RESUMO
Alzheimer's disease (AD) is characterized by the accumulation of aggregated amyloid peptides in the brain parenchyma and within the walls of cerebral vessels. The hippocampus-a complex brain structure with a pivotal role in learning and memory-is implicated in this disease. However, there is limited data on vascular changes during AD pathological degeneration in this susceptible structure, which has distinctive vascular traits. Our aim was to evaluate vascular alterations in the hippocampus of AD patients and PDAPP-J20 mice-a model of AD-and to determine the impact of Aß40 and Aß42 on endothelial cell activation. We found a loss of physical astrocyte-endothelium interaction in the hippocampus of individuals with AD as compared to non-AD donors, along with reduced vascular density. Astrocyte-endothelial interactions and levels of the tight junction protein occludin were altered early in PDAPP-J20 mice, preceding any signs of morphological changes or disruption of the blood-brain barrier in these mice. At later stages, PDAPP-J20 mice exhibited decreased vascular density in the hippocampus and leakage of fluorescent tracers, indicating dysfunction of the vasculature and the BBB. In vitro studies showed that soluble Aß40 exposure in human brain microvascular endothelial cells (HBMEC) was sufficient to induce NFκB translocation to the nucleus, which may be linked with an observed reduction in occludin levels. The inhibition of the membrane receptor for advanced glycation end products (RAGE) prevented these changes in HBMEC. Additional results suggest that Aß42 indirectly affects the endothelium by inducing astrocytic factors. Furthermore, our results from human and mouse brain samples provide evidence for the crucial involvement of the hippocampal vasculature in Alzheimer's disease.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Astrócitos , Hipocampo , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Humanos , Hipocampo/patologia , Hipocampo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Masculino , Idoso , Camundongos Transgênicos , Feminino , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Idoso de 80 Anos ou mais , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/metabolismo , Camundongos , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
A novel technique has been devised for the synthesis of microporous α-Cr(2)O(3) (eskolaite). The technique was based on the formation of amorphous-Cr(2)O(3) onto microporous activated carbon through adsorption-reduction of dichromate ions (Cr(2)O(7)(2-)) at the activated carbon/aqueous solution interface. Then, the Cr(2)O(3)-loaded carbon was thermally processed under oxidizing conditions to remove the carbon and recover the chromium oxide as α-Cr(2)O(3). Both the Cr(2)O(3)-loaded carbon and the synthetic product were characterized by XRD, SEM, surface area and pore volume measurements. The synthetic eskolaite assayed 97.3% Cr(2)O(3) and its specific surface area was 15.48 m(2)/g and pore size of 16.1 Å.
RESUMO
We present in this paper two cases of auto-immune hemolytic anemie caused by ingestion of alpha-metildope Coombs' test positive. We suggest to make Coombs test to every patient in whose treatment has been included the use of alpha-metildope.