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[PMID]:29200853
[Au] Autor:Briot T; Roger E; Lautram N; Verger A; Clavreul A; Lagarce F
[Ad] Endereço:Micro & Nanomédecines Translationelles - MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, MINT IBS-CHU.
[Ti] Título:Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia.
[So] Source:Int J Nanomedicine;12:8427-8442, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is used in Europe for the treatment of acute myeloid leukemia (AML) in patients aged ≥65 years. However, it can only be administered intravenously due to very low oral bioavailability and a large distribution volume. Oral administration would allow outpatient treatment, improving quality of life and reducing treatment costs. The present study proposes to develop lipid nanocapsules (LNCs), originally designed for lipophilic drugs, to encapsulate decitabine. Two different formulations of LNCs were designed: LNCs based on a high proportion of Transcutol HP (THP-LNCs) and LNCs associated with a mixture of Transcutol HP and Tween 80 (THP-T80-LNCs). The second formulation had a diameter of 26.5±0.5 nm, high encapsulation efficiency (>85%), and a drug payload of 472±64 µg/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML cell lines depending on their decitabine resistance: HEL (not resistant) and HL-60 (resistant). The permeability of decitabine-loaded THP-T80-LNCs was also evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL-60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent permeability on Caco-2 cell monolayers was also increased, suggesting a potentially useful formulation to increase the oral bioavailability of decitabine.
[Mh] Termos MeSH primário: Azacitidina/análogos & derivados
Portadores de Fármacos/química
Leucemia Mieloide Aguda/tratamento farmacológico
Nanocápsulas/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Antimetabólitos Antineoplásicos/administração & dosagem
Antimetabólitos Antineoplásicos/farmacocinética
Azacitidina/administração & dosagem
Azacitidina/farmacocinética
Disponibilidade Biológica
Células CACO-2
Linhagem Celular Tumoral
Portadores de Fármacos/administração & dosagem
Liberação Controlada de Fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Estabilidade de Medicamentos
Etilenoglicóis/química
Seres Humanos
Lipídeos/química
Nanocápsulas/química
Polissorbatos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Drug Carriers); 0 (Ethylene Glycols); 0 (Lipids); 0 (Nanocapsules); 0 (Polysorbates); 776B62CQ27 (decitabine); A1A1I8X02B (carbitol); M801H13NRU (Azacitidine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147659


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[PMID]:27770419
[Au] Autor:Milosavic NB; Prodanovic RM; Velickovic D; Dimitrijevic A
[Ad] Endereço:Division of Experimental Therapeutics, Department of Medicine, Columbia University, 630 West 168th Street, P&S 8-436, New York, NY, 10032, USA. nm2729@columbia.edu.
[Ti] Título:Macroporous Poly(GMA-co-EGDMA) for Enzyme Stabilization.
[So] Source:Methods Mol Biol;1504:139-147, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:One of the most used procedures for enzyme stabilization is immobilization. Although immobilization on solid supports has been pursued since the 1950s, there are no general rules for selecting the best support for a giving application. A macroporous copolymer of ethylene glycol dimethacrylate and glycidyl methacrylate (poly (GMA-co-EGDMA)) is a carrier consisting of macroporous beads for immobilizing enzymes of industrial potential for the production of fine chemicals and pharmaceuticals.
[Mh] Termos MeSH primário: Aspergillus niger/enzimologia
Reagentes para Ligações Cruzadas/química
Enzimas Imobilizadas/química
Etilenoglicóis/química
Glucana 1,4-alfa-Glucosidase/química
Glutaral/química
Metacrilatos/química
[Mh] Termos MeSH secundário: Aspergillus niger/química
Aspergillus niger/metabolismo
Estabilidade Enzimática
Enzimas Imobilizadas/metabolismo
Óxido de Etileno/química
Glucana 1,4-alfa-Glucosidase/metabolismo
Oxirredução
Porosidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 0 (Enzymes, Immobilized); 0 (Ethylene Glycols); 0 (Methacrylates); 0 (poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate)); EC 3.2.1.3 (Glucan 1,4-alpha-Glucosidase); JJH7GNN18P (Ethylene Oxide); T3C89M417N (Glutaral)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


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[PMID]:28794245
[Au] Autor:Lim YY; Mormino EC; Alzheimer's Disease Neuroimaging Initiative
[Ad] Endereço:From the Florey Institute of Neuroscience and Mental Health (Y.Y.L.), The University of Melbourne, Parkville, Australia; and the Department of Neurology and Neurological Sciences (E.C.M.), Stanford University, CA.
