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Full-Text Articles in Laboratory and Basic Science Research

Recent Developments In Alternatives To Animal Testing, Katy Taylor Jan 2019

Recent Developments In Alternatives To Animal Testing, Katy Taylor

Application of Alternative Methods Collection

Methods that replace techniques that use live animals, or methods of testing substances without live animal use, are known as alternatives, replacements or non-animal methods. Some prefer the term advanced technologies given the fact that they often rely on more sophisticated technology and are more human- relevant than the animal test they replace (see Langley et al., 2015). There have been efforts to replace animal tests since the 1960s. Significant progress initially came in replacing animals used to diagnose human disease; to produce biological drugs (such as vaccines); and to safety test batches of these drugs as they were produced. …


The Changing Paradigm In Preclinical Toxicology: In Vitro And In Silico Methods In Liver Toxicity Evaluations, Fozia Noor Jan 2019

The Changing Paradigm In Preclinical Toxicology: In Vitro And In Silico Methods In Liver Toxicity Evaluations, Fozia Noor

Application of Alternative Methods Collection

In vitro methods, based on human primary cells, cell lines, and genetically modified reporter cell lines, have greatly expanded the scope of in vitro toxicology. Other significant progress in the area of human-induced pluripotent stem cells (hiPSCs) (Asgari et al., 2010; Schwartz et al., 2014; Shinde et al., 2016; Shtrichman, Germanguz and Itskovitz-Eldor, 2013) is allowing the application of patient and disease-specific hiPSCs (Ghodsizadeh et al., 2010; McCracken et al., 2014; Siller et al., 2013). Moreover, the tools of precise genome editing with engineered nucleases, such as the zinc finger nucleases (zfns), the transcription activator-like effecter nucleases (talens) and, more …


How To Evaluate The Science Of Non-Human Animal Use In Biomedical Research And Testing: A Proposed Format For Debate, Ray Greek, Lisa A. Kramer Jan 2019

How To Evaluate The Science Of Non-Human Animal Use In Biomedical Research And Testing: A Proposed Format For Debate, Ray Greek, Lisa A. Kramer

Validation of Alternative Methods Collection

Over time, the interpretation of science has occasionally been corrupted by vested interest groups, be they financially motivated or ego driven. Scientific consensus and widespread public beliefs usually catch up with the evidence, but this can take a very long time and often costs lives. The use of non-human animals in biomedical research and testing is a scientific endeavor and, as such, can and should be evaluated in light of the best science currently available. But facts that have been accepted in all areas of science are routinely ignored or called into question by well-funded, vested interest groups, compromising the …


How Can The Final Goal Of Completely Replacing Animal Procedures Successfully Be Achieved?, Christiane Baumgartl-Simons, Christiane Hohense Jan 2019

How Can The Final Goal Of Completely Replacing Animal Procedures Successfully Be Achieved?, Christiane Baumgartl-Simons, Christiane Hohense

Validation of Alternative Methods Collection

Article 23 of European Union (EU) Directive 86/609/EEC required that Member States promote the development and validation of alternative technologies and stated that the European Commission (EC) “shall report before the end of 1987 on the possibility of modifying tests and guidelines” (European Parliament, 1986, Article 23). This Directive was replaced by Directive 2010/63/EU on the protection of animals used for scientific purposes, which now requires that Member States develop and validate alternative approaches much more precisely and specifies that the ultimate objective is the “full replacement of procedures on live animals for scientific and educational purposes, as soon as …


The Potential Of Organ On Chip Technology For Replacing Animal Testing, Malcolm Wilkinson Jan 2019

The Potential Of Organ On Chip Technology For Replacing Animal Testing, Malcolm Wilkinson

Human Clinical Trials Collection

The term organ on a chip is used to describe the latest stage of development of in vitro cell culture technology. Figure 26.1 shows its steady development since the 1960s. Each step forward has improved our ability to model human-clinical response to new drugs or therapies and has enabled safety risk assessment of existing cosmetics, personal care products, or other chemicals in the environment. Scientific evidence that the predictive power of in vitro tests is superior to the use of animals will trigger a major shift in the way that medical research, in many areas, is carried out. In this …


