Alternatives to laboratory animals : ATLA最新文献

{"title":"Determination of the Microinjected Cytosolic Concentration by Using Mathematical Models of Fluid Dynamics.","authors":"Manuel Rivas,&nbsp;Manuel Reina","doi":"10.1177/02611929211073038","DOIUrl":"https://doi.org/10.1177/02611929211073038","url":null,"abstract":"<p><p>The precise determination of the intracellular concentration of a drug is a major challenge in drug discovery. Microinjection is a very effective technique for the introduction of macromolecules into single cells. However, due to the large number of parameters that need to be adjusted and the complex physical mechanisms involved, there are currently no means by which the concentration of a microinjected intracellular compound could be theoretically estimated. In this paper, we present a method for the theoretical estimation of intracellular drug concentration, based on the framework of classical fluid mechanism theory - specifically, the modified Bernoulli equation. We introduce into Bernoulli's classical equation the effect of friction due to the non-laminar regimes of the injected fluid. We also study the compatibility of our theoretical estimation model with variations in injection time and concentration of the compound inside the microinjection needle. Finally, microinjected calcium concentrations estimated with the theoretical model were compared with those determined experimentally in several cell types, by using a Fura-2-based Ca²⁺ imaging technique.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"136-145"},"PeriodicalIF":2.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40312039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Alternatives to Laboratory Animals</i>: Trends in <i>Replacement</i> and the Three Rs.","authors":"Michael Balls","doi":"10.1177/02611929221082250","DOIUrl":"https://doi.org/10.1177/02611929221082250","url":null,"abstract":"<p><p>The significance of contributions in volumes 11-46 (1983 to 2018) of <i>Alternatives to Laboratory Animals</i> in relation to the reduction, refinement and replacement of animal experimentation in biomedical research and testing is reviewed and discussed by the journal's former editor-in-chief, with particular emphasis on the development and production of the journal itself, FRAME, the European Centre for the Validation of Alternative Methods and other organisations. The role of the journal in promoting the principles of humane research (as spelled out by William Russell and Rex Burch) and highlighting a range of important issues and focus topics is explored. These include: botulinum toxin potency testing; ethical issues; the use of human volunteers, and human cells and tissues; the use of non-human primates (especially chimpanzees) and dogs as laboratory animals; toxicity testing in relation to cosmetics, pharmaceuticals and chemicals; UK and EU politics and legislation; and test validation and invalidation. The review concludes by identifying some of the issues that still need to be discussed and some of the questions that urgently need to be addressed.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"10-26"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40307475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial.","authors":"Judith C Madden","doi":"10.1177/02611929211063517","DOIUrl":"https://doi.org/10.1177/02611929211063517","url":null,"abstract":"","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"163-164"},"PeriodicalIF":2.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39655346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage.","authors":"Courtney V Thompson, James W Firman, Michael R Goldsmith, Christopher M Grulke, Yu-Mei Tan, Alicia Paini, Peter E Penson, Risa R Sayre, Steven Webb, Judith C Madden","doi":"10.1177/02611929211060264","DOIUrl":"10.1177/02611929211060264","url":null,"abstract":"<p><p>Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration-time profile at the target site. Physiologically-based kinetic (PBK) models can predict organ-level concentration-time profiles, however, the models are time and resource intensive to generate <i>de novo</i>. Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel^® spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"197-208"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764633/pdf/nihms-1766186.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39671203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It's Time to Include Harm to Humans in Harm-Benefit Analysis - But How to Do It, That is the Question.","authors":"Michael Balls","doi":"10.1177/02611929211062223","DOIUrl":"https://doi.org/10.1177/02611929211062223","url":null,"abstract":"<p><p>The Three Rs (<i>reduction</i>, <i>refinement</i>, <i>replacement</i>) concept put forward by Russell and Burch now appears to be widely accepted. However, their warnings concerning reliance on animals as models for humans, the insurmountable problem of species differences and the impact of human variation, have been downplayed or even ignored. Schemes for harm-benefit analysis have been introduced, but the focus has largely been on harm to the animals, rather than on the direct and indirect benefit to humans, which is much more difficult to evaluate. Greater recognition should be given to the direct or indirect harm to humans resulting