1,050 results match your criteria ALTEX[Journal]


Infectability of human BrainSphere neurons suggests neurotropism of SARS-CoV-2.

ALTEX 2020 Jun 26. Epub 2020 Jun 26.

Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA.

Reports from Wuhan suggest that 36% of COVID-19 patients show neurological symptoms, and cases of viral encephalitis have been reported, suggesting that the virus is neurotropic under unknown circumstances. This is well established for other coronaviruses. In order to understand why some patients develop such symptoms and others do not, we address herein the infectability of the central nervous system (CNS). Read More

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http://dx.doi.org/10.14573/altex.2006111DOI Listing

Tradition, not science, is the basis of animal model selection in translational and applied research.

ALTEX 2020 Jun 22. Epub 2020 Jun 22.

Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands.

National and international laws and regulations exist to protect animals used for scientific purposes in  translational and applied research, which includes drug development. However, multiple animal models are available for each disease. We evaluated the argumentation behind the selection of a specific animal model using thematic content analysis in project applications, issued in 2017-2019 in the Netherlands. Read More

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http://dx.doi.org/10.14573/altex.2003301DOI Listing

Examination of microcystin neurotoxicity using central and peripheral human neurons.

ALTEX 2020 Jun 23. Epub 2020 Jun 23.

In vitro Toxicology and Biomedicine, Dept inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Konstanz, Germany.

Microcystins (MC) are a group of cyanobacterial toxins that comprises MC-LF and other cyclic heptapeptides, best known as potent hepatotoxicants. Cell culture and epidemiological studies suggest that MC might also affect the nervous system, when there is systemic exposure e.g. Read More

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http://dx.doi.org/10.14573/altex.2003182DOI Listing

The in vitro human fracture hematoma model - a tool for preclinical drug testing.

ALTEX 2020 Jun 9. Epub 2020 Jun 9.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Berlin, Germany.

The aim of the study was to establish an in vitro fracture hematoma (FH) model, which mimics the in vivo situation of the human fracture gap in order to assess drug efficacy and effectiveness for the treatment of fracture healing disorders. Therefore, human peripheral blood and mesenchymal stromal cells (MSCs) were coagulated to produce in vitro FH models, incubated in osteogenic medium under normoxia/hypoxia, and analyzed for cell composition, gene expression and cytokine/chemokine secretion. To evaluate the model, we studied the impact of dexamethasone (impairing fracture healing) and deferoxamine (promoting fracture healing). Read More

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http://dx.doi.org/10.14573/altex.1910211DOI Listing

The kinetic Direct Peptide Reactivity Assay (kDPRA): Intra- and inter-laboratory reproducibility in a seven-laboratory ring trial.

ALTEX 2020 Jun 10. Epub 2020 Jun 10.

Givaudan Schweiz AG, Kemptthal, Switzerland.

While the skin sensitization hazard of substances can be identified using non-animal methods, the classification of potency into UN GHS sub-categories 1A and 1B remains challenging. The kinetic direct peptide reactivity assay (kDPRA) is a modification of the DPRA wherein the reaction kinetics of a test substance towards a synthetic cysteine-containing peptide is evaluated. For this purpose, several concentrations of the test substance are incubated with the synthetic peptide for several incubation times. Read More

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http://dx.doi.org/10.14573/altex.2004291DOI Listing

New approach methodologies (NAMs) for human-relevant biokinetics predictions: Meeting the paradigm shift in toxicology towards an animal-free chemical risk assessment.

ALTEX 2020 Jun 8. Epub 2020 Jun 8.

