IF 5.6

ALTEX Pub Date : 2019-01-01 DOI: 10.14573/altex.1908271

Massimo Mastrangeli, Sylvie Millet, The Orchid Partners, Janny Van den Eijnden-van Raaij

引用次数: 40

An intact insect embryo for developmental neurotoxicity testing of directed axonal elongation. 用于定向轴突伸长发育性神经毒性试验的完整昆虫胚胎。

IF 5.6

ALTEX Pub Date : 2019-01-01 Epub Date: 2019-05-29 DOI: 10.14573/altex.1901292

Gregor A Bergmann, Sarah Froembling, Nina Joseph, Karsten Bode, Gerd Bicker, Michael Stern

{"title":"An intact insect embryo for developmental neurotoxicity testing of directed axonal elongation.","authors":"Gregor A Bergmann, Sarah Froembling, Nina Joseph, Karsten Bode, Gerd Bicker, Michael Stern","doi":"10.14573/altex.1901292","DOIUrl":"https://doi.org/10.14573/altex.1901292","url":null,"abstract":"Developmental neurotoxicity (DNT) of chemicals poses a serious threat to human health worldwide. Current in vivo test methods for assessing DNT require the use of high numbers of laboratory animals. Most alternative in vitro testing methods monitor rather simple toxicological endpoints, whereas the formation of a functional brain requires precisely timed navigation of axons within a complex tissue environment. We address this complexity by monitoring defects in axonal navigation of pioneer axons of intact locust embryos after exposure to chemicals. Embryos develop in serum-free culture with test chemicals, followed by immunolabeling of pioneer neurons. Defects in axon elongation of pioneer axons are quantified in concentration-response curves and compared to the general viability of the embryo, as measured by a resazurin assay. We show that selected chemical compounds interfering with calcium signaling, the cytoskeletal organization, and the reference developmental neurotoxicant rotenone, can be classified as DNT positive. The pesticide rotenone inhibits pioneer neuron elongation with a lower IC50 than the viability assay. The rho kinase inhibitor Y27632 can partially rescue outgrowth inhibition, supporting the classification of rotenone as a specific DNT positive compound. Since mechanisms of axonal guidance, such as growth cone navigation along molecular semaphorin gradients are conserved between locust and mammalian nervous systems, we will further explore the potential of this invertebrate preparation as an assay for testing the DNT potential of chemicals in humans.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"643-649"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37343248","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}

引用次数: 8

Preclinical alternative model for analysis of porous scaffold biocompatibility in bone tissue engineering. 骨组织工程多孔支架生物相容性分析的临床前替代模型。

IF 5.6

ALTEX Pub Date : 2019-01-01 Epub Date: 2018-11-23 DOI: 10.14573/altex.1807241

Eva Petrovova, Maria Giretova, Alena Kvasilova, Oldrich Benada, Jan Danko, Lubomir Medvecky, David Sedmera

{"title":"Preclinical alternative model for analysis of porous scaffold biocompatibility in bone tissue engineering.","authors":"Eva Petrovova, Maria Giretova, Alena Kvasilova, Oldrich Benada, Jan Danko, Lubomir Medvecky, David Sedmera","doi":"10.14573/altex.1807241","DOIUrl":"https://doi.org/10.14573/altex.1807241","url":null,"abstract":"Using scaffolds with appropriate porosity represents a potential approach for repair of critical-size bone defects. Vascularization is essential for bone formation and healing. This study investigates methods for monitoring angiogenesis within porous biopolymer scaffolds on the basis of polyhydroxybutyrate (PHB)/chitosan. We use the chick and quail chorioallantoic membrane (CAM) assay as an in vivo model focused on the formation of new blood vessels inside the implant structure. Chemical properties of the surface in biopolymer scaffold matrix were characterized as well as the tissue reaction of the CAM. Implantation of a piece of polymer scaffold results in vascular reaction, documented visually and by ultrasound biomicroscopy. Histological analysis shows myofibroblast reaction (smooth muscle actin-positive cells) without excessive collagen deposition. Cell invasion is observed inside the implant, and QH1 marker, detecting hemangioblasts and endothelial cells of quail origin, confirms the presence of vascular network. The CAM assay is a rapid and easy way to test biocompatibility and vasculogenic potential of new candidate scaffolds for bone tissue bioengineering with respect to the 3R´ s.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"121-130"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36714865","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}

