UP-REGULATION OF STRESS-INDUCED LIGANDS IS ASSOCIATED WITH ENHANCED HEPATOCYTE APOPTOSIS AND FIBROSIS IN PATIENTS WITH NASH

60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases -- OCT 30-NOV 03, 2009 -- Boston, MAWOS: 000270456001033…Amer Assoc Study Liver Di

Myocardial proteome analysis reveals reduced NOS inhibition and enhanced glycolytic capacity in areas of low local blood flow

In the heart, in situ local myocardial blood flow (MBF) varies greater than 10-fold between individual areas and displays a spatially heterogeneous pattern. To analyze its molecular basis, we analyzed protein expression of low and high flow samples (300 mg, 150% of mean MBF, each n=30) of six beagle dogs by 2-D polyacrylamide gel electrophoresis (380 +/- 78 spots/gel). In low flow samples, dimethylarginine dimethylaminohydrolase (DDAH1) was increased greatly (+377%, compared with high flow samples). This increase resulted in a 75% reduction of asymmetric dimethylarginine (ADMA), the potent endogenous inhibitor of NO synthase, whereas eNOS showed no difference. Low flow samples exhibited enhanced expression of GAPDH (+89%) and phosphoglycerate kinase (+100%), whereas hydroxyacyl-CoA dehydrogenase, electron transfer flavoprotein, myoglobin, and desmin were decreased. Assessing local MBF on different days within 2 weeks revealed a high degree of MBF stability (r2 > 0.79). Thus, stable differences in local MBF are associated with significant differences in local gene and protein expression. In low flow areas, the increased DDAH1 reduces ADMA concentration and NOS inhibition, which strongly suggests enhanced NO formation. Low flow areas are also characterized by a higher glycolytic and a lower fatty acid oxidation capacity. Both the shift in substrate utilization and the rise in NO may contribute to the known lower oxygen consumption in these area

Comparison of the sixth and the seventh editions of the UICC classification for intrahepatic cholangiocarcinoma

Abstract Background The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated. Methods Between 03/2001 and 02/2013, 98 patients with the diagnosis of an ICC were surgically treated at our center. Median survival times were calculated for these patients after separate classification by both sixth and seventh editions. Results Median overall survival was increased in patients classified to the lower tumor stages I and II using the seventh as compared to the sixth edition: stage I (54.9 vs. 47.3 months), stage II (19.9 vs. 18.9 months), stage III (17.2 vs. 19.9 months), and stage IV (23.2 vs. 15.3 months), respectively. The seventh edition definition of the T category resulted in an increased median survival regarding the T1 (50.4 vs. 47.3 months) as well as the T2 category (19.9 vs. 15.6 months) and revealed a reduced median survival of patients within the T3 (21.6 vs. 24.8 months) as well as the T4 category (19.9 vs. 27.0 months). Conclusions The UICC seventh edition TNM classification for ICC improves separation of patients with intermediate stage tumors as compared to the sixth edition. The prognostic value of the UICC staging system has been improved by the seventh edition. Trial registration The data for this study have been retrospectively registered and the study has been approved by the ethic committee of the medical faculty of the University Hospital of Essen, Germany (license number 15-6353-BO)