RIVM - The National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

For almost fifteen years, the availability and regulatory acceptance of new approach methodologies (NAMs) to assess the absorption, distribution, metabolism and excretion (ADME/biokinetics) in chemical risk evaluations are a bottleneck. To enhance the field, a team of 24 experts from science, industry, and regulatory bodies, including new generation toxicologists, met at the Lorentz Centre in Leiden, The Netherlands. A range of possibilities for the use of NAMs for biokinetics in risk evaluations were formulated (for example to define species differences and human variation or to perform quantitative in vitro-in vivo extrapolations). Read More

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http://dx.doi.org/10.14573/altex.2003242DOI Listing
June 2020
5.467 Impact Factor

Strategy to replace animal-derived ECM by a modular and highly defined matrix.

ALTEX 2020 Jun 4. Epub 2020 Jun 4.

Biophysics and Structural Biology, University of Konstanz, Konstanz, Germany.

Many extracellular matrices (ECM) used for modern cell culture are derived from animals. An alternative approach is the recombinant production of individual matrix protein components. A further development of this strategy uses a constant core protein polymer that is modifiable with functional domains of various ECM proteins. Read More

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http://dx.doi.org/10.14573/altex.2003181DOI Listing

Rapid hazard characterization of environmental chemicals using a compendium of human cell lines from different organs.

ALTEX 2020 Jun 8. Epub 2020 Jun 8.

Interdisciplinary Faculty of Toxicology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.

The lack of adequate toxicity data for the vast majority of chemicals in the environment has spurred the development of New Approach Methodologies (NAMs). This study aimed to develop a practical high-throughput in vitro model for rapidly evaluating potential hazards of chemicals using a small number of human cells. Forty-two compounds were tested using human induced pluripotent stem cell (iPSC)-derived cells (hepatocytes, neurons, cardiomyocytes and endothelial cells) and a primary endothelial cell line. Read More

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http://dx.doi.org/10.14573/altex.2002291DOI Listing

Optimization of the monocyte-activation-test for evaluating pyrogenicity of tick-borne encephalitis virus vaccine.

ALTEX 2020 05 26. Epub 2020 May 26.

Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.

Pyrogen content is a key quality feature that must be checked in all injectable products, including vaccines. Four tests are currently available in the European Pharmacopoeia to monitor pyrogen/endotoxin presence: 1) the Rabbit Pyrogen Test (RPT), 2) the Bacterial Endotoxin Test, 3) the Recombinant Factor C test and the Monocyte Activation Test (MAT). Here, we explored the possibility to replace RPT with the MAT in the quality control of a vaccine against tick-borne encephalitis virus (TBEV). Read More

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http://dx.doi.org/10.14573/altex.2002252DOI Listing

Azithromycin has lung barrier protective effects in a cell model mimicking ventilator-induced lung injury.

ALTEX 2020 May 19. Epub 2020 May 19.

Stem Cell Research Unit, BioMedical Center, School of Health Sciences, University of Iceland, Reykjavík, Iceland.

Azithromycin (AZM) is a broad-spectrum antibiotic widely used to treat infections. AZM has also been shown to have anti-inflammatory and immunomodulatory functions unrelated to its antibacterial activity which contribute to the effectiveness of this drug in chronic respiratory diseases. The mechanisms behind these beneficial effects are not yet fully elucidated. Read More

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http://dx.doi.org/10.14573/altex.2001271DOI Listing

Evaluation of the global performance of eight in silico skin sensitization models using human data.

ALTEX 2020 May 7. Epub 2020 May 7.

Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Allergic contact dermatitis, or the clinical manifestation of skin sensitization, is a leading occupational hazard.  Several testing approaches exist to assess skin sensitization, but in silico models are perhaps the most advantageous due to their high speed and low-cost results.  Many in silico skin sensitization models exist, though many have only been tested against results from animal studies (e. Read More

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http://dx.doi.org/10.14573/altex.1911261DOI Listing

Modeling chemotherapy-induced peripheral neuropathy using a Nerve-on-a-chip microphysiological system.

ALTEX 2020 May 7. Epub 2020 May 7.

AxoSim Inc., New Orleans, LA, USA.