[Ti] Título: genotype and early ß-amyloid accumulation in older adults without dementia.
[So] Source:Neurology;89(10):1028-1034, 2017 Sep 05.
[Is] ISSN:1526-632X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To clarify associations between ε4 allele and age on longitudinal rates of ß-amyloid (Aß) accumulation within Aß+ and Aß- older individuals without dementia. METHODS: We analyzed 595 older adults without dementia classified cross-sectionally as Aß- (n = 325) and Aß+ (n = 270) using longitudinal florbetapir PET. The influence of age and genotype on longitudinal accumulation of Aß was examined with linear mixed models. RESULTS: ε4 and older age were associated with higher risk of being classified as Aß+ at baseline. The annual rate of Aß accumulation was significantly greater than zero for Aß- ε3 (0.0021 ± 0.0007 standardized uptake value ratio [SUVR] units) and Aß- ε4 (0.0044 ± 0.0010 SUVR units), as well as Aß+ ε3 (0.0141 ± 0.0019 SUVR units) and Aß+ ε4 (0.0126 ± 0.0018 SUVR units). Aß accumulation was significantly faster in Aß- ε4 compared to Aß- ε3 and Aß- ε2. Rates of Aß accumulation did not differ significantly between Aß+ groups. Older age was associated with higher rates of Aß accumulation in the Aß- group. CONCLUSIONS: ε4 carriage and older age were predictors of longitudinal Aß accumulation within the Aß- group but not the Aß+ group. ε2 carriage was protective against longitudinal Aß accumulation within the Aß- group. genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting Aß accumulation before abnormal levels are reached.
[Mh] Termos MeSH primário: Envelhecimento/genética
Envelhecimento/metabolismo
Peptídeos beta-Amiloides/metabolismo
Apolipoproteína E2/genética
Apolipoproteína E4/genética
Encéfalo/metabolismo
[Mh] Termos MeSH secundário: Idoso
Compostos de Anilina
Apolipoproteína E3/genética
Encéfalo/diagnóstico por imagem
Estudos Transversais
Etilenoglicóis
Feminino
Heterozigoto
Seres Humanos
Modelos Lineares
Masculino
Tomografia por Emissão de Pósitrons
Compostos Radiofarmacêuticos
Fatores de Risco
Seio Sagital Superior
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Aniline Compounds); 0 (Apolipoprotein E2); 0 (Apolipoprotein E3); 0 (Apolipoprotein E4); 0 (Ethylene Glycols); 0 (Radiopharmaceuticals); 6867Q6IKOD (florbetapir)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1212/WNL.0000000000004336


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[PMID]:28779679
[Au] Autor:Lai C; Tang S; Yang B; Gao Z; Li X; Yong Q
[Ad] Endereço:Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037, China; College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.
[Ti] Título:Enhanced enzymatic saccharification of corn stover by in situ modification of lignin with poly (ethylene glycol) ether during low temperature alkali pretreatment.
[So] Source:Bioresour Technol;244(Pt 1):92-99, 2017 Nov.
