Advanced in vitro exposure systems.

7. Jul. 2016

3-D Nasal Cultures: Systems Toxicological Assessment of a Candidate Modified-Risk Tobacco Product

doi: 10.14573/altex.1605041

Anita R. Iskandar, Carole Mathis, Florian Martin, Patrice Leroy, Alain Sewer, Shoaib Majeed, Diana Kuehn, Keyur Trivedi, Davide Grandolfo, Maciej Cabanski, Emmanuel Guedj, Celine Merg, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch and Julia Hoeng

Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland

Human nasal epithelium is the first barrier against inhaled toxicants. The air-liquid interface human nasal culture MucilAir™ offers a more physiologically relevant and robust systems for studying the effects of exposure. This cells were exposed to 3R4F cigarettes and THS2.2 tobacco sticks
in the the Vitrocell® 24/48 exposure system. Results have been evaluated by measuring the cytotoxicity, histology processing, immunostaining, cilia beating frequency (CBF), cytochrome P450 (CYP) activity, luminex-based measurement of secreted analytes, RNA/miRNA purification and mRNA microarray.

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27. Jun. 2016

Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions

Different Effects of Heavy Fuel Oil and Refined Diesel Fuel

DOI:10.1371/journal.pone.0157964

Sean C. Sapcariu1,12, Tamara Kanashova2,12, Marco Dilger3,4,12, Silvia Diabaté3,12, Sebastian Oeder5,6,12,13, Johannes Passig7,12, Christian Radischat7,12, Jeroen Buters5,6,12,13, Olli Sippula8,12, Thorsten Streibel7,9,12, Hanns-Rudolf Paur4,12, Christoph Schlager4,12, Sonja Mülhopt4,12, Benjamin Stengel10,12, Rom Rabe10,12, Horst Harndorf10,12, Tobias Krebs11,12, Erwin Karg9, Thomas Gröger9, Carsten Weiss3,12, Gunnar Dittmar2,12, Karsten Hiller1,12, Ralf Zimmermann7,9,12

1 Luxembourg Centre for Systems Biomedicine 6, avenue du Swing, L-4362 Esch-sur-Alzette, Luxembourg,
2 Mass Spectrometry Core Unit, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany,
3 Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology, Campus North, Karlsruhe, Germany,
4 Institute for Technical Chemistry (ITC), Karlsruhe Institute of Technology, Campus North, Karlsruhe, Germany,
5 Center of Allergy and Environment (ZAUM), Helmholtz Zentrum München and Technische Universität München, Munich, Germany,
6 CK-CARE, Christine Kühne Center for Allergy Research and Education, Davos, Switzerland,
7 Joint Mass Spectrometry Centre, Division of Analytical and Technical Chemistry, Institute of Chemistry, University Rostock, Rostock, Germany,
8 University of Eastern Finland, Department of Environmental Science, P.O. Box 1627, FI-70211 Kuopio, Finland,
9 Joint Mass Spectrometry Centre, CMA – Comprehensive Molecular Analytics, Helmholtz Zentrum München, Neuherberg, Germany,
10 Chair of Piston Machines and Internal Combustion Engines, University Rostock, Rostock, Germany,
11 Vitrocell GmbH, Waldkirch, Germany,
12 HICE – Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health – Aerosols and Health, Neuherberg, Rostock, Munich, Karlsruhe, Berlin, Waldkirch, Germany; Kuopio, Finland; Cardiff, United Kingdom; Esch-Belval, Luxembourg,
13 German Center for Lung Research (DZL), Munich, Germany

An automated ALI exposure system station with 18 exposure positions was used as the interface for mouse macrophage RAW 264.7 cell line exposures of the diesel engine exhaust. The evaluation is devided in LDH release assay, Metabolite extraction and GC-MS processing, Stable isotope labeling by amino acids in cell culture (SILAC), Proteome extraction and LC-MS/MS analysis of peptides and Proteomics Data An

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24. Jun. 2016

An improved aerosol deposition device to assess safety and efficacy of dry powder formulations at the air/liquid interface

M Hittinger1, S Barthold2, A Gress3, B Wiegand1, L Siebenbürger1, C Börger1, M Berger4, T Krebs4, CM Lehr1, 2, 5, H Groß1

1PharmBioTec GmbH, Saarbrücken, Germany
2Saarland University, Department of Pharmacy, Saarbrücken, Germany
3Max Planck Institute for Informatics, Saarbrücken, Germany
4Vitrocell Systems GmbH, Waldkirch, Germany
5Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), HZI, Saarbrücken, Germany

This poster shows a newly developed instrument which can be used with commercial dry powder inhaler devices and offers flexible adjustment of the flow rate and other process parameters. Salbutamol sulfate dry powder formulation and sodium fluorescein were investigated in the device. The Results were estimated by electron microscop and the deposition of salbutamol sulfate was quantified by HPLC-MS analysis.

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16. Jun. 2016

Nanoparticles on human lung cells

The Vitrocell Exposure System for cell cultures at the air-liquid interface

Sonja Mülhopt1, Tobias Krebs2, Dr Silvia Diabaté3, Christoph Schlager1, Dr Hanns-Rudolf Paur1

1 Institute for Technical Chemistry, Karlsruhe Institute of Technology, 
2 Vitrocell Systems GmbH, 
3 Institute of Toxicology and Genetics, Karlsruhe Institute of Technology

 

This article shows the development of an automated exposure system which allows both reproducible sampling and conditioning of aerosols and exposure of the cell cultures under conditions imitating those of the human lung. Bioassays were developed and used for toxicological analysis of particulate emissions from the industry as well as of nanoparticles.

