Doxorubicin in vivo rapidly alters expression and translation of myocardial electron transport chain genes, leads to ATP loss and caspase 3 activation.

Background: Doxorubicin is one of the most effective anti-cancer drugs but its use is limited by cumulative cardiotoxicity that restricts lifetime dose. Redox damage is one of the most accepted mechanisms of toxicity, but not fully substantiated. Moreover doxorubicin is not an efficient redox cycling compound due to its low redox potential.

Pivotal role for two electron reduction in 2,3-dimethoxy-1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone metabolism and kinetics in vivo that prevents liver redox stress.

2,3-dimethoxy-1,4-naphthoquinone (CAS-RN 6959-96-3) (DMNQ) and 2-methyl-1,4-naphthoquinone (CAS-RN 58-27-5) (MNQ:menadione) are effective one electron redox cycling chemicals in vitro. In addition, in vitro MNQ forms a thioether conjugate with glutathione by nucleophilic attack at the third carbon. In contrast, here we demonstrate that in vivo the major metabolic route is directly to the dihydronaphthoquinone for both DMNQ and MNQ followed by conjugation to mono- and di-glucuronides and sulfate.

Over-complete discrete wavelet transformation of the normal auditory brainstem response improves prediction of outcome following severe acute closed head injury.

Previous research has shown that complex statistical analysis (discriminant function analysis) of a 'normal' auditory brainstem response (ABR) result can improve this measure's ability to predict subject outcome following severe acute closed head injury (ACHI). We hypothesized that adding the ABR's time-frequency information to such an analysis would improve this predictive value even further. 'Normal' ABR results were sampled from 69 severe ACHI subjects (22 of whom died and 47 of whom lived) and their time-frequency information extracted using an over-complete discrete wavelet transformation (OCDWT).