15 Some aspects of cirrhotic cardiomyopathy, such as diastolic dysfunction, reduced cardiac index, and Q-T interval prolongation, have been shown to be significantly associated with complications of cirrhosis, such as HRS, and death (Fig. 1).16, 17 Therefore, if NSBBs further impair cardiac function in a patient with cirrhotic cardiomyopathy, Selleck Roxadustat this could be another mechanism whereby propranolol administration would lead to an unfavorable outcome. From the opposite standpoint, propranolol reduces the risk of bleeding, and

therefore, bleeding-related death. By the same mechanism, NSBBs can also reduce bacterial translocation from the gut.18 Because bacterial translocation is the initial step in the pathogenesis of SBP, the use of propranolol has been shown to prevent the development of SBP18, 19 and postsurgical infections in cirrhosis (Fig.

1).20 It appears that the controversy regarding NSBB use in advanced cirrhosis might continue, the report from Lebrec et al. notwithstanding. NSBBs should continue to be used to prevent variceal bleeding. However, the risk/benefit ratio of such treatment may vary according to the stage of the cirrhosis, perhaps becoming unfavorable in patients with the most advanced stage. New studies BMS-907351 ic50 are necessary to establish if NSBBs exert different effects in different subsets of patients with cirrhosis, although it is unlikely that such studies are currently under way. Pending

the results of such studies, patients with ascites who are on NSBBs should be monitored closely, and consideration should be given to discontinuing NSBBs when either sepsis or HRS develop. “
“Peroxiredoxins (Prxs) are peroxidases that catalyze the reduction of reactive oxygen species (ROS). The active site cysteine residue of members of the 2-Cys Prx subgroup (Prx I to IV) of Prxs is hyperoxidized to cysteine sulfinic acid (Cys-SO2) during catalysis with concomitant loss of peroxidase activity. Reactivation of the MCE hyperoxidized Prx is catalyzed by sulfiredoxin (Srx). Ethanol consumption induces the accumulation of cytochrome P450 2E1 (CYP2E1), a major contributor to ethanol-induced ROS production in the liver. We now show that chronic ethanol feeding markedly increased the expression of Srx in the liver of mice in a largely Nrf2-dependent manner. Among Prx I to IV, only Prx I was found to be hyperoxidized in the liver of ethanol-fed wildtype mice, and the level of Prx I-SO2 increased to ≈30% to 50% of total Prx I in the liver of ethanol-fed Srx−/− mice. This result suggests that Prx I is the most active 2-Cys Prx in elimination of ROS from the liver of ethanol-fed mice and that, despite the up-regulation of Srx expression by ethanol, the capacity of Srx is not sufficient to counteract the hyperoxidation of Prx I that occurs during ROS reduction.