The feasibility of the determination of sub ppm to percentage levels of halogen elements (fluorine, chlorine, bromine, and iodine) in solid organic compounds and drug substances by double focusing sector field highresolution inductively coupled plasma mass spectrometry (HR-ICP-MS) was investigated. Samples were dissolved in appropriate solvents and then diluted in either deionized water or 5% (v/v) ammonium hydroxide. By applying medium or high resolution, the background counts can be lowered by up to five orders of magnitude compared to conventional quadrupole ICP-MS systems. The signal sensitivities and memory effects of all four elements in different solvents were compared and assessed. The methods were applied to the determination of sub ppm to percentage levels of F, Cl, Br and I in a series of organic compounds and Merck drug substances. The results were found to be in excellent-to-reasonable agreement with the known or theoretical values of these compounds or drug substances. The limit of detection in solution for F was estimated to be 5 mg ml 21 (medium resolution), and for Cl, Br and I was 3 (high resolution), 0.08 (high resolution) and 0.03 (high resolution) ng ml 21 , respectively.

Prion diseases are characterized by the conversion of the normal cellular prion protein (PrP C ) into a pathogenic isoform (PrP Sc ). PrP C binds copper, has superoxide dismutase (SOD)-like activity in vitro, and its expression aids in the cellular response to oxidative stress. However, the interplay between PrPs (PrP C , PrP Sc and possibly other abnormal species), copper, anti-oxidation activity and pathogenesis of prion diseases remain unclear. In this study, we reported dramatic depression of SOD-like activity by the af®nity-puri®ed PrPs from scrapie-infected brains, and together with signi®-cant reduction of Cu/Zn-SOD activity, correlates with signi®cant perturbations in the divalent metals contents. We also detected elevated levels of nitric oxide and superoxide in the infected brains, which could be escalating the oxidative modi®cation of cellular proteins, reducing gluathione peroxidase activity and increasing the levels of lipid peroxidation markers. Taken together, our results suggest that brain metal imbalances, especially copper, in scrapie infection is likely to affect the anti-oxidation functions of PrP and SODs, which, together with other cellular dysfunctions, predispose the brains to oxidative impairment and eventual degeneration. To our knowledge, this is the ®rst study documenting a physiological connection between brain metals imbalances, the anti-oxidation function of PrP, and aberrations in the cellular responses to oxidative stress, in scrapie infection.

No abstract

Catalysis-based signal amplification makes optical assays highly sensitive and widely useful in chemical and biochemical research. However, assays must be fine-tuned to avoid signal saturation, substrate depletion and nonlinear performance. Furthermore, once stopped, such assays cannot be restarted, limiting the dynamic range to two orders of magnitude with respect to analyte concentrations. In addition, abundant analytes are difficult to quantify under catalytic conditions due to rapid signal saturation. Herein, we report an approach in which a catalytic reaction competes with a concomitant inactivation of the catalyst or consumption of a reagent required for signal generation. As such, signal generation proceeds for a limited time, then autonomously and reversibly stalls. In two catalysis-based assays, we demonstrate restarting autonomously stalled reactions, enabling accurate measurement over five orders of magnitude, including analyte levels above substrate concentration. This indicates that the dynamic range of catalysis-based assays can be significantly broadened through competitive and reversible deactivation.

Alterations in MUC expression occur during colorectal tumorigenesis. The transformation process in MC and SRCC may be different from that in the traditional adenoma-carcinoma sequence.