Lung microdialysis—A powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review)

In vivo measurement of concentrations of drugs and endogenous substances at the site of action has become a primary focus of research. In this context the minimal invasive microdialysis (MD) technique has been increasingly employed for the determination of pharmacokinetics in lung. Although lung MD is frequently employed to investigate various drugs and endogenous substances, the majority of lung MD studies were performed to determine the pharmacokinetic profile of antimicrobials that can be related to the importance of respiratory tract infections. For the lower respiratory tract various methods, such as surgical collection of whole lung tissue and bonchoalveolar lavage (BAL), are currently available for the determination of pharmacokinetics of antimicrobials. Head-to-head comparison of pharmacokinetics of antibiotics in lung revealed high differences between MD and conventional methods. MD might be regarded as a more advantageous approach because of its higher anatomical resolution and the ability to obtain dynamic time-vs-concentration profiles within one subject. However, due to ethical objections lung MD is limited to animals or patients undergoing elective thoracic surgery. From these studies it was speculated that the concentrations in healthy lung tissue may be predicted reasonably by the measurement of concentrations in skeletal muscle tissue. However, until now this was only demonstrated for β-lactam antibiotics and needs to be confirmed for other classes of antimicrobials. In conclusion, the present review shows that MD is a promising method for the determination of antimicrobials in the lung, but might also be applicable for measuring a wide range of other drugs and for the investigation of metabolism in the lower respiratory tract

Skill assessment of three earth system models with common marine biogeochemistry

We have assessed the ability of a common ocean biogeochemical model, PISCES, to match relevant modern data fields across a range of ocean circulation fields from three distinct Earth system models: IPSL-CM4-LOOP, IPSL-CM5A-LR and CNRM-CM5.1. The first of these Earth system models has contributed to the IPCC 4th assessment report, while the latter two are contributing to the ongoing IPCC 5th assessment report. These models differ with respect to their atmospheric component, ocean subgrid-scale physics and resolution. The simulated vertical distribution of biogeochemical tracers suffer from biases in ocean circulation and a poor representation of the sinking fluxes of matter. Nevertheless, differences between upper and deep ocean model skills significantly point to changes in the underlying model representations of ocean circulation. IPSL-CM5A-LR and CNRM-CM5.1 poorly represent deep-ocean circulation compared to IPSL-CM4-LOOP degrading the vertical distribution of biogeochemical tracers. However, their representations of surface wind, wind stress, mixed-layer depth and geostrophic circulations (e.g., Antarctic Circumpolar Current) have been improved compared to IPSL-CM4-LOOP. These improvements result in a better representation of large-scale structure of biogeochemical fields in the upper ocean. In particular, a deepening of 20–40 m of the summer mixed-layer depth allows to capture the 0–0.5 μgChl L−1 concentrations class of surface chlorophyll in the Southern Ocean. Further improvements in the representation of the ocean mixed-layer and deep-ocean ventilation are needed for the next generations of models development to better simulate marine biogeochemistry. In order to better constrain ocean dynamics, we suggest that biogeochemical or passive tracer modules should be used routinely for both model development and model intercomparisons