[Is] ISSN:1873-2976
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A novel pretreatment process of corn stover was established in this study by in situ modification of lignin with poly (ethylene glycol) diglycidyl ether (PEGDE) during low temperature alkali pretreatment. The addition of PEGDE obviously improved the enzymatic hydrolysis by covalently modifying the residual lignins in substrates. Under the optimized conditions (pretreated with 10% (w/w) NaOH and 10% (w/w) PEGDE at 70°C for 2.5h), the total fermentable sugar yield was increased by 46.4%, from 23.7g to 34.7g per 100g raw materials. Additionally, the remaining activities of exo-glucanase and ß-glucosidase in supernatant were increased by 58.6% and 40.6% respectively, demonstrating that the enhancement of enzymatic hydrolysis was mainly due to the alleviation of enzyme non-productive binding. Although the isolated lignin modified with PEGDE enhanced the enzymatic hydrolysis of substrates as well, this in situ lignin modification provided an efficient but simple way to improve enzymatic saccharification.
[Mh] Termos MeSH primário: Etilenoglicóis
Lignina
Zea mays
[Mh] Termos MeSH secundário: Álcalis
Éteres
Hidrólise
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkalies); 0 (Ethers); 0 (Ethylene Glycols); 9005-53-2 (Lignin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE


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[PMID]:28689762
[Au] Autor:Fowles J; Banton M; Klapacz J; Shen H
[Ad] Endereço:Tox-Logic Consulting, Santa Rosa, CA, USA. Electronic address: tox-logic@hotmail.com.
[Ti] Título:A toxicological review of the ethylene glycol series: Commonalities and differences in toxicity and modes of action.
[So] Source:Toxicol Lett;278:66-83, 2017 Aug 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This review summarizes the hazards, exposure and risk that are associated with ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and penta-EG. All of the EGs are quickly and extensively absorbed following ingestion and inhalation, but not by the dermal route. Metabolism involves oxidation to the mono- and dicarboxylic acids. Elimination is primarily through the urine as the parent compound or the monoacid, and, in the case of EG, also as exhaled carbon dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS depression and metabolic acidosis in humans and rodents; the larger molecules being proportionally less acutely toxic on a strict mg/kg basis. Species differences exist in the metabolism and distribution of toxic metabolites, particularly with the formation of glycolic acids and oxalates (OX) from EG and diethylene glycol (DEG); OX are not formed to a significant degree in higher ethylene glycols. Among rodents, rats are more sensitive than mice, and males more sensitive than females to the acute and repeated-dose toxicity of EG. The metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are associated with nephrotoxicity in humans and rodents following single and repeated exposures. However, physiological and metabolic differences in the rate of formation of GA, DGA and OX and their distribution result in EG and DEG causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity indicates that EG and its higher oligomers are not anticipated to be embryotoxic in humans at environmentally relevant doses. None of the compounds present developmental toxicity concerns at doses that do not also cause significant maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented, which considers the common and distinct toxicological properties of each compound. It is concluded that EGs pose no risk to human health as a result of their intended use patterns.
[Mh] Termos MeSH primário: Etilenoglicóis/toxicidade
[Mh] Termos MeSH secundário: Animais
Biotransformação
Relação Dose-Resposta a Droga
Etilenoglicóis/farmacocinética
Seres Humanos
Camundongos
Estrutura Molecular
Coelhos
Ratos
Medição de Risco
Especificidade da Espécie
Relação Estrutura-Atividade
Testes de Toxicidade/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Ethylene Glycols)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE


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[PMID]:28575149
[Au] Autor:Yew B; Nation DA; Alzheimer's Disease Neuroimaging Initiative
[Ad] Endereço:Department of Psychology, University of Southern California, Los Angeles, CA, USA.
[Ti] Título:Cerebrovascular resistance: effects on cognitive decline, cortical atrophy, and progression to dementia.
