Institut für Chemie und Bioanalytik
Dauerhafte URI für die Sammlunghttps://irf.fhnw.ch/handle/11654/24
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10 Ergebnisse
Ergebnisse nach Hochschule und Institut
Publikation Development of a new reactor concept for oxidation reactions(Hochschule für Life Sciences FHNW, 2023) Lamanna Bürkler, Patrizia; Zogg, Andreas; DSM-FirmenichOxidation reactions comprises an important class of reactions. One key commercial product in DSM – Firmenich' s portfolio contains an oxidation step using 100% O2. Oxidation reactions are highly exothermic, often operated in an organic solvent. With a possible ignition source, this will lead to a high-risk potential regarding explosion. To obtain a safe process, it is desirable to avoid an explosive atmosphere, but this will cause limitations regarding process temperature and pressure. In reactions with 100% O2, very high explosion pressures must be expected. An inherently safe mode of operation is only possible if the apparatus were constructed to be pressure shock resistant and the process temperature is kept between a certain range. The goal of this master thesis is the development of a new reactor concept for gas-liquid phase reactions with focus on oxidation reactions. Based on the design of a loop-reactor, the gaseous oxidizing agent O2 is transferred to the liquid reaction mass using membrane technology. The concept keeps the liquid phase saturated with O2, while minimizing the creation of an explosive atmosphere inside the reactor. The approach of a head space free reactor is a significantly increase of process safety while minimizing the constraints with regards to the solvent selection and process conditions.11 - Studentische ArbeitPublikation Triphenylphosphanoxid Reduktion mit Silanen(Hochschule für Life Sciences FHNW, 2022) Brodmann, Nico; Zogg, Andreas; Zogg, Andreas; DSMTriphenylphosphan (TPP) ist ein häufig genutztes Reagenz bei der Wittig-Reaktion. Dabei wird es stöchiometrisch zu Triphenylphosphanoxid (TPPO) umgewandelt, welches zum heutigen Zeitpunkt entsorgt werden muss. Eine Rückführung zu TPP ist für die Industrie von grossem Nutzen. Deshalb wurde eine Reduktion mit Silanen für eine Implementierung untersucht. Es war möglich die grössten Hindernisse dieses Vorgehens für einen Prozess zu umgehen oder zu lösen. So wurde in diesem Zusammenhang die Aufarbeitung komplett neu entworfen und alle Abfallströme für eine Rückführung bzw. Weiterverarbeitung optimiert. Zudem konnten alle Reaktionsparameter und deren Einfluss quantifiziert und verbessert werden.11 - Studentische ArbeitPublikation Nitrosamine formation and scavenging in drug products(Hochschule für Life Sciences FHNW, 2022) Ammon-Kircher, Tamara; Zogg, Andreas; NovartisNitrosamines are considered potential mutagens in the absence of toxicological data and need to be controlled in nanogram quantities in medicinal products. In the case that a medicinal product contains a primary source of vulnerable amines, it would be desirable to have an inhibitor (nitrite scavenger) of nitrosamine formation that can be added to a formulation. Wet granulation has been identified as a critical process step in drug manufacture, this was simulated in this work.The nitrosamine formation was monitored using two systems. On the one hand, an HPLC UV/VIS analysis was implemented to monitor the nitrite level, on the other hand the nitrosamine content was detected using a Triple Quadrupole LC/MS analysis. The rate constant of nitrosation was obtained by regression of measured nitrite concentrations. Based on the results, the nitrite decomposition in water at different pH and temperature should be modelled in a mathematical model like MatLab11 - Studentische ArbeitPublikation Development of a setup to study electrostatic discharges(Hochschule für Life Sciences FHNW, 2023) Brönnimann, Benedikt; Zogg, AndreasTwo glass lined reactors in a launch platform facility operated by Syngenta have been damaged during a crystallization-process of an organic compound due to electrostatic discharges. The goal of this thesis was to design and commission a unique setup to measure charges and currents generated by such suspensions in a laboratory-scale reactor. These measurements made it possible to then calculate and estimate resulting discharge energies. An improved and more sophisticated setup was then proposed for possible implementation in their own laboratories. With this novel setup, the electrostatic charging of stirred suspensions involving non conductive solvents could be accurately measured in the context of a case study that involved the suspension that led to liner damages in the production facilities of Syngenta.11 - Studentische ArbeitPublikation Methotrexate-induced liver injury is associated with oxidative stress, impaired