from the current over-reliance of biomedical research and testing on data obtained from animal experiments. That will be hard to achieve in the current climate, given the vigorous defence of animal experimentation by those with vested interests, confusion over responsibilities for regulating animal experimentation, hierarchies of regulatory authorities which require or limit experiments on animals, and exaggerated claims about the current availability of new approach methodologies (NAMs) and relevant and reliable strategies for their use. Those who defend animal experimentation at almost any cost must bear part of the responsibility for the human harms which result. Meanwhile, much greater effort should be put into the development, validation and application of new approaches not involving animals.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"182-196"},"PeriodicalIF":2.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39759732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resources Round-up.","authors":"","doi":"10.1177/02611929211061912","DOIUrl":"https://doi.org/10.1177/02611929211061912","url":null,"abstract":"The acquisition of new knowledge and the development of cancer treatments, particularly immunotherapies, depend on the existence of human-relevant models, particularly preclinical models that are able to mimic and predict human responses to new therapies. To explore the state-of-the-art of human-based in vitro and in silico models being used in immuno-oncology, the JRC’s EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) organised a study based on a systematic review of publications in the field. The study retrieved and screened about 130,000 peerreviewed papers (published from January 2014 to March 2019), before selecting 542 for a deeper analysis of the nonanimal models used. The resulting knowledge base is presented in an easy-to-use spreadsheet format and is freely available to download from the EURL ECVAM collection in the JRC Data Catalogue (https://data.jrc.ec.europa.eu/ dataset/352f7dfd-05cf-434b-a96a-7e270dc76573). An accompanying technical report analyses the models identified in terms of their typical use and emerging trends. These resources are expected to be of interest not only to researchers, as it can help them to identify methods that could be employed in their own research, but also to funding bodies and competent authorities. Joint Research Centre Data Catalogue (https://data.jrc.ec.europa.eu/dataset/352f7dfd-05cf-434b-a96a-7e270dc76573)","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"168-170"},"PeriodicalIF":2.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39660712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish Beyond the Bench: The 'Plataforma Zebrafish Open Doors' Programme.","authors":"Geonildo Rodrigo Disner,&nbsp;Maria Alice Pimentel Falcão,&nbsp;Carla Lima,&nbsp;Monica Lopes-Ferreira","doi":"10.1177/02611929211057889","DOIUrl":"https://doi.org/10.1177/02611929211057889","url":null,"abstract":"<p><p>The Butantan Institute is a pioneering Brazilian health sciences institution, which also houses a large science park with museums that contribute to ongoing science education for schools and the wider community. In recent years, as part of Butantan Institute's <i>Plataforma Zebrafish</i>™, zebrafish embryos have been used for the dissemination of scientific knowledge during on-site events and as part of outreach campaigns to non-scientific audiences, mostly children. The aim of this work is mainly to demystify the activities of the scientific researcher, highlight the role of science in the furthering of knowledge, and increase public interest and confidence in science. In this article, the Institute's 'Plataforma Zebrafish Open Doors' programme is described, which offered guided tours of the laboratory facilities. The tours gave visitors the opportunity to observe zebrafish research and embryo development, and to use the knowledge gained from this experience as a framework for understanding fundamental ethical issues. During the 2-day event, around 800 visitors (most of them school-age children) attended. Together with the guided tours, our experience of outreach offered meaningful opportunities to bring children and members of the public closer to science and 'real-life' scientists, hopefully inspiring and encouraging the next generation of scientists. It also gave the scientists an opportunity to engage more closely with wider society. We believe that these activities also substantially contribute to the wider dissemination of relevant experimental results that have been obtained with public funding and that impact society in general.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"175-181"},"PeriodicalIF":2.