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https://www.readbyqxmd.com/read/29197217/rptec-tert1-cells-form-highly-differentiated-tubules-when-cultured-in-a-3d-matrix
#1
Philipp F Secker, Lisanne Luks, Nadja Schlichenmaier, Daniel R Dietrich
The proximal tubule is the primary site for renal solute reabsorption and secretion and thus a main target for drug-induced toxicity. Current nonclinical methods using 2D cell cultures are unable to fully recapitulate clinical drug responses mainly due to limited in vitro functional lifespan. Since extracellular matrices are known to be key regulators of cell development, culturing cells on classic 2D plastic surfaces inevitably results in loss of differentiation. Hence, 3D models of the human proximal tubule that recapitulate the in vivo morphology would allow for improved drug screening and disease modeling...
December 2, 2017: ALTEX
https://www.readbyqxmd.com/read/29184966/recommendations-to-improve-the-eu-non-technical-summaries-of-animal-experiments
#2
Katy Taylor, Laura Rego, Tilo Weber
Under the new Directive 2010/63/EC, member states have to publish non-technical summaries (NTS) of the projects involving animals that they authorise. These summaries must include information on the objectives of the project including the predicted harm and benefits and the number and types of animals to be used. Summaries should also demonstrate compliance with the 3Rs. The intention was that NTS would help increase the transparency of animal research in the EU. In this article, we review the status of the publication of NTS across member states and give some general observations on publication speed, identification, accessibility and quality...
November 29, 2017: ALTEX
https://www.readbyqxmd.com/read/29169185/co-culture-of-human-alveolar-epithelial-haelvi-and-macrophage-thp-1-cell-lines
#3
Stephanie Kletting, Sarah Barthold, Urska Repnik, Gareth Griffiths, Brigitta Loretz, Nicole Schneider-Daum, Cristiane de Souza Carvalho-Wodarz, Claus-Michael Lehr
The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages represent an immunological barrier, in particular for larger molecules and nanoparticles. This paper describes a new co-culture of human cell lines representing both cell types. Acquiring, culturing and maintaining primary alveolar epithelial cells presents significant logistical and technical difficulties. The recently established human alveolar epithelial lentivirus immortalized cell line, hAELVi, when grown on permeable filters, form monolayers with high functional and morphological resemblance to alveolar type I cells...
November 23, 2017: ALTEX
https://www.readbyqxmd.com/read/28968481/state-of-the-art-and-new-options-to-assess-t-cell-activation-by-skin-sensitizers-cosmetics-europe-workshop
#4
Erwin van Vliet, Jochen Kühnl, Carsten Goebel, Silvia Martinozzi-Teissier, Nathalie Alépée, Takao Ashikaga, Brunhilde Blömeke, Aurelia Del Bufalo, Magalie Cluzel, Emanuela Corsini, Nathalie Delrue, Bertrand Desprez, Nichola Gellatly, Christoph Giese, Laura Gribaldo, Sebastian Hoffmann, Martina Klaric, Bernard Maillere, Dean Naisbitt, Marc Pallardy, Marc Vocanson, Dirk Petersohn
Significant progress has been made in the development and validation of non-animal test methods for skin sensitization assessment. At present, three of the four key events of the Adverse Outcome Pathway (AOP) are assessable by OECD-accepted in vitro methods. The fourth key event describes the immunological response in the draining lymph node where activated dendritic cells present major histocompatibility complex-bound chemically modified peptides to naive T cells, thereby priming the proliferation of antigen-specific T cells...
October 2, 2017: ALTEX
https://www.readbyqxmd.com/read/28922667/integrated-strategy-for-mutagenicity-prediction-applied-to-food-contact-chemicals
#5
Serena Manganelli, Benoît Schilter, Emilio Benfenati, Alberto Manganaro, Elena Lo Piparo
Food contamination due to unintentional leakage of chemicals from food contact materials (FCM) is a source of increasing concern. Since for many of these substances, only limited or no toxicological data are available, the development of alternative methodologies to establish rapidly and cost-efficiently level of safety concern is critical to ensure adequate consumer protection. Computational toxicology methods are considered the most promising solutions to cope with this data gap. In particular, mutagenicity assessment has a particular relevance and is a mandatory requirement for all substances released from plastic FCM, regardless how low migration and exposure are...
September 18, 2017: ALTEX
https://www.readbyqxmd.com/read/28884783/ex-vivo-model-unravelling-cell-distribution-effect-in-hydrogels-for-cartilage-repair
#6
Vivian H M Mouser, Noël M M Dautzenberg, Riccardo Levato, Mattie H P van Rijen, Wouter J A Dhert, Jos Malda, Debby Gawlitta
The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell-therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect of spatial chondrocyte distribution on the reparative process. To reduce animal experiments, an ex vivo osteochondral plug model was used and evaluated. Finally, the role of the delivered and endogenous cells in the repair process was investigated...
