2015, Gabler, Carolin, Zietz, Carmen, Bieck, Richard, Göhler, Rebecca, Lindner, Tobias, Haenle, Maximilian, Finke, Birgit, Meichsner, Jürgen, Testrich, Holger, Nowottnick, Mathias, Frerich, Bernhard, Bader, Rainer

A 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.

2014, Matthäus, C., Cicchi, R., Meyer, T., Lattermann, A., Schmitt, M., Romeike, B.F.M., Krafft, C., Dietzek, B., Brehm, B.R., Pavone, F.S., Popp, J.

Cardiovascular diseases in general and atherothrombosis as the most common of its individual disease entities is the leading cause of death in the developed countries. Therefore, visualization and characterization of inner arterial plaque composition is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable morphological information but cannot deliver information about the chemical composition of individual plaques. Therefore, spectroscopic imaging techniques have recently drawn considerable attention. Based on the spectroscopic properties of the individual plaque components, as for instance different types of lipids, the composition of atherosclerotic plaques can be analyzed qualitatively as well as quantitatively. Here, we compare the feasibility of multimodal nonlinear imaging combining two-photon fluorescence (TPF), coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy to contrast composition and morphology of lipid deposits against the surrounding matrix of connective tissue with diffraction limited spatial resolution. In this contribution, the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin, collagen, triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods, providing a powerful label-free complement to standard histopathological methods with great potential for in vivo application.

2015, Bekeschus, Sander, Schmidt, Anke, Bethge, Lydia, Masur, Kai, von Woedtke, Thomas, Hasse, Sybille, Wende, Kristian

In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α), differentiation (retinoic acid signaling and interferon inducible factors), and cell growth (Yin Yang 1). Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1) and of the neutrophil attractant chemokine interleukin-8 (IL-8). Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

2015, Duller, Geoff A. T., Tooth, Stephen, Barham, Lawrence, Tsukamoto, Sumiko

Fluvial deposits can provide excellent archives of early hominin activity but may be complex to interpret, especially without extensive geochronology. The Stone Age site of Kalambo Falls, northern Zambia, has yielded a rich artefact record from dominantly fluvial deposits, but its significance has been restricted by uncertainties over site formation processes and a limited chronology. Our new investigations in the centre of the Kalambo Basin have used luminescence to provide a chronology and have provided key insights into the geomorphological and sedimentological processes involved in site formation. Excavations reveal a complex assemblage of channel and floodplain deposits. Single grain quartz optically stimulated luminescence (OSL) measurements provide the most accurate age estimates for the youngest sediments, but in older deposits the OSL signal from some grains is saturated. A different luminescence signal from quartz, thermally transferred OSL (TT-OSL), can date these older deposits. OSL and TT-OSL results are combined to provide a chronology for the site. Ages indicate four phases of punctuated deposition by the dominantly laterally migrating and vertically aggrading Kalambo River (∼500-300 ka, ∼300-50 ka, ∼50-30 ka, ∼1.5-0.49 ka), followed by deep incision and renewed lateral migration at a lower topographic level. A conceptual model for site formation provides the basis for improved interpretation of the generation, preservation, and visibility of the Kalambo archaeological record. This model highlights the important role of intrinsic meander dynamics in site formation and does not necessarily require complex interpretations that invoke periodic blocking of the Kalambo River, as has previously been suggested. The oldest luminescence ages place the Mode 2/3 transition between ∼500 and 300 ka, consistent with other African and Asian sites where a similar transition can be found. The study approach adopted here can potentially be applied to other fluvial Stone Age sites throughout Africa and beyond.

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.

2015, Abramowicz, H., Abusleme, A., Afanaciev, K., Aguilar, J., Alvarez, E., Avila, D., Benhammou, Y., Bortko, L., Borysov, O., Bergholz, M., Bozovic-Jelisavcic, I., Castro, E., Chelkov, G., Coca, C., Daniluk, W., Dumitru, L., Elsener, K., Fadeyev, V., Firlej, M., Firu, E., Fiutowski, T., Ghenescu, V., Gostkin, M., Henschel, H., Idzik, M., Ishikawa, A., Kananov, S., Kollowa, S., Kotov, S., Kotula, J., Kozhevnikov, D., Kruchonok, V., Krupa, B., Kulis, Sz., Lange, W., Lesiak, T., Levy, A., Levy, I., Lohmann, W., Lukic, S., Milke, C., Moron, J., Moszczynski, A., Neagu, A.T., Novgorodova, O., Oliwa, K., Orlandea, M., Pandurovic, M., Pawlik, B., Preda, T., Przyborowski, D., Rosenblat, O., Sailer, A., Sato, Y., Schumm, B., Schuwalow, S., Smiljanic, I., Smolyanskiy, P., Swientek, K., Teodorescu, E., Terlecki, P., Wierba, W., Wojton, T., Yamaguchi, S., Yamamoto, H., Zawiejski, L., Zgura, I.S., Zhemchugov, A.

Detector-plane prototypes of the very forward calorimetry of a future detector at an e+e− collider have been built and their performance was measured in an electron beam. The detector plane comprises silicon or GaAs pad sensors, dedicated front-end and ADC ASICs, and an FPGA for data concentration. Measurements of the signal-to-noise ratio and the response as a function of the position of the sensor are presented. A deconvolution method is successfully applied, and a comparison of the measured shower shape as a function of the absorber depth with a Monte-Carlo simulation is given.

