In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice

We describe a two-photon microscopy-based method to evaluate the in vivo systemic transport of compounds. This method comprises imaging of the intact liver, kidney and intestine, the main organs responsible for uptake and elimination of xenobiotics and endogenous molecules. The image quality of the acquired movies was sufficient to distinguish subcellular structures like organelles and vesicles. Quantification of the movement of fluorescent dextran and fluorescent cholic acid derivatives in different organs and their sub-compartments over time revealed significant dynamic differences. Calculated half-lives were similar in the capillaries of all investigated organs but differed in the specific sub-compartments, such as parenchymal cells and bile canaliculi of the liver, glomeruli, proximal and distal tubules of the kidney and lymph vessels (lacteals) of the small intestine. Moreover, tools to image immune cells, which can influence transport processes in inflamed tissues, are described. This powerful approach provides new possibilities for the analysis of compound transport in multiple organs and can support physiologically based pharmacokinetic modeling, in order to obtain more precise predictions at the whole body scale

Soy isoflavones and their relationship with microflora: beneficial effects on human health in equol producers

The bioavailability of soy isoflavones depends on the composition of the microflora for each subject. Bacteria act on different isoflavones with increased or reduced absorption and cause biotransformation of these compounds into metabolites with higher biological activity. S-equol is the most important metabolite and only 25–65 % of the population have the microflora that produces this compound. The presence of equol-producing bacteria in soy product consumers means that the consumption of such products for prolonged periods leads to lower cardiovascular risk, reduced incidence of prostate and breast cancer, and greater relief from symptoms related to the menopause such as hot flushes and osteoporosis

Forced chemical mixing of immiscible Ag-Cu heterointerfaces using high-pressure torsion

Forced chemical mixing in nanostructured Ag60Cu40 eutectic alloys during severe plastic deformation by high-pressure torsion (HPT) was quantitatively studied using x-ray diffraction, differential scanning calorimetry, and transmission electron microscopy. Nearly complete chemical homogenization of the original lamellar structure with a wavelength of ≈ 165 nm was achieved after a shear strain of ≈ 350. The chemical mixing is accompanied by extensive grain refinement leading to nanocrystalline grains with average sizes of ≈ 42 nm. A Monte Carlo computer simulation model, which attributes mixing to dislocation glide, shows reasonable agreement with the experimental results. The model also shows that the characteristic strain for chemical homogenization scales linearly with the length scale of the system L, and not with the square of the length scale L2, as would be expected for Fickian diffusion