema de Sinalização das MAP Quinases/fisiologia
Masculino
Transtornos Parkinsonianos/metabolismo
Fosforilação
Proteínas Proto-Oncogênicas c-fos/metabolismo
Distribuição Aleatória
Ratos Sprague-Dawley
Receptores de N-Metil-D-Aspartato/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Calcium Ionophores); 0 (Dopamine and cAMP-Regulated Phosphoprotein 32); 0 (Fosb protein, rat); 0 (N-methyl D-aspartate receptor subtype 2A); 0 (NMDA receptor A1); 0 (NR2B NMDA receptor); 0 (Ppp1r1b protein, rat); 0 (Proto-Oncogene Proteins c-fos); 0 (Receptors, N-Methyl-D-Aspartate); 3KX376GY7L (Glutamic Acid); 46627O600J (Levodopa); 56092-81-0 (Ionomycin); EC 3.1.3.16 (Calcineurin); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171224
[Lr] Data última revisão:
171224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28987055
[Au] Autor:Sitek EJ; Wieczorek D; Konkel A; Dabrowska M; Slawek J
[Ad] Endereço:Oddzial Neurologii Szpitala Specjalistycznego sw. Wojciecha w Gdansku.
[Ti] Título:The pattern of verbal, visuospatial and procedural learning in Richardson variant of progressive supranuclear palsy in comparison to Parkinson's disease.
[Ti] Título:Specyfika uczenia sie materialu slownego, wzrokowo-przestrzennego oraz proceduralnego w wariancie Richardsona postepujacego porazenia ponadjadrowego w porównaniu z choroba Parkinsona..
[So] Source:Psychiatr Pol;51(4):647-659, 2017 Aug 29.
[Is] ISSN:2391-5854
[Cp] País de publicação:Poland
[La] Idioma:eng; pol
[Ab] Resumo:OBJECTIVES: Progressive supranuclear palsy (PSP) is regarded either within spectrum of atypical parkinsonian syndromes or frontotemporal lobar degeneration. We compared the verbal, visuospatial and procedural learning profiles in patients with PSP and Parkinson's disease (PD). Furthermore, the relationship between executive factors (initiation and inhibition) and learning outcomes was analyzed. METHODS: Thirty-three patients with the clinical diagnosis of PSP-Richardson's syndrome (PSP-RS), 39 patients with PD and 29 age -and education -matched controls were administered Mini-Mental State Examination (MMSE), phonemic and semantic fluency tasks, Auditory Verbal Learning Test (AVLT), Visual Learning and Memory Test for Neuropsychological Assessment by Lamberti and Weidlich (Diagnosticum für Cerebralschädigung, DCS), Tower of Toronto (ToT) and two motor sequencing tasks. Patients with PSP-RS and PD were matched in terms of MMSE scores and mood. RESULTS: Performance on DCS was lower in PSP-RS than in PD. AVLT delayed recall was better in PSP-RS than PD. Motor sequencing task did not differentiate between patients. Scores on AVLT correlated positively with phonemic fluency scores in both PSP-RS and PD. ToT rule violation scores were negatively associated with DCS performance in PSP-RS and PD as well as with AVLT performance in PD. CONCLUSIONS: Global memory performance is relatively similar in PSP-RS and PD. Executive factors (initiation and inhibition) are closely related to memory performance in PSP-RS and PD. Visuospatial learning impairment in PSP-RS is possibly linked to impulsivity and failure to inhibit automatic responses.
[Mh] Termos MeSH primário: Cognição/fisiologia
Transtornos Parkinsonianos/psicologia
Paralisia Supranuclear Progressiva/psicologia
[Mh] Termos MeSH secundário: Adulto
Atenção/fisiologia
Seres Humanos
Masculino
Meia-Idade
Testes Neuropsicológicos
Percepção Espacial/fisiologia
Comportamento Verbal/fisiologia
Percepção Visual/fisiologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171008
[St] Status:MEDLINE


