scholarly journals Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro

2013 ◽  
Vol 7 (2) ◽  
pp. 215-224 ◽  
Author(s):  
S. Ng ◽  
S. March ◽  
A. Galstian ◽  
K. Hanson ◽  
T. Carvalho ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Human Hepatocytes ◽  
Liver Stage ◽  
Primary Human Hepatocytes

scholarly journals Gene Disruption of Plasmodium falciparum p52 Results in Attenuation of Malaria Liver Stage Development in Cultured Primary Human Hepatocytes

PLoS ONE ◽  
2008 ◽  
Vol 3 (10) ◽  
pp. e3549 ◽  
Author(s):  
Ben C. L. van Schaijk ◽  
Chris J. Janse ◽  
Geert-Jan van Gemert ◽  
Melissa R. van Dijk ◽  
Audrey Gego ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Disruption ◽  
Human Hepatocytes ◽  
Liver Stage ◽  
Primary Human Hepatocytes ◽  
Stage Development

scholarly journals Implications of Efficient Hepatic Delivery by Tenofovir Alafenamide (GS-7340) for Hepatitis B Virus Therapy

2015 ◽  
Vol 59 (6) ◽  
pp. 3563-3569 ◽  
Author(s):  
Eisuke Murakami ◽  
Ting Wang ◽  
Yeojin Park ◽  
Jia Hao ◽  
Eve-Irene Lepist ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Human Hepatocytes ◽  
Target Tissue ◽  
Small Contribution ◽  
Primary Human Hepatocytes ◽  
B Virus ◽  
Tenofovir Alafenamide ◽  
Pharmacologically Active

ABSTRACTTenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) currently in clinical evaluation for treatment for HIV and hepatitis B virus (HBV) infections. Since the target tissue for HBV is the liver, the hepatic delivery and metabolism of TAF in primary human hepatocytesin vitroand in dogsin vivowere evaluated here. Incubation of primary human hepatocytes with TAF resulted in high levels of the pharmacologically active metabolite tenofovir diphosphate (TFV-DP), which persisted in the cell with a half-life of >24 h. In addition to passive permeability, studies of transfected cell lines suggest that the hepatic uptake of TAF is also facilitated by the organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3, respectively). In order to inhibit HBV reverse transcriptase, TAF must be converted to the pharmacologically active form, TFV-DP. While cathepsin A is known to be the major enzyme hydrolyzing TAF in cells targeted by HIV, including lymphocytes and macrophages, TAF was primarily hydrolyzed by carboxylesterase 1 (CES1) in primary human hepatocytes, with cathepsin A making a small contribution. Following oral administration of TAF to dogs for 7 days, TAF was rapidly absorbed. The appearance of the major metabolite TFV in plasma was accompanied by a rapid decline in circulating TAF. Consistent with thein vitrodata, high and persistent levels of TFV-DP were observed in dog livers. Notably, higher liver TFV-DP levels were observed after administration of TAF than those given TDF. These results support the clinical testing of once-daily low-dose TAF for the treatment of HBV infection.

scholarly journals In VitroAnalysis of the Interaction between Atovaquone and Proguanil against Liver Stage Malaria Parasites

2016 ◽  
Vol 60 (7) ◽  
pp. 4333-4335 ◽  
Author(s):  
Lídia Barata ◽  
Pascal Houzé ◽  
Khadija Boutbibe ◽  
Gigliola Zanghi ◽  
Jean-François Franetich ◽  
...  
Keyword(s):  
Plasmodium Yoelii ◽  
Human Hepatocytes ◽  
High Efficacy ◽  
Liver Stage ◽  
Content Type ◽  
Cytochrome P450 Activity ◽  
Main Target ◽  
P450 Activity ◽  
Pharmacological Basis

ABSTRACTThe interaction between atovaquone and proguanil has never been studied against liver stage malaria, which is the main target of this drug combination when used for chemoprevention. Using human hepatocytes lacking cytochrome P450 activity, and thus avoiding proguanil metabolizing into potent cycloguanil, we showin vitrothat the atovaquone-proguanil combination synergistically inhibits the growth of rodentPlasmodium yoeliiparasites. These results provide a pharmacological basis for the high efficacy of atovaquone-proguanil used as malaria chemoprevention.

In vitro infection of primary human hepatocytes by HCV-positive sera: insights on a highly relevant model

Gut ◽  
2013 ◽  
Vol 63 (9) ◽  
pp. 1490-1500 ◽  
Author(s):  
Claire Gondeau ◽  
Philippe Briolotti ◽  
Francia Razafy ◽  
Cédric Duret ◽  
Pierre-Alain Rubbo ◽  
...  
Keyword(s):  
Human Hepatocytes ◽  
Relevant Model ◽  
Primary Human Hepatocytes

Long-term functional maintenance of primary human hepatocytes in vitro

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 399-402 ◽  
Author(s):  
Chengang Xiang ◽  
Yuanyuan Du ◽  
Gaofan Meng ◽  
Liew Soon Yi ◽  
Shicheng Sun ◽  
...  
Keyword(s):  
Cell Biology ◽  
Expression Profiles ◽  
Antiviral Drug ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Human Hepatocytes ◽  
Hbv Infection ◽  
Primary Human Hepatocytes

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

Long-term production of major coagulation factors and inhibitors by primary human hepatocytes in vitro: perspectives for clinical application

2007 ◽  
Vol 27 (6) ◽  
pp. 832-844 ◽  
Author(s):  
Kim A. Boost ◽  
Marcus K. H. Auth ◽  
Dirk Woitaschek ◽  
Hyun-Soo Kim ◽  
Philip Hilgard ◽  
...  
Keyword(s):  
Clinical Application ◽  
Coagulation Factors ◽  
Human Hepatocytes ◽  
Primary Human Hepatocytes

HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro

2011 ◽  
Vol 63 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Marc Lübberstedt ◽  
Ursula Müller-Vieira ◽  
Manuela Mayer ◽  
Klaus M. Biemel ◽  
Fanny Knöspel ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Cell Line ◽  
Hepatic Cell ◽  
Human Hepatocytes ◽  
Primary Human Hepatocytes ◽  
Hepatic Cell Line
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