Organ-on-a-chip devices that mimic in vivo physiology have the potential to identify effects of chemical and drug exposure in early preclinical stages of drug development while relying less heavily on animal models. We have designed a hydrogel rat nerve-on-a-chip (RNoaC) construct that promotes axon growth analogous to mature nerve anatomy and is the first 3D in vitro model to collect electrophysiological and histomorphic metrics that are used to assess in vivo pathophysiology. Here we culture embryonic rat dorsal root ganglia (DRG) in the construct to demonstrate its potential as a preclinical assay for screening implications of nerve dysfunction in chemotherapy-induced peripheral neuropathy (CIPN). Read More

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http://dx.doi.org/10.14573/altex.2001181DOI Listing

Automated integration of structural, biological and metabolic similarities to improve read-across.

ALTEX 2020 05 9. Epub 2020 May 9.

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri - IRCCS, Milan, Italy.

Read-across (RAX) is a popular data-gap filling technique that uses category and analogue approaches to predict toxicological endpoints for a target. Despite its increasing relevance, RAX relies on human expert judgement and lacks a reproducible and automated protocol. It also only relies on structural similarity for identifying the analogues, while other aspects are often neglected. Read More

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http://dx.doi.org/10.14573/altex.2002281DOI Listing

Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology.

ALTEX 2020 04 30. Epub 2020 Apr 30.

Center for Alternatives to Animal Testing, CAAT-Europe, University of Konstanz, Konstanz, Germany.

Read-across (RAx) translates available information from well-characterized chemicals to the substance for which there is a toxicological data gap. The OECD is working on case studies to probe general applicability of RAx, and several regulations (e.g. Read More

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http://dx.doi.org/10.14573/altex.1912181DOI Listing
April 2020
5.467 Impact Factor

Performance of a novel in vitro assay for skin sensitization based on activation of T lymphocytes.

ALTEX 2020 Apr 21. Epub 2020 Apr 21.

Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.

There are currently no skin sensitization assays based on T cell activation. We built a novel in vitro model to assess T cell activation and test its performance to discriminate skin sensitizers from non-sensitizers using 52 reference chemicals. Jurkat Clone E6-1 human T lymphocytes were exposed to a series of concentrations of test substances for 24 hours and CD69 expression was measured as a marker of early T cell activation with flow cytometry. Read More

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http://dx.doi.org/10.14573/altex.2001312DOI Listing
April 2020
5.467 Impact Factor

Inflammation-induced tissue damage mimicking GvHD in human skin models as test-platform for immunotherapeutics.

ALTEX 2020 Apr 14. Epub 2020 Apr 14.

Karolinska Institute and University Hospital, Department of Laboratory Medicine and Medicine Huddinge, Department of Cell Therapy and Allogeneic Stem Cell Transplantation (CAST), Stockholm, Sweden.

With cellular products being on the front run there is a rising demand for non-animal-based test platforms to predict, study and treat undesired immunity. Here, we generated human organotypic skin models from human biopsies isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells finally allowing to seed these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. Afterwards, we were able to induce inflammation-based tissue damage by pre-stimulated mismatched allogeneic lymphocytes and/or inflammatory cytokine containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin. Read More

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http://dx.doi.org/10.14573/altex.1907181DOI Listing
April 2020
5.467 Impact Factor

Erratum to Machine learning prediction of cyanobacterial toxin (microcystin) toxicodynamics in humans.

ALTEX 2020 ;37(2):337-338

Human and Environmental Toxicology, University of Konstanz, Konstanz, Germany.

In this manuscript, which appeared in ALTEX (2020), 37(1), 24-36, doi:10.14573/altex.1904031 , there were errors in Tables 1 and 3. Read More

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http://dx.doi.org/10.14573/altex.1904031eDOI Listing
January 2020

CaFFEE: A program for evaluating time courses of Ca2+ dependent signal changes of complex cells loaded with fluorescent indicator dyes.

ALTEX 2020 ;37(2):332-336

In vitro Toxicology and Biomedicine, Dept inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Konstanz, Germany.

