33 research outputs found
Engineered Three-Dimensional Liver Mimics Recapitulate Critical Rat-Specific Bile Acid Pathways
A critical hepatic function is the maintenance of optimal bile acid (BA) compositions to achieve cholesterol homeostasis. BAs are rarely quantified to assess hepatic phenotype in vitro since existing analytical techniques have inadequate resolution. We report a detailed investigation into the biosynthesis and homeostasis of eight primary rat BAs in conventional in vitro hepatocyte cultures and in an engineered liver mimic. The three-dimensional (3D) liver mimic was assembled with layers of primary rat hepatocytes and liver sinusoidal endothelial cells. A high-pressure liquid chromatography and mass spectrometry technique was developed with a detection limit of 1 ng/mL for each BA, which is significantly lower than previous approaches. Over a 2-week culture, only 3D liver mimics exhibited the ratio of conjugated cholic acid to chenodeoxycholic acid that has been observed in vivo. This ratio, an important marker of BA homeostasis, was significantly higher in stable collagen sandwich cultures indicating significant deviation from physiological behavior. The biosynthesis of tauro-β-muricholic acid, a key primary rat BA, doubled only in the engineered liver mimics while decreasing in the other systems. These trends demonstrate that the 3D liver mimics provide a unique platform to study hepatic metabolism
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2006 GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN SIGNIFICANTLY IMPROVES VIROLOGIC RESPONSE AND ALT NORMALIZATION AT END-OF-TREATMENT AND IMPROVES SVR24 COMPARED TO PEG-IFN/RIBAVIRIN IN GENOTYPE-1 CHRONIC HCV PATIENTS
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277 GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN IMPROVES BIOPSY NECRO-INFLAMMATORY SCORES AND ALT NORMALIZATION AT 48 WEEKS VERSUS PEG-IFN/RIBAVIRIN IN GENOTYPE 1 CHRONIC HCV PATIENTS
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