We tested the hypothesis that differential expression of liver plasma membrane transporters might account for variations in biliary lipid secretion rates between gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice. Plasma membrane fractions and total RNA isolated from livers of mice fed with a control or lithogenic (15% fat/1.25% cholesterol/0.5% cholic acid) diet were used for meas...

Cholyl-L-lysyl-fluorescein (CLF) is a fluorescent bile salt derivative that is being developed as an agent for determining in vivo liver function. However, the mechanisms of uptake and excretion by hepatocytes have not been rigorously studied. We have directly assessed the transport capacity of various hepatobiliary transporters for CLF. Uptake experiments were performed in Chinese hamster ovar...

Generation of bile is a key function of the liver. Its impairment leads to accumulation of cytotoxic bile salts in hepatocytes and, consequently, to liver disease. The bile salt export pump, BSEP, is critically involved in the secretion of bile salts into bile. Its function can be disturbed or abolished by inherited mutations. This will lead to progressive intrahepatic cholestais and severe liv...

BACKGROUND Intrahepatic cholestasis of pregnancy (ICP) is a cholestasis condition caused by elevated levels of serum bile acids that mainly occurs in the third trimester of pregnancy. Maternal symptoms include pruritus; elevation of transaminases, biliary enzymes, and bilirubin levels; and abnormal liver function tests. Fetal symptoms include spontaneous preterm labor, fetal distress, and intra...

The bile salt export pump (BSEP, ABCB11) plays an essential role in the formation of bile. In hepatocytes, BSEP is localized within the apical (canalicular) membrane and a deficiency of canalicular BSEP function is associated with severe forms of cholestasis. Regulation of correct trafficking to the canalicular membrane and of activity is essential to ensure BSEP functionality and thus normal b...

Intrahepatic bile acid accumulation due to inhibition of the bile salt export pump (BSEP) has been proposed as a mechanism for drug-induced cholestasis. Many cholestatic drugs do not initiate hepatotoxicity in rats, although they inhibit rat Bsep and cause elevated serum bile acid concentration. In this study, we examined changes in the taurocholate (TC) transport in response to cholestatic dru...

We induced gallstones in C57L mice fed with a high cholesterol diet and examined the expression of bile salt export pump (BSEP) on the canalicular membrane of hepatocytes and its relation with PKCα and HAX-1.Twenty-four gallstone-prone C57L mice were randomly assigned to receive a high cholesterol diet or a regular diet. Gallstone formation was recorded. BSEP, PKCα and phospho-PKCα expression w...

Inhibition of the bile salt export pump (BSEP) has been recognized as a key factor in the development of drug-induced cholestasis (DIC). The risk of DIC in humans has been previously assessed using in vitro BSEP inhibition data (IC50) and unbound systemic drug exposure under assumption of the "free drug hypothesis." This concept, however, is unlikely valid, as unbound intrahepatic drug concentr...

INTRODUCTION The bile salt export pump (BSEP/ABCB11), residing in the apical membrane of hepatocyte, mediates the secretion of bile salts into the bile. A range of human diseases is associated with the malfunction of BSEP, including fatal hereditary liver disorders and mild cholestatic conditions. Manifestation of these diseases primarily depends on the mutation type; however, other factors suc...

BACKGROUND Little objective evidence exists regarding what makes a good lecture. Our purpose was to determine qualities of radiology review course lectures that are associated with positive audience evaluation. METHODS 57 presentations from the Ottawa Resident Review Course (2012) were analyzed by a PGY4 radiology resident blinded to the result of audience evaluation. Objective data extracted...