mitochondrial respiration, and endoplasmic reticulum stress in vitro(MDPI, 01.12.2022) Schmidt, Saskia; Messner, Catherine; Gaiser, Carine; Hämmerli, Carina; Suter-Dick, LauraLow-dose methotrexate (MTX) is a standard therapy for rheumatoid arthritis due to its low cost and efficacy. Despite these benefits, MTX has been reported to cause chronic drug-induced liver injury, namely liver fibrosis. The hallmark of liver fibrosis is excessive scarring of liver tissue, triggered by hepatocellular injury and subsequent activation of hepatic stellate cells (HSCs). However, little is known about the precise mechanisms through which MTX causes hepatocellular damage and activates HSCs. Here, we investigated the mechanisms leading to hepatocyte injury in HepaRG and used immortalized stellate cells (hTERT-HSC) to elucidate the mechanisms leading to HSC activation by exposing mono- and co-cultures of HepaRG and hTERT-HSC to MTX. The results showed that at least two mechanisms are involved in MTX-induced toxicity in HepaRG: (i) oxidative stress through depletion of glutathione (GSH) and (ii) impairment of cellular respiration in a GSH-independent manner. Furthermore, we measured increased levels of endoplasmic reticulum (ER) stress in activated HSC following MTX treatment. In conclusion, we established a human-relevant in vitro model to gain mechanistical insights into MTX-induced hepatotoxicity, linked oxidative stress in HepaRG to a GSH-dependent and -independent pathway, and hypothesize that not only oxidative stress in hepatocytes but also ER stress in HSCs contribute to MTX-induced activation of HSCs.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Metabolomic serum abnormalities in dogs with hepatopathies(Nature, 29.03.2022) Imbery, Carolin A.; Dieterle, Frank; Ottka, Claudia; Weber, Corinna; Müller, Elisabeth; Lohi, Hannes; Giger, Urs; Schlotterbeck, GötzHepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Electrochemical membrane-assisted pH-swing extraction and back-extraction of lactic acid(Elsevier, 2022) Gausmann, Marcel; Bertram, Franziska; Schuur, Boelo; Jupke, Andreas; Gössi, Angelo; Riedl, WolfgangReactive extraction of carboxylic acids such as lactic acid with tertiary amines is a state-of-the-art process but suffers strongly from reduced extraction efficiency in buffered environments like fermentation broths. In order to increase the efficiency of in-situ product removal, we here propose the combination of a membrane-assisted reactive extraction with an electrochemical pH shift. Prior to extraction in the membrane module, the fermentation broth containing the lactic acid at neutral pH is treated by anodic electrolysis to reduce the pH and thereby improve the extraction yield. Additionally, the cathodic reaction is used to increase the pH of the aqueous stream used for back-extraction of the loaded organic phase. Model solutions were used to develop a mathematical model, capable of calculating the required membrane area for in-situ extractions, considering the effect of the aqueous pH on the extraction performance. Additionally, using electrochemical pH shift, we were able to concentrate lactic acid from 1 wt% in the dilute broth to 7 wt% in the back extract.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Evaluation of dioxin induced transcriptomic responses in a 3D human liver microtissue model(Elsevier, 2022) Tian, Mingming; Gou, Xiao; Zhang, Xiaowei; Messner, Catherine; Suter-Dick, Laura; Yan, LuThree-dimensional human liver microtissue model provides a promising method for predicting the human hepatotoxicity of environmental chemicals. However, the dynamics of transcriptional responses of 3D human liver microtissue model to dioxins exposure remain unclear. Herein, time-series transcriptomic analysis was used to characterize modulation of gene expression over 14 days in 3D human liver microtissues exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD, 31 nM, 10 ng/ml). Changes in gene expression and modulation of biological pathways were evaluated at several time points. The results showed that microtissues stably expressed genes related to toxicological pathways (e.g. highly of genes involved in external stimuli and maintenance of cell homeostasis pathways) during the 14-day culture period. Furthermore, a weekly phenomenon pattern was observed for the number of the differentially expressed genes in microtissues exposed to TCDD at each time point. TCDD led to an induction of genes involved in cell cycle regulation at day three. Metabolic pathways were the main significantly induced pathways during the subsequent days, with the immune/inflammatory response enriched on the fifth day, and the cellular response to DNA damage was identified at the end of the exposure. Finally, relevant transcription patterns identified in microtissues were compared with published data on rodent and human cell-line studies to elucidate potential species-specific responses to TCDD over time. Cell development and cytochrome P450 pathway were mainly affected after a 3-day exposure, with the DNA damage response identified at the end of exposure in the human microtissue system but not in mouse/rat primary hepatocytes models. Overall, the 3D human liver microtissue model is a valuable tool to predict the toxic effects of environmental chemicals with a relatively long exposure.