Synthese, Löslichkeit und biologische Aktivität von Silber-Nanopartikeln

Die Nanotechnologie beschäftigt sich mit der Forschung und Herstellung von Strukturen im Nanometerbereich. Ein Nanometer entspricht einem Milliardenstel Meter. Unter den Begriff Nanopartikel fallen Teilchen, die in mindestens einer Dimension kleiner als 100 nm sind. Diese Teilchen sind etwa 1000mal kleiner als der Durchmesser eines Menschenhaars. Nanopartikel haben wegen ihrer geringen Größe andere physikalische Eigenschaften als große Partikel des gleichen Materials. Die Oberflächeneigenschaften sind in den Nanopartikeln gegenüber den Volumeneigenschaften der Materialien von größerer Bedeutung. Auch quantenphysikalische Effekte spielen eine immer größere Rolle. Dadurch steigt das Interesse an der Nanotechnologie immer weiter an. Viele Nanomaterialen sind heutzutage kommerziell verfügbar und werden in handelsüblichen Produkten eingesetzt. Beispielsweise wird nanoskaliges Titandioxid als UV-Schutzfilter in Sonnencremes verwendet, oder Nanobeschichtungen nutzen den Lotuseffekt für selbstreinigende Oberflächen. Aufgrund der bakteriziden Wirkung von Silberionen nimmt die Beschichtung von Gebrauchsgegenständen mit Silber-Nanopartikeln immer weiter zu. Antimikrobiell wirkende Silber-Nanopartikel werden in einigen Bekleidungstextilien wie Sportsocken und Schuheinlagen verwendet. In Socken eingearbeitete Silberfäden töten unter anderem die Bakterien, welche die stechenden Gerüche bei Schweißfüßen entwickeln. Auch mit Silber-Nanopartikeln beschichtete Kühlschränke, Wasserhähne oder Waschmaschinen sind immer häufiger zu finden. Dadurch sollen die Verbraucher vor Keimen und Bakterien geschützt werden. Gelangt das Silber mit Wasser in Kontakt, löst es sich jedoch langsam auf. Dadurch geht zum einen die antibakterielle Wirkung verloren, und zum anderen gelangen die Nanoteilchen in die Umwelt. Über die Haut, die Atemwege und den Magen-Darm-Trakt können die Nanopartikel dann auch in den menschlichen Körper gelangen, wo sie unter Umständen toxische Wirkungen entfalten. Was die Nanopartikel wirklich im Körper machen, ist bis jetzt kaum erforscht. Im Rahmen dieser Arbeit werden die Wirkungen von Silber-Nanopartikeln auf menschliche Zellen untersucht. Um erste Hinweise darauf zu bekommen, wodurch die Toxizität von Silber tatsächlich hervorgerufen wird, wird zunächst die Löslichkeit der Silber-Nanopartikel in wässrigen Medien untersucht. Auch das Agglomerationsverhalten der Partikel in verschiedenen Zellkulturmedien spielt eine wichtige Rolle für das Verständnis der biologischen Aktivität der Silber-Nanopartikel. Anhand dieser Ergebnisse können dann am Ende erste Aussagen darüber gemacht werden, wie sich menschliche Zellen gegenüber den Silber-Nanopartikeln verhalten und wie gefährlich diese Nanopartikel wirklich sind

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

Process Mining and Conformance Checking of Long Running Processes in the Context of Melanoma Surveillance

Background: Process mining is a relatively new discipline that helps to discover and analyze actual process executions based on log data. In this paper we apply conformance checking techniques to the process of surveillance of melanoma patients. This process consists of recurring events with time constraints between the events. Objectives: The goal of this work is to show how existing clinical data collected during melanoma surveillance can be prepared and pre-processed to be reused for process mining. Methods: We describe an approach based on time boxing to create process models from medical guidelines and the corresponding event logs from clinical data of patient visits. Results: Event logs were extracted for 1023 patients starting melanoma surveillance at the Department of Dermatology at the Medical University of Vienna between January 2010 and June 2017. Conformance checking techniques available in the ProM framework and explorative applied process mining techniques were applied. Conclusions: The presented time boxing enables the direct use of existing process mining frameworks like ProM to perform process-oriented analysis also with respect to time constraints between events

PVP-coated, negatively charged silver nanoparticles: A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma

Abstract Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists’ decisions has not yet been evaluated. Building upon previous research, we introduce an XAI system that provides precise and domain-specific explanations alongside its differential diagnoses of melanomas and nevi. Through a three-phase study, we assess its impact on dermatologists’ diagnostic accuracy, diagnostic confidence, and trust in the XAI-support. Our results show strong alignment between XAI and dermatologist explanations. We also show that dermatologists’ confidence in their diagnoses, and their trust in the support system significantly increase with XAI compared to conventional AI. This study highlights dermatologists’ willingness to adopt such XAI systems, promoting future use in the clinic

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field