Welcome to ATLA

Welcome to ATLA
Welcome to ATLA 2018-03-27T14:51:32+00:00

LATEST ISSUE

Volume 46, Issue 1 - March 2018

Human-based diabetes research

Human-based diabetes research

Why Are Validated Alternatives Not Being Used to Replace Animal Tests?

Michael Balls

The stipulation in Directive 2010/63/EU that animal tests are replaced when validated alternative methods are available has no value, unless, as with all laws and regulations, this requirement is rigorously enforced, and unless governments, scientists and industries show greater respect for the scientific method
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News and Views

ATLA staff

Major Relaunch of FRAME in Run-up to 50th Anniversary

FRAME Makes Senior Appointment to Bolster Profile-raising Campaign

REACHing for Alternatives to Animal Testing

TB Tissue Explant Model

Zebrafish Model

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CAAT News and Views

CAAT staff

Society of Toxicology (SOT) Satellite Meeting, Organised by CAAT and The Human Toxicology Project Consortium

2018 Symposium on Social Housing of Laboratory Animals

2nd Pan-American Conference for Alternative Methods

Thomas Hartung Interviewed by Deutsche Welle on the Future of Animal Testing

Paul Locke Discusses Recent Volkwagen Monkey Experiments

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IIVS News and Views

IIVS staff

IIVS and BASF Collaborate to Distribute Test Method to Replace Animal Testing

IIVS at SOT 2018

ARDF Grants Available

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Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward

Zeeshan Ali, P. Charukeshi Chandrasekera and John J. Pippin

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.

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Applicability of the Monocyte Activation Test (MAT) in the Quality Control of the 17DD Yellow Fever Vaccine

Katherine Antunes de Mattos, Elaine Cristina Azevedo Navega, Vitor Fernandes Silva, Alessandra Santos Almeida, Cristiane Caldeira da Silva, Octavio Augusto França Presgrave, Daniel da Silva Guedes Junior and Isabella Fernandes Delgado

The need for alternatives to animal use in pyrogen testing has been driven by the Three Rs concept. This has resulted in the inclusion of the monocyte activation test (MAT) in the European Pharmacopoeia, 2010. However, some technical and regulatory obstacles must be overcome to ensure the effective implementation of the MAT by the industry, especially for the testing of biological products. The yellow fever (YF) vaccine (17DD-YFV) was chosen for evaluation in this study, in view of: a) the 2016–2018 outbreak of YF in Brazil; b) the increase in demand for 17DD-YFV doses; c) the complex production process with live attenuated virus; d) the presence of possible test interference factors, such as residual process components (e.g. ovalbumin); and e) the need for the investigation of other pyrogens that are not detectable by the methods prescribed in the YF vaccine monograph. The product-specific testing was carried out by using cryopreserved and fresh whole blood, and IL-6 and IL-1β levels were used as the marker readouts. After assessing the applicability of the MAT on a 1:10 dilution of 17DD-YFV, endotoxin and non-endotoxin pyrogens were quantified in spiked batches, by using the lipopolysaccharide and lipoteichoic acid standards, respectively. The quantitative analysis demonstrated the correlation between the MAT and the Limulus amoebocyte lysate (LAL) assays, with respect to the limits of endotoxin recovery in spiked batches and the detection of no pyrogenic contamination in commercial batches of 17DD-YFV. The data demonstrated the applicability of the MAT for 17DD-YFV pyrogen testing, and as an alternative method that can contribute to biological quality control studies.

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