引用次数: 19

Investigating cell type specific mechanisms contributing to acute oral toxicity. 研究导致急性口腔毒性的细胞类型特异性机制。

IF 5.6

ALTEX Pub Date : 2019-01-01 Epub Date: 2018-07-12 DOI: 10.14573/altex.1805181

Pilar Prieto, Rabea Graepel, Kirsten Gerloff, Lara Lamon, Magdalini Sachana, Francesca Pistollato, Laura Gribaldo, Anna Bal-Price, Andrew Worth

{"title":"Investigating cell type specific mechanisms contributing to acute oral toxicity.","authors":"Pilar Prieto, Rabea Graepel, Kirsten Gerloff, Lara Lamon, Magdalini Sachana, Francesca Pistollato, Laura Gribaldo, Anna Bal-Price, Andrew Worth","doi":"10.14573/altex.1805181","DOIUrl":"https://doi.org/10.14573/altex.1805181","url":null,"abstract":"The replacement of animals in acute systemic toxicity testing remains a considerable challenge. Only animal data are currently accepted by regulators, including data generated by reduction and refinement methods. The development of Integrated Approaches to Testing and Assessment (IATA) is hampered by an insufficient understanding of the numerous toxicity pathways that lead to acute systemic toxicity. Therefore, central to our work has been the collection and evaluation of the mechanistic information on eight organs identified as relevant for acute systemic toxicity (nervous system, cardiovascular system, liver, kidney, lung, blood, gastrointestinal system and immune system). While the nervous and cardiovascular systems are the most frequent targets, no clear relationship emerged between specific mechanisms of target organ toxicity and the level (category) of toxicity. From a list of 114 chemicals with acute oral in vivo and in vitro data, 98 were identified with target organ specific effects, of which 93% were predicted as acutely toxic by the 3T3 neutral red uptake cytotoxicity assay and 6% as non-toxic. This analysis will help to prioritise the development of adverse outcome pathways for acute oral toxicity, which will support the assessment of chemicals using mechanistically informed IATA.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"39-64"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36319815","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}

引用次数: 22

Developing context appropriate toxicity testing approaches using new alternative methods (NAMs). 使用新的替代方法(NAMs)开发适合环境的毒性测试方法。

IF 5.6

ALTEX Pub Date : 2019-01-01 DOI: 10.14573/altex.1906261

Melvin E Andersen, Patrick D McMullen, Martin B Phillips, Miyoung Yoon, Salil N Pendse, Harvey J Clewell, Jessica K Hartman, Marjory Moreau, Richard A Becker, Rebecca A Clewell

{"title":"Developing context appropriate toxicity testing approaches using new alternative methods (NAMs).","authors":"Melvin E Andersen, Patrick D McMullen, Martin B Phillips, Miyoung Yoon, Salil N Pendse, Harvey J Clewell, Jessica K Hartman, Marjory Moreau, Richard A Becker, Rebecca A Clewell","doi":"10.14573/altex.1906261","DOIUrl":"https://doi.org/10.14573/altex.1906261","url":null,"abstract":"In the past 10 years, the public, private, and non-profit sectors have found agreement that hazard identification and risk assessment should capitalize on the explosion of knowledge in the biological sciences, moving away from in life animal testing toward more human-relevant in vitro and in silico methods, collectively referred to as new approach methodologies (NAMs). The goals for implementation of NAMs are to efficiently identify possible chemical hazards and to gather dose-response data to inform more human-relevant safety assessment. While work proceeds to develop NAMs, there has been less emphasis on creating decision criteria or showing how risk context should guide selection and use of NAMs. Here, we outline application scenarios for NAMs in different risk contexts and place different NAMs and conventional testing approaches into four broad levels. Level 1 relies solely on computational screening; Level 2 consists of high throughput in vitro screening with human cells intended to provide broad coverage of possible responses; Level 3 focuses on fit-for-purpose assays selected based on presumptive modes of action (MOA) and designed to provide more quantitative estimates of relevant dose responses; Level 4 has a variety of more complex multi-dimensional or multi-cellular assays and might include targeted in vivo studies to further define MOA. Each level also includes decision-appropriate exposure assessment tools. Our aims here are to (1) foster discussion about context-dependent applications of NAMs in relation to risk assessment needs and (2) describe a functional roadmap to identify where NAMs are expected to be adequate for chemical safety decision-making.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"523-534"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40453431","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}

