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Jon T Hamm, Patricia Ceger, David Allen, Matt Stout, Elizabeth A Maull, Greg Baker, Amy Zmarowski, Stephanie Padilla, Edward Perkins, Antonio Planchart, Donald Stedman, Tamara Tal, Robert L Tanguay, David C Volz, Mitch S Wilbanks, Nigel J Walker
There is a need for fast, efficient, and cost-effective hazard identification and characterization of chemical hazards. This need is generating increased interest in the use of zebrafish embryos as both a screening tool and an alternative to mammalian test methods. A Collaborative Workshop on Aquatic Models and 21st Century Toxicology identified the lack of appropriate and consistent testing protocols as a challenge to the broader application of the zebrafish embryo model. The National Toxicology Program established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) initiative to address the lack of consistent testing guidelines and identify sources of variability for zebrafish-based assays...
November 10, 2018: ALTEX
Anita Birke, Stefan Scholz
The zebrafish embryo test has been discussed as an alternative test system to provide data on acute fish toxicity required by diverse regulations. A meta-analysis of zebrafish embryo acute toxicity (ZFET) data has revealed conflicting evidence that narcotic compounds (i.e. compounds with baseline toxicity) may exhibit weaker sensitivity in the ZFET if compared to the acute (adult) fish toxicity test (AFT). Therefore, six compounds with presumably narcotic or unknown mode of action, and for which a previous meta-analysis has indicated weaker sensitivity were experimentally analysed for their fish embryo acute toxicity and exposure concentrations were monitored...
October 29, 2018: ALTEX
Edward J Perkins, Kalyan Gayen, Jason E Shoemaker, Philipp Antczak, Lyle Burgoon, Francesco Falciani, Steve Gutsell, Geoff Hodges, Aude Kienzler, Dries Knapen, Mary McBride, Catherine Willett, Francis J Doyle, Natàlia Garcia-Reyero
Current efforts in chemical safety are focused on utilizing human in vitro or alternative animal data in biological pathway context. However, it remains unclear how biological pathways, and toxicology data developed in that context, can be used to quantitatively facilitate decision-making.  The objective of this work is to determine if hypothesis testing using Adverse Outcome Pathways (AOPs) can provide quantitative chemical hazard predictions.  Current methods for predicting hazards of chemicals in a biological pathway context were extensively reviewed, specific case studies examined and computational modeling used to demonstrate quantitative hazard prediction based on an AOP...
October 16, 2018: ALTEX
Katy Taylor, Corina Gericke, Laura Rego Alvarez
There have been significant developments in the use of animals to test Botulinum toxin products in Europe in recent years. This paper summarises and discusses these from the perspective of the animal protection organisation. A cell-based assay has been validated by Allergan and is now being used for the replacement of the mouse bioassay for the batch testing of their Botulinum toxin A products. Two further companies (Merz and Ipsen) have recently validated similar cell-based assays to replace animals in their batch testing...
October 10, 2018: ALTEX
Mathijs G A Broeren, Claire E J Waterborg, Renske Wiegertjes, Rogier M Thurlings, Marije I Koenders, Peter L E M Van Lent, Peter M Van der Kraan, Fons A J Van de Loo
Therapeutic agents that are used by patients with rheumatic and musculoskeletal diseases were originally developed and tested in animal models, and although retrospective studies show a limited predictive value, it could be explained by the fact that there are no good in vitro alternatives. In this study, we developed a 3-dimensional synovial membrane model made of either human primary synovial cell suspensions or a mix of primary fibroblast-like synoviocytes and CD14+ mononuclear cells. We analyzed the composition of the mature micromasses by immunohistochemical staining and flow cytometry and show that the outer surface forms a lining layer consisting out of fibroblast-like and macrophage-like cells, reflecting the in vivo naïve synovial membrane...
October 9, 2018: ALTEX
Kathrin Herrmann, Paul Flecknell
Pain has a profound effect on an animal's wellbeing. In Germany, researchers using animals have been legally required since 1972 to reduce any possible pain, suffering, distress or lasting harm to an absolute minimum. To evaluate how these provisions have been implemented in practice, an assessment of refinements to experimental techniques was conducted by retrospectively reviewing 684 surgical interventions described in 506 animal research applications that were sent to the German competent authorities for approval in 2010...
September 14, 2018: ALTEX
Wen Y Chung, Joseph J Wanford, Rohan Kumar, John D Isherwood, Richard D Haigh, Marco R Oggioni, Ashley R Dennison, Giuseppe Ercoli
An ex vivo, porcine spleen perfusion model was established to study the early events occurring in the spleen prior to the onset of bacterial sepsis, using organs retrieved from animals slaughtered for food production. Porcine spleens were harvested from adult pigs and connected to a normothermic extracorporeal perfusion circuit. A constant perfusion of heparinized blood was performed for 6 hours. After injection of Streptococcus pneumoniae to the circuit serial samples of both blood and spleen biopsies were collected and analysed...
