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- ItemQuantification of osseointegration of plasma-polymer coated titanium alloyed implants by means of microcomputed tomography versus histomorphometry(New York [u.a.] : Hindawi, 2015) Gabler, Carolin; Zietz, Carmen; Bieck, Richard; Göhler, Rebecca; Lindner, Tobias; Haenle, Maximilian; Finke, Birgit; Meichsner, Jürgen; Testrich, Holger; Nowottnick, Mathias; Frerich, Bernhard; Bader, RainerA common method to derive both qualitative and quantitative data to evaluate osseointegration of implants is histomorphometry. The present study describes a new image reconstruction algorithm comparing the results of bone-to-implant contact (BIC) evaluated by means of µCT with histomorphometry data. Custom-made conical titanium alloyed (Ti6Al4V) implants were inserted in the distal tibial bone of female Sprague-Dawley rats. Different surface configurations were examined: Ti6Al4V implants with plasma-polymerized allylamine (PPAAm) coating and plasma-polymerized ethylenediamine (PPEDA) coating as well as implants without surface coating. After six weeks postoperatively, tibiae were explanted and BIC was determined by µCT (3D) and afterwards by histomorphometry (2D). In comparison to uncoated Ti6Al4V implants demonstrating low BIC of 32.4% (histomorphometry) and 51.3% (µCT), PPAAm and PPEDA coated implants showed a nonsignificant increase in BIC (histomorphometry: 45.7% and 53.5% and µCT: 51.8% and 62.0%, resp.). Mean BIC calculated by µCT was higher for all surface configurations compared to BIC detected by histomorphometry. Overall, a high correlation coefficient of 0.70 () was found between 3D and 2D quantification of BIC. The μCT analysis seems to be suitable as a nondestructive and accurate 3D imaging method for the evaluation of the bone-implant interface.
- ItemInhibition of cardiac CaMKII to cure heart failure: step by step towards translation?(Heidelberg : Springer, 2016) Cuello, Friederike; Lorenz, Kristina[no abstract available]
- ItemSurface-assisted laser desorption/ionization mass spectrometry using ordered silicon nanopillar arrays(Cambridge : Royal Society of Chemistry, 2014) Alhmoud, Hashim Z.; Guinan, Taryn M.; Elnathan, Roey; Kobus, Hilton; Voelcker, Nicolas H.Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is ideally suited for the high-throughput analysis of small molecules in bodily fluids (e.g. saliva, urine, and blood plasma). A key application for this technique is the testing of drug consumption in the context of workplace, roadside, athlete sports and anti-addictive drug compliance. Here, we show that vertically-aligned ordered silicon nanopillar (SiNP) arrays fabricated using nanosphere lithography followed by metal-assisted chemical etching (MACE) are suitable substrates for the SALDI-MS detection of methadone and small peptides. Porosity, length and diameter are fabrication parameters that we have explored here in order to optimize analytical performance. We demonstrate the quantitative analysis of methadone in MilliQ water down to 32 ng mL-1. Finally, the capability of SiNP arrays to facilitate the detection of methadone in clinical samples is also demonstrated.
- ItemAn experimental study on the influence of trace impurities on ionization of atmospheric noble gas dielectric barrier discharges(Cambridge : Royal Society of Chemistry, 2016) Klute, F.D.; Schütz, A.; Michels, A.; Vadla, C.; Veza, D.; Horvatic, V.; Franzke, J.While the influence of trace impurities in noble gas discharges is well established in theoretical work, experimental approaches are difficult. Particularly the effects of trace concentrations of N2 on He discharges are complicated to investigate due to the fact that for He 5.0 the purity of He is only 99.999%. This corresponds to a residual concentration of 10 ppm, thereof 3 ppm of N2, in He. Matters are made difficult by the fact that He DBD plasmajets are normally operated under an ambient atmosphere, which has a high abundance of N2. This work tackles these problems from two sides. The first approach is to operate a DBD plasmajet under a quasi-controlled He atmosphere, therefore diminishing the effect of atmospheric N2 and making a defined contamination with N2 possible. The second approach is using Ar as the operating gas and introducing propane (C3H8) as a suitable substitute impurity like N2 in He. As will be shown both discharges in either He or Ar, with their respective impurity show the same qualitative behaviour.
- ItemProteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts(Orchard Park : Impact Journals, 2014) Waldera-Lupa, Daniel M.; Kalfalah, Faiza; Florea, Ana-Maria; Sass, Steffen; Kruse, Fabian; Rieder, Vera; Tigges, Julia; Fritsche, Ellen; Krutmann, Jean; Busch, Hauke; Boerries, Melanie; Meyer, Helmut E.; Boege, Fritz; Theis, Fabian; Reifenberger, Guido; Stühle, KaiWe analyzed an ex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the differentially abundant proteins have not been described in the context of fibroblasts' aging before, but the deduced biological processes confirmed known hallmarks of aging and led to a consistent picture of eight biological categories involved in fibroblast aging, namely proteostasis, cell cycle and proliferation, development and differentiation, cell death, cell organization and cytoskeleton, response to stress, cell communication and signal transduction, as well as RNA metabolism and translation. The exhaustive analysis of protein and mRNA data revealed that 77 % of the age-associated proteins were not linked to expression changes of the corresponding transcripts. This is in line with an associated miRNA study and led us to the conclusion that most of the age-associated alterations detected at the proteome level are likely caused post-transcriptionally rather than by differential gene expression. In summary, our findings led to the characterization of novel proteins potentially associated with fibroblast aging and revealed that primary cultures of in situ aged fibroblasts are characterized by moderate age-related proteomic changes comprising the multifactorial process of aging.
