BACKGROUND AND PURPOSEPharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K + (mitoKATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca 2+ homeostasis during PPC, particularly changes in Ca 2+ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca 2+ channels. EXPERIMENTAL APPROACHPPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca 2+ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the a1c subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTSPPC was accompanied by a 50% reduction in a1c subunit levels, and by a reversible fall in L-type current amplitude and Ca 2+ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the a1c subunit and Ca 2+ channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONSPPC downregulated the a1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca 2+ channel, which in turn reduced Ca 2+ influx, which may attenuate Ca 2+ overload during reperfusion. Abbreviations

BackgroundThe solution for infusion bags prepared by the pharmacy contains an unknown and variable volume of solution in order to keep a minimum volume.PurposeTo determine the potential under-dosing of oncology patients related to the loss of cytostatic drugs in the remaining volume of the solution for infusion bags.Material and methodsProspective observational study. We randomly assessed 50 cytostatics mixtures prepared by the Pharmacy Service.Studied variables: total dose of cytostatic drug prescribed, total volume of the mixture and the volume remaining after the intravenous administration. The remaining volume was indicated by the infusion pump. The total volume was obtained from the cytostatics compounding program (Farmatools).As we found from the literature, it is acceptable that up to 5% of the total dose prescribed by the oncologist may be lost in the process of IV administration.ResultsOverfilling was detected in all 50 solutions (100%). In 10 cases (20%), the volume of the solution remaining after administration contained a cytostatic dose less than 5% of the total dose. In 40 cases (80%) the remaining dose was higher than 5%. In 16 of these 40 cases (40%), the non-infused dose was higher than 10% of the total dose (32% of the total of mixtures) and in 6 cases (15% of these 40 cases) was higher than 20% of the dose prescribed (10% of all the preparations).ConclusionThe solutions for infusion bags contain more fluid than that specified on the commercial label. If this is not corrected for, the total volume of the mixture will be greater than that shown on the label issued by the Pharmacy Service. The measure adopted is to program an additional volume in the infusion pump, while maintaining the speed shown on the label, so that the entire mixture is administered to the patient.References and/or acknowledgementsL. SantosNo conflict of interest.