Assessment of the Activity of Decoquinate and Its Quinoline-O-Carbamate Derivatives against Toxoplasma gondii In Vitro and in Pregnant Mice Infected with T. gondii Oocysts

The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacterial and parasitic infections, most notably, coccidiosis in poultry and in ruminants. We have investigated the effects of treatment of Toxoplasma gondii in infected human foreskin fibroblasts (HFF) with DCQ. This induced distinct alterations in the parasite mitochondrion within 24 h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect. Based on the low half-maximal effective concentration (IC₅₀) of 1.1 nM and the high selectivity index of >5000, the efficacy of oral treatment of pregnant mice experimentally infected with T. gondii oocysts with DCQ at 10 mg/kg/day for 5 days was assessed. However, the treatment had detrimental effects, induced higher neonatal mortality than T. gondii infection alone, and did not prevent vertical transmission. Thus, three quinoline-O-carbamate derivatives of DCQ, anticipated to have better physicochemical properties than DCQ, were assessed in vitro. One such compound, RMB060, displayed an exceedingly low IC₅₀ of 0.07 nM, when applied concomitantly with the infection of host cells and had no impact on HFF viability at 10 µM. As was the case for DCQ, RMB060 treatment resulted in the alteration of the mitochondrial matrix and loss of cristae, but the changes became apparent at just 6 h after the commencement of treatment. After 48 h, RMB060 induced the expression of the bradyzoite antigen BAG1, but TEM did not reveal any other features reminiscent of bradyzoites. The exposure of infected cultures to 300 nM RMB060 for 52 days did not result in the complete killing of all tachyzoites, although mitochondria remained ultrastructurally damaged and there was a slower proliferation rate. The treatment of mice infected with T. gondii oocysts with RMB060 did reduce parasite burden in non-pregnant mice and dams, but vertical transmission to pups could not be prevented.     

Absorption cross-sections and lifetimes as a function of size in Si nanocrystals embedded in SiO2

The photoluminescence (PL) emission yield of Si nanocrystals embedded in SiO₂ depends on their size and on Si–SiO₂ interface passivation. In this work we aim at clarifying the relative importance of both contributions by studying lifetimes and absorption cross-sections as a function of size, for samples with and without passivation in forming gas. We find that while the PL lifetime increases steadily (quasi-linear dependence), the radiative lifetime increases exponentially with the nanocrystal size. Thus, as expected, radiative oscillator strengths are much smaller for large nanocrystals, but this reduction is partially compensated by a less effective quenching at interfacial non-radiative states. The absorption cross-section per nanocrystal rises as the nanocrystal size decreases, for all excitation wavelengths, implying that the variation of oscillator strength dominates over the reduction of the density of states. Passivation processes do not affect the emission mechanism and increase the emission yield while reducing the density of non-radiative recombination centers at the Si–SiO₂ interface (P_b centers).