ATLA 41.5, November 2013

//ATLA 41.5, November 2013

News & Views

ATLA Staff Writer

Human Tissue Used for Research on Parkinson’s Disease
Non-invasive Imaging Used for the Identification of Biomarker in Parkinson’s Disease
Social Development in Primates
Differences in mRNA and Protein Expression
Human Studies Shed Light on Brain Ageing
Pain Research on Humans
3-D In Vitro Skin Model
Human-derived Culture Media Supplement
Beagle Farm Plan Rejected
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2017-01-09T06:38:10+00:00

An Analysis of the Use of Dogs in Predicting Human Toxicology and Drug Safety

Jarrod Bailey, Michelle Thew and Michael Balls

Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1–4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no evidence that adverse drug reactions (ADRs) will also be absent in humans. While the LRs suggest that the presence of toxic effects in dogs can provide considerable evidential weight for a risk of potential ADRs in humans, this is highly inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Our results therefore have important implications for the value of the dog in predicting human toxicity, and suggest that alternative methods are urgently required.

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IIVS News & Views

ATLA Staff Writer

IIVS, HSI, HSUS and HTPC Sign a Memorandum of Understanding
Chinese Society of Dermatology Meeting
Training and Mentoring Quality Assurance Personnel and Study Directors
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2017-01-09T06:38:10+00:00 Tags: |

News and Views

ATLA staff writer

Human Tissue Used for Research on Parkinson’s Disease
Non-invasive Imaging Used for the Identification of Biomarker in Parkinson’s Disease
Social Development in Primates
Differences in mRNA and Protein Expression
Human Studies Shed Light on Brain Ageing
Pain Research on Humans
3-D In Vitro Skin Model
Human-derived Culture Media Supplement
Beagle Farm Plan Rejected
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2017-01-09T06:38:54+00:00 Tags: |

Current Status of Animal Welfare and Animal Rights in China

Jiaqi Lu, Kathryn Bayne and Jianfei Wang

In the past few years, new social passions have sparked on the Chinese mainland. At the centre of these burgeoning passions is a focus on animal welfare, animal treatment, and even animal rights, by the public and academic sectors. With China’s rapid economic changes and greater access to information from around the world, societal awareness of animal issues is rising very fast. Hastening this paradigm shift were several highly public incidents involving animal cruelty, including exposés on bear bile harvesting for traditional Chinese medicine, the thousands of dogs rescued from China’s meat trade, and the call to boycott shark fin soup and bird nest soup. This article outlines the current status of campaigning by animal advocates in China (specifically the animal rights movement) from three interlinked perspectives: wildlife conservation, companion animal protection, and laboratory animal protection. By reviewing this campaigning, we attempt to present not only the political and social impact of the concept of animal rights, but also the perceptions of, and challenges to, animal rights activities in China.

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Validation of the Hepatocyte-like HPCT-1E3 Cell Line as an In Vitro Model for the Prediction of Acute In Vivo Toxicity

Sandra Halwachs, Cathleen Lakoma and Walther Honscha

In a pilot study, we tested 20 randomly-selected chemicals for their cytotoxicity toward the HPCT-1E3 cell model, in order to prove the ability of this in vitro model to predict human acute in vivo toxicity. The study revealed that, in contrast to most other in vitro models, results from the HPCT-1E3 cellbased system show better correlation with the more-relevant human acute lethal doses, whereas results from most other systems have a high predictivity for human lethal serum concentrations. For the prevalidation of the HPCT-1E3 model as a surrogate for regulatory acute in vivo toxicity tests, we have now expanded the list of tested chemicals to 57 substances, and have compared the results with data from the HepG2 cell assay. Again, a better correlation of HPCT-1E3 IC50 values with human oral lethal doses, as comparedto correlation with human lethal serum concentrations, was observed after the pooling of all the tested substances (r2 = 0.53 [P < 0.001] and r2 = 0.41 [P = 0.009], respectively). Therefore, the HPCT-1E3 in vitro model may be a valuable tool for prediction of human oral toxicity, and may help to further reduce the number of animals used for in vivo toxicity tests.
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2017-01-09T06:39:00+00:00

A Phantom Pig Abdomen as an Alternative for Testing Robotic Surgical Systems: Our Experience

Asko Ristolainen,  Gianluca Colucci and Maarja Kruusmaa

The use of animals for testing and validating new medical devices and surgical techniques has raised ethical issues for a long time. Following the introduction of the Three Rs principle, significant efforts have been made to achieve a reduction in the numbers of animals used in testing. Nevertheless, the number of large animals used for testing purposes is still too high. This article describes a potential alternative to the use of large animals in the early phase of the development of surgical equipment — a high-definition phantom pig abdomen. The phantom pig abdomen was developed from computed tomography scans by using affordable materials, and it was used with two different robotic platforms. It permitted the testing of minimally-invasive robotic pancreatic enucleation, with or without intraoperative ultrasound guidance. The phantom pig abdomen has proven to be a realistic tool, with the potential to reduce the cost and time-frame of the experiments.

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2017-01-09T06:39:00+00:00

Comment – A Critical Review of Anaesthetised Animal Models and Alternatives for Military Research, Testing and Training, with a Focus on Blast Damage, Haemorrhage and Resuscitation

Robert D. Combes

Military research, testing, and surgical and resuscitation training, are aimed at mitigating the consequences of warfare and terrorism to armed forces and civilians. Traumatisation and tissue damage due to explosions, and acute loss of blood due to haemorrhage, remain crucial, potentially preventable, causes of battlefield casualties and mortalities. There is also the additional threat from inhalation of chemical and aerosolised biological weapons. The use of anaesthetised animal models, and their respective replacement alternatives, for military purposes — particularly for blast injury, haemorrhaging and resuscitation training — is critically reviewed. Scientific problems with the animal models include the use of crude, uncontrolled and non-standardised methods for traumatisation, an inability to model all key trauma mechanisms, and complex modulating effects of general anaesthesia on target organ physiology. Such effects depend on the anaesthetic and influence the cardiovascular system, respiration, breathing, cerebral haemodynamics, neuroprotection, and the integrity of the blood–brain barrier. Some anaesthetics also bind to the NMDA brain receptor with possible differential consequences in control and anaesthetised animals. There is also some evidence for gender-specific effects. Despite the fact that these issues are widely known, there is little published information on their potential, at best, to complicate data interpretation and, at worst, to invalidate animal models. There is also a paucity of detail on the anaesthesiology used in studies, and this can hinder correct data evaluation. Welfare issues relate mainly to the possibility of acute pain as a side-effect of traumatisation in recovered animals. Moreover, there is the increased potential for animals to suffer when anaesthesia is temporary, and the procedures invasive. These dilemmas can be addressed, however, as a diverse range of replacement approaches exist, including computer and mathematical dynamic modelling of the human body, cadavers, interactive human patient simulators for training, in vitro techniques involving organotypic cultures of target organs, and epidemiological and clinical studies. While the first four of these have long proven useful for developing protective measures and predicting the consequences of trauma, and although many phenomena and their sequelae arising from different forms of trauma in vivo can be induced and reproduced in vitro, non-animal approaches require further development, and their validation and use need to be coordinated and harmonised. Recommendations to these ends are proposed, and the scientific and welfare problems associated with animal models are addressed, with the future focus being on the use of batteries of complementary replacement methods deployed in integrated strategies, and on greater transparency and scientific cooperation.

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