Recently, we reported that oxidative stress due to 3,3,5-triiodothyronine (T 3 )-induced calorigenesis up-regulates the hepatic expression of mediators promoting cell protection. In this study, T 3 administration in rats (single dose of 0.1 mg/kg intraperitoneally) induced significant depletion of reduced liver glutathione (GSH), with higher protein oxidation, O 2 consumption, and Kupffer cell function (carbon phagocytosis and carbon-induced O 2 uptake). These changes occurred within a period of 36 hours of T 3 treatment in animals showing normal liver histology and lack of alteration in serum AST and ALT levels. Partial hepatic ischemia-reperfusion (IR) (1 h of ischemia via vascular clamping and 20 h reperfusion) led to 11-fold and 42-fold increases in serum AST and ALT levels, respectively, and significant changes in liver histology, with a 36% decrease in liver GSH content and a 133% increase in that of protein carbonyls. T 3 administration in a time window of 48 hours was substantially protective against hepatic IR injury, with a net 60% and 90% reduction in liver GSH depletion and protein oxidation induced by IR, respectively. Liver IR led to decreased DNA binding of nuclear factor-B (NF-B) (54%) and signal transducer and activator of transcription 3 (STAT3) (53%) (electromobility shift assay), with 50% diminution in the protein expression of haptoglobin (Western blot), changes that were normalized by T 3 preconditioning. Conclusion: T 3 administration involving transient oxidative stress in the liver exerts significant protection against IR injury, a novel preconditioning maneuver that is associated with NF-B and STAT3 activation and acute-phase response. (HEPATOLOGY 2007;45:170-177.)

Background: Two strategies for same-admission cholecystectomy in mild gallstone pancreatitis (MGP) exist: early surgery (within 48-72 h from admission) and delayed surgery until resolution of symptoms and normalization of pancreatic tests.Methods: This was a single-center, open-label RCT. Patients with MGP according to revised Atlanta classification-2012 and SIRS criteria were randomly assigned to early laparoscopic cholecystectomy (E-LC) within 72 h from admission or delayed laparoscopic cholecystectomy (D-LC). Laparoscopicendoscopic rendezvous was performed when common bile duct stones were found at systematic intraoperative cholangiography. The primary outcome was length of stay (LOS), and the secondary outcomes were complications at 90 days, need for ERCP/choledocolithiasis, conversion, and readmission. One year of follow-up was carried-on.Results: At interim analysis, 52 patients were randomized (26 E-LC, 26 D-LC). E-LC versus D-LC was associated with a significantly shorter LOS (median 58 versus 167 h; P = 0.001). There were no differences in ERCP necessity for choledocolithiasis between the two approaches (E-LC 26.9% versus D-LC 23.1%, P = 1.00). No differences in postoperative complications were found.Conclusions: E-LC approach in patients with MGP significantly reduced LOS and was not associated with clinically relevant postoperative complications.Trial registration: clinicaltrials.gov (NCT02590978).

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