Transmissible subacute spongiform encephalopathies (TSSE) are neurodegenerative diseases characterized by the presence of a modified, partially proteinase-resistant host protein, PrP s~, which accumulates in the brains of infected individuals. Recently it has been reported that amphotericin B (AmB) treatment of hamsters infected with scrapie strain 263K prolongs the incubation period of the disease, and dissociates in vivo replication of the scrapie agent from PrP s~ accumulation. We report here on data obtained after treatment with AmB and one of its derivatives, MS-8209, in experimental scrapie of mouse and hamster. Treatment was carried out by the intraperitoneal route 6 days per week, at three different dosages initiated at the time of infection. Two regimens were used: during the early time of infection or throughout the experimental infection. Results indicate that MS-8209 was as efficient as AmB in prolonging the incubation time and decreasing PrP se accumulation in the hamster scrapie model. A dose-dependent response was observed in mice treated early after experimental infection. At a dose of 2.5 mg/kg, MS-8209 significantly prolonged the incubation period (by 11.9 %). In longterm treatment of mice, MS-8209 and AmB markedly reduced PrP se levels in the preclinical stage of the disease. These data demonstrate that the effect of AmB is not restricted to one model (hamster-263K). This regimen leads to an inversion of the PrP s~ to proteinasesensitive protein (PrP sens) ratio, suggesting PrP senS (presumably cellular PrP c) accumulation occurs before its conversion into PrP sc. As it has been shown that AmB does not modify the infectivity titre, we conclude that the drugs could act by inhibiting either the interaction of the scrapie agent with PrP sen~ during the early times of infection or the conversion of PrP sen~ into prp s~.

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The experimental magnetic phase diagram of a Gd/Fe multilayer with compensation temperature is reported. Aligned and twisted states are shown to occur as predicted by theoretical simulations. The critical field for the aligned-to-twisted state transition is maximum at 4.2 K and goes to a minimum at the compensation temperature.The magnetic susceptibility is largest at the onset of the twisted state, with a maximum at the compensation temperature.The critical field for the aligned-to-twisted state transition increases when the thickness of the layers decreases.

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