Maternal vaccination against nicotine reduces nicotine distribution to fetal brain in rats.

Cigarette smoking during pregnancy is associated with a variety of adverse fetal outcomes. Nicotine is a likely contributor to these adverse effects, with fetal brain as one target organ. Vaccination of adult male rats against nicotine has been shown to reduce nicotine distribution to the brain.

Protection of superoxide-induced cholesterol oxidation by antioxidants in protic conditions.

It was found in previous experiments that superoxide in the presence of added hydrogen peroxide in protic conditions produces oxysterols. The oxysterols formed under these conditions were 7beta-ketocholesterol, 7alpha-hydroxycholesterol and 7beta-hydroxycholesterol. In the present experiments, the inhibitory effects of three antioxidants, alpha-tocopherol (alpha-T), butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), on the oxidation of cholesterol in the presence of superoxide anion, water and hydrogen peroxide were investigated.

Acetaminophen-induced suppression of hepatic AdoMet synthetase activity is attenuated by prodrugs of L-cysteine.

Administration of acetaminophen (ACP, 400 mg/kg, i.p.) to fasted, male Swiss-Webster mice caused a rapid 90% decrease in total hepatic glutathione (GSH) and a 58% decrease in mitochondrial GSH by 2 h post ACP.

Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine.

The effects of continuous nicotine infusion on nicotine self-administration (NSA) were studied in rats as a model of nicotine replacement therapy (NRT) in humans. A NSA model in which rats had 23-h/day access to nicotine was used to approximate nicotine access conditions in cigarette smokers. In order to estimate serum nicotine concentrations associated with NSA, arterial and venous serum nicotine concentrations were measured during a simulation of NSA.

N-hydroxybenzenecarboximidic acid derivatives: a new class of nitroxyl-generating prodrugs.

On the basis of the propensity of Piloty's acid to generate nitroxyl (HNO), we previously prepared a number of N,O-bisacylated Piloty's acid derivatives and showed that such prodrugs underwent a disproportionation reaction following ester hydrolysis to give an unstable intermediate that hydrolyzed to nitroxyl. To expand the versatility of this series, we desired some mixed N,O-diacylated Piloty's acid derivatives and devised a synthetic route to them. Such efforts led us, serendipitously, to a new series of heretofore unreported nitroxyl-generating compounds.