[So] Source:Brain;140(7):1987-2001, 2017 Jul 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:See Markus (doi:10.1093/awx161) for a scientific commentary on this article.Evidence for vascular contributions to Alzheimer's disease has been increasingly identified, with increased blood pressure and decreased cerebral blood flow both linked to in vivo biomarkers and clinical progression of Alzheimer's disease. We therefore hypothesized that an elevated ratio of blood pressure to cerebral blood flow, indicative of cerebrovascular resistance, would exhibit earlier and more widespread associations with Alzheimer's disease than cerebral blood flow alone. Further, we predicted that increased cerebrovascular resistance and amyloid retention would synergistically influence cognitive performance trajectories, independent of neuronal metabolism. Lastly, we anticipated associations between cerebrovascular resistance and later brain atrophy, prior to amyloid accumulation. To evaluate these hypotheses, we investigated associations between cerebrovascular resistance and amyloid retention, cognitive decline, and brain atrophy, controlling for neuronal metabolism. North American older adults (n = 232) underwent arterial spin labelling magnetic resonance imaging to measure regional cerebral blood flow in brain regions susceptible to ageing and Alzheimer's disease. An estimated cerebrovascular resistance index was then calculated as the ratio of mean arterial pressure to regional cerebral blood flow. Positron emission tomography with 18F-florbetapir and fludeoxyglucose was used to quantify amyloid retention and neuronal metabolism, respectively. Cognitive performance was evaluated via annual assessments of global cognition, memory, and executive function. Results indicated diminished inferior parietal and temporal cerebral blood flow for patients with Alzheimer's disease (n = 33) relative to both non-demented groups, but no cerebral blood flow differences between non-demented amyloid-positive (n = 87) and amyloid-negative (n = 112) cases. In contrast, the cerebrovascular resistance index was significantly elevated in amyloid-positive versus amyloid-negative cases, with additional elevation in patients with Alzheimer's disease. Furthermore, cerebrovascular resistance index group differences were of greater statistical effect size and encompassed a greater number of brain regions than those for cerebral blood flow alone. Cognitive decline over 2-year follow-up was accelerated by elevated baseline cerebrovascular resistance index, particularly for amyloid-positive individuals. Increased baseline cerebrovascular resistance index also predicted greater progression to dementia, beyond that attributable to amyloid-positivity. Finally, increased cerebrovascular resistance index predicted greater regional atrophy among non-demented older adults who were amyloid-negative. Findings suggest that increased cerebrovascular resistance may represent a previously unrecognized contributor to Alzheimer's disease that is independent of neuronal hypometabolism, predates changes in brain perfusion, exacerbates and works synergistically with amyloidosis to produce cognitive decline, and drives amyloid-independent brain atrophy during the earliest stage of disease.
[Mh] Termos MeSH primário: Doença de Alzheimer/fisiopatologia
Doença de Alzheimer/psicologia
Atrofia/patologia
Encéfalo/fisiopatologia
Córtex Cerebral/patologia
Disfunção Cognitiva/fisiopatologia
Resistência Vascular/fisiologia
[Mh] Termos MeSH secundário: Idoso
Doença de Alzheimer/complicações
Amiloide/metabolismo
Compostos de Anilina/metabolismo
Pressão Sanguínea/fisiologia
Encéfalo/irrigação sanguínea
Encéfalo/metabolismo
Disfunção Cognitiva/complicações
Disfunção Cognitiva/patologia
Progressão da Doença
Etilenoglicóis/metabolismo
Feminino
Fluordesoxiglucose F18/metabolismo
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Neuroimagem
Neurônios/metabolismo
Testes Neuropsicológicos
Tomografia por Emissão de Pósitrons
Marcadores de Spin
Substância Branca/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid); 0 (Aniline Compounds); 0 (Ethylene Glycols); 0 (Spin Labels); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 6867Q6IKOD (florbetapir)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx112


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[PMID]:28558099
[Au] Autor:Farrell ME; Kennedy KM; Rodrigue KM; Wig G; Bischof GN; Rieck JR; Chen X; Festini SB; Devous MD; Park DC
[Ad] Endereço:Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas.
[Ti] Título:Association of Longitudinal Cognitive Decline With Amyloid Burden in Middle-aged and Older Adults: Evidence for a Dose-Response Relationship.
[So] Source:JAMA Neurol;74(7):830-838, 2017 Jul 01.
