Armstrong, Victor William

[["dc.bibliographiccitation.firstpage","107"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Clinical Biochemistry"],["dc.bibliographiccitation.lastpage","113"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Wieland, Eberhard"],["dc.contributor.author","Shipkova, Maria"],["dc.contributor.author","Schellhaas, Ulrike"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Niedmann, Paul Dieter"],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2021-06-01T10:50:05Z"],["dc.date.available","2021-06-01T10:50:05Z"],["dc.date.issued","2000"],["dc.description.abstract","Objectives: We have identified an acyl glucuronide (M-2) of the immunosuppressant mycophenolic acid (MPA). Acyl glucuronides have toxic potential and may contribute to drug toxicity. Whether acyl glucuronides are able to induce release of proinflammatory cytokines is unknown. Gastrointestinal disturbances have been observed during MPA therapy and may involve an inflammatory reaction. This study investigated whether M-2 can induce IL-6 and TNF-alpha release as well as gene expression of these cytokines in leukocytes. Design and methods: M-2 was produced by incubation of MPA with human liver microsomes. Human mononuclear leukocytes were incubated in the presence of M-2. Concentrations of IL-6 and TNF-alpha were measured by ELISA. Expression of mRNA was determined by quantitative RT-PCR. Results: Incubation of 3 x 10(6) cells with M-2 resulted in a time and dose dependent release of cytokines, whereas MPA or its phenolic glucuronide MPAG were without effect. Cytokine liberation depended on mRNA induction. Response to M-2 showed much inter individual variability (30-fold for IL-6, 3-fold for TNF-alpha). Conclusions: If M-2 promotes release of cytokines in vivo, these may mediate some of the toxic actions of MPA. Copyright (C) 2000 The Canadian Society of Clinical Chemists."],["dc.identifier.doi","10.1016/S0009-9120(99)00101-0"],["dc.identifier.isi","000086461900005"],["dc.identifier.pmid","10751588"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86520"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0009-9120"],["dc.title","Induction of cytokine release by the acyl glucuronide of mycophenolic acid: A link to side effects?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","53"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Biochemistry"],["dc.bibliographiccitation.lastpage","57"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Wieland, Eberhard"],["dc.contributor.author","Shipkova, Maria"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Braun, Felix"],["dc.contributor.author","Niedmann, Paul-Dieter"],["dc.contributor.author","Armstrong, Victor W."],["dc.contributor.author","Ringe, Burckhardt"],["dc.contributor.author","Svinarov, Dobrin A."],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2021-06-01T10:50:04Z"],["dc.date.available","2021-06-01T10:50:04Z"],["dc.date.issued","2001"],["dc.description.abstract","Objectives: Little is known about the effect of ischemia/reperfusion with xenogenic blood on function and gene expression of CYP3A4, the enzyme largely responsible for the metabolism of the immunosuppressants Cyclosporin A (CsA) and Tacrolimus. Design and methods: In a pig liver perfusion model, we have compared the effect of perfusion (3 h) after 20 h cold storage, with either pig or human blood on CsA metabolism and CYP3A4-mRNA expression. CYP3A4-mRNA was quantified by RT-PCR, CsA and its major metabolites AM1, AM9, AM4N by RP-HPLC. IL-6 served as inflammation marker, GLDH and ALT to estimate tissue damage. Results: Inflammatory response and tissue damage were more extensive during xenoperfusion. CYP3A4 expression decreased similarly during xenogenic and allogenic perfusion. CsA conversion to its metabolites was also comparable during xeno- and alloperfusion. Conclusion: There is no evidence that during the early reperfusion period pig liver CYP3A4 is severely affected if the organ is xenoperfused with human blood in comparison with alloperfusion. (C) 2001 The Canadian Society of Clinical Chemists. All rights reserved."],["dc.identifier.doi","10.1016/S0009-9120(00)00203-4"],["dc.identifier.isi","000169234600010"],["dc.identifier.pmid","11239516"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86518"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.conference","Analytical Conference 2000"],["dc.relation.eventlocation","MUNICH, GERMANY"],["dc.relation.issn","0009-9120"],["dc.title","Preliminary report on the effect of xenoperfusion with human blood on cyclosporin A metabolism and cytochrome-P-4503A4-mRNA expression in a pig liver perfusion model"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","113"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","116"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Tenderich, Gero"],["dc.contributor.author","Zittermann, Armin"],["dc.contributor.author","Oezpeker, Cenk"],["dc.contributor.author","Koerfer, Reiner"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Armstrong, Victor William"],["dc.date.accessioned","2021-06-01T10:46:58Z"],["dc.date.available","2021-06-01T10:46:58Z"],["dc.date.issued","2008"],["dc.description.abstract","In two separate pharmacokinetic studies, the drug interaction between immunosuppressive agents was examined in a total of 12 cardiac transplant recipients by conversion of the concomitant immunosuppressant. In, six