Release of Danger Signals during Ischemic Storage of the Liver: A Potential Marker of Organ Damage?

Liver grafts suffer from unavoidable injury due to ischemia and manipulation before implantation. Danger signals such as high-mobility group box -1(HMGB1) and macrophage migration inhibitory factor (MIF) play a pivotal role in the immune response. We characterized the kinetics of their release into the effluent during cold/warm ischemia and additional manipulation-induced mechanical damage. Furthermore, we evaluated the relationship between HMGB1/MIF release and ischemic/mechanical damage. Liver enzymes and protein in the effluent increased with increasing ischemia time. HMGB1/MIF- release correlated with the extent of hepatocellular injury. With increasing ischemia time and damage, HMGB1 was translocated from the nucleus to the cytoplasma as indicated by weak nuclear and strong cytoplasmic staining. Enhancement of liver injury by mechanical damage was indicated by an earlier HMGB1 translocation into the cytoplasm and earlier release of danger signals into the effluent. Our results suggest that determination of HMGB1 and MIF reflects the extent of ischemic injury. Furthermore, HMGB1and MIF are more sensitive than liver enzymes to detect the additional mechanical damage inflicted on the organ graft during surgical manipulation

A fast and robust hepatocyte quantification algorithm including vein processing

<p>Abstract</p> <p>Background</p> <p>Quantification of different types of cells is often needed for analysis of histological images. In our project, we compute the relative number of proliferating hepatocytes for the evaluation of the regeneration process after partial hepatectomy in normal rat livers.</p> <p>Results</p> <p>Our presented automatic approach for hepatocyte (HC) quantification is suitable for the analysis of an entire digitized histological section given in form of a series of images. It is the main part of an automatic hepatocyte quantification tool that allows for the computation of the ratio between the number of proliferating HC-nuclei and the total number of all HC-nuclei for a series of images in one processing run. The processing pipeline allows us to obtain desired and valuable results for a wide range of images with different properties without additional parameter adjustment. Comparing the obtained segmentation results with a manually retrieved segmentation mask which is considered to be the ground truth, we achieve results with sensitivity above 90% and false positive fraction below 15%.</p> <p>Conclusions</p> <p>The proposed automatic procedure gives results with high sensitivity and low false positive fraction and can be applied to process entire stained sections.</p

Proteolytic cleavage of FOXM1 by caspases

published_or_final_versionMedical SciencesMasterMaster of Medical Science

J. Mat. Chem. B

Superparamagnetic iron oxide nanoparticles (SPIONs) offer unique properties for magnetic resonance imaging (MRI). Targeting imaging of rheumatoid arthritis in vivo requires a specific, magnetic sensitive and ultra-stable MRI contrast agent. In this study, SPIONs with a preferable colloid stability and optimized size were obtained by using an in situ polyol method with the diblock copolymer PEG-b-PAA acting as a surface ligand. Increasing the degree of polymerization (DP) of PAA from 18 to 36 to 57 led to the decreasing size of the iron oxide nanoparticles from 52 nm to 17 nm to 9 nm, respectively. Folic acid was conjugated onto PEG-PAA(x)@ SPION as a specific targeting molecule for activated macrophages in a rheumatoid arthritis joint. To evaluate the stability and magnetic properties of the particle, a series of tests were conducted to evaluate and optimize the nanoparticles. In vitro endocytosis experiments confirmed the better performance of the folic acid conjugated SPIONs than the non-folic acid modified SPIONs. In vivo MRI clearly demonstrated the significant signal diminishment of the arthritis joint in antigen induced arthritis (AIA) rats by intravenous injection of the optimized nanoparticles FA-PEG-bPAA(36)@ SPION. These results indicated that FA-PEG-b-PAA(36)@ SPION could serve as a promising candidate for the MRI of rheumatoid arthritis.Superparamagnetic iron oxide nanoparticles (SPIONs) offer unique properties for magnetic resonance imaging (MRI). Targeting imaging of rheumatoid arthritis in vivo requires a specific, magnetic sensitive and ultra-stable MRI contrast agent. In this study, SPIONs with a preferable colloid stability and optimized size were obtained by using an in situ polyol method with the diblock copolymer PEG-b-PAA acting as a surface ligand. Increasing the degree of polymerization (DP) of PAA from 18 to 36 to 57 led to the decreasing size of the iron oxide nanoparticles from 52 nm to 17 nm to 9 nm, respectively. Folic acid was conjugated onto PEG-PAA(x)@ SPION as a specific targeting molecule for activated macrophages in a rheumatoid arthritis joint. To evaluate the stability and magnetic properties of the particle, a series of tests were conducted to evaluate and optimize the nanoparticles. In vitro endocytosis experiments confirmed the better performance of the folic acid conjugated SPIONs than the non-folic acid modified SPIONs. In vivo MRI clearly demonstrated the significant signal diminishment of the arthritis joint in antigen induced arthritis (AIA) rats by intravenous injection of the optimized nanoparticles FA-PEG-bPAA(36)@ SPION. These results indicated that FA-PEG-b-PAA(36)@ SPION could serve as a promising candidate for the MRI of rheumatoid arthritis