Quantification of changes in intracellular free Ca2+ concentrations [Ca2+]i is fundamental to the understanding of the physiology of single cells in response to both environmental and endogenous stimuli. Here we present easy to use freeware that allows especially the evaluation of [Ca2+]i signals in complex and mixed cultures. The program CaFFEE (Calcium Fluorescent Flash Evaluating Engine) enables the user to evaluate the response of hundreds of cells to treat-ments that influence [Ca2+]i. Read More

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http://dx.doi.org/10.14573/altex.2003191DOI Listing
January 2020

3R-related research funding: Insights from a meeting hosted by the German Centre for the Protection of Laboratory Animals (Bf3R).

ALTEX 2020;37(2):320-323

German Centre for the Protection of Laboratory Animals (Bf3R), German Federal Institute for Risk Assessment (BfR), Berlin, Germany.

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http://dx.doi.org/10.14573/altex.2002201DOI Listing
January 2020

R2N Science Camp.

ALTEX 2020;37(2):315-316

Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.

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http://dx.doi.org/10.14573/altex.2002211DOI Listing
January 2020

EFSA - Johns Hopkins Food Safety Symposium 2019.

ALTEX 2020;37(2):312-314

Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

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http://dx.doi.org/10.14573/altex.2002181DOI Listing
January 2020

One year Charité 3R - Results and perspectives.

ALTEX 2020;37(2):307-308

Charité 3R, Charité Universitaetsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.14573/altex.2002251DOI Listing
January 2020

First Swiss 3Rs Day - Implementing the 3Rs to improve animal welfare and research quality.

Authors:
Chantal Britt

ALTEX 2020;37(2):304-307

Swiss 3RCC, Bern, Switzerland.

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http://dx.doi.org/10.14573/altex.2003021DOI Listing
January 2020

Open access webinars bring 3R experts to your web browser: The Berlin experience.

ALTEX 2020;37(2):300-303

Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.

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http://dx.doi.org/10.14573/altex.2002091DOI Listing
January 2020

New European Union statistics on laboratory animal use - what really counts!

ALTEX 2020 ;37(2):167-186

Center for Alternatives to Animal Testing, CAAT-Europe, University of Konstanz, Konstanz, Germany.

Seven years after the last release, the European Commission has again collated and released data on laboratory animal use. The new report is the first to correspond to the requirements of the new Directive 2010/63/EU. Beside minor problems in reporting, the new reporting format is a major step forward, with additional new categories like severity allowing insight into animal use related questions that goes far beyond the previous reports. Read More

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http://dx.doi.org/10.14573/altex.2003241DOI Listing
January 2020
5.467 Impact Factor

Introducing the concept of virtual control groups into preclinical toxicology testing.

ALTEX 2020 Mar 31. Epub 2020 Mar 31.

Lhasa Ltd. Leeds, UK.

Sharing legacy data from in vivo toxicity studies offers the opportunity to analyze the variability of control groups stratified for strain, age, duration of study, vehicle and other experimental conditions. Historical animal control group data may lead to a repository, which could be used to construct virtual control groups (VCGs) for toxicity studies. VCGs are an established concept in clinical trials, but the idea of replacing living beings with virtual data sets has so far not been introduced into the design of regulatory animal studies. Read More

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http://dx.doi.org/10.14573/altex.2001311DOI Listing

Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies.

ALTEX 2020 Mar 7. Epub 2020 Mar 7.

In vitro Toxicology and Biomedicine, Dept inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Konstanz, Germany.

Human cell-based neural organoids are increasingly being used for investigations of neurotoxicity, and to study the pathophysiology of neurodegenerative diseases. Here, we present a fast and robust method to generate 3D cultured human dopaminergic neurons (LUHMES) for toxicity testing and long-term culture. Moreover, a plating step was introduced to allow generation of neurite networks with defined 2D orientation and several mm length, while all cell bodies (somata) remained in a 3D, dome-like structure. Read More

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http://dx.doi.org/10.14573/altex.1911111DOI Listing

Towards an animal-free human health assessment: starting from the current regulatory needs.

