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      Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation

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          Abstract

          Animals have been used in research and teaching for a long time. However, clear ethical guidelines and pertinent legislation were instated only in the past few decades, even in developed countries with Judeo‐Christian ethical roots. We compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, “our” fundamentals of institutional animal research ethics teaching, and emerging alternatives to animal research. This treatise was meticulously constructed for scientists interested/involved in animal research. Herein, we discuss key animal ethics principles – Replacement/Reduction/Refinement. Despite similar undergirding principles across developed countries, ethical reviewing and compliance guidelines for animal experimentation vary. The chronology and evolution of mandatory institutional ethical reviewing of animal experimentation (in its pioneering nations) are summarised. This is followed by a concise rendition of the fundamentals of teaching animal research ethics in institutions. With the advent of newer methodologies in human cell‐culturing, novel/emerging methods aim to minimise, if not avoid the usage of animals in experimentation. Relevant to this, we discuss key extant/emerging alternatives to animal use in research; including organs on chips, human‐derived three‐dimensional tissue models, human blood derivates, microdosing, and computer modelling of various hues.

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          Most cited references57

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          Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis.

          We show that a single clinical isolate of the human opportunistic pathogen Pseudomonas aeruginosa (strain PA14), which previously was shown to be pathogenic in mice and plants, also kills Caenorhabditis elegans. The rate of PA14-mediated killing of C. elegans depends on the composition of the agar medium on which PA14 is grown. When PA14 is grown on minimal medium, killing occurs over the course of several days and is referred to as "slow" killing. When PA14 is grown on high-osmolarity medium, killing occurs over the course of several hours and is referred to as "fast" killing. Several lines of evidence, including the fact that heat-killed bacteria are still capable of fast but not slow killing of C. elegans, indicate that fast and slow killing occur by distinct mechanisms. Slow killing involves an infection-like process and correlates with the accumulation of PA14 within worm intestines. Among 10 PA14 virulence-related mutants that had been shown previously to affect pathogenicity in plants and mice, 6 were less effective in killing C. elegans under both fast- and slow-killing conditions, indicating a high degree of commonalty among the P. aeruginosa factors required for pathogenicity in disparate eukaryotic hosts. Thus, we show that a C. elegans pathogenicity model that is genetically tractable from the perspectives of both host and pathogen can be used to model mammalian bacterial pathogenesis.
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            Microdosing and drug development: past, present and future.

            Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date.
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              Evolution of three dimensional skin equivalent models reconstructed in vitro by tissue engineering.

              Since the culture of keratinocytes on feeder layers, research to produce skin equivalents has been motivated by the challenge of treating large burns and chronic wounds and by European regulations which both require proof of the innocuousness and the effectiveness of cosmetic products, and which forbid animal testing. The dynamism in fundamental research, dermocosmetology and the pharmaceutical industry has led to the evolution and complexification of reconstructed skin. The Collagen-GAG-Chitosan sponge, as well as the self-assembly model, allow dermal reconstruction in which the neosynthesized extracellular matrix contains all of the desired macromolecules. It is deposited forming an ultrastructurally organised architecture. The quality of the dermis obtained allows the development and regeneration of a pluristratified and differentiated epidermis firmly anchored by an organised dermal-epidermal junction. Evolution of reconstructed skin into models which are more and more similar to the physiological skin results in higher graft take rates in the treatment of burns and chronic wounds, and brings to research, to dermocosmetology and to the pharmaceutical industry, a wide range of products such as pigmented, endothelialized, immunocompetent, and now adipose reconstructed skins. The present review will mainly concentrate on the latest developments in skin engineering and will mostly concern the studies carried out by our groups.
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                Author and article information

                Contributors
                Rajaraman.Eri@utas.edu.au
                Journal
                Pharmacol Res Perspect
                Pharmacol Res Perspect
                10.1002/(ISSN)2052-1707
                PRP2
                Pharmacology Research & Perspectives
                John Wiley and Sons Inc. (Hoboken )
                2052-1707
                09 August 2017
                August 2017
                : 5
                : 4 ( doiID: 10.1002/prp2.2017.5.issue-4 )
                : e00332
                Affiliations
                [ 1 ] Department of Medicine St. George Clinical School University of New South Wales Sydney New South Wales Australia
                [ 2 ] Department of Animal Services University of Tasmania Hobart Tasmania Australia
                [ 3 ] Mucosal Biology Laboratory School of Health Sciences University of Tasmania Launceston Tasmania Australia
                Author notes
                [*] [* ] Correspondence

                Rajaraman Eri, School of Health Sciences, University of Tasmania, Newnham, Launceston 7248, Australia. Tel: +61‐3‐6324 5467; Fax: +61‐3‐6324 3995; E‐mail: Rajaraman.Eri@ 123456utas.edu.au

                Author information
                http://orcid.org/0000-0002-3472-9591
                Article
                PRP2332
                10.1002/prp2.332
                5684868
                28805976
                d3146599-a84b-419e-9ba0-c6214ad5398e
                © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 May 2017
                : 23 May 2017
                Page count
                Figures: 1, Tables: 1, Pages: 14, Words: 9145
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                prp2332
                August 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.1 mode:remove_FC converted:24.10.2017

                alternatives,animal ethics committee,animal experimentation,animal research,code,distress,ethics,pain,pathophysiology,reduction,replacement

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