ABSTRACT
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates lipid metabolism and inflammatory responses. Certain PPARgamma ligands improve nonalcoholic steatohepatitis (NASH). The role of PPARgamma itself in NASH remains poorly understood. The functional consequences of PPARgamma in the development of steatohepatitis through gene deficiency or gene overexpression of PPARgamma delivered by adenovirus (Ad-PPARgamma) were examined. Our results show that PPARgamma-deficient (PPARgamma(+/-)) mice fed the methionine- and choline-deficient (MCD) diet developed more severe steatohepatitis than wild-type mice, and were unaffected by PPARgamma ligand rosiglitazone. Overexpression of PPARgamma delivered by Ad-PPARgamma attenuated steatohepatitis. This effect was associated with redistribution of fatty acid from liver to adipose tissue by enhancing expression of fatty acid uptake genes (fatty acid binding protein-4 (aP2), fatty acid translocase (CD36), lipoprotein lipase (LPL) and fatty acid transport protein-1 (FATP-1)) and lipogenic genes (sterol regulatory element binding protein isoform-1 (SREBP-1) and stearoyl-CoA desaturase isoform-1 (SCD-1)) in adipose tissue and to a lesser extent in liver. The anti-steatohepatitis action of PPARgamma was also mediated via regulating adipokines through suppressing tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and inducing adiponectin. Moreover, PPARgamma activation suppressed hepatic lipoperoxide and reduced hepatic pro-inflammatory cytokines (TNF-alpha and IL-6) production. In conclusion, PPARgamma is an important endogenous regulator and potential therapeutic target for nutritional steatohepatitis.
Subject(s)
Fatty Liver/prevention & control , PPAR gamma/metabolism , Adenoviridae/genetics , Animals , Choline Deficiency , Fatty Liver/etiology , Fatty Liver/genetics , Gene Transfer Techniques , Genetic Therapy , Methionine/deficiency , Mice , PPAR gamma/deficiency , PPAR gamma/genetics , Rosiglitazone , Thiazolidinediones/pharmacologyABSTRACT
OBJECTIVE: To compare the short-term outcome of patients undergoing robot-assisted versus open radical prostatectomy. DESIGN: Retrospective analysis of prospectively collected data. SETTING: A university teaching hospital in Hong Kong. PATIENTS: Twenty consecutive cases having robot-assisted radical prostatectomy were compared with the last 20 cases of open radical prostatectomy (prior to November 2005 when the robotic system was introduced). MAIN OUTCOME MEASURES: Perioperative functional evaluation (with special emphasis on continence) and oncological evaluation (included margin studies and prostate-specific antigen levels). RESULTS: Regarding baseline clinical characteristics of the patients, there was no statistically significant difference between the robotic and open radical prostatectomy groups. For perioperative outcome, in the robotic group the blood transfusion rate was significantly lower (5 vs 65%), hospital stay was shorter (8 vs 17 days), and the catheter time was shorter (12 vs 18 days). For early oncological outcome, there was no statistically significant difference in the margin positive rate and early prostate-specific antigen results. Regarding continence (use of 0-1 pads/day), it was achieved by 95% in the robotic group with a mean follow-up of 6 months compared to 85% in the open group with a mean follow-up of 42 months. CONCLUSIONS: Robot-assisted radical prostatectomy offered the benefits of a minimally invasive operation with less blood loss, shorter catheter time and hospital stay, and earlier continence. It has therefore become the preferred surgical option in our institution.
