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Short- and long-term effects of biliary drainage on hepatic cholesterol metabolism in the rat.

ABSTRACT: The present study concerns short- and long-term effects of interruption of the enterohepatic circulation (EHC) on hepatic cholesterol metabolism and biliary secretion in rats. For this purpose, we employed a technique that allows reversible interruption of the EHC, during normal feeding conditions, and excludes effects of anaesthesia and surgical trauma. [3H]Cholesteryl oleate-labelled human low-density lipoprotein (LDL) was injected intravenously in rats with (1) chronically (8 days) interrupted EHC, (2) interrupted EHC at the time of LDL injection and (3) intact EHC. During the first 3 h after interruption of the EHC, bile flow decreased to 50% and biliary bile acid, phospholipid and cholesterol secretion to 5%, 11% and 19% of their initial values respectively. After 8 days of bile diversion, biliary cholesterol output and bile flow were at that same level, but bile acid output was increased 2-3-fold and phospholipid output was about 2 times lower. The total amount of cholesterol in the liver decreased after interruption of the EHC, which was mainly due to a decrease in the amount of cholesteryl ester. Plasma disappearance of LDL was not affected by interruption of the EHC. Biliary secretion of LDL-derived radioactivity occurred 2-4 times faster in chronically interrupted rats as compared with the excretion immediately after interruption of the EHC. Radioactivity was mainly in the form of bile acids under both conditions. This study demonstrates the very rapid changes that occur in cholesterol metabolism and biliary lipid composition after interruption of the EHC. These changes must be taken into account in studies concerning hepatic metabolism of lipoprotein cholesterol and subsequent secretion into bile.

SUBMITTER: Smit MJ

PROVIDER: S-EPMC1131655 | biostudies-other | 1990 Aug

REPOSITORIES: biostudies-other

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Project description:A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored more permanently in an intermediary form or memory between WM and long-term memory.

Project description:Objectives: Whether pre-operative biliary drainage (PBD) affects long-term survival of patients with obstructive jaundice with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy is still controversial. Most of the previous research did not include the important total serum bilirubin (TB) level before intervention as well as before surgery. The aim of this study is to evaluate the impact of PBD on long-term survival after considering the TB level. Methods: Data were collected retrospectively from patients with obstructive jaundice who underwent resection of pancreatic head cancer in a high-volume center. X-Tile software and Kaplan-Meier survival analysis were applied to determine the optimal cut-off levels for TB and age based on the minimal probability (P)-value and the largest χ2-value. Multivariate Cox regression analyses were performed after univariate analysis to assess independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Results: Of 426 patients with obstructive jaundice who underwent pancreaticoduodenectomy for resectable pancreatic head cancer during a 7 year period, 242 (56.8%) received PBD and 184 (43.2%) underwent surgery directly. The OS of patients who received PBD was significantly worse than that of patients who did not receive PBD by univariate analysis (median of 16.6 vs. 22.2 months, P = 0.048). After including liver function parameters in the multivariate Cox regression, we found that the use of PBD was not associated with OS or DFS, while TB before intervention >150 μmol/L was an independent adverse prognostic factor for both OS [hazard ratio (HR), 1.42; 95% CI, 1.05-1.91] and DFS (HR, 1.38; 95% CI, 1.08-1.77). Conclusions: In patients with obstructive jaundice with resectable pancreatic head cancer, undergoing PBD before pancreaticoduodenectomy did not impair or benefit survival rates compared with surgery alone. However, TB before intervention >150 μmol/L predicted an unfavorable prognosis, irrespective of the PBD procedure.

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Short- and long-term effects of biliary drainage on hepatic cholesterol metabolism in the rat.

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