September 8, 2017: ALTEX
https://www.readbyqxmd.com/read/28817164/prediction-of-acute-inhalation-toxicity-using-in-vitro-lung-surfactant-inhibition
#7
Jorid B Sørli, Yishi Huang, Emilie Da Silva, Jitka S Hansen, Yi Y Zuo, Marie Frederiksen, Asger W Nørgaard, Niels E Ebbehøj, Søren T Larsen, Karin S Hougaard
Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals...
August 17, 2017: ALTEX
https://www.readbyqxmd.com/read/28800376/fetal-bovine-serum-fbs-past-present-future
#8
Jan van der Valk, Karen Bieback, Christiane Buta, Brett Cochrane, Wilhelm G Dirks, Jianan Fu, James J Hickman, Christiane Hohensee, Roman Kolar, Manfred Liebsch, Francesca Pistollato, Markus Schulz, Daniel Thieme, Tilo Weber, Joachim Wiest, Stefan Winkler, Gerhard Gstraunthaler
The supplementation of culture medium with fetal bovine serum (FBS, also referred to as 'fetal calf serum') is still common practice in cell culture applications. Due to a number of disadvantages in terms of quality and reproducibility of in vitro data, animal welfare concerns, and in light of recent cases of fraudulent marketing, the search for alternatives and the development of serum-free medium formulations gained global attention. Here, we report on the 3rd Workshop on FBS, Serum Alternatives and Serum-free Media, where (a) regulatory aspects, (b) the serum dilemma, (c) alternatives to FBS, (d) case-studies of serum-free in vitro applications, and (e) the establishment of serum-free databases, were discussed...
August 9, 2017: ALTEX
https://www.readbyqxmd.com/read/28738424/use-of-high-throughput-in-vitro-toxicity-screening-data-in-cancer-hazard-evaluations-by-iarc-monograph-working-groups
#9
Weihsueh A Chiu, Kathryn Z Guyton, Matthew T Martin, David M Reif, Ivan Rusyn
Evidence regarding carcinogenic mechanisms serves a critical role in International Agency for Research on Cancer (IARC) Monograph evaluations. Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112 -113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream...
July 24, 2017: ALTEX
https://www.readbyqxmd.com/read/28653737/a-validated-algorithm-for-selecting-non-toxic-chemical-concentrations
#10
Julita Stadnicka-Michalak, Melanie Knöbel, Anže Županič, Kristin Schirmer
The maximal chemical concentration that causes an acceptably small or no effect in an organism or isolated cells is an often-sought-after value in toxicology. Existing approaches to derive this value have raised several concerns; thus, it is often chosen case-by-case based on personal experience. To overcome this ambiguity, we propose an approach for choosing the non-toxic concentration (NtC) of a chemical in a rational, tractable way. We developed an algorithm that identifies the highest chemical concentration which causes no more than 10% effect (=EC10) including the modeled 95% confidence intervals and considering each of the measured biological replicates; and whose toxicity is not significantly different from no effect...
June 26, 2017: ALTEX
https://www.readbyqxmd.com/read/28539002/from-in-vivo-to-in-vitro-the-medical-device-testing-paradigm-shift
#11
Dayna Kerecman Myers, Alan M Goldberg, Albrecht Poth, Michael F Wolf, Joseph Carraway, James McKim, Kelly P Coleman, Richard Hutchinson, Ronald Brown, Harald F Krug, Anthony Bahinski, Thomas Hartung
Amid growing efforts to advance the replacement, reduction, and refinement of the use of animals in research, there is a growing recognition that in vitro testing of medical devices can be more effective, both in terms of cost and time, and also more reliable than in vivo testing. Although the technological landscape has evolved rapidly in support of these concepts, regulatory acceptance of alternative testing methods has not kept pace. Despite the acceptance by regulators of some in vitro tests (cytotoxicity, gene toxicity, and some hemocompatibility assays), many toxicity tests still rely on animals (irritation, sensitization, acute toxicity, reproductive/developmental toxicity), even where other industrial sectors have already abandoned them...
May 25, 2017: ALTEX
https://www.readbyqxmd.com/read/28470333/extracorporeal-perfusion-of-isolated-organs-of-large-animals-bridging-the-gap-between-in-vitro-and-in-vivo-studies
#12
Carola R Daniel, Raphael Labens, David Argyle, Theresia F Licka
Since the early 20th century extracorporeal perfusion of large animal organs has been used to investigate a broad variety of research questions, thereby overcoming common draw backs of in vitro studies without suffering from ethical concerns associated with live animal research. The technique is in accordance with the 3R principles and represents an excellent opportunity to investigate in detail the physiology of organs under standardised conditions. It is also suitable for the translation of basic pre-clinical research into a more relevant arena prior to or avoiding altogether live animal research...
