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| 1 | RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic prosthesis loosening显示文摘AIM To assess serum levels of RANK-ligand(RANKL) and osteoprotegerin(OPG) as biomarkers for periprosthetic joint infection(PJI) and compare their accuracy with standard tests.METHODS One hundred and twenty patients presenting with a painful total knee or hip arthroplasty with indication for surgical revision were included in this prospective clinical trial. Based on standard diagnostics(joint aspirate, microbiological, and histological samples) and Musculoskeletal Infection Society consensus classification,patients were categorized into PJI, aseptic loosening,and control groups. Implant loosening was assessed radiographically and intraoperatively. Preoperative serum samples were collected and analyzed for RANKL, OPG, calcium, phosphate, alkaline phosphatase(AP), and the bone-specific subform of AP(b AP). Statistical analysis was carried out, testing for significant differences between the three groups and between stable and loose implants. RESULTS All three groups were identical in regards to age, gender, and joint distribution. No statistically significant differences in the serum concentration of RANKL(P = 0.16) and OPG(P = 0.45) were found between aseptic loosening and PJI, with a trend towards lower RANKL concentrations and higher OPG concentrations in the PJI group. The RANKL/OPG ratio was significant for the comparison between PJI and non-PJI(P = 0.005). A ratio > 60 ruled out PJI in all cases(specificity: 100%, 95%CI: 89, 11% to 100.0%) but only 30% of non-PJI patients crossed this threshold. The positive predictive value remained poor at any cut-off. In the differentiation between stable and loose implants, none of the parameters measured(calcium, phosphate, AP, and b AP) showed a significant difference, and only AP and b AP measurements showed a tendency towards higher values in the loosened group(with P = 0.09 for AP and P = 0.19 for b AP). CONCLUSION Lower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance. | Max J Friedrich Matthias D Wimmer Jan Schmolders Andreas C Strauss Milena M Ploeger Hendrik Kohlhof Dieter C Wirtz Sascha Gravius Thomas M Randau | 2017 | World Journal of Orthopedics2017，8，4： | 4 |
| 2 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 3 | Stable transformation of a Mamestra brassicae (lepidoptera) cell line with the lepidopteran-derived transposon piggyBac 显示文摘 | Mandrioli M Wimmer EA | 2003 | Insect Biochem Mol Biol2003，33，1： | 1 |
| 4 | Gas chro- matography analysis of blackcurrant oil in relation to its stability 显示文摘 | STRANSKY K ZAREVUCKA M WIMMER Z | 2005 | Food Chem2005，92，3： | 1 |
| 5 | Boron-and-salt interactions in wheat areaffected by boron supply显示文摘 | Wimmer M A Goldbach H E | 2012 | Journal of Plant Nutrition and Soil Science、2012，175，2： | 1 |
| 6 | Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease显示文摘 | Stumpflen I Stumpflen A Wimmer M | 1996 | Lancet1996，348，9031： | 1 |
| 7 | Analysis of diflubenzuron by gas chromatography/mass spectrometry using deuterated diflubenzuron as internal standard显示文摘 | Wimmer M J Smith R R Jones J P | 1991 | Journal Agriculture Food Chemistry1991，39，2： | 1 |
| 8 | A European Perspective towards Online One-Stop Government:The eGOV Project显示文摘 | | 2002 | Electronic Com-merce Research and Applications2002，1，1： | 1 |
| 9 | Improved electriceal transport in Al-doped zinc oxide by thermal treatment显示文摘 | Roczen M Lee K Wimmer M | 2010 | J Appl Phys2010，107，01： | 1 |
| 10 | Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis 显示文摘 | Seinost G Wimmer G Skerget M | 2005 | Am Heart J2005，149，6： | 1 |
| 11 | Long term hemodynamic effects of nitedipine on congenital heart disease with Eisenmenger's mechanism in children显示文摘 | Wimmer M Schlemmer M | 1992 | Cardiovasc Drugs Ther1992，6，1： | 1 |
| 12 | Associations of functional candidate genes derived from gene-expression profiles of prenatal porcine muscle tissue with meat quality and muscle deposition显示文摘 | Wimmers K Murani E Te Pas M F W | 2007 | Anim Genet2007，38，5： | 1 |
| 13 | Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening 显示文摘 | Randau TM Friedrich M J Wimmer MD | 2014 | PLoS One2014，9，89： | 1 |
| 14 | Phase relationship in the system Si3N4–Y2O3–SiO2 显示文摘 | WILLS R R HOLMQUIST S WIMMER J M | 1976 | J Mater Sci1976，，13： | 1 |
| 15 | Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congential heart disease显示文摘 | Stumpflen I Stumpflen A Wimmer M | 1996 | Lancet1996，348，9031： | 1 |
| 16 | Progression in lacuna stroke is related to elevated acute phase parameters显示文摘 | AUDEBERT H J PELLKOFER T S WIMMER M L | 2004 | Eur Neurol2004，51，3： | 1 |
| 17 | 7-Deoxy-desulfocylindrospermopsin and 7-deoxy-desulfo-12-acetylcylindrospermopsin:Two new cylindrospermopsin analogs isolated from a Thai strain of Cylindrospermopsisraciborskii显示文摘 | Wimmer K M Strangman W K Wright J L C | 2014 | Harmful Algae2014，，20： | 1 |
| 18 | Effect of detail fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease显示文摘 | Stumphlen I Stumphlen A Wimmer M | 1996 | Lancet1996，348，： | 1 |
| 19 | Image-based representations for accelerated rendering of complex scenes显示文摘 | JESCHKE S WIMMER M PURGATHOFER W | 2005 | Proceedings of EUROGRAPHICS2005，，： | 1 |
| 20 | Characteristics of radial growth and stable isotopes in a single oak tree to be used in climate studies显示文摘 | Weigl M Grabner M Helle G Schleser GH Wimmer R | | 0，，： | 1 |
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