引用次数: 35

Advanced in vitro models analysis. 先进的体外模型分析。

IF 5.6

ALTEX Pub Date : 2019-01-01 DOI: 10.14573/altex.1812131

Katarzyna S Kopanska, Markus Rimann, Sandra Latenser, Michael Raghunath

引用次数: 1

Assessment of iron oxide nanoparticle ecotoxicity on regeneration and homeostasis in the replacement model system Schmidtea mediterranea. 氧化铁纳米颗粒对地中海施米德替代系统再生和动态平衡的生态毒性评价。

IF 5.6

ALTEX Pub Date : 2019-01-01 Epub Date: 2019-04-26 DOI: 10.14573/altex.1902061

Thao A Tran, Michelle Hesler, Oscar H Moriones, Alba Jimeno-Romero, Benjamin Fischer, Neus G Bastús, Victor Puntes, Sylvia Wagner, Yvonne L Kohl, Luca Gentile

{"title":"Assessment of iron oxide nanoparticle ecotoxicity on regeneration and homeostasis in the replacement model system Schmidtea mediterranea.","authors":"Thao A Tran, Michelle Hesler, Oscar H Moriones, Alba Jimeno-Romero, Benjamin Fischer, Neus G Bastús, Victor Puntes, Sylvia Wagner, Yvonne L Kohl, Luca Gentile","doi":"10.14573/altex.1902061","DOIUrl":"https://doi.org/10.14573/altex.1902061","url":null,"abstract":"Iron oxide nanoparticles (IONs) are used in a number of applications, from food to cosmetics, from medical applications to magnetic storage. In spite of the 550 tons produced each year in Europe alone, no effective dose limit recommendations are established and the overall risks connected to IONs are still debated. The incorporation of IONs in daily life raises a concern about their effects on the environment, on living organisms, and on human health. In this study, we used freshwater planarians to assess the nanoecotoxicity of IONs. Planarians are free-living invertebrates known for their astonishing regenerative ability. Because of their sensitivity to toxicants, they are often used to determine the effects of toxic, genotoxic and carcinogenic environmental compounds with an approach in line with the 3Rs (Reduce, Refine, Replace) principle. Planarians were exposed to IONs at concentrations up to 1 mg/mL and their effects were evaluated at the behavioral, morphofunctional and molecular levels, with a special emphasis on the regeneration process. Our results indicate that IONs did not affect the stem cell population dynamics, nor did they induce substantial changes in either homeostatic or regenerating planarians. As positive controls, gold nanoparticles coated with the pro-apoptotic anti-cancer drug hexadecylmethylammonium bromide, silver nanoparticles and highly concentrated polystyrene nanoparticles were used. These all elicited toxic effects. Therefore, we conclude that IONs at environmental concentrations are safe for planarians, and that the planarian is a powerful model system that can replace vertebrate animal models in nanoecotoxicology research and for nanoecotoxicology studies.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"583-596"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37188659","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}

引用次数: 4

Innovative in vitro method to study ventilator induced lung injury. 创新体外方法研究呼吸机所致肺损伤。

IF 5.6

ALTEX Pub Date : 2019-01-01 Epub Date: 2019-06-05 DOI: 10.14573/altex.1901182

Jon P Joelsson, Iwona T Myszor, Ari J Arason, Saevar Ingthorsson, Paulina Cherek, Gabriel S Windels, Kristjan Leosson, Gudmundur H Gudmundsson, Thorarinn Gudjonsson, Sigurbergur Karason

