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- Conference Diary
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-11-27T07:56:59Z
DOI: 10.1177/02611929231218598
- The Numbers of Animals Used in Mexico for Scientific and Educational
Purposes-
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Authors: Patricia Frías-Álvarez, Gustavo Ortiz-Millán
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
In Mexico, there are no official public and reliably reported data on the total number and species of non-human animals used for scientific purposes. The aim of the current study was to calculate the total numbers of animals used for scientific and educational purposes in Mexico, from January 2015 to October 2021, based on data requested from the National Institute of Transparency, Access to Information and Protection of Personal Data (INAI, in Spanish). In this period, authorised laboratory animal facilities reported the use of 5,437,263 animals for scientific and educational purposes. However, these data should be viewed with caution, since there is no official register of all Mexican institutions that use animals for these purposes. The use of various species of different taxonomic groups was reported, including mammals, birds, reptiles, amphibians, fish and invertebrates. The main scientific purposes of this animal use were: technological development; innovation; laboratory testing; production of biologicals; quality control; diagnostic purposes; basic and applied research; and education. A robust system for the licensing and approval of animal use, as well as a means to ensure compliance with the relevant regulations, are both urgently required. In addition, in order to regulate animal use, monitor animal care and protect their welfare, the creation of a publicly accessible national database that records the number and species of the animals used is imperative.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-11-25T09:42:38Z
DOI: 10.1177/02611929231217033
- Conference Diary
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-25T05:29:33Z
DOI: 10.1177/02611929231206952
- The 3Ranker: An AI-based Algorithm for Finding Non-animal Alternative
Methods-
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Authors: Niels van Beuningen, Sinne Alkema, Nils Hijlkema, Brun Ulfhake, Rafael Frias, Merel Ritskes-Hoitinga, Wynand Alkema
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
The search for existing non-animal alternative methods for use in experiments is currently challenging because of the lack of both comprehensive structured databases and balanced keyword-based search strategies to mine unstructured textual databases. In this paper we describe 3Ranker, which is a fast, keyword-independent algorithm for finding non-animal alternative methods for use in biomedical research. The 3Ranker algorithm was created by using a machine learning approach, consisting of a Random Forest model built on a dataset of 35 million abstracts and constructed with weak supervision, followed by iterative model improvement with expert curated data. We found a satisfactory trade-off between sensitivity and specificity, with Area Under the Curve (AUC) values ranging from 0.85–0.95. Trials showed that the AI-based classifier was able to identify articles that describe potential alternatives to animal use, among the thousands of articles returned by generic PubMed queries on dermatitis and Parkinson’s disease. Application of the classification models on time series data showed the earlier implementation and acceptance of Three Rs principles in the area of cosmetics and skin research, as compared to the area of neurodegenerative disease research. The 3Ranker algorithm is freely available at www.open3r.org; the future goal is to expand this framework to cover multiple research domains and to enable its broad use by researchers, policymakers, funders and ethical review boards, in order to promote the replacement of animal use in research wherever possible.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-21T08:47:54Z
DOI: 10.1177/02611929231210777
- Barriers to the Use of Recombinant Bacterial Endotoxins Test Methods in
Parenteral Drug, Vaccine and Device Safety Testing-
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Authors: Elizabeth Baker, Jessica Ponder, Johannes Oberdorfer, Ingo Spreitzer, Jay Bolden, Marine Marius, Thierry Bonnevay, Kristie Sullivan
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
The Bacterial Endotoxins Test (BET) is a critical safety test that is used to detect bacterial endotoxins, which are the major contributor to fever-inducing contamination risks known as pyrogens. All parenteral therapies, including every lot of injected drugs, vaccines, medical devices, must be tested for pyrogens to ensure patient safety. Bacterial endotoxins test methods were developed as a highly sensitive detection method for bacterial endotoxins, after the discovery of a clotting cascade in horseshoe crab blood. However, horseshoe crab species are limited to some inshore coastal habitats along the Atlantic coast of the USA and others throughout Asia. Fully functional horseshoe crab clotting factors can be manufactured via recombinant protein production, and several BET methods featuring recombinant horseshoe crab proteins have now been developed for commercial use. Recombinant Bacterial Endotoxins Test (rBET) methods based on the use of recombinant Factor C (rFC) were established in the European Pharmacopoeia — however, these methods have not yet been granted compendial status in the United States Pharmacopoeia (USP). In order to facilitate dialogue between stakeholders, the Physicians Committee for Responsible Medicine hosted two virtual roundtable discussions on the perceived barriers to the use of rBET methods for US FDA requirements. Stakeholders agreed that multiple rFC-based methods have been demonstrated to have suitable analytical performance, as described in ICH Q2 on the Validation of Analytical Procedures and USP on the Validation of Compendial Procedures. United States Pharmacopoeia compendial inclusion of the rFC-based and other rBET methods was favoured, in order to reduce the additional burdens created by a lack of global harmonisation on BET testing requirements.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-19T08:23:56Z