patients under continuous tacrolimus therapy, the concomitant drug azathioprine was converted to everolimus (PK-TAC study). No significant effect on tacrolimus pharmacokinetic parameters was observed. In the second study in which the patients were converted from cyclosporine to tacrolimus under continuous everolimus therapy (PK-EVL study), a significant decrease in everolimus predose concentration (from 4.2 to 2.3 mu g/L), maximum concentration. (from 9.1 to 5.9 mu g/L), and area under the concentration time curve (mean values decreased from 64.2 to 33.7 mu g h/L) was found, indicating a lower everolimus exposure. A pharmacokinetic interaction between cyclosporine and everolimus has been described previously for healthy volunteers after single-dose application and presumably originates from a comparatively greater inhibition of hepatic CYP3A4 or P-glycoprotein efflux transporter with a low-dose cyclosporine regimen. Our results confirm this interaction under clinical conditions and suggest close drug monitoring when converting the calcineurin inhibitor under concomitant mammalian target of rapamycin-inhibitor therapy."],["dc.identifier.doi","10.1097/FTD.0b013e318161a335"],["dc.identifier.isi","000252877900019"],["dc.identifier.pmid","18223473"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85436"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Everolimus Exposure in Cardiac Transplant Recipients is Influenced by Concomitant Calcineurin Inhibitor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","ChemInform"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Armstrong, Victor W."],["dc.contributor.author","Shipkova, Maria"],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2021-12-08T12:29:19Z"],["dc.date.available","2021-12-08T12:29:19Z"],["dc.date.issued","2005"],["dc.identifier.doi","10.1002/chin.200502276"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/96028"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-476"],["dc.relation.eissn","1522-2667"],["dc.relation.issn","0931-7597"],["dc.rights.uri","http://doi.wiley.com/10.1002/tdm_license_1.1"],["dc.title","Analytic Aspects of Monitoring Therapy with Thiopurine Medications"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","73"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","78"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Brehmer, Franziska"],["dc.contributor.author","Petrova, Darinka T"],["dc.contributor.author","Gross, Oliver"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Armstrong, Victor W"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2021-06-01T10:46:58Z"],["dc.date.available","2021-06-01T10:46:58Z"],["dc.date.issued","2010"],["dc.description.abstract","Within the scope of this study, the potential antifibrotic effect of mycophenolate mofetil (MMF) on COL4A3-deficient mice as an animal model for progressive renal fibrosis was investigated regarding kidney function and survival. Thirty-five animals were randomly assigned to one of five groups and treated with doses of 0, 10, 50, 100, or 150 mg/kg MMF per day, respectively. When increasing somnolence was observed, indicating end-stage renal disease, the mice were euthanized and blood was obtained. Serum concentrations of creatinine, urea nitrogen, total protein, mycophenolic acid (MPA), and mycophenolic acid glucuromide (MPAG) were quantified. The kidney histology was examined using hematoxylin and eosin as well as trichrome staining. The mean overall survival was 65.9 (+/- 6.1) days with no significant difference between the treatment groups (P > 0.05, Mantel-Cox test). Serum predose concentrations of MPA and MPAG showed considerable interindividual variability. There was no correlation between Survival time and MPA or MPAG concentrations (P > 0.05, Spearman rank correlation). However, an apparent decrease in serum creatinine and urea nitrogen concentrations was observed at higher doses of MMF, eg, -54% for creatinine in the 150-mg/kg/day group compared with placebo. A highly significant reciprocal correlation between MPA concentrations and serum creatinine was demonstrated (P < 0.01, r = -0.655, Spearman rank correlation). In conclusion, MMF may be a candidate drug for preserving kidney function in progressive renal fibrosis."],["dc.identifier.doi","10.1097/FTD.0b013e3181c91fc4"],["dc.identifier.isi","000274072000011"],["dc.identifier.pmid","20042922"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85439"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Mycophenolic Acid Predose Concentrations and Renal Function in a Mouse Model for Progressive Renal Fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1194"],["dc.bibliographiccitation.issue","16-17"],["dc.bibliographiccitation.journal","Clinical Biochemistry"],["dc.bibliographiccitation.lastpage","1200"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Dresing, Klaus"],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Leip, Casper-Lennart"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Burchardi, Hilmar"],["dc.contributor.author","Stuermer, Klaus-Michael"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2018-11-07T10:55:48Z"],["dc.date.available","2018-11-07T10:55:48Z"],["dc.date.issued","2007"],["dc.description.abstract","Objectives: The aim was to investigate the outcome MODS/MOF in critically ill patients with regard to early hepatic dysfunction. Methods: Thirty adult polytrauma