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Now showing 1 - 10 of 52
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    Inhibition of cardiac CaMKII to cure heart failure: step by step towards translation?
    (Heidelberg : Springer, 2016) Cuello, Friederike; Lorenz, Kristina
    [no abstract available]
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    An 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.
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    Human 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.
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    Polyphenols 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, Giuseppe
    Nanotechnology 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.
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    Characterization and prediction of the mechanism of action of antibiotics through NMR metabolomics
    (London : BioMed Central, 2016) Hoerr, Verena; Duggan, Gavin E.; Zbytnuik, Lori; Poon, Karen K.H.; Große, Christina; Neugebauer, Ute; Methling, Karen; Löffler, Bettina; Vogel, Hans J.
    Background: The emergence of antibiotic resistant pathogenic bacteria has reduced our ability to combat infectious diseases. At the same time the numbers of new antibiotics reaching the market have decreased. This situation has created an urgent need to discover novel antibiotic scaffolds. Recently, the application of pattern recognition techniques to identify molecular fingerprints in ‘omics’ studies, has emerged as an important tool in biomedical research and laboratory medicine to identify pathogens, to monitor therapeutic treatments or to develop drugs with improved metabolic stability, toxicological profile and efficacy. Here, we hypothesize that a combination of metabolic intracellular fingerprints and extracellular footprints would provide a more comprehensive picture about the mechanism of action of novel antibiotics in drug discovery programs. Results: In an attempt to integrate the metabolomics approach as a classification tool in the drug discovery processes, we have used quantitative 1H NMR spectroscopy to study the metabolic response of Escherichia coli cultures to different antibiotics. Within the frame of our study the effects of five different and well-known antibiotic classes on the bacterial metabolome were investigated both by intracellular fingerprint and extracellular footprint analysis. The metabolic fingerprints and footprints of bacterial cultures were affected in a distinct manner and provided complementary information regarding intracellular and extracellular targets such as protein synthesis, DNA and cell wall. While cell cultures affected by antibiotics that act on intracellular targets showed class-specific fingerprints, the metabolic footprints differed significantly only when antibiotics that target the cell wall were applied. In addition, using a training set of E. coli fingerprints extracted after treatment with different antibiotic classes, the mode of action of streptomycin, tetracycline and carbenicillin could be correctly predicted. Conclusion: The metabolic profiles of E. coli treated with antibiotics with intracellular and extracellular targets could be separated in fingerprint and footprint analysis, respectively and provided complementary information. Based on the specific fingerprints obtained for different classes of antibiotics, the mode of action of several antibiotics could be predicted. The same classification approach should be applicable to studies of other pathogenic bacteria.
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    Bioactive secondary metabolites with multiple activities from a fungal endophyte
    (Oxford : Wiley-Blackwell, 2016) Bogner, Catherine W.; Kamdem, Ramsay S.T.; Sichtermann, Gisela; Matthäus, Christian; Hölscher, Dirk; Popp, Jürgen; Proksch, Peter; Grundler, Florian M.W.; Schouten, Alexander
    In order to replace particularly biohazardous nematocides, there is a strong drive to finding natural product-based alternatives with the aim of containing nematode pests in agriculture. The metabolites produced by the fungal endophyte Fusarium oxysporum 162 when cultivated on rice media were isolated and their structures elucidated. Eleven compounds were obtained, of which six were isolated from a Fusarium spp. for the first time. The three most potent nematode-antagonistic compounds, 4-hydroxybenzoic acid, indole-3-acetic acid (IAA) and gibepyrone D had LC50 values of 104, 117 and 134 μg ml−1, respectively, after 72 h. IAA is a well-known phytohormone that plays a role in triggering plant resistance, thus suggesting a dual activity, either directly, by killing or compromising nematodes, or indirectly, by inducing defence mechanisms against pathogens (nematodes) in plants. Such compounds may serve as important leads in the development of novel, environmental friendly, nematocides.
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    Nanotopography mediated osteogenic differentiation of human dental pulp derived stem cells
    (Cambridge : RSC Publ., 2017) Bachhuka, Akash; Delalat, Bahman; Ghaemi, Soraya Rasi; Gronthos, Stan; Voelcker, Nicolas H.; Vasilev, Krasimir
    Advanced medical devices, treatments and therapies demand an understanding of the role of interfacial properties on the cellular response. This is particularly important in the emerging fields of cell therapies and tissue regeneration. In this study, we evaluate the role of surface nanotopography on the fate of human dental pulp derived stem cells (hDPSC). These stem cells have attracted interest because of their capacity to differentiate to a range of useful lineages but are relatively easy to isolate. We generated and utilized density gradients of gold nanoparticles which allowed us to examine, on a single substrate, the influence of nanofeature density and size on stem cell behavior. We found that hDPSC adhered in greater numbers and proliferated faster on the sections of the gradients with higher density of nanotopography features. Furthermore, greater surface nanotopography density directed the differentiation of hDPSC to osteogenic lineages. This study demonstrates that carefully tuned surface nanotopography can be used to manipulate and guide the proliferation and differentiation of these cells. The outcomes of this study can be important in the rational design of culture substrates and vehicles for cell therapies, tissue engineering constructs and the next generation of biomedical devices where control over the growth of different tissues is required.
