Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial.

Background And Objectives: Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing.

Methods: This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland.

Adenine nucleotide metabolism and cell fate after oxidant exposure of rat cortical neurons: effects of inhibition of poly(ADP-ribose) polymerase.

We exposed cultured neurons prelabeled with 14C-adenine to H2O2 with or without the poly(ADP-ribose) polymerase (PARP) inhibitor 3,4-Dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ) to quantify its effects on acute ATP depletion, later ATP synthesis, cellular and nuclear morphology, extent of DNA fragmentation, and PARP cleavage. According to the extent of the acute ATP depletion, the exposures were classified as 'mild' (50 microM H2O2), 'moderate' (100-250 microM H2O2), or 'severe' (500 microM-1 mM H2O2) insults. Mild exposure had no significant effects on the parameters studied.

Biphasic ATP depletion caused by transient oxidative exposure is associated with apoptotic cell death in rat embryonal cortical neurons.

Hypoxia-ischemia leads to an acute depletion of high-energy phosphates in neonatal brain. After reperfusion, energy status is restored, but may show progressive secondary failure, associated with neuronal loss, brain damage, or death. Oxidants are produced on reperfusion.