When we exposed GSK3235025 ic50 Hep G2 and VL-17A cells to MG132 (16 hr) and then rapamycin (100 nM) four hr before harvest, aggresome content in MG132-treated cells declined significantly. Conclusion: Our findings indicate that EtOH- and MG132-induced proteasome down-regulation in VL-17A cells caused accumulation of protein aggregates. Aggresomes increased in an alcohol dose-independent but a time-dependent manner. Because

an increasing degree of proteasome inhibition occurred with rising EtOH doses, which did not intensify protein aggregation, we postulate that other compensatory mechanisms prevent further aggresome accumulation. Supported by Grant 1-R01-AA16546 from the NIAAA. Disclosures: The following people have nothing to disclose: Paul G. Thomes, Casey S. Trambly, Natalia A. Osna, Kusum K.

Kharbanda, Dahn L. Clemens, Terrence M. Donohue Background: Over 250, 000 Americans annually receive isoniazid (INH). In 2006, the American Thoracic Society (ATS) established guidelines for when to stop INH for hepatotoxicity. However it is unclear if these guidelines can reduce the frequency or severity of liver injury. Aim: To analyze the presenting features of patients with well-characterized INH hepatotoxicity and determine correlates of DILI severity. Methods: Patients with INH hepatotoxicity enrolled in the DILIN from Sep 2004 through April 2013 with a causality score of definite, very likely, or probable were identified. Delay in stopping INH was defined as time from meeting ATS Ruxolitinib concentration stopping criteria (hepatitis symptoms and/or liver enzyme elevation) to INH discontinuance. Case severity was assessed by the 5-point DILIN Severity Index Score (SIS) that ranges from enzyme elevations without jaundice (SIS=1) to transplant or death

(SIS=5). Several variables including age, sex, race, body mass index (BMI), presence of underlying liver disease, and delay in stopping INH were examined for associations with SIS. Results: Amongst 1091 DILIN patients, INH was the 2nd most commonly implicated agent with 69 cases, of which MCE公司 60 met inclusion criteria [48% definitely, 38% highly likely and 13% probably attributable to INH]. Median age was 49 years (range 4 to 68), 70% were female, 27% Caucasian, 25% Hispanic, 18% African American and 8% Asian. 58 (97%) took INH for latent TB. Patients presented with either hepatocellular (92%) or mixed cholestatic-hepatocellular (7%) biochemical injury patterns; 72% were jaundiced. Cases were evenly distributed across the 5-point SIS scale with 13 (22%) undergoing transplant and/or dying. Median delay between reaching ATS stopping criteria and INH discontinuance was 9 days (range 0-99). Only 27 (45%) stopped INH within 7 days of meeting criteria, 15 (25%) remained on therapy for 15-28 days and 9 (15%) continued >28 days.