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    Biocompatibility assessment of silk nanoparticles: hemocompatibility and internalization by human blood cells
    (New York, NY : Elsevier, 2017) Maitz, Manfred F.; Sperling, Claudia; Wongpinyochit, Thidarat; Herklotz, Manuela; Werner, Carsten; Seib, F. Philipp
    Many nanoparticles are designed for use as potential nanomedicines for parenteral administration. However, emerging evidence suggests that hemocompatibility is important, but is highly particle- and test-bed dependent. Thus, knowledge of bulk material properties does not predict the hemocompatibility of uncharacterized nanoparticles, including silk nanoparticles. This study compares the hemocompatibility of silk versus silica nanoparticles, using whole human blood under quasi-static and flow conditions. Substantial hemocompatibility differences are noted for some nanoparticles in quasi-static versus dynamic studies; i.e., the inflammatory response to silk nanoparticles is significantly lower under flow versus quasi-static conditions. Silk nanoparticles also have very low coagulant properties - an observation that scales from the macro- to the nano-level. These nanoparticle hemocompatibility studies are complemented by preliminary live cell measurements to evaluate the endocytosis and trafficking of nanoparticles in human blood cells. Overall, this study demonstrates that nanoparticle hemocompatibility is affected by several factors, including the test bed design.
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    German claims data analysis to assess impact of different intraocular lenses on posterior capsule opacification and related healthcare costs
    (Heidelberg : Springer, 2017) Kossack, Nils; Schindler, Christian; Weinhold, Ines; Hickstein, Lennart; Lehne, Moritz; Walker, Jochen; Neubauer, Aljoscha S.; Häckl, Dennis
    Aim: Cataract extraction is one of the most frequent surgeries in Germany. In most cases, the clouded natural lens is replaced by a hydrophobic or hydrophilic acrylic intraocular lens (IOL) implant. The most common long-term complication after cataract surgery is the development of a posterior capsule opacification (PCO). Although no precise real world data are available, published evidence suggests a lower risk for PCO development for hydrophobic acrylic IOLs compared to hydrophilic acrylic IOLs. Therefore, in the present study we assessed real world data on the impact of different IOL material types on the incidence of post-operative PCO treatment. Subject and methods: In this retrospective study, we included 3,025 patients who underwent cataract extraction and implantation of either an acrylic hydrophobic or hydrophilic IOL in 2010. We assessed clinical outcomes and direct costs in a 4-year follow-up period after cataract surgery from a statutory health insurance (SHI) perspective in Germany. Results: PCO that required capsulotomies occurred significantly (p < 0.0001) less frequent in patients who had received a hydrophobic IOL (31.57% of 2,078 patients) compared to the group with hydrophilic IOL implants (56.6% of 947 patients) and costs per patient for postoperative treatment in a 4-year follow-up were 50.03 € vs. 87.81 € (i.e. 75% higher in the latter group, p < 0.0001). Conclusion: Considering the high prevalence of cataract, the economic burden associated with adverse effects of cataract extraction is of great relevance for the German SHI. Hydrophobic lenses seem to be superior regarding both medical and economic results.
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    Thermo-responsive cell culture carrier: Effects on macrophage functionality and detachment efficiency
    (London : Sage, 2017) Rennert, Knut; Nitschke, Mirko; Wallert, Maria; Keune, Natalie; Raasch, Martin; Lorkowski, Stefan; Mosig, Alexander S.
    Harvesting cultivated macrophages for tissue engineering purposes by enzymatic digestion of cell adhesion molecules can potentially result in unintended activation, altered function, or behavior of these cells. Thermo-responsive polymer is a promising tool that allows for gentle macrophage detachment without artificial activation prior to subculture within engineered tissue constructs. We therefore characterized different species of thermo-responsive polymers for their suitability as cell substrate and to mediate gentle macrophage detachment by temperature shift. Primary human monocyte- and THP-1-derived macrophages were cultured on thermo-responsive polymers and characterized for phagocytosis and cytokine secretion in response to lipopolysaccharide stimulation. We found that both cell types differentially respond in dependence of culture and stimulation on thermo-responsive polymers. In contrast to THP-1 macrophages, primary monocyte–derived macrophages showed no signs of impaired viability, artificial activation, or altered functionality due to culture on thermo-responsive polymers compared to conventional cell culture. Our study demonstrates that along with commercially available UpCell carriers, two other thermo-responsive polymers based on poly(vinyl methyl ether) blends are attractive candidates for differentiation and gentle detachment of primary monocyte–derived macrophages. In summary, we observed similar functionality and viability of primary monocyte–derived macrophages cultured on thermo-responsive polymers compared to standard cell culture surfaces. While this first generation of custom-made thermo-responsive polymers does not yet outperform standard culture approaches, our results are very promising and provide the basis for exploiting the unique advantages offered by custom-made thermo-responsive polymers to further improve macrophage culture and recovery in the future, including the covalent binding of signaling molecules and the reduction of centrifugation and washing steps. Optimizing these and other benefits of thermo-responsive polymers could greatly improve the culture of macrophages for tissue engineering applications.