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Sprühtrocknung von BSA- und Interferon-beta beladenen Chitosan-Partikeln

2012 , Gruber-Traub, C. , Burger-Kentischer, A. , Gretzinger, S. , Hirth, Thomas , Weber, A.

The formulation and oral application of therapeutic petides and proteins is still a challenge due to the proteolytic gastritic degradation and the poor adsorption mechanism out of the gut lumen. A particulate chitosan-based formulation of Interferon--1b was prepared for the future oral administration using a spray drying process. The quantification of the biological activity of Interferon--1b was carried out by means of an Anti Viral Assay (AVA) and an ELISA. The activity test showed no loss of the biological activity of Interferon after the manufacturing process.

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Communication in biofilms between different species: Candida albicans and Pseudomonas aeruginosa

2010 , Purschke, F. , Burger-Kentischer, A. , Rupp, S. , Trick, Iris , Hirth, Thomas

Candida albicans, a polymorphic fungus, and Pseudomonas aeruginosa, a Gram-negative bacterium, are two opportunistic pathogens that can cause serious infections in different sites within the human host. Growing in a particular lifestyle called biofilm they are well protected against the human immune system compared to conspecific in planctonic growth. Therefore these organisms are used as model systems for fungal and bacterial biofilm research. Biofilms are structured communities of microorganisms enclosed in a selfproduced polymeric matrix and adherent to an inert or living surface. One of the hallmarks required for the formation of biofilms is the so-called quorum sensing modulated by specific molecules which regulate this developmental process via defined signal cascades. Farnesol is a quorum sensing molecule used by C. albicans which inhibits fungal biofilm formation. It is mediated through a two-component signal transduction histidin kinase Chk1p. In P. aeruginosa N-3-oxo-dodecanoyl-L-homoserine lactone (3OC12HSL) represents a quorum sensing molecule. It acts as a positive regulator via LasR. Both molecules, which contain twelve-carbon backbones, repress C. albicans filamentation without altering its growth rate. To see how the organisms communicate with each other in biofilms a method to quantify the influence of quorum sensing molecules on C. albicans and P. aeruginosa biofilms was used. To visualize the interaction between both organisms mixed biofilms have been studied. Reporter strains have been constructed to analyse the influence of quorum sensing molecules during biofilm formation. Our results indicate that 3OC12HSL has impact on C. albicans biofilm formation and biofilms of P. aeruginosa are manipulated by farnesol.

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Breitband-Biosensor AquaBioTox zur onlinefähigen Trinkwasserüberwachung

2011 , Bernard, Thomas , Müller, Thomas , Jacubasch, Andreas , Schuchert, Tobias , Burger-Kentischer, A. , Maucher, T. , Geiger, Georg-Ullrich , Trick, Iris , Sedehizade, F.

Wassernetze sind einer Gefährdung durch absichtliche oder unabsichtliche Verunreinigungen ausgesetzt. Im Rahmen des BMBF-Projektes AquaBioTox wurde ein generisches onlinefähiger Breitband-Toxizitätssensor entwickelt und prototypisch realisiert. Es basiert auf dem "Vorkoster-Prinzip": Die Vitalität sehr schnell reagierender, biologischer Kleinstlebewesen, die in einem Bypass der Trinkwasserleitung ausgesetzt werden, wird durch eine Kamera mit automatischer Bildauswertung online überwacht, um signifikante Veränderungen innerhalb kurzer Zeit zu diagnostizieren. Das Monitoringsystem wurde in einer stillgelegten Leitungsstrecke auf dem Betriebsgelände der Berliner Wasserbetriebe getestet. Anhand von repräsentativen Teststoffen wurde die Funktionalität des Breitbandsensorsystems nachgewiesen.

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Identification of novel antifungal compounds using a HTS activity-selectivity assay

2009 , Keller, P. , Burger-Kentischer, A. , Finkelmeier, D. , Kleymann, G. , Wiesmüller, K.H. , Lemuth, Karin , Hiller, E. , Rupp, S.

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Identification of novel antifungal compounds using a HTS activity-selectivity assay

2010 , Keller, P. , Burger-Kentischer, A. , Finkelmeier, D. , Kleymann, G. , Wiesmüller, K.H. , Lemuth, Karin , Hiller, E. , Rupp, S.

Fungal infections represent a serious health problem in industrialized countries. Especially immune suppressed patients are highly susceptible to life-threatening infections by opportunistic fungi. In addition transplant therapy and anticancer drugs have provided an opportunity for fungi to cause serious infections. Treatment of fungal infections largely relies on chemotherapy and is limited by the high cost of the most potent antifungals as well as by the reported emerging resistance to some antifungals. To find novel compounds with broad selective antifungal activity we have developed an assay to identify, evaluate and optimize tolerable and potent antimicrobial agents in compound libraries for drug therapy. This assay covers all potential in vitro targets of the pathogen and the host simultaneously. Moreover it constitutes the smallest unit of a natural infection by incubating host cells in the presence of antimicrobial compounds and the pathogen, e.g. Candida species. Host cell survival is determined to asses the efficiency and selectivity of the respective compound. In addition to the minimal inhibitory concentration for the pathogen, this test system provides the tolerability of the active compound by the host cells, expressed as selectivity index. Using this assay about 100 000 compound derived from pre-selected basic chemical structures have been screened. One of the hits identified in the compound library was investigated in more detail by chemical modification of the lead structure and target identification using transcriptional profiling of C. albicans. Tissue models derived from primary cells are used as second test system providing further information about tissue penetration and tolerability of the test compound. Furthermore the most effective compound is currently tested against other Candida and Aspergillus species. Transcriptome analyses of the fungi treated with the novel compounds are in progress to reveal the cellular targets of the new substances and their mode of action.

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Onlinefähige Trinkwasserüberwachung auf Grundlage eines biologischen Breitbandsensors mit automatischer Bildauswertung (AquaBioTox)

2009 , Sedehizade, F. , Trick, Iris , Bernard, T. , Burger-Kentischer, A. , Maucher, T. , Geiger, Georg-Ullrich , Kuntze, H.-B. , Müller, T. , Sawo, F. , Moldaenke, C.

Water networks are exposed to deliberate or accidental contamination. Especially the drinking water supply is in potential danger to be a terroristic target and public health risks need to be detected in due time. This is why drinking water regulations provide for examining special germs and chemical substances on a regular basis. But today's analytical techniques which are carried out offline in special laboratories are time-consuming to warn the population of contamination risks in time. Their application spectrum is limited, e. g. by separating affected parts of the water supply mains. On the other side they are only limited in spectrum - unknown or unexpected toxical substances are unconsidered which can threaten people's health in the same way. Considering the changed level of threats an early identification of contaminants in drinking water is very important. It should respond quickly and reliably, be robust against false alarm, easy to handle by persons without scientific qualification and the operation should be economically in view of costs of purchase and maintenance. The project AquaBioTox aims to develop and realize such a system. Its operating principle is as follows: Highly sensitive biological microorganisms are exposed to drinking water taken from the main water current, their reaction is continuously monitored by a camera and the data is automatically analyzed in an online procedure. Any characteristic changes, for example regarding their vitality, movement, colouring or glowing, are automatically indicated. The system is properly combined with other sensors available on the market in order to ensure maximum diagnosis reliability and robustness against false alarm in online diagnosis. This combined broadband sensor concept can be used not only to diagnose contamination with hazardous substances but also in more general quality and safety checks on water supply facilities. Ongoing works deal with the prototypical realization of the biological sensors as well as with the automatization and image evaluation of the processes. The project aims to show the efficiency of the sensor system at a test track of the Berlin Waterworks.