[Is] ISSN:2168-6157
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Presently, the clinical standard for reporting the results of an amyloid positron emission tomography scan is to assign a dichotomous rating of positive or negative for the presence of amyloid. In a 4-year longitudinal study, we investigated whether using a continuous measure of the magnitude of baseline amyloid burden would provide valuable information about the rate of future cognitive decline over the subsequent 4 years compared with a dichotomous measure in middle-aged and older adults. Objective: To examine whether a continuous, dose-response relationship between amyloid burden and cognitive decline was present among middle-aged and older adults. Design, Setting, and Participants: This cohort study included 174 participants from the Dallas Lifespan Brain Study who were 40 to 89 years old at the beginning of the study, were cognitively normal at baseline (a Mini-Mental State Examination score of 26 or higher) with no history of neurological or psychiatric disorders, and had completed amyloid imaging ([18F]-florbetapir) at baseline and cognitive assessments at baseline and a 4-year follow-up. Continuous amyloid burden was measured as the mean cortical standardized uptake value ratio (SUVR) at baseline. Main Outcomes and Measures: Linear mixed models assessed the effect of increasing baseline amyloid over time (SUVR × time interaction) on episodic memory, reasoning, processing speed, vocabulary, and Mini-Mental State Examination performance. Age, sex, education, apolipoprotein ε4, and the random effect of intercepts were included as covariates. Results: The mean (SD) age for all participants (n = 174) was 66.44 (11.74) years, and 65 participants (37%) were men. The primary analyses yielded significant SUVR × time interactions in episodic memory, processing speed, vocabulary, and Mini-Mental State Examination performance, but not in reasoning performance. Higher baseline SUVR projected greater cognitive decline over 4 years. When controlling for variance related to a dichotomized positive/negative classification, most effects on cognition remained. Dichotomized amyloid status alone yielded fewer significant effects of amyloid on cognitive decline than continuous SUVR. Among amyloid-positive participants, increasing baseline SUVR predicted an increasing decline in episodic memory, but other effects on cognition were more limited. Finally, higher baseline amyloid burden among middle-aged adults was related to changes in vocabulary, with the effect driven by 3 apolipoprotein ε4 homozygotes. Conclusions and Relevance: These results suggest that the magnitude of amyloid burden at baseline is associated with the rate of cognitive decline over 4 years and potentially provides important information about the rate of future cognitive decline that is not available from a dichotomous positive/negative categorization.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/metabolismo
Disfunção Cognitiva
Progressão da Doença
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Compostos de Anilina
Disfunção Cognitiva/diagnóstico por imagem
Disfunção Cognitiva/metabolismo
Disfunção Cognitiva/fisiopatologia
Etilenoglicóis
Seres Humanos
Estudos Longitudinais
Masculino
Meia-Idade
Tomografia por Emissão de Pósitrons
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Aniline Compounds); 0 (Ethylene Glycols); 6867Q6IKOD (florbetapir)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1001/jamaneurol.2017.0892


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[PMID]:28542444
[Au] Autor:Akhtar RS; Xie SX; Chen YJ; Rick J; Gross RG; Nasrallah IM; Van Deerlin VM; Trojanowski JQ; Chen-Plotkin AS; Hurtig HI; Siderowf AD; Dubroff JG; Weintraub D
[Ad] Endereço:Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
[Ti] Título:Regional brain amyloid-ß accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.
[So] Source:PLoS One;12(5):e0177924, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-ß accumulation to these problems is unclear. We hypothesized that amyloid-ß PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-ß plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-ß amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/metabolismo
Encéfalo/metabolismo
Encéfalo/patologia
Transtornos Cognitivos/metabolismo
Transtornos Cognitivos/patologia
Cognição/fisiologia
Demência/metabolismo
[Mh] Termos MeSH secundário: Idoso
Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Amiloide/metabolismo
Compostos de Anilina/administração & dosagem
Demência/patologia
Etilenoglicóis/administração & dosagem
Feminino
Seres Humanos
Masculino
Meia-Idade
Doença de Parkinson/metabolismo
Doença de Parkinson/patologia
Placa Amiloide/metabolismo
Tomografia por Emissão de Pósitrons/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid); 0 (Amyloid beta-Peptides); 0 (Aniline Compounds); 0 (Ethylene Glycols); 6867Q6IKOD (florbetapir)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177924


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[PMID]:28507436
[Au] Autor:Liu J; Zeng Y; Shi S; Xu L; Zhang H; Pathak JL; Pan Y
[Ad] Endereço:School and Hospital of Stomatology.