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[PMID]:28931619
[Au] Autor:Buchman AS; Leurgans SE; Nag S; VanderHorst VGJM; Kapasi A; Schneider JA; Bennett DA
[Ad] Endereço:From the Rush Alzheimer's Disease Center (A.S.B., S.E.L., S.N., A.K., J.A.S., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., J.A.S., D.A.B.), and Department of Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology, Beth Israel
[Ti] Título:Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism.
[So] Source:Stroke;48(10):2792-2798, 2017 Oct.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults. METHODS: We documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. We examined the associations of spinal arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex. RESULTS: Microinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; =14.58; <0.001). Arteriolosclerosis was more severe in the spinal cord than in the brain (cord: 4.10, SD=0.70; brain: 3.5, SD=0.98; =10.39; <0.001). The severity of spinal arteriolosclerosis was associated with spinal white matter pallor ( =0.47; <0.001). Spinal arteriolosclerosis accounted for ≈3% of the variation in parkinsonism in models controlling for age, sex, brain arteriolosclerosis, and cerebrovascular disease pathologies. Further models showed that the association of spinal arteriolosclerosis and parkinsonism was not mediated via spinal white matter pallor. CONCLUSIONS: Although the regional distribution of microvascular pathologies varies within the central nervous system, spinal arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.
[Mh] Termos MeSH primário: Envelhecimento/patologia
Arteriolosclerose/patologia
Microvasos/patologia
Transtornos Parkinsonianos/patologia
Medula Espinal/patologia
[Mh] Termos MeSH secundário: Idoso de 80 Anos ou mais
Arteriolosclerose/mortalidade
Encéfalo/irrigação sanguínea
Encéfalo/patologia
Estudos de Coortes
Feminino
Seguimentos
Seres Humanos
Masculino
Transtornos Parkinsonianos/mortalidade
Medula Espinal/irrigação sanguínea
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.117.017643


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[PMID]:28918840
[Au] Autor:Aksoy D; Solmaz V; Çavusoglu T; Meral A; Ates U; Erbas O
[Ad] Endereço:Department of Neurology, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey. Electronic address: dbekar@yahoo.com.
[Ti] Título:Neuroprotective Effects of Eexenatide in a Rotenone-Induced Rat Model of Parkinson's Disease.
[So] Source:Am J Med Sci;354(3):319-324, 2017 Sep.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKROUND: Several studies suggest an association between Parkinson's disease (PD) and type 2 diabetes mellitus; these 2 diseases are both known to affect the common molecular pathways. As a synthetic agonist for the glucagon-like peptide 1 receptor, exenatide has been evaluated as a neuroprotective agent in multiple animal models. Rotenone models of PD have great potential for the investigation of PD pathology and motor and nonmotor symptoms, as well as the role of gene-environment interactions in PD causation and pathogenesis. Therefore, in this study, the neurochemical, behavioral and histologic effects of exenatide on a rotenone-induced rat model of PD were examined. MATERIALS AND METHODS: Eighteen adult male rats were randomly divided into the following 3 groups (n = 6): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1) and the others received stereotaxical infusion of rotenone (groups 2 and 3). Apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered exenatide for 28 days. RESULTS: Malondialdehyde and tumor necrosis factor alpha levels increased in the rats with PD induced by rotenone, whereas malondialdehyde and tumor necrosis factor alpha levels markedly decreased in the rats treated with exenatide. The apomorphine-induced rotation test scores of exenatide-treated rats were determined to be lower compared with the untreated group. Additionally, treatment with exenatide significantly reduced the loss of dopaminergic neurons in striatum. CONCLUSIONS: These results have shown that exenatide has neuroprotective, anti-inflammatory and antioxidant effects in a rotenone-induced rat model of PD.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Fármacos Neuroprotetores/uso terapêutico
Transtornos Parkinsonianos/tratamento farmacológico
Peptídeos/uso terapêutico
Rotenona/farmacologia
Peçonhas/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Encéfalo/metabolismo
Encéfalo/patologia
Neurônios Dopaminérgicos/efeitos dos fármacos
Neurônios Dopaminérgicos/patologia
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Fármacos Neuroprotetores/administração & dosagem
Transtornos Parkinsonianos/induzido quimicamente
Transtornos Parkinsonianos/patologia
Peptídeos/administração & dosagem
Ratos
Ratos Sprague-Dawley
Fator de Necrose Tumoral alfa/metabolismo
Peçonhas/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neuroprotective Agents); 0 (Peptides); 0 (Tumor Necrosis Factor-alpha); 0 (Venoms); 03L9OT429T (Rotenone); 9P1872D4OL (exenatide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE


  9 / 5714 MEDLINE  
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[PMID]:28910611
[Au] Autor:Mamaligas AA; Ford CP
[Ad] Endereço:Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106-4970, USA.
[Ti] Título:Revealing a Role for NMDA Receptors in Regulating STN Inputs following the Loss of Dopamine.
[So] Source:Neuron;95(6):1227-1229, 2017 Sep 13.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this issue of Neuron, Chu et al. (2017) show that dopamine depletion using a 6-OHDA model causes a decrease in hyperdirect inputs from the motor cortex directly to the STN and that rescuing this loss alleviates Parkinsonian symptoms.
[Mh] Termos MeSH primário: Dopamina
Receptores de N-Metil-D-Aspartato
[Mh] Termos MeSH secundário: Seres Humanos
Oxidopamina
Transtornos Parkinsonianos
Núcleo Subtalâmico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, N-Methyl-D-Aspartate); 8HW4YBZ748 (Oxidopamine); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE


  10 / 5714 MEDLINE  
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[PMID]:28893517
[Au] Autor:Kühn J; Haumesser JK; Beck MH; Altschüler J; Kühn AA; Nikulin VV; van Riesen C
[Ad] Endereço:Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
[Ti] Título:Differential effects of levodopa and apomorphine on neuronal population oscillations in the cortico-basal ganglia loop circuit in vivo in experimental parkinsonism.
[So] Source:Exp Neurol;298(Pt A):122-133, 2017 Dec.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The current pharmacotherapy of Parkinson's disease (PD) is primarily based on two classes of drugs: dopamine precursors, namely levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents exert their beneficial clinical effects on motor and non-motor symptoms in PD via dopamine receptors, clinical efficiency and side effects differ substantially between levodopa and apomorphine. Levodopa can provide a greater symptomatic relief than dopamine receptor agonists. However, because long-term levodopa use is associated with early debilitating motor fluctuations, dopamine receptor agonists are often recommended in younger patients. The pharmacodynamic basis of these profound differences is incompletely understood. It has been hypothesized that levodopa and dopamine receptor agonists may have diverging effects on beta and gamma oscillations that have been shown to be of importance for the pathophysiology of PD. Here, we used electrophysiological recordings in anesthetized dopamine-intact and dopamine-depleted rats to systemically compare the impact of levodopa or apomorphine on neuronal population oscillations in three nodes of the cortico-basal ganglia loop circuit. Our results showed that levodopa had a higher potency than apomorphine to suppress the abnormal beta oscillations often associated with bradykinesia while simultaneously enhancing the gamma oscillations often associated with increased movement. Our data suggests that the higher clinical efficacy of levodopa as well as some of its side effects, as e.g. dyskinesias may be based on its characteristic ability to modulate beta-/gamma-oscillation dynamics in the cortico-basal ganglia loop circuit.
[Mh] Termos MeSH primário: Apomorfina/uso terapêutico
Gânglios da Base/efeitos dos fármacos
Córtex Cerebral/efeitos dos fármacos
Levodopa/uso terapêutico
Rede Nervosa/efeitos dos fármacos
Transtornos Parkinsonianos/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Apomorfina/farmacologia
Gânglios da Base/fisiologia
Córtex Cerebral/fisiologia
Relação Dose-Resposta a Droga
Levodopa/farmacologia
Masculino
Rede Nervosa/fisiologia
Neurônios/efeitos dos fármacos
Neurônios/fisiologia
Transtornos Parkinsonianos/fisiopatologia
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
46627O600J (Levodopa); N21FAR7B4S (Apomorphine)
[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:170913
[St] Status:MEDLINE



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