Novel transcutaneous sensor combining optical tcPO2 and electrochemical tcPCO2 monitoring with reflectance pulse oximetry

This study investigated the accuracy, drift, and clinical usefulness of a new optical transcutaneous oxygen tension (tcPO2) measuring technique, combined with a conventional electrochemical transcutaneous carbon dioxide (tcPCO2) measurement and reflectance pulse oximetry in the novel transcutaneous OxiVenT™ Sensor. In vitro gas studies were performed to measure accuracy and drift of tcPO2 and tcPCO2. Clinical usefulness for tcPO2 and tcPCO2 monitoring was assessed in neonates. In healthy adult volunteers, measured oxygen saturation values (SpO2) were compared with arterially sampled oxygen saturation values (SaO2) during controlled hypoxemia. In vitro correlation and agreement with gas mixtures of tcPO2 (r = 0.999, bias 3.0 mm Hg, limits of agreement − 6.6 to 4.9 mm Hg) and tcPCO2 (r = 0.999, bias 0.8 mm Hg, limits of agreement − 0.7 to 2.2 mm Hg) were excellent. In vitro drift was negligible for tcPO2 (0.30 (0.63 SD) mm Hg/24 h) and highly acceptable for tcPCO2 (− 2.53 (1.04 SD) mm Hg/12 h). Clinical use in neonates showed good usability and feasibility. SpO2-SaO2 correlation (r = 0.979) and agreement (bias 0.13%, limits of agreement − 3.95 to 4.21%) in healthy adult volunteers were excellent. The investigated combined tcPO2, tcPCO2, and SpO2 sensor with a new oxygen fluorescence quenching technique is clinically usable and provides good overall accuracy and negligible tcPO2 drift. Accurate and low-drift tcPO2 monitoring offers improved measurement validity for long-term monitoring of blood and tissue oxygenation.

The reconstituted P-glycoprotein multidrug transporter is a flippase for glucosylceramide and other simple glycosphingolipids

The Pgp (P-glycoprotein) multidrug transporter, which is linked to multidrug resistance in human cancers, functions as an efflux pump for non-polar drugs, powered by the hydrolysis of ATP at its nucleotide binding domains. The drug binding sites of Pgp appear to be located within the cytoplasmic leaflet of the membrane bilayer, suggesting that Pgp may function as a ‘flippase’ for hydrophobic compounds. Pgp has been shown to translocate fluorescent phospholipids, and it has been suggested that it may also interact with GlcCer (glucosylceramide). Here we use a dithionite fluorescence quenching technique to show that reconstituted Pgp can flip several NBD (nitrobenzo-2-oxa-1,3-diazole)-labelled simple glycosphingolipids, including NBD–GlcCer, from one leaflet of the bilayer to the other in an ATP-dependent, vanadate-sensitive fashion. The rate of NBD–GlcCer flipping was similar to that observed for NBD-labelled PC (phosphatidylcholine). NBD–GlcCer flipping was inhibited in a concentration-dependent, saturable fashion by various Pgp substrates and modulators, and inhibition correlated well with the Kd for binding to the protein. The addition of a second sugar to the headgroup of the glycolipid to form NBD–lactosylceramide drastically reduced the rate of flipping compared with NBD–PC, probably because of the increased size and polarity contributed by the additional sugar residue. We conclude that Pgp functions as a broad-specificity outwardly-directed flippase for simple glycosphingolipids and membrane phospholipids.