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1.
Med Monatsschr Pharm ; 40(4): 147-50, 2017 Apr.
Article in English, German | MEDLINE | ID: mdl-29952162

ABSTRACT

During the last years, treatment of chronic hepatitis C virus infection (HCV) was characterized by the development of new therapeutic agents and their combined use. By now the problem of treating HCV seems to be largely solved. The broad range of available therapeutics has the potential to enable a complete cure of this liver disease, which is associated with many complications, thus providing also economic benefits.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Drug Therapy, Combination , Hepacivirus , Hepatitis C/history , Hepatitis C, Chronic/drug therapy , History, 20th Century , History, 21st Century , Humans
2.
Eur J Gastroenterol Hepatol ; 17(2): 169-77, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15674094

ABSTRACT

BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, improves biochemical, immunopathological and histological parameters in chronic cholestatic liver diseases. The immunomodulatory properties of UDCA show interesting similarities with the effects of glucocorticoids. We investigated the activation of the glucocorticoid receptor by UDCA and the glucocorticoid receptor dependent gene expression in primary rat hepatocytes as well as binding of radiolabelled UDCA to the glucocorticoid receptor ligand binding site expressed in a glucocorticoid receptor fusion protein. METHODS: Primary rat hepatocytes in culture were co-transfected with a luciferase reporter gene construct (GRE-luc) containing a glucocorticoid receptor responsive element (GRE) and a glucocorticoid receptor expression vector (6RGR) followed by stimulation with dexamethasone or UDCA. Luciferase activity was determined and specific binding of glucocorticoid receptor to the GRE was confirmed by an electrophoretic mobility shift assay (EMSA). The glucocorticoid receptor binding site was expressed in a GR-myc fusion protein and binding of radiolabelled UDCA to the fusion protein was determined. RESULTS: Incubation of co-transfected hepatocytes with 0.1-1.000 microM dexamethasone or 0.1-1.000 microM UDCA led to an 11.9- to 20.85-fold (dexamethasone) and 2.6- to 4.3-fold (UDC) increase of luciferase activity. Mobility shift assays using nuclear extracts from transfected and stimulated hepatocytes also showed a dose dependent increase of DNA binding after stimulation with UDCA. However, incubation of the GR-myc fusion protein with radiolabelled UDCA yielded no specific binding of UDCA to the glucocorticoid receptor binding site, whereas dexamethasone showed specific binding of the fusion protein. CONCLUSIONS: UDCA activates the intracellular glucocorticoid receptor in a dose-dependent manner. Direct binding of the glucocorticoid receptor by radiolabelled UDCA at the glucocorticoid receptor binding site could be excluded as the mechanism of activation. The mechanisms involved in UDCA-mediated glucocorticoid receptor activation and possible targeted glucocorticoid receptor activation due to partial UDCA tissue specificity warrant further elucidation.


Subject(s)
Hepatocytes/drug effects , Receptors, Glucocorticoid/drug effects , Ursodeoxycholic Acid/pharmacology , Animals , Cells, Cultured , Dexamethasone/pharmacology , Electrophoretic Mobility Shift Assay , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Gene Expression Regulation/drug effects , Genes, Reporter , Genetic Vectors , Glucocorticoids/pharmacology , Hepatocytes/metabolism , Luciferases/genetics , Luciferases/metabolism , Male , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Transduction, Genetic , Transfection , Ursodeoxycholic Acid/metabolism
3.
Dermatology ; 205(2): 174-5, 2002.
Article in English | MEDLINE | ID: mdl-12218237

ABSTRACT

Induction of multiple eruptive dermal and atypical melanocytic naevi has frequently been reported in children with malignant haematological diseases and chemotherapy-induced immunosuppression. This is the first report of an adult patient to develop multiple eruptive melanocytic skin lesions while undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing cancer. Our observation adds further evidence to the link between systemic (iatrogenic or intrinsic) immunosuppression and the induction of melanocyte proliferation and transformation.


Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Carcinoma/drug therapy , Carcinoma/secondary , Colorectal Neoplasms/pathology , Deoxycytidine/analogs & derivatives , Deoxycytidine/adverse effects , Drug Eruptions/etiology , Hutchinson's Melanotic Freckle/chemically induced , Prodrugs/adverse effects , Skin Neoplasms/diagnosis , Administration, Oral , Antimetabolites, Antineoplastic/administration & dosage , Capecitabine , Deoxycytidine/administration & dosage , Drug Eruptions/diagnosis , Drug Eruptions/pathology , Fluorouracil , Humans , Hutchinson's Melanotic Freckle/diagnosis , Hutchinson's Melanotic Freckle/pathology , Male , Melanoma/physiopathology , Middle Aged , Neoplasms, Second Primary/chemically induced , Neoplasms, Second Primary/pathology , Nevus, Pigmented/chemically induced , Nevus, Pigmented/diagnosis , Nevus, Pigmented/pathology , Prodrugs/administration & dosage , Skin/pathology , Skin Neoplasms/chemically induced , Skin Neoplasms/pathology , Skin Neoplasms/physiopathology
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