DOI: 10.1177/02611929231204782
- Resources Round-up
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-16T11:46:50Z
DOI: 10.1177/02611929231206955
- Spotlight on Three Rs Progress
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-16T06:39:02Z
DOI: 10.1177/02611929231206974
- Editorial
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Authors: Judith C. Madden
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-16T06:35:52Z
DOI: 10.1177/02611929231206692
- Optimisation of a Method for the Differentiation of Human Umbilical
Cord-derived Mesenchymal Stem Cells Toward Renal Epithelial-like Cells-
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Authors: Rakhshinda Habib, Shumaila Fahim, Mohsin Wahid, Jahanara Ainuddin
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Human umbilical cord-derived mesenchymal stem cells (hucMSCs) can differentiate into multiple cell lineages, but few methods have been developed to generate kidney lineage cells. Due to their human origin, pluripotent nature and immunomodulatory properties, these stem cells are attractive candidates for clinical applications such as the repair or regeneration of damaged organs. This study evaluated the renal differentiation potential of hucMSCs, when exposed for 10 days to optimised concentrations of retinoic acid, activin-A and bone morphogenetic protein-7 (BMP-7) in various combinations, with and without the priming of the cells with a Wnt signalling pathway activator (CHIR99021). The hucMSCs were isolated and characterised according to surface marker expression (CD73, CD90, CD44, CD146 and CD8) and tri-lineage differentiation potential. The expression of key marker genes (OSR1, TBXT, HOXA13, SIX2, PAX2, KRT18 and ZO1) was examined by qRT-PCR. Specific marker protein expression (E-cadherin, cytokeratin-8 and cytokeratin-19) was analysed by immunocytochemistry. CHIR99021-primed cells treated with the retinoic acid, activin-A and BMP-7 cocktail showed epithelial cell-like differentiation — i.e. distinct phenotypic changes, as well as upregulated gene and protein expression, were observed that were consistent with an epithelial cell phenotype. Thus, our results showed that hucMSCs can efficiently differentiate into renal epithelial-like cells. This work may help in the development of focused therapeutic strategies, in which lineage-defined human stem cells can be used for renal regeneration.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-13T04:31:33Z
DOI: 10.1177/02611929231207774
- Development of an In Vitro Sensitisation Test Using a Coculture System of
Human Bronchial Epithelium and Immune Cells-
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Authors: Ikuya Tanabe, Kunitaka Yoshida, Shinkichi Ishikawa, Kanae Ishimori, Tsuneo Hashizume, Takayuki Yoshimoto, Takao Ashikaga
Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Chemical respiratory sensitisation is a serious health problem. However, to date, there are no validated test methods available for identifying respiratory sensitisers. The aim of this study was to develop an in vitro sensitisation test by modifying the human cell line activation test (h-CLAT) to detect respiratory sensitisers and distinguish them from skin sensitisers. THP-1 cells were exposed to the test chemicals (two skin sensitisers and six respiratory sensitisers), either as monocultures or as cocultures with air–liquid interface-cultured reconstructed human bronchial epithelium. The responses were analysed by measuring the expression levels of surface markers on THP-1 cells (CD86, CD54 and OX40L) and the concentrations of cytokines in the culture media (interleukin (IL)-8, IL-33 and thymic stromal lymphopoietin (TSLP)). The cocultures exhibited increased CD54 expression on THP-1 cells; moreover, in the cocultures but not in the monocultures, exposure to two uronium salts (i.e. respiratory sensitisers) increased CD54 expression on THP-1 cells to levels above the criteria for a positive h-CLAT result. Additionally, exposure to the respiratory sensitiser abietic acid, significantly increased IL-8 concentration in the culture medium, but only in the cocultures. Although further optimisation of the method is needed to distinguish respiratory from skin sensitisers by using these potential markers (OX40L, IL-33 and TSLP), the coculture of THP-1 cells with bronchial epithelial cells offers a potentially useful approach for the detection of respiratory sensitisers.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-10-05T03:47:58Z
DOI: 10.1177/02611929231204823
- Thanks to Reviewers
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2023-02-02T03:12:50Z
DOI: 10.1177/02611929231154972
- Corrigendum to Case Studies Exemplifying the Transition to Animal
Component-Free Cell Culture-
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2022-12-01T11:00:56Z
DOI: 10.1177/02611929221141160
- Corrigendum to The Relevance of In Silico, In Vitro and Non-human Primate
Based Approaches to Clinical Research on Major Depressive Disorder-
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals
PubDate: 2020-09-24T12:17:20Z
DOI: 10.1177/0261192920964278
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