Hepatic Drug Metabolism, Uremic Toxins and Bacterial Composition Over Chronic Kidney Disease Progression

Uremic toxin retention and an altered gut microbiota are suspected to influence cytochrome P450s (CYPs) contributing to the unpredictable pharmacokinetics in chronic kidney disease (CKD). We aim to characterize dysbiosis and uremia to elucidate associations between CYP expression and CKD progression. Rats fed control or CKD-inducing diet were subsequently sacrificed across five time points over 42 days. CYP expression and activity were compared to alterations in the 1) plasma and liver metabolome and 2) bacterial microbiota. CYP3A2 and CYP2C11, respectively, were downregulated in CKD by ≥76% (p\u3c0.001) simultaneously or slightly premature to CKD onset defined by creatinine. Metabolite profiles were altered before the gut microbiota and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11. Identified bacterial genera, Turicibacter and Parabacteroides, characterized CKD and require future study. In conclusion, CYP3A2 and CYP2C11 are downregulated prior to dysbiosis but correlate with select uremic toxins

Performance of a GridPix detector based on the Timepix3 chip

A GridPix readout for a TPC based on the Timepix3 chip is developed for future applications at a linear collider. The GridPix detector consists of a gaseous drift volume read out by a single Timepix3 chip with an integrated amplification grid. Its performance is studied in a test beam with 2.5 GeV electrons. The GridPix detector detects single ionization electrons with high efficiency. The Timepix3 chip allowed for high sample rates and time walk corrections. Diffusion is found to be the dominating error on the track position measurement both in the pixel plane and in the drift direction, and systematic distortions in the pixel plane are below 10 $\mu$m. Using a truncated sum, an energy loss (dE/dx) resolution of 4.1% is found for an effective track length of 1 m.Comment: To be published in Nuclear Instruments and Methods in Physics Research Section