NO donor KMUP-1 improves hepatic ischemia-reperfusion and hypoxic cell injury by inhibiting oxidative stress and pro-inflammatory signaling.

This study investigates whether KMUP-1 improves hepatic ischemia-reperfusion (I/R) and hypoxic cell injury via inhibiting Nox2- and reactive oxygen species (ROS)-mediated pro-inflammation. Rats underwent ischemia by occlusion of the portal vein and hepatic artery for 45 minutes. Reperfusion was allowed for 4 h. Serum was used for analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). DNA extracted from liver homogenate was analyzed by electrophoresis to observe the fragmentation. Lipid peroxidation (LPO) was evaluated by measuring thiobarbituric acid-reactive substances (TBARS). NO and ROS contents were measured using Griess reagent and 2'-7'-dichlorofluorescein, respectively. Proteins levels were visualized by Western blotting. Liver damage was observed under a microscope. Intravenous KMUP-1 (0.25, 0.5 and 1 mg/kg) reduced I/R-induced ALT and AST levels, DNA fragmentation, ROS and malondialdehyde (MDA) and restored the NO levels of I/R rats. KMUP-1 protected the liver architecture from worsening of damage and focal sinusoid congestion, increased endothelium NO synthase (eNOS), guanosine 3', 5'cyclic monophosphate (cGMP), protein kinase G (PKG) and the B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, attenuated phosphodiesterase 5A (PDE-5A) and cleaved caspase-3 expression in I/R-liver. In hypoxic HepG2 cells, KMUP-1 increased cGMP/PKG, restored peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and decreased matrix metalloproteinases-9 (MMP-9), Rho kinase II (ROCK II), hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelium growth factor (VEGF). KMUP-1 protects liver from I/R-injury and hypoxic hepatocytes from apoptosis-associated free radical generation and pro-inflammation by restoring/increasing NO/cGMP/PPAR-gamma, reducing ROS/Nox2 and inhibiting ROCKII/MMP-9.

An investigation into the practice of concurrent chronic ambulatory peritoneal dialysis catheter insertion and arteriovenous fistula formation in patients needing dialysis.

To review the practice of concurrent chronic ambulatory peritoneal dialysis catheter insertion and arteriovenous fistula formation in patients needing dialysis, we retrospectively assessed the results of arteriovenous fistula procedures, the risk factors for fistula failure, and the selection strategy used to choose which patients with end-stage renal disease would be given dialysis. We analysed the medical records of 136 patients who had first-time arteriovenous fistulae created between 1 July 1986 and 1 May 1994 at a public hospital in Sydney, Australia. As many as 36% of fistulae were never used (24.5% due to primary failure) and 30.1% of the fistulae used had to be abandoned for various reasons. In addition, 22.8% of patients experienced complications, the most common being thrombosis and stenosis. None of the factors associated with fistula formation were significant in terms of fistula patency rates, but smokers and female patients had inferior fistula patency rates. Whereas the overall results were satisfactory, the practice of concurrent chronic ambulatory peritoneal dialysis catheter insertion and arteriovenous fistula formation to give vascular access for dialysis is questionable.