May 3, 2017: ALTEX
https://www.readbyqxmd.com/read/28403479/the-gard-platform-for-potency-assessment-of-skin-sensitizing-chemicals
#13
Kathrin S Zeller, Andy Forreryd, Tim Lindberg, Robin Gradin, Aakash Chawade, Malin Lindstedt
Contact allergy induced by certain chemicals is a common health concern, and several alternative methods have been developed to fulfill the requirements of European legislation with regard to hazard assessment of potential skin sensitizers. However, validated methods, which provide information about the potency of skin sensitizers, are still lacking. The cell-based assay Genomic Allergen Rapid Detection (GARD), targeting key event 3, dendritic cell activation, of the skin sensitizer AOP, uses gene expression profiling and a machine learning approach for the prediction of chemicals as sensitizers or non-sensitizers...
April 12, 2017: ALTEX
https://www.readbyqxmd.com/read/28403478/non-animal-approaches-for-toxicokinetics-in-risk-evaluations-of-food-chemicals
#14
Ans Punt, Ad A C M Peijnenburg, Ron L A P Hoogenboom, Hans Bouwmeester
The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans...
April 12, 2017: ALTEX
https://www.readbyqxmd.com/read/28230889/quantification-of-the-borderline-range-and-implications-for-evaluating-non-animal-testing-methods-precision
#15
Maria Leontaridou, Daniel Urbisch, Susanne N Kolle, Katharina Ott, Denis S Mulliner, Silke Gabbert, Robert Landsiedel
Testing methods to assess the skin sensitisation potential of a substance usually use threshold criteria to dichotomise continuous experimental read-outs into yes/no conclusions. The threshold criteria are prescribed in the respective OECD test guidelines and the conclusion is used for regulatory hazard assessment, i.e. classification and labelling of the substance. We can identify a borderline range (BR) around the classification threshold within which test results are non-conclusive due to a testing method's biological and technical variability...
February 23, 2017: ALTEX
https://www.readbyqxmd.com/read/28214915/evaluation-of-the-gard-assay-in-a-blind-cosmetics-europe-study
#16
Henrik Johansson, Robin Gradin, Andy Forreryd, Maria Agemark, Kathrin Zeller, Angelica Johansson, Olivia Larne, Erwin van Vliet, Carl Borrebaeck, Malin Lindstedt
Chemical hypersensitivity is an immunological response towards foreign substances, commonly referred to as sensitizers, which gives rise primarily to the clinical symptoms known as allergic contact dermatitis. For the purpose of mitigating risks associated with consumer products, chemicals are screened for sensitizing effects. Historically, such predictive screenings have been performed using animal models. However, due to industrial and regulatory demand, animal models for the purpose of sensitization assessment are being replaced by animal-free testing methods, a global trend that is spreading across industries and market segments...
February 17, 2017: ALTEX
https://www.readbyqxmd.com/read/29156079/the-gard-platform-for-potency-assessment-of-skin-sensitizing-chemicals
#17
Kathrin S Zeller, Andy Forreryd, Tim Lindberg, Robin Gradin, Aakash Chawade, Malin Lindstedt
Contact allergy induced by certain chemicals is a common health concern, and several alternative methods have been developed to fulfill the requirements of European legislation with regard to hazard assessment of potential skin sensitizers. However, validated methods, which provide information about the potency of skin sensitizers, are still lacking. The cell-based assay Genomic Allergen Rapid Detection (GARD), targeting key event 3, dendritic cell activation, of the skin sensitization AOP, uses gene expression profiling and a machine learning approach for the prediction of chemicals as sensitizers or non-sensitizers...
2017: ALTEX
https://www.readbyqxmd.com/read/29101770/progress-towards-the-replacement-of-the-rabbit-blood-sugar-bioidentity-assay-by-an-in-vitro-test-for-batch-release-of-insulins-in-quality-control
#18
LETTER
Rüdiger Hack, Sabrina Rueggeberg, Lea Schneider, Dirk Mayert, Norbert Tennagels, Stefan Welte, Birgit Niederhaus, Wilfried Arz, Dirk Usener, Götz Troschau, Johannes Meiwes, Jochen Maas
No abstract text is available yet for this article.
2017: ALTEX
https://www.readbyqxmd.com/read/29101769/computational-approaches-to-chemical-hazard-assessment
#19
Thomas Luechtefeld, Thomas Hartung
Computational prediction of toxicity has reached new heights as a result of decades of growth in the magnitude and diversity of biological data. Public packages for statistics and machine learning make model creation faster. New theory in machine learning and cheminformatics enables integration of chemical structure, toxicogenomics, simulated and physical data in the prediction of chemical health hazards, and other toxicological information. Our earlier publications have characterized a toxicological dataset of unprecedented scale resulting from the European REACH legislation (Registration Evaluation Authorisation and Restriction of Chemicals)...
2017: ALTEX
https://www.readbyqxmd.com/read/28735340/alternative-approach-to-animal-testing-and-cell-cultures-according-to-european-laws
#20
Chiara Scanarotti, Costanza Rovida, Susanna Penco, Stefania Vernazza, Sara Tirendi, Rosagemma Ciliberti, Anna Maria Bassi
No abstract text is available yet for this article.
2017: ALTEX
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