Size and composition of synthetic calcium sulfate beads influence dissolution and elution rates in vitro.

Treatments of osteomyelitis lag behind bacterial resistance to antibiotics. We tested different-sized calcium sulfate beads and their ability to elute multiple antibiotics in vitro as a possible method to improve the therapeutic delivery in patients. Two sizes of calcium sulfate beads (4.8 and 3.0 mm diameter) that contained vancomycin, tobramycin, or both were dissolved in phosphate-buffered saline, and the rate of dissolution by weight and antibiotic elution by the disc diffusion assay and high-pressure liquid chromatography were measured. The 4.8 mm beads showed significantly higher dissolution rates relative to the 3.0 mm beads (2.3 mg/day vs. 1.3 mg/day). While the vancomycin-loaded 4.8 mm beads eluted for a longer time relative to the 3.0 mm beads (20 days vs. 10 days), the smaller beads had threefold higher elution for the first 2 days, before dropping to near zero elution by day 4. The presence of tobramycin extended the elution of the vancomycin to day 40, which closely matches the recommended 6 weeks to treat orthopedic staphylococcus infections. These data suggest that size and content of the bead are variables that could affect their clinical success, and both could be exploited to tailor treatments of specific infections and injuries.

Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster.

Disrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT1A,7 agonist, 8-OH-DPAT. To explore the basis of these effects in the whole animal, we used microdialysis to characterize the pharmacokinetics of intraperitoneal injection of EtOH in the hamster SCN extracellular fluid compartment and then studied the effects of such EtOH treatment on photic and serotonergic phase resetting of the circadian locomotor activity rhythm. Peak EtOH levels (approximately 50 mM) from a 2 g/kg injection occurred within 20-40 min with a half-life of approximately 3 h. EtOH treatment dose-dependently attenuated photic phase advances but had no effect on phase delays and, contrary to in vitro findings, markedly attenuated 8-OH-DPAT-induced phase advances. In a complementary experiment using reverse microdialysis to deliver a timed SCN perfusion of EtOH during a phase-advancing light pulse, the phase advances were blocked, similar to systemic EtOH treatment. These results are evidence that acute EtOH significantly affects photic and nonphotic phase-resetting responses critical to circadian clock regulation. Notably, EtOH inhibition of photic signaling is manifest through direct action in the SCN. Such actions could underlie the disruption of circadian rhythmicity associated with alcohol abuse.