RESUMO
There is an ongoing debate regarding the culprits of cytotoxicity associated with amyloid disorders. Although small pre-fibrillar amyloid oligomers have been implicated as the primary toxic species, the fibrillar amyloid material itself can also induce cytotoxicity. To investigate membrane disruption and cytotoxic effects associated with intact and fragmented fibrils, the novel in situ spectroscopic technique of Total Internal Reflection Ellipsometry (TIRE) was used. Fibril lipid interactions were monitored using natively derived whole cell membranes as a model of the in vivo environment. We show that fragmented fibrils have an increased ability to disrupt these natively derived membranes by causing a loss of material from the deposited surface when compared with unfragmented fibrils. This effect was corroborated by observations of membrane disruption in live cells, and by dye release assay using synthetic liposomes. Through these studies we demonstrate the use of TIRE for the analysis of protein-lipid interactions on natively derived lipid surfaces, and provide an explanation on how amyloid fibrils can cause a toxic gain of function, while entangled amyloid plaques exert minimal biological activity.
Assuntos
Amiloide/metabolismo , Amiloide/toxicidade , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Fenômenos Ópticos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Linhagem Celular Tumoral , Humanos , Lipossomos/metabolismo , Muramidase/metabolismo , Muramidase/toxicidade , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade , Ligação Proteica , alfa-Sinucleína/metabolismo , alfa-Sinucleína/toxicidadeRESUMO
BACKGROUND: Our aim was to document how often travel histories were taken and the quality of their content. METHODS: Patients admitted over 2 months to acute medical units of two hospitals in the Northwest of England with a history of fever, rash, diarrhea, vomiting, jaundice, or presenting as "unwell post-travel" were identified. The initial medical clerking was assessed. RESULTS: A total of 132 relevant admissions were identified. A travel history was documented in only 26 patients (19.7%). Of the 16 patients who had traveled, there was no documentation of pretravel advice or of sexual/other activities abroad in 15 (93.8%) and 12 (75.0%) patients, respectively. CONCLUSIONS: There needs to be better awareness and education about travel-related illness and the importance of taking an adequate travel history.