August 3, 2018: ALTEX
Pilar Prieto, Rabea Graepel, Kirsten Gerloff, Lara Lamon, Magdalini Sachana, Francesca Pistollato, Laura Gribaldo, Anna Bal-Price, Andrew Worth
The replacement of animals in acute systemic toxicity testing remains a considerable challenge. Only animal data are currently accepted by regulators, including data generated by reduction and refinement methods. The development of Integrated Approaches to Testing and Assessment (IATA) is hampered by an insufficient understanding of the numerous toxicity pathways that lead to acute systemic toxicity. Therefore, central to our work has been the collection and evaluation of the mechanistic information on eight organs identified as relevant for acute systemic toxicity (nervous system, cardiovascular system, liver, kidney, lung, blood, gastrointestinal system and immune system)...
July 12, 2018: ALTEX
Francesca Caloni, Yula Sambuy, Guerino Lombardi, Silvia Dotti, Isabella De Angelis
No abstract text is available yet for this article.
2018: ALTEX
Tilo Weber
No abstract text is available yet for this article.
2018: ALTEX
Konradin Metze, Fernanda Aparecida Borges da Silva, Irene Lorand-Metze
No abstract text is available yet for this article.
2018: ALTEX
Roberta De Souza Santos, Aaron P Frank, Biff F Palmer, Deborah J Clegg
Cell culture has enhanced our understanding of cellular physiology and constitutes an important tool in advancing mechanistic insight. Researchers should be reminded, however, that there are limitations in extrapolating data derived from cultured cells to questions focusing on the impact of sex. In this Opinion, we highlight two underappreciated aspects of cell culture systems regarding sex: how cell culture media alters the sex hormone environment, and how the innate sex of the cell is often not factored into the overall analysis...
2018: ALTEX
Aldo Dekker, Froukje Van Hemert-Kluitenberg, Anna H Oosterbaan, Kimberly Moonen, Laure Mouton
Titration of foot-and-mouth disease cattle challenge virus in cattle tongue has been the standard for many years in many countries, although titration in animals has been replaced by in vitro methods for all other applications. The objective of the analysis was the replacement of in vivo titration of cattle challenge virus by in vitro titration. Using data from 32 in vivo titration experiments together with the in vitro titration results of the same samples obtained by plaque count on primary lamb or pig kidney cells, as well as data from the virus isolation control chart used in the laboratory, we show that the reproducibility of the in vitro titration is much higher than that of the in vivo titration...
2018: ALTEX
Marcel Leist, Jan G Hengstler
Methods papers are important for the progress of biomedical research, as they provide the essential tools to explore new questions and help to better answer old ones. However, it is often not clear how a methods paper differs from a methods protocol. Confusion between these two very different types of publication is widespread. The resultant misunderstanding contributes to a relatively poor reputation of methods research in biology despite the fact that many Nobel prizes have been awarded specifically for method development...
2018: ALTEX
Hanna Vuorenpää
No abstract text is available yet for this article.
2018: ALTEX
Julika Fitzi-Rathgen
No abstract text is available yet for this article.
2018: ALTEX
Andras-Laszlo Nagy, Cornel Catoi, Carmen Socaciu, Adela Pintea, Nechita A Oros, Cristina Coman, Dumitrita Rugina, Cristian T Matea, Teodora Mocan, Teresa Coccini, Uliana De Simone, Isabella De Angelis, Alessia Bertero, Yula Sambuy, Francesca Caloni
No abstract text is available yet for this article.
2018: ALTEX
Megan Chesnut, Takashi Yamada, Timothy Adams, Derek Knight, Nicole Kleinstreuer, George Kass, Thomas Luechtefeld, Thomas Hartung
No abstract text is available yet for this article.
2018: ALTEX
Lucy Meigs, Lena Smirnova, Costanza Rovida, Marcel Leist, Thomas Hartung
For a long time, the discussion about animal testing vs its alternatives centered on animal welfare. This was a static warfare, or at least a gridlock, where life scientists had to take a position and make their value choices and hardly anyone changed sides. Technical advances have changed the frontline somewhat, with in vitro and in silico methods gaining more ground. Only more recently has the economic view begun to have an impact: Many animal tests are simply too costly, take too long, and give misleading results...
2018: ALTEX
Brian D Chapron, Alenka Chapron, Brian Phillips, Miracle C Okoli, Danny D Shen, Edward J Kelly, Jonathan Himmelfarb, Kenneth E Thummel
The role of megalin in the regulation of renal vitamin D homeostasis has previously been evaluated in megalin-knockout mice and rat proximal tubule epithelial cells. We revisited these hypotheses that were previously tested solely in rodent models, this time using a 3-dimensional proximal tubule microphysiological system incorporating primary human proximal tubule epithelial cells. Using this human cell-derived model, we confirmed that 25OHD3 is transported into the human proximal tubule epithelium via megalin-mediated endocytosis while bound to vitamin D binding protein...
2018: ALTEX
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