2015, Kroker, Matthias, Sydlik, Ulrich, Autengruber, Andrea, Cavelius, Christian, Weighardt, Heike, Kraegeloh, Annette, Unfried, Klaus

Background Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation. Methods Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. Results Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. Conclusions Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.n.

2015, Mendes, Rafael Gregorio, Koch, Britta, Bachmatiuk, Alicja, Ma, Xing, Sanchez, Samuel, Damm, Christine, Schmidt, Oliver G., Gemming, Thomas, Eckert, Jürgen, Rümmeli, Mark H.

Graphene oxide (GO) has attracted great interest due to its extraordinary potential for biomedical application. Although it is clear that the naturally occurring morphology of biological structures is crucial to their precise interactions and correct functioning, the geometrical aspects of nanoparticles are often ignored in the design of nanoparticles for biological applications. A few in vitro and in vivo studies have evaluated the cytotoxicity and biodistribution of GO, however very little is known about the influence of flake size and cytotoxicity. Herein, we aim at presenting an initial cytotoxicity evaluation of different nano-sized GO flakes for two different cell lines (HeLa (Kyoto) and macrophage (J7742)) when they are exposed to samples containing different sized nanographene oxide (NGO) flakes (mean diameter of 89 and 277 nm). The obtained data suggests that the larger NGO flakes reduce cell viability as compared to smaller flakes. In addition, the viability reduction correlates with the time and the concentration of the NGO nanoparticles to which the cells are exposed. Uptake studies were also conducted and the data suggests that both cell lines internalize the GO nanoparticles during the incubation periods studied.

2015, Oetjen, Janina, Veselkov, Kirill, Watrous, Jeramie, McKenzie, James S., Becker, Michael, Hauberg-Lotte, Lena, Kobarg, Jan Hendrik, Strittmatter, Nicole, Mróz, Anna K., Hoffmann, Franziska, Trede, Dennis, Palmer, Andrew, Schiffler, Stefan, Steinhorst, Klaus, Aichler, Michaela, Goldin, Robert, Guntinas-Lichius, Orlando, von Eggeling, Ferdinand, Thiele, Herbert, Maedler, Kathrin, Walch, Axel, Maass, Peter, Dorrestein, Pieter C., Takats, Zoltan, Alexandrov, Theodore

Background: Three-dimensional (3D) imaging mass spectrometry (MS) is an analytical chemistry technique for the 3D molecular analysis of a tissue specimen, entire organ, or microbial colonies on an agar plate. 3D-imaging MS has unique advantages over existing 3D imaging techniques, offers novel perspectives for understanding the spatial organization of biological processes, and has growing potential to be introduced into routine use in both biology and medicine. Owing to the sheer quantity of data generated, the visualization, analysis, and interpretation of 3D imaging MS data remain a significant challenge. Bioinformatics research in this field is hampered by the lack of publicly available benchmark datasets needed to evaluate and compare algorithms. Findings: High-quality 3D imaging MS datasets from different biological systems at several labs were acquired, supplied with overview images and scripts demonstrating how to read them, and deposited into MetaboLights, an open repository for metabolomics data. 3D imaging MS data were collected from five samples using two types of 3D imaging MS. 3D matrix-assisted laser desorption/ionization imaging (MALDI) MS data were collected from murine pancreas, murine kidney, human oral squamous cell carcinoma, and interacting microbial colonies cultured in Petri dishes. 3D desorption electrospray ionization (DESI) imaging MS data were collected from a human colorectal adenocarcinoma. Conclusions: With the aim to stimulate computational research in the field of computational 3D imaging MS, selected high-quality 3D imaging MS datasets are provided that could be used by algorithm developers as benchmark datasets.

2015, Lautenschläger, Stefan, Striegler, Christin, Dakischew, Olga, Schütz, Iris, Szalay, Gabor, Schnettler, Reinhard, Heiß, Christian, Appelhans, Dietmar, Lips, Katrin S.

The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-compatibility. Essentially the latter has to be addressed as first point on the agenda. We present a study on the biological interaction of maltose-modified poly(ethyleneimine) (PEI-Mal) on primary human mesenchymal stem cell, harvested from reaming debris (rdMSC) and osteoblasts obtained from four different male donors. PEI-Mal-nanoparticles with two different molecular weights of the PEI core (5000 g/mol for PEI-5k-Mal-B and 25,000 g/mol for PEI-25k-Mal-B) have been administered to both cell lines. As well dose as incubation-time dependent effects and interactions have been researched for concentrations between 1 μg/ml to 1 mg/ml and periods of 24 h up to 28 days. Studies conducted by different methods of microscopy as light microscopy, fluorescence microscopy, transmission-electron-microscopy and quantitative assays (LDH and DC-protein) indicate as well a good cellular uptake of the nanoparticles as a particle- and concentration-dependent impact on the cellular macro- and micro-structure of the rdMSC samples. In all experiments PEI-5k-Mal-B exhibits a superior biocompatibility compared to PEI-25k-Mal-B. At higher concentrations PEI-25k-Mal-B is toxic and induces a directly observable mitochondrial damage. The alkaline phosphatase assay (ALP), has been conducted to check on the possible influence of nanoparticles on the differentiation capabilities of rdMSC to osteoblasts. In addition the production of mineralized matrix has been shown by von-Kossa stained samples. No influence of the nanoparticles on the ALP per cell has been detected. Additionally, for all experiments, results are strongly influenced by a large donor-to-donor variability of the four different rdMSC samples. To summarize, while featuring a good cellular uptake, PEI-5k-Mal-B induces only minimal adverse effects and features clearly superior biocompatibility compared to the larger PEI-25k-Mal-B.