patients admitted to the ICU, with ISS >= 16 were prospectively investigated. Real-time liver function was assessed using the MEGX test and arterial ketone body ratio (AKBR) 12-24 h after admittance to ICU, and on days 3, 5, 8, 12. Results: Six patients (19%) died between days 4 and 29. Non-survivors were older (64.2 vs. 31.5 years), had a significantly higher ISS (40.5 vs. 30; p=0.002) and MODS score (9.5 vs. 5; p=0.001) on admittance to the ICU than survivors. On day 3 MEGX values (31 vs. 71.3 mu g/L; p=0.001) and the AKBRs (0.6 vs. 1.3; p=0.001) were significantly lower in non-survivors than in survivors whereas IL-6 levels were significantly higher in the former group (519 vs. 61 mu g/L; p = 0.05). Conclusions: The MEGX test and AKBR are sensitive early indicators of hepatic dysfunction in severely injured polytrauma patients at risk for developing MODS/MOF. (C) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.clinbiochem.2007.06.013"],["dc.identifier.isi","000250605200004"],["dc.identifier.pmid","17707362"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49869"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0009-9120"],["dc.title","Real-time assessment of hepatic function is related to clinical outcome in critically ill patients after polytrauma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","677"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Heller, Tanja"],["dc.contributor.author","Kirchheiner, Julia"],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Luthe, Hilmar"],["dc.contributor.author","Tzvetkov, Mladen"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2018-11-07T09:14:09Z"],["dc.date.available","2018-11-07T09:14:09Z"],["dc.date.issued","2006"],["dc.description.abstract","Methods for Cytochrome P450-2D6 (CYP2D6) genotyping are often time-consuming and laborious, which can restrict their use in pretherapeutic screening programs. Gene chip technology could overcome this problem. The aim of this study was to evaluate CYP2D6 genotyping by a new improved gene chip compared to a PCR-RFLP method. AmpliChip CYP450 GeneChip (R) (AmpliChip) is a microarray hybridization method for genotyping CYP2D6 and CYP2C19. One hundred fifty-nine DNA samples were genotyped both by AmpliChip as well as by PCR-RFLP and, where applicable, by a SNaPshot technique which detects single nucleotide polymorphisms based on the single base extension principle. In 152 of the 159 samples, CYP2D6 genotypes determined with the AmpliChip were in accordance with the results of PCR-RFLP. All seven discrepant samples had gene duplications and were subjected to SNaPshot analysis. SNaPshot results concurred with those of the AmpliChip for six out of seven samples. In the one divergent result, DNA sequencing confirmed that the AmpliChip had assigned the correct genotype. In conclusion, AmpliChip is a highly reliable method for CYP2D6 genotyping that allows the correct determination of all relevant CYP2D6 alleles in one single run. It therefore represents a very efficient and fast method, offering new perspectives for the application of pharmacogenetics in clinical medicine."],["dc.identifier.doi","10.1097/01.ftd.0000246764.67129.2a"],["dc.identifier.isi","000241347600017"],["dc.identifier.pmid","17038884"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27336"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","AmpliChip CYP450 GeneChip (R): A new gene chip that allows rapid and accurate CYP2D6 genotyping"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2873"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Diabetes"],["dc.bibliographiccitation.lastpage","2879"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Nyirenda, Moffat J."],["dc.contributor.author","Carter, Roderick"],["dc.contributor.author","Tang, Justin I."],["dc.contributor.author","de Vries, Annick"],["dc.contributor.author","Schlumbohm, Christina"],["dc.contributor.author","Hillier, Stephen G."],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Fuchs, Eberhard"],["dc.contributor.author","Seckl, Jonathan R."],["dc.date.accessioned","2018-11-07T11:21:24Z"],["dc.date.available","2018-11-07T11:21:24Z"],["dc.date.issued","2009"],["dc.description.abstract","OBJECTIVE-Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), which amplifies local I issue glucocorticoid concentrations. The reasons for this 11 beta-HSD1 dystegulation are unknown. Here, we tested whether 11 beta-HSD1 expression, like the metabolic syndrome, is \"programmed\" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey. RESEARCH DESIGN AND METHODS-We used a \"fetal programming\" paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11 beta-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age. RESULTS-Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11 beta-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous-but not visceral-fat. The increase in 11 beta-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets. CONCLUSIONS-These data suggest that long-term upregulation of 11 beta-HSD1 in metabolically active tissues may follow prenatal \"stress\" hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome. Diabetes 58:2873-2879, 2009"],["dc.description.sponsorship","European Commission [QLRT-2001-02758]; MRC"],["dc.identifier.doi","10.2337/db09-0873"],["dc.identifier.isi","000272522000021"],["dc.identifier.pmid","19720800"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55764"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Diabetes