In spite of the consequences and in the absence of effective liver assist therapies, mere supportive care

still remains the only treatment option for operated patients. The novel insights into the inflammatory component of hepatic I/R injury, however, could spur the development of second-generation selleck chemicals intervention modalities. As most proximal triggers, neutralizing DAMPs directly should prevent the onset of inflammation as well as the second wave of oxidative/nitrosative stress, although the vital role of DAMPs in healthy cells could hinder this approach. Alternatively, more targeted (e.g. antibody) therapies could be employed to prevent DAMP release or neutralize the pro-inflammatory effects of selective DAMPs, thereby deterring the self-amplifying cycle of cell death, DAMP release, leukocyte activation, and ROS/RNS generation. In that respect, it could be feasible to block the function of DAMP receptors. Further downstream, defining the cytokines that attract and activate effector leukocytes could also reveal viable targets for intervention. Lastly, it could be worthwhile to directly neutralize ROS/RNS with second-generation compounds that slow down the rate of ROS/RNS production during the (hyper)acute reperfusion phase or that target physiologically relevant non-radical ROS/RNS that

serve as templates for the formation of free radicals. In any case, the field of liver surgery needs a novel set of treatment modalities to replace the selleck currently available options (Table 1), which have largely proven inadequate. The

authors are grateful to Dr Michael Murphy from the MRC Mitochondrial Biology Unit, Cambridge, UK, for providing detailed information on MitoSNO, and to Inge Kos from the Medical Illustration Service for the artwork. This work was supported by a PhD scholarship from the Academic Medical Center. “
“The thiopurines, azathioprine and 6-mercaptopurine (6-MP), are immunosuppressive drugs used in a number of clinical settings, such as following transplantation and for the management of inflammatory conditions like inflammatory bowel disease (IBD). Allopurinol, a xanthine oxidase inhibitor used in the treatment of gout, is not infrequently coincidentally co-prescribed with the thiopurines. A recent MCE公司 safety report from the New South Wales Department of Health (NSW, Australia) highlights the potential risk with the co-administration of these two drugs.1 This commentary reviews the interaction of these drugs and highlights important precautions that should be taken by clinicians when using them together. On May 7th, 2009, the New South Wales Department of Health issued a Safety Notice regarding the interaction between allopurinol and azathioprine.1 This notice followed the death of a patient who had been admitted to a hospital on existing azathioprine therapy. The patient was commenced on allopurinol by a consulting team.