ATLA 45.4, September 2017

//ATLA 45.4, September 2017

IIVS News and Views

IIVS staff

IIVS at the 10th World Congress on Alternatives and Animal Use in the Life Sciences

Registration Open for 2018 IIVS Practical Methods Workshop

Chinese FDA and IIVS Re-affirm Their Collaboration for Non-animal Tests

Collaborative Effort Aims to Replace Rabbit Test for Personal Lubricant Products

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2017-10-10T20:25:57+00:00 Tags: |

CAAT News and Views

CAAT staff

CAAT at the 10th World Congress on Alternatives and Animal Use in the Life Sciences

CAAT-Europe/CAAT Academy’s François Busquet Speaks at European Parliament’s Intergroup on the Welfare and Conservation of Animals

Next Generation Humane Science Award: Deadline 30 November 2017

CAAT at EUROTOX: Symposium on Investigative Toxicology

CAAT-Europe’s Costanza Rovida on ‘New Approach Methodologies (NAMs) for Biomedical Research’

CAAT and ESTIV One-day Training Course

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2017-10-10T20:22:56+00:00 Tags: |

Human Aortic Endothelial Cells Respond to Shear Flow in Well-Plate Microfluidic Devices

Om Makwana, Hannah Flockton, Gary P. Watters, Rizwan Nisar, Gina A. Smith, Wanda Fields and Betsy Bombick

Although chronic progressive cardiovascular diseases such as atherosclerosis are often challenging to fully model in vitro, it has been shown that certain in vitro methods can effectively evaluate some aspects of disease progression. This has been demonstrated in in vitro and in vivo studies of endothelial cells that have illustrated the effects of nitric oxide (NO) production, filamentous actin (F-actin) formation, and cell and actin angle alignment on vascular function and homeostasis. Systems utilising shear flow have been established, in order to create a physiologically relevant environment for cells that require shear flow for homeostasis. Here, we investigated the use of a well-plate microfluidic system and associated devices (0–20dyn/cm2) to demonstrate applied shear effects on primary Human Aortic Endothelial Cells (HAECs). Changes in cell and actin alignment in the direction of flow, real-time production of NO and gross cell membrane shape changes in response to physiological shear flow were observed. These commercial systems have a range of potential applications, including within the consumer and pharmaceutical industries, thereby reducing the dependency on animal testing for regulatory safety assessments.

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Use of the Bovine Udder Skin Model to Evaluate the Tolerability of Mesem Cosmetic Cream

Christa Raak, Friedrich Molsberger, Wolfgang Pittermann, Mathias Bertram, Sibylle Robens and Thomas Ostermann

Observational studies of Mesem cream (based on Mesembryanthemum crystallinum L. plant extract) found that it had positive effects on skin hydration and smoothing of the skin. However, some patients reported skin irritation effects. The current study evaluated the skin tolerability of Mesem cream, as compared to the carrier cream (without the active ingredient), by using the isolated perfused bovine udder skin model. The primary outcomes investigated were cytotoxicity (i.e. cell viability), assessed with the MTT assay, and irritancy and inflammation, assessed by measuring PGE2 tissue levels. A total reaction score was calculated by combining the results for each parameter. In the case of a single topical application, significant differences were found between the carrier cream and the Mesem cream. While the application of carrier cream resulted in low cytotoxicity (–8.4% change in viability, as compared to the untreated control), the Mesem cream was more cytotoxic (–18.7% change). In addition, one hour after application, PGE2 levels were higher in Mesem cream-treated skin, as compared to carrier cream-treated skin (16.6% versus 11.3%). Further experiments (tape-stripped skin and repeated application) also found significant differences between the two creams in the results obtained. Evaluation of the effectiveness, safety and tolerability of phyto-cosmetic products is important. Our results confirmed the findings of two previous human observational studies (the human patch test and open application study). Future experiments to understand the underlying principles of its effectiveness, safety and tolerability should include extracts of M. crystallinum L. juice, as well as the Mesem cream itself.
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In Vitro Models as a Platform to Investigate Traumatic Brain Injury

Ashwin Kumaria

Traumatic Brain Injury (TBI) remains a significant cause of mortality and morbidity, affecting individuals of all age groups. Much remains to be learned about its complex pathophysiology, with a view to designing effective neuroprotective strategies to protect sublethally injured brain tissue that would otherwise die in secondary injury processes. Experimental in vivo models offer the potential to study TBI in the laboratory, however, treatments that were neuroprotective in animals have, thus far, largely failed to translate in human clinical studies. In vitro models of neurotrauma can be used to study specific pathophysiological cascades — individually and without confounding factors — and to test potential neuroprotective strategies. These in vitro models include transection, compression, barotrauma, acceleration, hydrodynamic, chemical injury and cell-stretch methodologies. Various cell culture systems can also be utilised, including brain-on-a-chip, immortalised cell lines, primary cultures, acute preparations and organotypic cultures. Potential positive outcomes of the increased use of in vitro platforms to study TBI would be the refinement of in vivo experiments, as well as enhanced translation of the results into clinically meaningful neuroprotective strategies for the future. In addition, the replacement of in vivo experiments by suitable in vitro studies would lead to a welcome reduction in the numbers of animal procedures in this ethically-challenging field.

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