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39744166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spotlight on Three Rs Progress.","authors":"","doi":"10.1177/02611929211061913","DOIUrl":"https://doi.org/10.1177/02611929211061913","url":null,"abstract":"The mechanisms by which viruses evolve new characteristics (e.g. resistance to therapy) when passing between human hosts have been challenging to study, partly due to the scarcity of appropriate preclinical models, and the complexity and costs of the studies required. To determine whether this gap could be addressed with microfluidics technology, Si et al. created a system of interconnected human lung organ-on-a-chip devices that permitted the sequential passage of virus strains via the air channel and the administration of antivirals via the blood channel. Drug pressure was applied by infecting the chips with an influenza virus (H1N1) and treating them with known antiviral medication (amantadine or oseltamivir). Both drugs became less effective with increasing passages. The same approach was used to test the human serine protease inhibitor, nafamostat, which did not induce viral resistance. The data obtained with the chip system are in agreement with that from the clinic, in that the drugs targeting viral proteins led to the emergence of resistant strains, while the drug targeting the host protein did not, even after 30 chip-to-chip passages. Furthermore, the systemwas inoculatedwith three virus strains at the same time (one drug-sensitive, and two amantadineand oseltamivir-resistant, respectively) in the presence of oseltamivir and amantadine. Sequencing revealed the presence of double mutant strains that were resistant to both drugs. To test whether the system could support influenza virus antigenic shift through gene reassortment, as is the case when different virus strains coinfect the same host, two influenza strains (H3N2 and H1N1) were introduced into the system. After two days, viruses were isolated and their genome sequenced to identify the presence of novel strains. While parental viral strains were the most common, distinct genotypes were detected. Of note, one of the reassortants predicted by the on-chip system was detected in patients during an influenza season in which H1N1 and H3N2 cocirculated. A deeper understanding of the mutation and gene reassortment mechanisms involved in viral infections, and a better ability to predict the evolution of viral resistance will improve society’s preparedness to fight global threats due to viral infections. This in vitro system might represent a potential tool in such cases by permitting the study of within-host viral evolution, including of viral drug resistance and likely future mutations.","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"165-167"},"PeriodicalIF":2.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39767302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Long-term Human Precision-cut Lung Slice Culture Methodology and Response to Challenge: An Argument for Standardisation.","authors":"Vivek Patel,&nbsp;Khalid Amin,&nbsp;David Allen,&nbsp;Lindsey Ukishima,&nbsp;Adam Wahab,&nbsp;Chad Grodi,&nbsp;Holger Behrsing","doi":"10.1177/02611929211061884","DOIUrl":"https://doi.org/10.1177/02611929211061884","url":null,"abstract":"<p><p>As non-animal alternatives gain acceptance, a need for harmonised testing strategies has emerged. Arguably the most physiologically-relevant model for assessing potential respiratory toxicants, that based on human precision-cut lung slices (hPCLS) has been utilised in many laboratories, but a variety of culture methodologies are employed. In this pilot study, combinations of three different hPCLS culture methods (dynamic organ roller culture (DOC), air-liquid interface (ALI) and submersion) and various media (based on E-199, DMEM/F12 and RPMI-1640) were compared. The hPCLS were assessed in terms of their viability and responsiveness to challenge. The endpoints selected to compare the medium-method (M-M) combinations, which included histological features and viability, were evaluated at day 14 (D14) and day 28 (D28); protein and adenylate kinase (AK) content, and cytokine response to immunostimulants (lipopolysaccharide (LPS) at 5 μg/ml; polyinosinic:polycytidylic acid (Poly I:C) at 15 μg/ml) were evaluated at D28 only. Based on the set of endpoints assessed at D28, it was clear that certain culture conditions significantly affected the hPCLS, with the tissue retaining more of its native features and functionality (in terms of cytokine response) in some of the M-M combinations tested more than others. This pilot study indicates that the use of appropriate M-M combinations can help maintain the health and functional responses of hPCLS, and highlights the need for the standardisation of culture conditions in order to facilitate effective inter-laboratory comparisons and encourage greater acceptance by the regulatory community.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"209-222"},"PeriodicalIF":2.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39670780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal 'models': How a mechanistic approach can reduce suffering and improve translatability.","authors":"Elliot Lilley","doi":"10.1177/026119291704500307","DOIUrl":"https://doi.org/10.1177/026119291704500307","url":null,"abstract":"<p><p>Poorly predictive animal models of disease cause avoidable suffering and hamper the discovery of new treatments for patients. A focus on mechanistic modelling has the potential to reduce animal suffering as well as improving translation from the bench to the bedside.</p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"159-160"},"PeriodicalIF":2.7,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/026119291704500307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35325997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}