In vitro circuit stability of 5-fluorouracil and oxaliplatin in support of hyperthermic isolated hepatic perfusion.

Over the years, a large number of drugs have been used in isolated perfusion of extremities or organs. To interpret the pharmacokinetics of these drugs correctly, the contributions of tissue or organ clearance and chemical degradation, respectively, to overall drug elimination from the circuit need to be identified. In support of a phase I clinical trial of isolated hepatic perfusion (IHP), delivering 5-fluorouracil (5-FU) and oxaliplatin to patients with colorectal cancer hepatic metastases, we aimed to characterize the stability of 5-FU and oxaliplatin in the IHP circuit. Stability of 5-FU and oxaliplatin was assessed in human blood, lactated Ringer infusion (LRI), and in an in vitro IHP circuit consisting of both blood and LRI. Samples were analyzed with liquid chromatography tandem mass spectrometry (5-FU) and atomic absorption spectrophotometry (oxaliplatin). 5-FU was stable under all tested in vitro conditions, but ultrafilterable platinum concentrations decreased slowly with a half-life of 85 minutes in both IHP perfusate and whole blood. The stability of 5-FU in the media containing blood is likely attributable to saturation of dihydropyrimidine dehydrogenase. The decrease of ultrafilterable platinum in blood-containing media with an 85 minutes half-life is in agreement with previous reports on oxaliplatin biotransformation. Oxaliplatin and 5-FU are sufficiently stable in the circuit for the 1-hour perfusion in ongoing and planned clinical trials.

Dynamics of social behavior in fruit fly larvae.

We quantified the extent and dynamics of social interactions among fruit fly larvae over time. Both a wild-type laboratory population and a recently-caught strain of larvae spontaneously formed social foraging groups. Levels of aggregation initially increased during larval development and then declined with the wandering stage before pupation. We show that larvae aggregated more on hard than soft food, and more at sites where we had previously broken the surface of the food. Groups of larvae initiated burrowing sooner than solitary individuals, indicating that one potential benefit of larval aggregations is an improved ability to dig and burrow into the food substrate. We also show that two closely related species, D. melanogaster and D. simulans, differ in their tendency to aggregate, which may reflect different evolutionary histories. Our protocol for quantifying social behavior in larvae uncovered robust social aggregations in this simple model, which is highly amenable to neurogenetic analyses, and can serve for future research into the mechanisms and evolution of social behavior.