ABSTRACT
Objective@#To analysis the alterations of CaM and its downstream factors in the brains of scrapie infected mice.@*Methods@#Using the methods of Western blot and immunohistochemistry assay to detect the levels and distributions of CaM, as well as the expressing alterations of the downstream substrates of CaM in the brains of mice infected with scrapie.@*Results@#Compared with the normal controls, the levels of CaM are significantly increased in the brains of scrapie-infected mice and particularly distributing in the regions of cortex, thamalus and cerebellum. Remarkable high levels of CaMKII, p-CaMKII and p-CaMKIV are observed in the brain homogenates of scrapie-infected mice. The regulatory protein of cAMP response element binding protein (CREB) and p-CERB are also increased, while the levels of BDNF which is regulated by p-CREB are obeviously downregulated.@*Conclusions@#The synthesis of BDNF may be influenced by the prion replication in neuron and further attenuates its neuronal protective features.
ABSTRACT
The aim of this investigation was to assess the in-vitro interaction of two antifungal agents, econazole-nitrate and chelerythrine, against ten fluconazole-resistant clinical isolates and one ATCC type strain 10231 of Candida albicans. The checkerboard microdilution method was performed according to the recommendations of the National Committee for Clinical Laboratory Standards, and the results were determined by visual examination. The interaction intensity was tested in all isolates using the fractional inhibitory concentration index [FICI]. These experiments showed synergism between econazole-nitrate and chelerythrine in antifungal activity against C. albicans, and no antagonistic activity was observed in any of the strains tested. Moreover, time-kill curves were performed with selected strains to confirm the positive interactions. The similarity between the results of the FICI values and the time-kill curves revealed that chelerythrine greatly enhances the antifungal effects of econazole-nitrate against isolates of C. albicans. This synergistic effect may markedly reduce the dose of econazole-nitrate required to treat candidiasis, thereby decreasing the econazole-nitrate toxic side effects. This novel synergism might provide a potential combination treatment against fungal infections