Replacing Animal Tests To Improve Safety For Humans, Kathy Archibald, Robert Coleman, Tamara Drake Jan 2019

Replacing Animal Tests To Improve Safety For Humans, Kathy Archibald, Robert Coleman, Tamara Drake

Application of Alternative Methods Collection

In this chapter, we propose a new, pragmatic approach that could accelerate the replacement of most, if not all, regulatory animal tests with superior tests based on human biology. We also propose that changes to the requirements for safety testing, issued by the us Food and Drug Administration (fda), must be made in order to enable the use of superior new tests, which are currently disadvantaged by the outdated language of the regulations. But first, it is imperative to establish some level of understanding of the efficacy of existing animal-based methods in order to know whether any possible replacement is …


Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing, Elin Törnqvist, Anita Annas, Britta Granath, Elisabeth Jalkesten, Ian Cotgreave, Mattias Öberg Jul 2014

Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing, Elin Törnqvist, Anita Annas, Britta Granath, Elisabeth Jalkesten, Ian Cotgreave, Mattias Öberg

Application of Alternative Methods Collection

The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. …


Clinical Trials And Late-Stage Drug Development In Alzheimer’S Disease: An Appraisal From 1984 To 2014, L. S. Schneider, F. Mangialasche, S. Andreasen, H. Feldman, E. Giacobini, R. Jones, V. Mantua, P. Mecocci, L. Pani, B. Winblad, M. Kivipelto Mar 2014

Clinical Trials And Late-Stage Drug Development In Alzheimer’S Disease: An Appraisal From 1984 To 2014, L. S. Schneider, F. Mangialasche, S. Andreasen, H. Feldman, E. Giacobini, R. Jones, V. Mantua, P. Mecocci, L. Pani, B. Winblad, M. Kivipelto

Human Clinical Trials Collection

The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, …


Lost In Translation: Animal Models And Clinical Trials In Cancer Treatment, Isabella W.Y. Mak, Nathan Evaniew, Michelle Ghert Jan 2014

Lost In Translation: Animal Models And Clinical Trials In Cancer Treatment, Isabella W.Y. Mak, Nathan Evaniew, Michelle Ghert

Human Clinical Trials Collection

Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal models can serve as an important source of in vivo information, but alternative translational approaches have emerged that may eventually replace the link between in vitro studies and …


Inflammatory Findings On Species Extrapolations: Humans Are Definitely No 70-Kg Mice, Marcel Leist, Thomas Hartung Apr 2013

Inflammatory Findings On Species Extrapolations: Humans Are Definitely No 70-Kg Mice, Marcel Leist, Thomas Hartung

Validation of Alternative Methods Collection

Modern toxicology has embraced in vitro methods, and major hopes are based on the Omics technologies and systems biology approaches they bring along (Hartung and McBride in ALTEX 28(2):83–93, 2011; Hartung et al. in ALTEX 29(2):119–28, 2012). A culture of stringent validation has been developed for such approaches (Leist et al. in ALTEX 27(4):309–317, 2010; ALTEX 29(4):373–88, 2012a; Toxicol Res 1:8–22, 2012b), while the quality and usefulness of animal experiments have been little scrutinized. A new study (Seok et al. 2013) now shows the low predictivity of animal responses in the field of inflammation. These findings corroborate earlier findings from …


Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens Jan 2013

Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens

Experimentation Collection

Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …


Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey Aug 2008

Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey

Experimentation Collection

Despite considerable research, effective and safe treatments for human pain disorders remain elusive. Understanding the biology of different human pain conditions and researching effective treatments continue to be dominated by animal models, some of which are of limited value. British and European legislation demands that non-animal approaches should be considered before embarking on research using experimental animals. Recent scientific and technical developments, particularly in human neuroimaging, offer the potential to replace some animal procedures in the study of human pain. A group of pain research experts from academia and industry met with the aim of exploring creatively the tools, strategies …


Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley Mar 2005

Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley

Application of Alternative Methods Collection

In this report, we argue specifically that acute toxicity data should not be sought from animal tests. The underlying principle of such tests on rats and mice is that the results can be effectively extrapolated to humans. In fact, after nearly 80 years of use of these tests, the predictivity of rodent data for human acute toxic effects has been disputed but never proven.