[Ti] Título:Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone.
[So] Source:Int J Nanomedicine;12:3561-3575, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) -PEG-PCL nanoparticles by cancer cells. (Asp) -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10-800 µg/mL. (Asp) -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) -PEG-PCL. (Asp) -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Neoplasias Ósseas/tratamento farmacológico
Portadores de Fármacos/química
Nanopartículas/química
Polímeros/química
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Neoplasias Ósseas/secundário
Linhagem Celular Tumoral
Curcumina/administração & dosagem
Portadores de Fármacos/administração & dosagem
Estabilidade de Medicamentos
Durapatita/metabolismo
Etilenoglicóis/administração & dosagem
Etilenoglicóis/química
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Injeções Intravenosas
Camundongos Endogâmicos BALB C
Microscopia Eletrônica de Transmissão
Nanopartículas/administração & dosagem
Peptídeos/química
Poliésteres/administração & dosagem
Poliésteres/química
Polímeros/administração & dosagem
Ratos Sprague-Dawley
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Carriers); 0 (Ethylene Glycols); 0 (Peptides); 0 (Polyesters); 0 (Polymers); 0 (poly(epsilon-caprolactone)-b-poly(ethylene glycol)); 26063-13-8 (polyaspartate); 91D9GV0Z28 (Durapatite); IT942ZTH98 (Curcumin)
[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:170517
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S133787


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[PMID]:28507434
[Au] Autor:Yeom DW; Chae BR; Son HY; Kim JH; Chae JS; Song SH; Oh D; Choi YW
[Ad] Endereço:College of Pharmacy, Chung-Ang University, Seoul.
[Ti] Título:Enhanced oral bioavailability of valsartan using a polymer-based supersaturable self-microemulsifying drug delivery system.
[So] Source:Int J Nanomedicine;12:3533-3545, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was successfully formulated to enhance the dissolution and oral absorption of valsartan (VST), a poorly water-soluble drug, while reducing the total quantity for administration. Poloxamer 407 is a selectable, supersaturating agent for VST-containing SMEDDS composed of 10% Capmul MCM, 45% Tween 20, and 45% Transcutol P. The amounts of SMEDDS and Poloxamer 407 were chosen as formulation variables for a 3-level factorial design. Further optimization was established by weighting different levels of importance on response variables for dissolution and total quantity, resulting in an optimal S-SMEDDS in large quantity (S-SMEDDS_LQ; 352 mg in total) and S-SMEDDS in reduced quantity (S-SMEDDS_RQ; 144.6 mg in total). Good agreement was observed between predicted and experimental values for response variables. Consequently, compared with VST powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed excellent in vitro dissolution and in vivo oral bioavailability in rats. The magnitude of dissolution and absorption-enhancing capacities using quantity-based comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or suspension. Thus, we concluded that, in terms of developing an effective SMEDDS preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate.
[Mh] Termos MeSH primário: Emulsões/administração & dosagem
Valsartana/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Disponibilidade Biológica
Caprilatos/química
Sistemas de Liberação de Medicamentos/métodos
Emulsões/química
Emulsões/farmacocinética
Etilenoglicóis/química
Glicerídeos/química
Masculino
Polímeros
Polissorbatos/química
Ratos Sprague-Dawley
Solubilidade
Valsartana/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caprylates); 0 (Emulsions); 0 (Ethylene Glycols); 0 (Glycerides); 0 (Polymers); 0 (Polysorbates); 80M03YXJ7I (Valsartan); A1A1I8X02B (carbitol); VFU0OU98LO (monooctanoin)
[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:170517
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S136599



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