ALTEX 2020 Feb 25. Epub 2020 Feb 25.

National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Societal concern for animal welfare and scientific concerns about the predictive power of animal models for the human situation are driving forces for the development of animal-free approaches for the safety testing of chemicals. A paradigm shift towards an assessment of human health risks that is fully based on non-animal approaches is not foreseen within the next decades. To accelerate the use of non-animal innovations (e. Read More

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http://dx.doi.org/10.14573/altex.1912041DOI Listing
February 2020

Evaluation of phototoxic and cytotoxic potential of TiO2 nanosheets in a 3D reconstructed human skin model.

ALTEX 2020 Feb 25. Epub 2020 Feb 25.

Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, Slovak Republic.

Despite a continuous increase of commercial products containing nanoparticles, only few materials are currently used in such large amounts, forms and sizes as titanium dioxide - TiO2. Besides its use in cosmetics, food industry and biomedicine, TiO2 nanoparticles (NPs) are also used as highly efficient photocatalysts due to their unique ability to convert complex organic materials to carbon dioxide, water and simple mineral acids via complex radical and electron transfer reactions. The main objective of the current project was to assess the potential dermal effect (phototoxicity and skin toxicity) of TiO2 nanosheets (TIG-800) synthesized from the lyophilized aqueous colloids of peroxo-titanic acid by high-temperature treatment. Read More

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http://dx.doi.org/10.14573/altex.1910012DOI Listing
February 2020
5.467 Impact Factor

Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development

ALTEX 2020 02 28. Epub 2020 Feb 28.

F. Hoffmann-La Roche Ltd, Roche Innovation Center Basel, Switzerland.

The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Read More

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http://dx.doi.org/10.14573/altex.2001241DOI Listing
February 2020
5.467 Impact Factor

An advanced in vitro model to assess glaucoma onset.

ALTEX 2020 27;37(2):265-274. Epub 2020 Jan 27.

Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy.

Glaucoma is the second leading cause of blindness worldwide. Currently, glaucoma treatments aim to lower intraocular pressure by decreasing aqueous humor production or increasing aqueous humor outflow through pharmacological approaches or trabeculectomy. The lack of an effective cure requires new therapeutic strategies. Read More

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http://dx.doi.org/10.14573/altex.1909262DOI Listing
January 2020

Safety assessment of excipients (SAFE) for orally inhaled drug products.

ALTEX 2020 29;37(2):275-286. Epub 2020 Jan 29.

PharmBioTec GmbH, Saarbrücken, Germany.

The development of new orally inhaled drug products requires their demonstration of safety, which must be proven in animal experiments. New in vitro methods may replace, or at least reduce, these animal experiments, provided they are able to correctly predict safety or possible toxicity in humans. However, the challenge is to link in vitro data obtained in human cells to human in vivo data. Read More

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http://dx.doi.org/10.14573/altex.1910231DOI Listing
January 2020

Animalfree Research Forum 2019: Animal-free education.

ALTEX 2020;37(1):140-142

Animalfree Research, Bern, Switzerland.

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http://dx.doi.org/10.14573/altex.1909261DOI Listing
January 2020

The exposome - a new approach for risk assessment.

ALTEX 2020 ;37(1):3-23

Johns Hopkins University, Bloomberg School of Public Health and Whiting School of Engineering, Environmental Health and Engineering, Baltimore, MD, USA.

Complementing the human genome with an exposome reflects the increasingly obvious impact of environmental exposure, which far exceeds the role of genetics, on human health. Considering the complexity of exposures and, in addition, the reactions of the body to exposures - i.e. Read More

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http://dx.doi.org/10.14573/altex.2001051DOI Listing
January 2020

Computational systems biology as an animal-free approach to characterize toxicological effects of persistent organic pollutants.