Anatomy And Three-Dimensional Reconstructions Of The Brain Of A Bottlenose Dolphin (Tursiops Truncatus) From Magnetic Resonance Images, Lori Marino, Keith D. Sudheimer, Timothy L. Murphy, Kristina K. Davis, D. Ann Pabst, William A. Mclellan, James K. Rilling, John I. Johnson Dec 2001

Anatomy And Three-Dimensional Reconstructions Of The Brain Of A Bottlenose Dolphin (Tursiops Truncatus) From Magnetic Resonance Images, Lori Marino, Keith D. Sudheimer, Timothy L. Murphy, Kristina K. Davis, D. Ann Pabst, William A. Mclellan, James K. Rilling, John I. Johnson

Veterinary Science and Medicine Collection

Cetacean (dolphin, whale, and porpoise) brains are among the least studied mammalian brains because of the formidability of collecting and histologically preparing such relatively rare and large specimens. Magnetic resonance imaging offers a means of observing the internal structure of the brain when traditional histological procedures are not practical. Furthermore, internal structures can be analyzed in their precise anatomic positions, which is difficult to accomplish after the spatial distortions often accompanying histological processing. In this study, images of the brain of an adult bottlenose dolphin, Tursiops truncatus, were scanned in the coronal plane at 148 antero-posterior levels. From these scans …


Magnetic Resonance Imaging And Three-Dimensional Reconstructions Of The Brain Of A Fetal Common Dolphin, Delphinus Delphis, Lori Marino, Timothy L. Murphy, Lyad Gozal, John I. Johnson May 2001

Magnetic Resonance Imaging And Three-Dimensional Reconstructions Of The Brain Of A Fetal Common Dolphin, Delphinus Delphis, Lori Marino, Timothy L. Murphy, Lyad Gozal, John I. Johnson

Veterinary Science and Medicine Collection

To demonstrate the kinds of data that can be obtained non-destructively and non-invasively from preserved museum specimens using modern imaging technology the head region of a whole body fetal specimen of the common dolphin, Delphinus delphis, aged 8–9 months post-conception, was scanned using Magnetic Resonance Imaging (MRI). Series of scans were obtained in coronal, sagittal and horizontal planes. A digital three-dimensional reconstruction of the whole brain was prepared from the coronal series of scans. Sectional areas and three-dimensional volumes were obtained of the cerebral hemispheres and of the brainstemplus-cerebellum. Neuroanatomical features identified in the scans include the major sulci of …


The Significance Of Alternative Techniques In Biomedical Research: An Analysis Of Nobel Prize Awards, Martin Stephens Jan 1986

The Significance Of Alternative Techniques In Biomedical Research: An Analysis Of Nobel Prize Awards, Martin Stephens

Experimentation Collection

No abstract provided.


Protection Of Animals And Animal Experimentation: A Survey Of Scientific Experts, Norbert Lagoni, Joachim Fiebelkorn, Hans-Joachim Wormuth Jan 1983

Protection Of Animals And Animal Experimentation: A Survey Of Scientific Experts, Norbert Lagoni, Joachim Fiebelkorn, Hans-Joachim Wormuth

Experimentation Collection

This article summarizes information from a survey of biomedical scientists, specifically pharmacologists and toxicologists, on the use of laboratory animals and the potential for replacing their use with alternative methods for the development and evaluation of pharmaceutical substances. The majority of those surveyed felt that the alternatives could supplement or complement animal tests, but not replace the tests altogether. However, most favored the use of nonsentient material in safety tests.