{"title":"Innovative in vitro method to study ventilator induced lung injury.","authors":"Jon P Joelsson, Iwona T Myszor, Ari J Arason, Saevar Ingthorsson, Paulina Cherek, Gabriel S Windels, Kristjan Leosson, Gudmundur H Gudmundsson, Thorarinn Gudjonsson, Sigurbergur Karason","doi":"10.14573/altex.1901182","DOIUrl":"https://doi.org/10.14573/altex.1901182","url":null,"abstract":"Mechanical ventilation (MV) is a life-saving therapy for critically ill patients, alleviating the work of breathing and supporting adequate gas exchange. However, MV can cause ventilator induced lung injury (VILI) by baro/volu- and atelectrauma, even lead to acute respiratory distress syndrome (ARDS), and substantially augment mortality. There is a need for specific biomarkers and novel research platforms for VILI/ARDS research to study these detrimental disorders and seek ways to avoid or prevent them. Previous in vitro studies on bronchial epithelium, cultured in air-liquid interface (ALI) conditions, have generally utilized static or constant pressure. We have developed a Cyclical Pressure ALI Device (CPAD) that enables cyclical stress on ALI cultured human bronchial cells, with the aim of mimicking the effects of MV. Using CPAD we were able to analyze differentially expressed VILI/ARDS and innate immunity associated genes along with increased expression of associated proteins. CPAD provides an easy and accessible way to analyze functional and phenotypic changes that occur during VILI and may provide a platform for future drug testing.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"634-642"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37078550","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}

引用次数: 4

Toward Good In Vitro Reporting Standards. 迈向良好的体外报告标准。

IF 5.6

ALTEX Pub Date : 2019-01-01 DOI: 10.14573/altex.1812191

Thomas Hartung, Rob De Vries, Sebastian Hoffmann, Helena T Hogberg, Lena Smirnova, Katya Tsaioun, Paul Whaley, Marcel Leist

{"title":"Toward Good In Vitro Reporting Standards.","authors":"Thomas Hartung, Rob De Vries, Sebastian Hoffmann, Helena T Hogberg, Lena Smirnova, Katya Tsaioun, Paul Whaley, Marcel Leist","doi":"10.14573/altex.1812191","DOIUrl":"https://doi.org/10.14573/altex.1812191","url":null,"abstract":"A good experiment reported badly is worthless. Meaningful contributions to the body of science are made by sharing the full methodology and results so that they can be evaluated and reproduced by peers. Erroneous and incomplete reporting does not do justice to the resources spent on conducting the experiment and the time peers spend reading the article. In theory peer-review should ensure adequate reporting - in practice it does not. Many areas have developed reporting standards and checklists to support the adequate reporting of scientific efforts, but in vitro research still has no generally accepted criteria. It is characterized by a \"Wild West\" or \"anything goes\" attitude. Such a culture may undermine trust in the reproducibility of animal-free methods, and thus parallel the \"reproducibility crisis\" discussed for other life science fields. The increasing data retrieval needs of computational approaches (in extreme as \"big data\" and artificial intelligence) makes reporting quality even more important so that the scientific community can take full advantage of the results. The first priority of reporting standards is to ensure the completeness and transparency of information provided (data focus). The second tier is a quality of data display that makes information digestible and easy to grasp, compare and further analyze (information focus). This article summarizes a series of initiatives geared towards improving the quality of in vitro work and its reporting. This shall ultimately lead to Good In Vitro Reporting Standards (GIVReSt).","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"3-17"},"PeriodicalIF":5.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36898820","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}

引用次数: 40

The 3Rs and replacement methods - better research, less animal harm. 3R 和替代方法--更好的研究，更少的动物伤害。

IF 5.6

ALTEX Pub Date : 2019-01-01 DOI: 10.14573/altex.1909261

Julika Fitzi-Rathgen

引用次数: 4

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