No abstract

Specific inhibition of apoptosis executor caspases effectively reduces graft ischemia-reperfusion injury and improves survival in liver transplantation. Better tissue preservation after caspase inhibition correlates with reduced apoptosis execution, improved microvascular perfusion, and bcl-2 up-regulation. Therefore, specific caspase inhibition represents a promising regimen for clinical use in liver transplantation.

Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.

Summary Inhibition or destruction of Kupffer cells (KC) may protect against ischemia‐reperfusion (IR) induced primary graft nonfunction (PNF) in liver transplantation. Besides KC activation, PNF is characterized by microvascular perfusion failure, intrahepatic leukocyte accumulation, cell death and hepatocellular dysfunction. KCs can be inactivated by different agents including gadolinium chloride (GdCl3), methyl palmitate (MP) and glycine. The effects of three KC inactivators on IR‐injury after rat liver transplantation were compared in the present study. Lewis liver donors were treated with GdCl3, MP, glycine or saline (control). Liver grafts were transplanted following 24 h storage (UW solution). KC populations and IR damage were assessed by histologic analysis, quantitative real‐time polymerase chain reaction (RT‐PCR) and intravital microscopy. The number of hepatic ED‐1 positive macrophages was diminished after GdCl3 (114.8 ± 4.4/mm2 liver tissue) and MP treatment (176.0 ± 5.0), versus the glycine (263.9 ± 5.5) and control (272.1 ± 5.6) groups. All three treatment modalities downregulated phagocytic activity for latex particles, paralleled by reduced microvascular injury (acinar perfusion index, GdCl3: 0.75 ± 0.03; MP: 0.83 ± .03; glycine: 0.84 ± 0.03; 0.63 ± 0.03). Quantitative RT‐PCR revealed elevated myeloperoxidase mRNA after glycine versus GdCl3 and MP pretreatment (3.2‐ and 3.4‐fold, P = 0.011, respectively), without difference to controls (2.9‐fold of glycine). TNFα‐mRNA was reduced after glycine‐ (5.2‐fold), GdCl3‐ (19.7‐fold), MP‐treatment (39.5‐fold) compared with controls. However, profound prevention of intrahepatic cell death and liver graft failure was solely achieved with glycine preconditioning. Different than GdCl3 and MP, glycine modulates rather than destroys KCs. Glycine appears to preserve cell viability and to TNFα/leukocyte dependent organ regeneration capacity, which is related to increase graft survival following liver transplantation.