Clinical investigation of the cystic duct variation based on the anatomy of the hepatic vasculature.

PURPOSE: Anatomical variation of the cystic duct (CD) is rare but can result in misunderstanding of the CD anatomy during laparoscopic cholecystectomy, potentially leading to bile duct injury. Therefore, the precise preoperative identification of CD variation is important. However, preoperative imaging analyses of the biliary system are not always possible or sufficient. We therefore investigated CD variations based on the anatomy of the hepatic vasculature. METHODS: This study enrolled 480 patients who underwent imaging before hepatobiliary pancreatic surgery. We assessed the variation of the CD and hepatic vasculature and evaluated the correlations among these variations. RESULTS: A variant CD anatomy was identified in 12 cases (2.5%) as CD draining into the right hepatic bile duct (BD) in 4 cases and into the right posterior BD in 8 cases. CD variation was significantly more common in cases with portal vein (PV) and BD variation than in those without the variation. We developed a scoring system based on the presence of PV and BD variations that showed good discriminatory power for identification of CD variants. CONCLUSION: Cases with a variant CD anatomy were more likely to exhibit variant PV and BD anatomies than cases with a normal CD anatomy. These findings will be useful for the preoperative identification of CD variants.

Compensatory role of the Nrf2-ARE pathway against paraquat toxicity: Relevance of 26S proteasome activity.

Oxidative stress and the ubiquitin-proteasome system play a key role in the pathogenesis of Parkinson disease. Although the herbicide paraquat is an environmental factor that is involved in the etiology of Parkinson disease, the role of 26S proteasome in paraquat toxicity remains to be determined. Using PC12 cells overexpressing a fluorescent protein fused to the proteasome degradation signal, we report here that paraquat yielded an inhibitory effect on 26S proteasome activity without an obvious decline in 20S proteasome activity. Relative low concentrations of proteasome inhibitors caused the accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is targeted to the ubiquitin-proteasome system, and activated the antioxidant response element (ARE)-dependent transcription. Paraquat also upregulated the protein level of Nrf2 without increased expression of Nrf2 mRNA, and activated the Nrf2-ARE pathway. Consequently, paraquat induced expression of Nrf2-dependent ARE-driven genes, such as γ-glutamylcysteine synthetase, catalase, and hemeoxygenase-1. Knockdown of Nrf2 or inhibition of γ-glutamylcysteine synthetase and catalase exacerbated paraquat-induced toxicity, whereas suppression of hemeoxygenase-1 did not. These data indicate that the compensatory activation of the Nrf2-ARE pathway via inhibition of 26S proteasome serves as part of a cellular defense mechanism to protect against paraquat toxicity.