Assoc"],["dc.relation.issn","0012-1797"],["dc.title","Prenatal Programming of Metabolic Syndrome in the Common Marmoset Is Associated With Increased Expression of 11 beta-Hydroxysteroid Dehydrogenase Type 1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","570"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","575"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Weber, Lutz T."],["dc.contributor.author","Hoecker, Britta"],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Toenshoff, Burkhard"],["dc.date.accessioned","2018-11-07T11:10:51Z"],["dc.date.available","2018-11-07T11:10:51Z"],["dc.date.issued","2008"],["dc.description.abstract","Data on exposure to mycophenolic acid (MPA), the active moiety of mycophenolate mofetil (MMF), in pediatric renal transplant recipients beyond the first year posttransplant are scarce. The authors therefore analyzed the long-term pharmacokinetics of MPA in 25 pediatric patients treated with 600 mg MMF/m(2) body surface area twice a day in conjunction with cyclosporine A and prednisone. Plasma samples for 12-hour pharmacokinetic profiles were collected on day 7, and after 3, 9, 24, and 36 months posttransplant. Both the actual and the dose-normalized MPA-area under the concentration-time curve (AUC(0-12)) increased approximately 2-fold between day 7 and month 9 but stabilized thereafter. Both the actual and the dose-normalized MPA-AUC(0-12) at months 24 and 36 were comparable to that at month 9. Presuming a therapeutic window of 30-60 mg h/L, 15 (60%) of 25 patients at day 7 had an MPA-AUC(0-12) < 30 mg h/L, indicating potential underexposure, whereas the proportion of patients with an MPA-AUC(0-12) <30 mg h/L between months 3 and 36 was low (5%-17%). These data suggest that the recommended MMF dose of 600 mg/m(2) body surface area twice a day in conjunction with cyclosporine A leads to MPA underexposure early posttransplant in a significant subset of patients, indicating a need for a higher initial MMF dose. Dose-normalized MPA exposure increases in the first 9 months posttransplant, consistent with a reduced MPA metabolism and increased enterohepatic recycling of MPA."],["dc.identifier.doi","10.1097/FTD.0b013e31818752d9"],["dc.identifier.isi","000259730700004"],["dc.identifier.pmid","18758392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53301"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Long-term pharmacokinetics of mycophenolic acid in pediatric renal transplant recipients over 3 years posttransplant"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","393"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biochimie"],["dc.bibliographiccitation.lastpage","402"],["dc.bibliographiccitation.volume","89"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Voland, Antje"],["dc.contributor.author","Wieland, Eberhard"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Shipkova, Maria"],["dc.date.accessioned","2018-11-07T11:04:13Z"],["dc.date.available","2018-11-07T11:04:13Z"],["dc.date.issued","2007"],["dc.description.abstract","Covalent binding of the acyl glucuronide (AcMPAG) metabolite of the immunosuppressant mycophenolic acid (MPA) to proteins is considered a possible initiating event for organ toxicity. Since the kidney is involved in the formation and excretion of AcMPAG, it can be hypothesized that this tissue may be exposed to relatively high concentrations of this metabolite and would, therefore, be a particularly suitable organ to investigate AcMPAG protein targets. In the present study we identified potential AcMPAG target proteins in kidney tissues from Wistar rats treated with mycophenolate mofetil (40 mg/kg/day over 21 days). Proteins were separated by 2-DE and covalent protein adducts were detected by Western blotting with an antibody specific for MPA/AcMPAG. The corresponding coomassie blue stained proteins from parallel gels were subjected to in-gel tryptic digestion and peptides were characterized on a Q-TOF Ultima Global. The protein targets were further verified by immunoprecipitation with anti-MPA/AcMPAG antibody to purify the modified proteins followed by 1-DE and MS analysis. Database searches revealed several AcMPAG target proteins that could be related to ultrastructural abnormalities, metabolic effects, and altered oxidative stress/detoxification responses. Predominately cytosolic proteins such as selenium binding protein, protein disulfide isomerase, aldehyde dehydrogenase, triosephosphate isomerase, and kidney aminoacylase were involved in adduct formation. Two cytoskeletal proteins tropomyosin 1 and 4 as well as the antioxidant proteins peroxiredoxin 3 and 6 were also targets of AcMPAG. Functional consequences from these protein modifications remain to be demonstrated. (c) 2006 Elsevier Masson SAS. All rights reserved."],["dc.identifier.doi","10.1016/j.biochi.2006.09.016"],["dc.identifier.isi","000245998900015"],["dc.identifier.pmid","17069946"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51788"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier France-editions Scientifiques Medicales Elsevier"],["dc.relation.issn","0300-9084"],["dc.title","Proteins identified as targets of the acyl glucuronide metabolite of mycophenolic acid in kidney tissue from mycophenolate mofetil treated rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]