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In this article, the authors have extended their earlier work defining mechanisms associated with the manganese-bilirubin (Mn-BR) model of experimentally-induced intrahepatic cholestasis.

The authors have been using this model for over 20 years because of the similarities in the pathophysiological changes in BCM to those observed in cases of cholestasis in humans.

The question left unanswered was this: What is the metabolic basis that accounts for the newly synthesized cholesterol in BCM in the Mn-BR cholestasis model?

The investigators address this important question in the highlighted paper.

A major function of the liver is the formation of bile and hepatobiliary excretion of endogenous substances and xenobiotics, such as chemicals, drugs, and their metabolites.

In some forms of cholestasis, cholesterol metabolism is perturbed, resulting in cholesterol accumulation in liver bile canalicular membranes (BCM).

"A highly interesting contribution to the debate on Wittgenstein's philosophy.Because of their observation that the activity of this enzyme was decreased by over 50% after the Mn-BR treatment regimen (Duguay ., 2000), the authors concluded that factors other than an enhanced rate of cholesterol synthesis must account for the accumulation of newly synthesized cholesterol.Thus, prior to the present highlighted study, confounding data sets existed that could not explain the accumulation of newly synthesized cholesterol.Intrahepatic cholestasis can be caused by drugs, sepsis, total parenteral nutrition, lymphomas, tuberculosis, sarcoidosis, and amyloidosis.Other causes of this form of the disorder include primary biliary cirrhosis, primary sclerosing cholangitis, viral hepatitis, alcoholic liver disease, pregnancy, and inborn errors or mutations of bile acid metabolism.

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