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1.
Sci Rep ; 3: 2859, 2013 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-24091529

RESUMO

Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain - insights that would be difficult or impossible to extract by use of radiolabeled compounds.


Assuntos
Barreira Hematoencefálica/metabolismo , Imagem Molecular/métodos , Preparações Farmacêuticas/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Biomarcadores/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Modelos Animais de Doenças , Cloridrato de Erlotinib , Glioma/metabolismo , Glioma/patologia , Heme/metabolismo , Xenoenxertos , Humanos , Camundongos , Neovascularização Patológica , Imagem Óptica/métodos , Permeabilidade , Preparações Farmacêuticas/química , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacocinética , Quinazolinas/química , Quinazolinas/metabolismo , Quinazolinas/farmacocinética , Reprodutibilidade dos Testes
2.
J Exp Psychol Learn Mem Cogn ; 38(4): 1045-56, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22288816

RESUMO

Research from the adaptive memory framework shows that thinking about words in terms of their survival value in an incidental learning task enhances their free recall relative to other semantic encoding strategies and intentional learning (Nairne, Pandeirada, & Thompson, 2008). We found similar results. When participants used incidental survival encoding for a list of words (e.g., "Will this object enhance my survival if I were stranded in the grasslands of a foreign land?"), they produced better free recall on a surprise test than did participants who intentionally tried to remember those words (Experiment 1). We also found this survival processing advantage when the words were presented within the context of a survival or neutral story (Experiment 2). However, this advantage did not extent to memory for a story's factual content, regardless of whether the participants were tested by cued recall (Experiment 3) or free recall (Experiments 4-5). Listening to a story for understanding under intentional or incidental learning conditions was just as good as survival processing for remembering story content. The functionalist approach to thinking about memory as an evolutionary adaptation designed to solve reproductive fitness problems provides a different theoretical framework for research, but it is not yet clear if survival processing has general applicability or is effective only for processing discrete stimuli in terms of fitness-relevant scenarios from our past.


Assuntos
Atenção , Memória , Aprendizagem Verbal , Adolescente , Feminino , Humanos , Masculino , Pensamento , Adulto Jovem
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