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30. Apr. 2016

Assessing the mutagenic activities of smoke from different cigarettes in direct exposure experiments using the modified Ames Salmonella assay

Shinkichi Ishikawa, Yuki Kanemaru, Hidenori Nara, Kazuo Erami, Yasufumi Nagata

Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa 227-8512, Japan

 

This article shows the successful exposition exposure of cigarette smoke on two different Ames bacteria strains by using the Vitrocell exposure system including the VC10 smoking robot. Conventional 1 mg tar commercial cigarettes (CC1), 1R5F reference cigarettes (University of Kentucky,Lexington, KY, USA), and 3R4F reference cigarettes (University of Kentucky) were compared with a prototype heated cigarette (HC).

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15. Mar. 2016

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function

DOI: 10.1165/rcmb.2015-0294MA

Jorid B. Sørli1, Emilie Da Silva1, Per Bäckman2, Marcus Levin1, Birthe L. Thomsen1, Ismo K. Koponen1, and Søren T. Larsen1
1The National Research Centre for the Working Environment, Copenhagen, Denmark
2AstraZeneca, Mölndal, Sweden

This study has demonstrated that the modified CDS, a novel method that mimics the conditions for the lung surfactant, is a useful bioassay to assess the acute effects of dry powder aerosols on the lung. The in vitro method, based on the constrained drop surfactometer, different Turbuhaler as well as empty Turbuhaler filled with albumin or lactose were tested. A quartz crystal microbalance was fitted in the chamber to estimate the dose of the deposited particles.


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14. Mar. 2016

Cellular Effects in an In Vitro Human 3D Cellular Airway Model and A549/BEAS-2B In Vitro Cell Cultures Following Air Exposure to Cerium Oxide Particles at an Air–Liquid Interface

DOI: 10.1089/aivt.2015.0030

Ingeborg M. Kooter,1 Mariska Gröllers-Mulderij,1 Maaike Steenhof,1 Evert Duistermaat,2 Frederique A.A. van Acker,2 Yvonne C.M. Staal,2 Peter C. Tromp,1 Eric Schoen,1 C. Frieke Kuper,1 and Eugene van Someren1

1The Netherlands Organisation for Applied Scientific Research, TNO, Utrecht, The Netherlands.
2TNO Triskelion BV, Zeist, The Netherlands.

BEAS-2B, A549, and MucilAir cells were exposed to CeO2 particles and are cultured at air–liquid interface. LDH, cytokine analysis, gene expression analyses, HO-1 analyses and Comet assay were used for evaluation. Cell responses in the MucilAir model exposed via air to CeO2 were minimal compared to those of the cell lines.

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9. Mar. 2016

Toxicity testing of combustion aerosols at the air-liquid interface with a self-contained and easy-to-use exposure system

doi:10.1016/j.jaerosci.2016.02.005

Sonja Mülhopt a, i, Marco Dilger a, b, i, Silvia Diabaté b, i, Christoph Schlager a, i, Tobias Krebs c, i, Ralf Zimmermann d, h, i, Jeroen Buters e, i, Sebastian Oeder e, g, i, Thomas Wäscher f, Carsten Weiss b, i, Hanns-Rudolf Paur a, i

a Karlsruhe Institute of Technology, Institute for Technical Chemistry, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
b Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
c Vitrocell Systems GmbH, Fabrik Sonntag 3, 79183 Waldkirch, Germany
d University of Rostock, Institute of Chemistry, Dr.-Lorenz-Weg 1, 18051 Rostock, Germany
e Center of Allergy & Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Biedersteiner Str. 29, 80802 München, Germany
f Ingenieurbüro für Energie- und Verfahrenstechnik, Von-Dalheim-Str. 2, 69231 Rauenberg, Germany
g Kühne Foundation, Christine Kühne Center for Allergy Research and Education (CK- CARE), München, Germany
h Cooperation Group “Comprehensive Molecular Analytics” – CMA, Helmholtz Zentrum München, 85764 Oberschleißheim/ Germany
i HICE – Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health – Aerosols and Health

 

Highlights

• We present a fully automated Air-Liquid-Interface Exposure System.
• System characterisation shows a high reproducibility.
• Wood combustion aerosol causes cytotoxicity in human lung epithelial cells.
• Gene regulation caused by ship diesel emissions in human lung epithelial cells.

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8. Jan. 2016

Carbonbeton – eine neue Art des Bauens

Projekt C³-Carbon Concrete Composite

VITROCELL® Systems GmbH ist Teil dieses größten Bauforschungsprojektes Deutschlands, dem Projekt C³-Carbon Concrete Composite. Zusammen mit mehr als 130 Partnern aus Forschung, Unternehmen und Verbänden wird im C³-Projekt einen neuer Materialverbund aus Carbonfasern und Hochleistungsbeton mit unserer Technologie getestet.

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31. Oct. 2015

Roflumilast partially reverses smoke-induced mucociliary dysfunction

DOI 10.1186/s12931-015-0294-3

Andreas Schmid, Nathalie Baumlin, Pedro Ivonnet, John S. Dennis, Michael Campos, Stefanie Krick and Matthias Salathe*

* Correspondence: msalathe@med.miami.edu
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, RMSB #7058, Miami, FL 33136, USA

 

Primary normal human bronchial epithelial cells (NHBE) from non-smokers, cultured at the air-liquid interface (ALI), were exposed to cigarette smoke in a Vitrocell VC-10 smoking robot. The results show that roflumilast can rescue smoke-induced mucociliary dysfunction.Therefor the ELIZA Assay and qPCR were used.

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