Ramadori, Giuliano

[["dc.bibliographiccitation.firstpage","1807"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","1821"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Alwahsh, Salamah Mohammad"],["dc.contributor.author","Xu, Min"],["dc.contributor.author","Seyhan, Hatice Ali"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Schultze, Frank Christian"],["dc.date.accessioned","2018-11-07T09:43:39Z"],["dc.date.available","2018-11-07T09:43:39Z"],["dc.date.issued","2014"],["dc.description.abstract","AIM: To explore lipocalin-2 (LCN-2) expression and its possible role and mechanism(s) of production in rat models of diet-inducible fatty liver. METHODS: Fatty liver was triggered in male Sprague-Dawley rats fed either with liquid Lieber-DeCarli (LDC) or LDC + 70% cal fructose (L-HFr) diet for 4 or 8 wk. Chow-nourished animals served as controls. Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting. Serum LCN-2, fasting leptin, and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay, Radioimmunoassay, and colorimetric assays, respectively. The localization of LCN-2 in the liver was detected by using immunofluorescence staining. Furthermore, HE stain was used to evaluate hepatic fat degeneration and inflammation. RESULTS: Both LDC-fed and L-HFr-fed rat histologically featured fatty liver. In the liver, mRNA transcriptions of Mcp-1, a2-m, Il-8 and Glut5 were increased in the L-HFr group at both time points (P < 0.001), while the transcription of Tlr4, Inos, and Tnf-alpha was significantly up-regulated at week 4. Interestingly, hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control (P < 0.001). In contrast to HDL-cholesterol, systemic levels of LCN-2, fasting leptin and triglycerides were elevated in the L-HFr regimen (P < 0.001). Moreover, protein expression of hepatic LCN-2, CD14, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal was increased in the L-HFr group. Conversely, the hepatic expression of PGC-1 alpha (a mitochondrial-biogenic protein) was reduced in the L-HFr category at week 8. The localization of LCN-2 in the liver was predominantly restricted to MPO+ granulocytes. CONCLUSION: Fructose diet up-regulates hepatic LCN-2 expression, which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction. The LCN-2 may be involved in liver protection. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved."],["dc.description.sponsorship","Open Access Publikationsfonds 2014"],["dc.identifier.doi","10.3748/wjg.v20.i7.1807"],["dc.identifier.isi","000331966100016"],["dc.identifier.pmid","24587658"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34228"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Baishideng Publ Grp Co Ltd"],["dc.relation.issn","2219-2840"],["dc.relation.issn","1007-9327"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e104220"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Alwahsh, Salamah Mohammad"],["dc.contributor.author","Xu, Min"],["dc.contributor.author","Schultze, Frank Christian"],["dc.contributor.author","Wilting, Joerg"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T09:36:45Z"],["dc.date.available","2018-11-07T09:36:45Z"],["dc.date.issued","2014"],["dc.description.abstract","Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (<= 3rd week), whereas fructose-fed animals had higher LW than controls ( P < 0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide: insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial beta-oxidation of fatty acids (Cpt1 alpha and Ppar-alpha expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage."],["dc.description.sponsorship","Open Access Publikationsfonds 2014"],["dc.identifier.doi","10.1371/journal.pone.0104220"],["dc.identifier.isi","000339993900050"],["dc.identifier.pmid","25101998"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10788"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32686"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Combination of Alcohol and Fructose Exacerbates Metabolic Imbalance in Terms of Hepatic Damage, Dyslipidemia, and Insulin Resistance in Rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","218"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Digestion"],["dc.bibliographiccitation.lastpage","227"],["dc.bibliographiccitation.volume","86"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Goralczyk, Armin Dietmar"],["dc.contributor.author","Schneider, S."],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Lindhorst, Alexander"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","van Thiel, D. H."],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T09:14:47Z"],["dc.date.available","2018-11-07T09:14:47Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-a and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. Methods: Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. Results:The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low gamma-glutamyltransferase (gamma-GT) serum activities, a low pretreatment gamma-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1-16.7, p < 0.001), low pretreatment gamma-GT/ALT ratio (OR = 2.5, CI: 1.7-3.3, p <0.001), age (OR = 0.96, CI: 0.94-0.98, p = 0.001) and RVR (OR = 4.18, CI: 2.85-8.65, p <0.001) to be significantly related to treatment outcome. Patients with the IL28B rs12979860 CC genotype and a low pretreatment gamma-GT/ALT ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10-71.1, p<0.0001). Conclusion: The pretreatment gamma-GT/ALT ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-alpha-based combination therapy in a nontriaged ordinary setting. Copyright (C) 2012 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000339879"],["dc.identifier.isi","000310717600007"],["dc.identifier.pmid","22964578"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9079"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27501"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1421-9867"],["dc.relation.issn","0012-2823"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","High Predictability of a Sustained Virological Response (87%) in Chronic Hepatitis C Virus Genotype 1 Infection Treatment by Combined IL28B Genotype Analysis and gamma-Glutamyltransferase/Alanine Aminotransferase Ratio: A Retrospective Single-Center Study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3296"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Digestive Diseases and Sciences"],["dc.bibliographiccitation.lastpage","3304"],["dc.bibliographiccitation.volume","56"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Goralczyk, Armin"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Schaefer, Inga-Marie"],["dc.contributor.author","van Thiel, David H."],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:50:09Z"],["dc.date.available","2018-11-07T08:50:09Z"],["dc.date.issued","2011"],["dc.description.abstract","Background and Aims The standard treatment regimen for chronic HCV genotype 3 (HCV-G3) hepatitis consists of PEGylated interferon-alpha (IFN-alpha) and ribavirin at varying doses ranging from 400 to 1,200 mg and results in response rates of 80%. However, this therapy has substantial side-effects including anemia, is teratogenic, and costly. To reduce the side-effects of therapy, the role of monotherapy consisting of only IFN-alpha was investigated. Methods A retrospective analysis of individual therapy courses of HCV-G3-infected patients who were treated with IFN-alpha(2a) monotherapy or a combination therapy with attention to the treatment outcome and the presence of IL28B rs12979860 and IL28B rs8099917 single-nucleotide polymorphism genotypes was performed. Conventional prognostic features in each case were assessed as well. Results In the study, 15/30 (50%) of patients treated with IFN-alpha(2a) monotherapy and 32/36 (89%) treated with combination therapy achieved a sustained virological response (SVR). In addition, 7/11 (64%) of those treated initially with monotherapy and subsequently with combination therapy achieved an SVR. An \"ultra-rapid\" virological response occurring within 2 weeks of initiation of therapy (p = 0.005), young age (< 40; p < 0.001) and low initial gamma-GT/ALT-ratio (p = 0.03) were associated with a SVR to IFN-alpha(2a) monotherapy. An SVR in those treated with combination therapy was found to be associated with a rapid virological response (RVR) (p = 0.03). The absence of histologic steatosis was associated with SVR in all patient groups (p = 0.01). Therapy duration (24 vs. 48 weeks) did not affect the SVR in either group. As expected, combination therapy resulted in more hematological side-effects than did monotherapy. Conclusions An \"ultra-rapid\" virological response, young age, low initial gamma-GT/ALT-ratio and absence of steatosis were each associated with an SVR in those receiving IFN-alpha(2a) monotherapy. Therefore, monotherapy in these patients should still be discussed independently of the existence of the IL28B polymorphisms."],["dc.identifier.doi","10.1007/s10620-011-1933-2"],["dc.identifier.isi","000296643400027"],["dc.identifier.pmid","21994136"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21634"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0163-2116"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Ultra-Rapid Virological Response, Young Age, Low gamma-GT/ALT-Ratio, and Absence of Steatosis Identify a Subgroup of HCV Genotype 3 Patients Who Achieve SVR with IFN-alpha(2a) Monotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e84026"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Kopp, Waltraut"],["dc.contributor.author","Spengler, Ulrich"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Mihm, Sabine"],["dc.date.accessioned","2018-11-07T09:16:29Z"],["dc.date.available","2018-11-07T09:16:29Z"],["dc.date.issued","2013"],["dc.description.abstract","Eradication of hepatitis C virus (HCV) infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype allele TT of a dinucleotide polymorphism, ss469415590, located within a new protein-coding gene. While the TT allele introduces a frame-shift and disrupts the open reading frame, only the variant allele, Delta G, creates a novel type III interferon (IFN) protein, IFN-lambda(4)/IFNL4. Absence of IFNL4 is thus supposed to favor resolution of HCV infection. As to date IFNL4 mRNA transcription has only been investigated in polyl:C-stimulated primary human hepatocytes and not yet in HCV infection in vivo, this study analyzed IFNL4 mRNA expression in human liver biopsy specimens. Samples were obtained from patients with a broad panel of disorders including no liver disease, liver diseases of non-viral etiology, chronic hepatitis B and chronic hepatitis C. Hepatic IFNL4 transcripts were detectable exclusively in a subgroup of chronic hepatitis C patients (24/45). Their amounts were positively related to liver HCV RNA copy numbers (p = 0.0023, r = 0.56) suggesting that the hepatic viral load influences IFNL4 transcription irrespective of IFNL4 governing genotype. Both, the IFNL4 creating allele Delta G (p<0.0001) and actual IFNL4 transcription (p = 0.0015) were found to be correlated to the activation of IFN stimulatory genes (ISGs). By contrast, IFNL4 ss469415590 genotypes were not found to be related to IFN-lambda(2/3)/IL28 or IFN-lambda(1)/IL29 gene expression. In conclusion, this study is the first report on intrahepatic transcript levels of the recently discovered IFNL4 gene. Data indicate that HCV infection in particular might activate IFNL4 transcription in the liver. It provides a possible explanation as to why hepatitis C patients show ISG stimulation in their livers in the apparent absence of an induction of other IFN subtypes."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2013"],["dc.identifier.doi","10.1371/journal.pone.0084026"],["dc.identifier.isi","000328745100154"],["dc.identifier.pmid","24376784"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9755"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27945"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Interferon- lambda(4) (IFNL4) Transcript Expression in Human Liver Tissue Samples"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","815"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Molecular Medicine"],["dc.bibliographiccitation.lastpage","824"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Mertens, Jasmin"],["dc.contributor.author","Bregadze, Rusudan"],["dc.contributor.author","Mansur, Ashham"],["dc.contributor.author","Askar, Eva"],["dc.contributor.author","Bickeboeller, Heike"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Mihm, Sabine"],["dc.date.accessioned","2018-11-07T08:27:20Z"],["dc.date.available","2018-11-07T08:27:20Z"],["dc.date.issued","2009"],["dc.description.abstract","The polymorphism rs2569190 within the CD14 endotoxin (lipopolysaccharide, LPS) receptor gene is associated with various disease conditions that are assumed to rely on endotoxin sensitivity. In vitro experiments suggest that the T allele sensitizes the host for exogenous or endogenous LPS via an enhanced CD14 expression. To prove the impact of this single nucleotide polymorphism in its natural genomic context in vivo, two parameters of gene transcription were analyzed in peripheral blood mononuclear cells (PBMC) from single healthy individuals: (a) recruitment of RNA polymerase II by haplotype-specific chromatin immunoprecipitation and (b) the relative amount of transcripts by allele-specific transcript quantification (ASTQ). RNA polymerase II was found to be twice as much bound to the most prevalent haplotype, C-T-C-G, the only one carrying a T at the position rs2569190 of interest. ASTQ employing two independent read-out assays revealed, however, similar transcript numbers originating from C-T-C-G and non-C-T-C-G haplotypes. Total CD14 mRNA levels from freshly isolated PBMC, moreover, were neither related to donors' geno- nor haplogenotypes. Our data argue for a functional impact of the rs2569190 polymorphism in terms of a stronger transcription initiation on T allele gene variants even if preferential allele-specific binding does not result in an increase in transcript numbers. Endotoxin sensitivity associated with this genetic variation appears not to rely solely on a cis-acting regulatory impact of rs2569190 on CD14 gene transcription in PBMC."],["dc.identifier.doi","10.1007/s00109-009-0479-7"],["dc.identifier.isi","000267827100008"],["dc.identifier.pmid","19468702"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3474"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16187"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0946-2716"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Functional impact of endotoxin receptor CD14 polymorphisms on transcriptional activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]