- ItemRaf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells(London : Nature Publishing Group, 2012) Sanges, C.; Scheuermann, C.; Zahedi, R.P.; Sickmann, A.; Lamberti, A.; Migliaccio, N.; Baljuls, A.; Marra, M.; Zappavigna, S.; Reinders, J.; Rapp, U.; Abbruzzese, A.; Caraglia, M.; Arcari, P.We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes.
- ItemProdukthaftung in der Apotheke(Stuttgart : Deutscher Apotheker Verlag, 2005) Diebold, Steffen M.Stellt ein Apotheker Arzneimittel, Medizinprodukte oder andere apothekenübliche Waren (z.B. Kosmetika oder Mixturen nach Angaben von Heilpraktikern, Homöopathen oder Anthroposophen) in seiner Offizin selbst her, so haftet er (grundsätzlich) einem dadurch ggf. geschädigten Kunden (auch) nach den Vorschriften des Produkthaftungsgesetzes. Diese Haftung besteht unabhängig vom eigenen Verschulden. Sie greift auch bei der Einfuhr von Arzneimitteln aus Staaten, die nicht zum Europäischen Wirtschaftsraum gehören, sowie bei Import und Abgabe von aus Drittländern eingeführten und im Geltungsbereich des Arzneimittelgesetzes (AMG) nicht zugelassenen Fertigarzneimitteln nach § 73 (3) AMG.
- ItemTargeting malignant melanoma with physical plasmas(Amsterdam [u.a.] : Elsevier, 2018) Pasqual-Melo, Gabriella; Gandhirajan, Rajesh Kumar; Stoffels, Ingo; Bekeschus, SanderMelanoma is the deadliest form of cutaneous neoplasia. With a five-year survival rate of only 5–19%, metastatic melanoma presents severe challenges in clinical therapies. In addition, palliation is often problematic due to large numbers of fast growing metastasis. This calls for new therapeutic avenues targeting highly aggressive melanoma in palliative patients. One recently suggested innovative approach for eradication of topical tumor lesions is the application of cold physical plasma. This partially ionized gas emits a cocktail of reactive oxygen and nitrogen species (ROS/RNS). ROS/RNS have been shown to be a double-edged sword in fueling cancer growth at low doses but abrogating it at higher doses. The ROS/RNS output of plasma devices is tunable, and many studies have successfully decreased cancer cell growth in vitro and tumor burden in vivo. In general, increasing numbers of clinical trials suggest combination therapies to outperform monotherapies with regard to prognosis in patients. This review describes current challenges in melanoma treatment and highlights the concept of plasma therapy in experimental studies performed in melanoma research. Future perspectives are given that combine the usage of physical plasma with e.g. chemotherapy, immunotherapy, and ionizing radiation in melanoma medical oncology.
- ItemHuman health risk evaluation of a microwave-driven atmospheric plasma jet as medical device(Amsterdam [u.a.] : Elsevier, 2017) Lehmann, A.; Pietag, F.; Arnold, T.Purpose: The aim of this study was the characterisation of a microwave-driven atmospheric plasma jet (APJ) dedicated for medical applications. The scientific focus includes harmless sterilization of surfaces and therapeutic treatments in dentistry. Methodes: The plasma was investigated with respect to potential health risks for human beings, which could occur especially by the gas temperature, heat flow, patient leakage current, UV emission and ozone emission from the plasma jet, according to DIN SPEC 91315:2014-06 (General requirements for plasma sources in medicine) [1]. Results: The results of the experiments indicate a high potential of the plasma jet to be used as a medical device exhibiting low gas temperatures up to 34 °C. The calculated leakage currents are mostly below the 10 μA threshold. The limiting UV exposure duration for the APJ with a calculated maximum effective irradiance of 2.6 μW/cm2 is around 19 min, based on the exposure limits of the international commission on non-ionizing radiation protection guidelines (ICNIRP) [2]. A significant ozone concentration was observed mainly in the axial effluent gas flow. Ozone concentration strongly decreases with increasing distance from the plasma source exit nozzle. Conclusion: The investigated APJ exhibits physical properties that might not constitute health risks to humans, e.g. during treatment in dentistry. Thus, the APJ shows a high potential for application as a device in dental therapy.
- ItemPolyphenols delivery by polymeric materials: challenges in cancer treatment(Abingdon : Taylor & Francis Group, 2017-2-3) Vittorio, Orazio; Curcio, Manuela; Cojoc, Monica; Goya, Gerardo F.; Hampel, Silke; Iemma, Francesca; Dubrovska, Anna; Cirillo, GiuseppeNanotechnology can offer different solutions for enhancing the therapeutic efficiency of polyphenols, a class of natural products widely explored for a potential applicability for the treatment of different diseases including cancer. While possessing interesting anticancer properties, polyphenols suffer from low stability and unfavorable pharmacokinetics, and thus suitable carriers are required when planning a therapeutic protocol. In the present review, an overview of the different strategies based on polymeric materials is presented, with the aim to highlight the strengths and the weaknesses of each approach and offer a platform of ideas for researchers working in the field.