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The oxidative stress resulting from the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the mitochondrial ATPase 6 gene was investigated in cultured skin fibroblasts from two patients presenting an isolated complex V deficiency. Taken as an index for superoxide overproduction, a huge induction of the superoxide dismutase (SOD) activity was(More)
Hyperpolarized magnetic resonance via dissolution dynamic nuclear polarization necessitates the transfer of the hyperpolarized molecules from the polarizer to the imager prior to in vivo measurements. This process leads to unavoidable losses in nuclear polarization, which are difficult to evaluate once the solution has been injected into an animal. We(More)
Dynamic nuclear polarization (DNP) can enhance the nuclear polarization, that is the difference between the populations of the Zeeman levels j ai and j bi of spin I = 1/2, by up to four orders of magnitude with respect to their Boltzmann distribution at room temperature. [1] This enhancement arises from thermal mixing, which is brought about by microwave(More)
Linear polymers of PARACEST agents were prepared by using classical free radical chain polymerization conditions. The Eu3+-polymers exhibited similar intermediate-to-slow water exchange and CEST characteristics as the Eu3+-monomers. This provided an avenue to lower the detection limit of these imaging agents substantially and makes them potentially useful(More)
Here we report that ferricytochrome c (cyt c(3+)) induces oxidation of hydroethidine (HE) and mitochondria-targeted hydroethidine (Mito-HE or MitoSOX Red) forming highly characteristic homo- and heterodimeric products. Using an HPLC-electrochemical (EC) method, several products were detected from cyt c(3+)-catalyzed oxidation of HE and Mito-HE and(More)
Herein we describe a high-throughput fluorescence and HPLC-based methodology for global profiling of reactive oxygen and nitrogen species (ROS/RNS) in biological systems. The combined use of HPLC and fluorescence detection is key to successful implementation and validation of this methodology. Included here are methods to specifically detect and quantitate(More)
Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its(More)
A new polarizing agent with superior performance in dynamic nuclear polarization experiments is introduced, and utilizes two TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) moieties connected through a rigid spiro tether (see structure). The observed NMR signal intensities were enhanced by a factor of 1.4 compared to those of TOTAPOL, a previously described(More)
A general synthetic route to prepare derivatives of the DEPMPO nitrone (5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide) functionalized at C-4 was established via the synthesis of 4-HMDEPMPO nitrone (5-diethoxyphosphoryl-4-hydroxymethyl-5-methyl-1-pyrroline-N-oxide) that was obtained from reduction of the nitro compound 1. (4R*,5S*)-4-HMDEPMPO was(More)
The synthesis and characterization of oxidized bis-thioketal-trispiro dinitroxide biradicals that orient the nitroxides in a rigid, approximately orthogonal geometry are reported. The biradicals show better performance as polarizing agents in dynamic nuclear polarization (DNP) NMR experiments as compared to biradicals lacking the constrained geometry. In(More)