P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

Contains fulltext : 51690.pdf (publisher's version ) (Closed access)BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection. METHODS: Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured. RESULTS: During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTalpha levels. Hepatocyte injury was followed by an inflammatory response. CONCLUSIONS: This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand

The bomb attack in Oslo and the shootings at Utøya, 2011 : Kamedo report 97

The Kamedo observer reports study the medical, psychological, organizational and social aspects of disasters. This report summaries experiences from the bomb attack in Oslo and the shootings at Utøya, 2011. That may be valuable for the further development of the Swedish disaster preparedness system.(Article number: 2012-12-23)Co-author and editor: Anders Eklund, Investigator at the National Board of Health and Welfare's Unit for Emergency Preparedness</p