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation How to Foster ‘New Approach Methodology’ Toxicologists(SAGE, 18.02.2022) Doktorova, Tatyana Y.; Azzi, Pamela; Hofer, Joelle; Werner, Sophie; Singh, Pranika; Hardy, Barry; Chesne, Christophe; Messner, Catherine; Gaiser, Carine; Suter-Dick, LauraThe need to reduce, refine and replace animal experimentation has led to a boom in the establishment of new approach methodologies (NAMs). This promising trend brings the hope that the replacement of animals by using NAMs will become increasingly accepted by regulators, included in legislation, and consequently more-often implemented by industry. The majority of NAMs, however, are still not very well understood, either due to the complexity of the applied approach or the data analysis workflow. A potential solution to this problem is the provision of better educational resources to scientists new to the area — showcasing the added value of NAMs and outlining various ways of overcoming issues associated with knowledge gaps. In this paper, the educational exchange between four institutions — namely, two universities and two SMEs — via a series of video training sessions, is described. The goal of this exchange was to showcase an exemplary event to help introduce scientists to non-animal approaches, and to actively support the development of resources enabling the use of alternatives to laboratory animals.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Novel Titanium Nanospike Structure Using Low-Energy Helium Ion Bombardment for the Transgingival Part of a Dental Implant(MDPI, 24.03.2022) Mukaddam, Khaled; Astasov-Frauenhoffer, Monika; Fasler-Kan, Elizaveta; Marot, Laurent; Kisiel, Marcin; Steiner, Roland; Sanchez, Fabien; Meyer, Ernst; Bornstein, Michael M.; Kühl, Sebastian; Köser, JoachimAim(s): The aim of the study was to fabricate a nanospike surface on a titanium alloy surface using a newly established method of low-energy helium ion bombardment. Various methods to achieve nanospike formation on titanium have been introduced recently, and their antibacterial properties have been mainly investigated with respect to Escherichia coli and Staphylococcus aureus. Oral pathogens such as Porphyromonas gingivalis play an important role in the development of peri-implantitis. For that reason, the antibacterial properties of the novel, nanostructured titanium surface against P. gingivalis were assessed, and a possible effect on the viability of gingival fibroblasts was evaluated. Materials and Methods: Helium sputtering was employed for developing titanium surfaces with nanospikes of 500 nm (ND) in height; commercially available smooth-machined (MD) and sandblasted and acid-etched titanium disks (SLA) were used as controls. Surface structure characterization was performed through scanning electron microscopy (SEM) and atomic force microscopy (AFM). Following incubation with P. gingivalis, antibacterial properties were determined via conventional culturing and SEM. Additionally, the viability of human gingival fibroblasts (HGFs) was tested through MTT assay, and cell morphology was assessed through SEM. Results: SEM images confirmed the successful establishment of a nanospike surface with required heights, albeit with heterogeneity. AFM images of the 500 nm nanospike surface revealed that the roughness is dominated by large-scale hills and valleys. For frame sizes of 5 × 5 μm and smaller, the average roughness is dominated by the height of the titanium spikes. ND successfully induces dysmorphisms within P. gingivalis cultures following the incubation period, while conventional culturing reveals a 17% and 20% reduction for ND compared to MD and SLA, respectively. Moreover, the nanospike surfaces did not affect the viability of human growth fibroblasts despite their sharp surface. Conclusion(s): This study successfully developed a novel titanium-nanospike-based structuration technique for titanium surfaces. In addition, the nanospikes did not hinder gingival fibroblast viability. Enhanced antimicrobial effects for such a novel nanospike-based resurfacing technique can be achieved through further optimizations for nanospike spacing and height parameters.01A - Beitrag in wissenschaftlicher Zeitschrift