Guest guest Posted January 14, 2009 Report Share Posted January 14, 2009 Thank you for once again providing valuable information for everyone here ! I think it's a must read for me too- even though I am not a hepatologist :-) I would love to see the full artcle if possible and would really like to share it with Braden's doctors- thanks ! Lori lucky mom blessed with triplets In , " " wrote: > > Br. J. Pharmacol. 156: 7-27 (2009) > > Nuclear receptors as therapeutic targets in cholestatic liver > diseases. > > Zollner G, Trauner M > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 19, 2009 Report Share Posted January 19, 2009 Hey , I hope this finds you and your family well. I was curious if you would be willing to forward the article that you mentioned to me. Any intrest from in going to Chicago in May? Take care, Ross Subject: An excellent reviewTo: Date: Wednesday, January 14, 2009, 1:02 AM Br. J. Pharmacol. 156: 7-27 (2009)Nuclear receptors as therapeutic targets in cholestatic liver diseases.Zollner G, Trauner MLaboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.Cholestasis results in intrahepatic accumulation of cytotoxic bile acids, which cause liver damage ultimately leading to biliary fibrosis and cirrhosis. Cholestatic liver injury is counteracted by a variety of adaptive hepatoprotective mechanisms including alterations in bile acid transport, synthesis and detoxification. The underlying molecular mechanisms are mediated mainly at a transcriptional level via a complex network involving nuclear receptors including the farnesoid X receptor, pregnane X receptor, vitamin D receptor and constitutive androstane receptor, which target overlapping, although not identical, sets of genes. Because the intrinsic adaptive response to bile acids cannot fully prevent liver injury in cholestasis, therapeutic targeting of these receptors via specific and potent agonists may further enhance the hepatic defence against toxic bile acids. Activation of these receptors results in repression of bile acid synthesis, induction of phases I and II bile acid hydroxylation and conjugation and stimulation of alternative bile acid export while limiting hepatocellular bile acid import. Furthermore, the use of nuclear receptor ligands may not only influence bile acid transport and metabolism but may also directly target hepatic fibrogenesis and inflammation. Many drugs already used to treat cholestasis and its complications such as pruritus (e.g. ursodeoxycholic acid, rifampicin, fibrates) may act via activation of nuclear receptors. More specific and potent nuclear receptor ligands are currently being developed. This article will review the current knowledge on nuclear receptors and their potential role in the treatment of cholestatic liver diseases. PMID: 19133988.This is a "must read" for hepatologists. I can provide the full paper on request.Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 19, 2009 Report Share Posted January 19, 2009 Hey , I hope this finds you and your family well. I was curious if you would be willing to forward the article that you mentioned to me. Any intrest from in going to Chicago in May? Take care, Ross Subject: An excellent reviewTo: Date: Wednesday, January 14, 2009, 1:02 AM Br. J. Pharmacol. 156: 7-27 (2009)Nuclear receptors as therapeutic targets in cholestatic liver diseases.Zollner G, Trauner MLaboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.Cholestasis results in intrahepatic accumulation of cytotoxic bile acids, which cause liver damage ultimately leading to biliary fibrosis and cirrhosis. Cholestatic liver injury is counteracted by a variety of adaptive hepatoprotective mechanisms including alterations in bile acid transport, synthesis and detoxification. The underlying molecular mechanisms are mediated mainly at a transcriptional level via a complex network involving nuclear receptors including the farnesoid X receptor, pregnane X receptor, vitamin D receptor and constitutive androstane receptor, which target overlapping, although not identical, sets of genes. Because the intrinsic adaptive response to bile acids cannot fully prevent liver injury in cholestasis, therapeutic targeting of these receptors via specific and potent agonists may further enhance the hepatic defence against toxic bile acids. Activation of these receptors results in repression of bile acid synthesis, induction of phases I and II bile acid hydroxylation and conjugation and stimulation of alternative bile acid export while limiting hepatocellular bile acid import. Furthermore, the use of nuclear receptor ligands may not only influence bile acid transport and metabolism but may also directly target hepatic fibrogenesis and inflammation. Many drugs already used to treat cholestasis and its complications such as pruritus (e.g. ursodeoxycholic acid, rifampicin, fibrates) may act via activation of nuclear receptors. More specific and potent nuclear receptor ligands are currently being developed. This article will review the current knowledge on nuclear receptors and their potential role in the treatment of cholestatic liver diseases. PMID: 19133988.This is a "must read" for hepatologists. I can provide the full paper on request.Dave (father of (23); PSC 07/03; UC 08/03) Quote Link to comment Share on other sites More sharing options...
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