RESUMO
The purpose of this study was to examine the relationship between language pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis complex (TSC). An advanced diffusion-weighted magnetic resonance imaging (MRI) was performed on 42 patients with TSC and 42 age-matched controls. Using a validated automatic method, white matter language pathways were identified and microstructural characteristics were extracted, including fractional anisotropy (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD had a lower FA than controls in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA, lower than the FA for those without ASD. Similarly, TSC patients without ASD had a greater MD than controls in the AF; TSC patients with ASD had even a higher MD, greater than the MD in those without ASD. It remains unclear why some patients with TSC develop ASD, while others have better language and socio-behavioral outcomes. Our results suggest that language pathway microstructure may serve as a marker of the risk of ASD in TSC patients. Impaired microstructure in language pathways of TSC patients may indicate the development of ASD, although prospective studies of language pathway development and ASD diagnosis in TSC remain essential.
Assuntos
Encéfalo/patologia , Transtornos Globais do Desenvolvimento Infantil/patologia , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/patologia , Esclerose Tuberosa/patologia , Adolescente , Adulto , Anisotropia , Criança , Transtornos Globais do Desenvolvimento Infantil/complicações , Pré-Escolar , Imagem de Tensor de Difusão , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Lactente , Idioma , Transtornos da Linguagem/patologia , Masculino , Esclerose Tuberosa/complicações , Adulto JovemRESUMO
Recently, a series of potent and selective neuronal nitric oxide synthase inhibitors containing two basic nitrogen atoms was reported (Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. J. Am. Chem. Soc. 2008, 130, 3900-3914). In an effort to improve their bioavailability, three compounds (2a-c) were designed with electron-withdrawing groups near one of the basic nitrogen atoms to lower its pK(a). Inhibition studies with these compounds showed that two of them not only retained most of the potency and selectivity of the best analogue of the earlier series, but also showed improved membrane permeability based on data from a cell-based assay.