ALTEX 2020 21;37(2):287-299. Epub 2020 Jan 21.

Université de Paris, Inserm UMR S-1124, Paris, France.

Exposure to persistent organic pollutants (POPs), as defined by the Stockholm Convention, may alter biological systems and cause toxic effects. Computational studies appear to be a relevant approach to increase our understanding of the molecular mechanisms triggered by POPs. We investigated the use of a systems toxicology approach to explore the effects of POPs on human health. Read More

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http://dx.doi.org/10.14573/altex.1910161DOI Listing
January 2020

Increasing the use of animal-free recombinant antibodies.

ALTEX 2020 8;37(2):309-311. Epub 2020 Jan 8.

PETA International Science Consortium Ltd., London, United Kingdom.

Antibodies are used in a range of research, diagnostic, and regulatory applications. Traditional methods for producing such reagents involve the immunization of animals, which introduces variability into the methods that use them and is not aligned with efforts to replace and reduce animal use. Experts from academia, biotechnology, government, and animal protection organizations met December 3, 2019, at the National Institutes of Health in Bethesda, MD, USA to discuss the status of development and use of animal-free recombinant antibodies and their potential to replace antibodies derived from animals. Read More

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http://dx.doi.org/10.14573/altex.2001071DOI Listing
January 2020

In vitro demonstration of intestinal absorption mechanisms of different sugars using 3D organotypic tissues in a fluidic device.

ALTEX 2020 30;37(2):255-264. Epub 2019 Dec 30.

React4life S.r.l., Genoa, Italy.

Intestinal permeability is crucial in regulating the bioavailability and, consequently, the biological effects of drugs and compounds. However, systematic and quantitative studies of the absorption of molecules are quite limited due to a lack of reliable experimental models able to mimic human in vivo responses. In this work, we present an in vitro perfused model of the small intestinal barrier using a 3D reconstructed intestinal epithelium integrated into a fluid-dynamic biore­actor (MIVO®) resembling the physiological stimuli of the intestinal environment. Read More

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http://dx.doi.org/10.14573/altex.1908311DOI Listing
December 2019
5.467 Impact Factor

Rheumatoid arthritis research in the 21st century: Limitations of traditional models, new technologies, and opportunities for a human biology-based approach.

ALTEX 2020 17;37(2):223-242. Epub 2019 Dec 17.

Nutrition and Food Science Group, Department of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo, Spain.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease characterized by progressive bone and cartilage destruction, functional impairment, and long-term disability. Although RA has been described in the medical lit­erature for over two hundred years, its etiology and pathophysiology are insufficiently understood. The current treatment of RA is mainly empirical or based on drugs that interfere with generic steps of the immune response, with limited efficacy and/or significant side effects. Read More

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http://dx.doi.org/10.14573/altex.1910011DOI Listing
December 2019

The value of organs-on-chip for regulatory safety assessment.

ALTEX 2020 13;37(2):208-222. Epub 2019 Dec 13.

National Institute of Public Health and the Environment, Bilthoven, The Netherlands.

Organs-on-chip (OC) have gained much interest as animal-free toxicity testing methods due to their closer resemblance to human tissues and longer culture viability than conventional in vitro methods. The current paper discusses where and how OCs may take a role in the transition to a more predictive, animal-free safety assessment for regulatory purposes. From a preliminary analysis of a repeated dose toxicity database, ten organs of priority for OC development for regu­latory use have been identified. Read More

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http://dx.doi.org/10.14573/altex.1910111DOI Listing
December 2019

Determination of benchmark concentrations and their statistical uncertainty for cytotoxicity test data and functional in vitro assays.

ALTEX 2020 12;37(1):155-163. Epub 2019 Dec 12.

In vitro Toxicology and Biomedicine, Department inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Konstanz, Germany.

