The analytical results show that there
exists a globally asymptotically stable infection-free state when the impulsive period T and drug-treatment proportion p satisfy R-0(p,T) < 1. The numerical simulation results indicate that there exist T and p such that R-0(p, T) < 1. Due to pulses, it would be difficult to obtain the optimal pulse interval in the age distribution of population. However, our results demonstrate the effect of the impulsive drug-treatment strategy on the dynamics of HIV/AIDS. (C) 2008 Elsevier Ltd. All rights reserved.”
“Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which LY2109761 price causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), selleck chemicals llc edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is corntrionly used to investigate
the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with irnageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects.
Methods: LF, EF and PA were radiolabeled with Re-188 and Tc-99m, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays selleckchem and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected Tc-99m-and T-123-labeled
toxins was performed in BALB/c mice.
Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6×10(4) binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either Tc-99m-or I-123-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. BiodistribUtion studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo.
Conclusions: The availability of Re-188 and Tc-99m-labeled PA, LF and EF toxins allowed us to confirm the number of PA binding sites per cell, to provide an estimate of the dissociation constant of PA for its receptor and to demonstrate tissue distribution of toxins in mice after intravenous injection. (C) 2008 Elsevier Inc. All rights reserved.