Simultaneous measurement of inhaled air and exhaled breath by double multicapillary column ion-mobility spectrometry, a new method for breath analysis: results of a feasibility study.

The high sensitivity of the methods applied in breath analysis entails a high risk of detecting analytes that do not derive from endogenous production. Consequentially, it appears useful to have knowledge about the composition of inhaled air and to include alveolar gradients into interpretation. The current study aimed to standardise sampling procedures in breath analysis, especially with multicapillary column ion-mobility spectrometry (MCC-IMS), by applying a simultaneous registration of inhaled air and exhaled breath. A "double MCC-IMS" device, which for the first time allows simultaneous analysis of inhaled air and exhaled breath, was developed and tested in 18 healthy individuals. For this, two BreathDiscovery instruments were coupled with each other. Measurements of inhaled air and exhaled breath in 18 healthy individuals (mean age 46±10.9 years; nine men, nine women) identified 35 different volatile organic compounds (VOCs) for further analysis. Not all of these had positive alveolar gradients and could be regarded as endogenous VOCs: 16 VOCs had a positive alveolar gradient in mean; 19 VOCs a negative one. 12 VOCs were positive in >12 of the healthy subjects. For the first time in our understanding, a method is described that enables simultaneous measurement of inhaled air and exhaled breath. This facilitates the calculation of alveolar gradients and selection of endogenous VOCs for exhaled breath analysis. Only a part of VOCs in exhaled breath are truly endogenous VOCs. The observation of different and varying polarities of the alveolar gradients needs further analysis.

Expression and Function of Organic Cation Transporter 2 in Pancreas.

Organic cation transporters (OCT) play an important role in mediating cellular uptake of several pharmaceuticals, such as the antidiabetic drug metformin and the platinum-derived chemotherapeutics. Since these drugs can also affect the pancreas, here it was investigated whether these transporters are expressed in this organ. An interaction between OCT2 and the glucose transporter 2 (GLUT2), which is expressed with important functional consequences in the kidneys and in the pancreas, has already been demonstrated elsewhere. Therefore, here it was further investigated whether the two proteins have a functional relationship. It was demonstrated that OCT2 is expressed in pancreas, probably in ß cells of Langerhans islets, together with GLUT2. However, a co-localization was only evident in a cell-line model of rat pancreatic ß cells under incubation with high glucose concentration. High glucose stimulated OCT2 expression and activity. On the other side, studies conducted in human embryonic kidney cells stably expressing OCT2, showed that overexpression of GLUT2 decreased OCT2 activity. Unfortunately, pull-down experiments aimed to confirm a physical OCT2/GLUT2 interaction were not successful. Renal glucose excretion was reduced in mice with genetic deletion of OCT2. Nonetheless, in these mice no regulation of known kidney glucose transporters was measured. Therefore, it may be speculated that OCT2 may influence cellular trafficking of GLUT2, without changing its amount. OCT2 may play a role in drug uptake of the pancreas, and its activity may be regulated by glucose and GLUT2. Vice versa, GLUT2 activity may be regulated through an interaction with OCT2.