Thirty-three healthy individuals participated in an open-label, randomized, three-way crossover study designed to compared the bioavailability of a single 200-mg oral dose of itraconazole when administered alone or after treatment with ranitidine, both with and without coadministration of a cola beverage. Each treatment phase was separated by a 2-week washout period. Participants pretreated with ranitidine were required to have a gastric pH of at least 6.0 before receiving itraconazole. An analysis of the area under the curve (AUC) and peak plasma concentration (Cmax) data indicated that the bioavailability of itraconazole was significantly reduced when the gastric pH was increased by pretreatment with ranitidine but showed that this effect was counteracted by the coadministration of an acidic solution (e.g., a cola beverage) that transiently reduced the gastric pH. These findings suggest that the coadministration of an acidic beverage with itraconazole may be an effective approach in improving the bioavailability of itraconazole in patients who are hypochlorhydric or who are taking gastric acid suppressants.

The act of feeding in mammals can generate such powerful cues for peripheral organs that, under certain conditions, they can override the entraining signals coming from the clock in the brain. Restricting the feeding time to the inactivity period, for example, can completely and quickly reverse the rhythms of gene expression in the liver. This manipulation does not affect the central oscillator in the suprachiasmatic nucleus, which is phase-locked to the light-dark cycle, but does release the peripheral oscillations in the liver from central control. It seems reasonable to predict the existence of one or more immediate response systems designed to sense the need to acutely reverse the sequence of absorptive and postabsorptive phases in the liver. In this study, the authors monitored the posttranslational activation of the sterol response element binding proteins from a circadian point of view to evaluate the role they might play in the circadian organization of the liver transcriptome as well as in the reversal of hepatic physiology that accompanies diurnal restricted feeding. This study highlights a possible direct link between the immediate effects of food consumption on the level of key membrane and humoral factors and the expression status of a set of coordinately regulated target genes in the liver.

No abstract

Far-field exposures of male albino rats to 2.45-GHz microwaves (10-microseconds pulses, 100 pps) at a low average power density (10 mW/cm2; SAR approximately 2 W/kg) and short durations (30-120 min) resulted in increased uptakes of tracer through the blood-brain barrier (BBB). The uptake of systemically administered rhodamine-ferritin complex by capillary endothelial cells (CECs) of the cerebral cortex was dependent on power density and on duration of exposure. At 5 mW/cm2, for example, a 15-min exposure had no effect. Near-complete blockade of uptake resulted when rats were treated before exposure to microwaves with a single dose of colchicine, which inhibits microtubular function. A pinocytotic-like mechanism is presumed responsible for the microwave-induced increase in BBB permeability.