Many toxicological test methods, including assays of cell viability and function, require an evaluation of concentration-response data. This often involves curve fitting, and the resulting mathematical functions are then used to determine the concentration at which a certain deviation from the control value occurs (e.g. Read More

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http://dx.doi.org/10.14573/altex.1912021DOI Listing
December 2019

Procurement and ex-situ perfusion of isolated slaughterhouse-derived livers as a model of donors after circulatory death.

ALTEX 2019 12 12. Epub 2019 Dec 12.

Center for Preclinical Research, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Read More

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http://dx.doi.org/10.14573/altex.1909131DOI Listing
December 2019

A rational approach of early humane endpoint determination in a murine model for cholestasis.

ALTEX 2020 9;37(2):197-207. Epub 2019 Dec 9.

Rudolf-Zenker-Institute of Experimental Surgery, University Medical Center Rostock, Rostock, Germany.

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of score sheets and do not attempt to reduce the suffering of animals by determining earlier and, therefore, more humane endpoints. The present study uses data from BALB/cANCrl mice after bile duct ligation to retrospectively analyze which score sheet criteria are informative to determine humane endpoints. Read More

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http://dx.doi.org/10.14573/altex.1909111DOI Listing
December 2019

Integrating adverse outcome pathways (AOPs) and high throughput in vitro assays for better risk evaluations, a study with drug-induced liver injury (DILI).

ALTEX 2020 8;37(2):187-196. Epub 2019 Nov 8.

National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.

The emergence of high throughput in vitro assays has the potential to significantly improve toxicological evaluations and lead to more efficient, accurate, and less animal-intensive testing. However, directly using all available in vitro assays in a model is usually impractical and inefficient. On the other hand, mechanistic knowledge has always been critical for toxicological evaluations and should not be ignored even with the increasing availability of data. Read More

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http://dx.doi.org/10.14573/altex.1908151DOI Listing
November 2019
4 Reads
5.467 Impact Factor

Bisphenol A binding promiscuity: A virtual journey through the universe of proteins.

ALTEX 2020 8;37(1):85-94. Epub 2019 Nov 8.

Food Safety Research, Nestlé Research, Lausanne, Switzerland.

Significant efforts are currently being made to move toxicity testing from animal experimentation to human relevant, mechanism-based approaches. In this context, the identification of molecular target(s) responsible for mechanisms of action is an essential step. Inspired by the recent concept of polypharmacology (the ability of drugs to interact with multiple targets) we argue that whole proteome virtual screening might become a breakthrough tool in toxicology reflecting the real complexity of chemical-biological interactions. Read More

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http://dx.doi.org/10.14573/altex.1906141DOI Listing
November 2019

Development of an ex vivo aneurysm model for vascular device testing.

ALTEX 2020 23;37(1):110-120. Epub 2019 Oct 23.

LifeTec Group BV, Eindhoven, The Netherlands.

An ex vivo aneurysm model that closely resembles the in vivo situation can provide an important tool for testing therapies. The model should mimic a variety of conditions, such as in vivo hemodynamics and native arterial structure and characteristics, avoiding animal experimentation.  Therefore, the aim of this study is to develop an ex vivo aneurysm model by vessel wall stiffening to be used to assess treatment strategies. Read More

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http://dx.doi.org/10.14573/altex.1906253DOI Listing
October 2019

Towards animal-free neurotoxicity screening: Applicability of hiPSC-derived neuronal models for in vitro seizure liability assessment.

ALTEX 2020 2;37(1):121-135. Epub 2019 Nov 2.

Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

A sizeable proportion of drug attrition is due to drug-induced seizures. Current available animal models frequently fail to predict human seizure liability. Therefore, there is a need for in vitro alternatives, preferably based on human-derived neurons to circumvent interspecies translation. Read More

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http://dx.doi.org/10.14573/altex.1907121DOI Listing
November 2019

Give meaning to alternative methods to animal testing.

ALTEX 2019 ;36(4):669-670

Centro 3R (Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Italy.

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http://dx.doi.org/10.14573/altex.1907051DOI Listing