Laboratory Animals最新文献

The use of Vascular Access Buttons™ (VABs) is gaining traction in animal research as a less invasive alternative to traditional venipuncture methods and a superior option compared with existing alternatives, such as vascular access ports (VAPs). By enabling repeated blood collection and intravenous drug administration with reduced stress and discomfort for the animals, VABs contribute to improved data quality and enhanced animal welfare in animal studies. While increasingly used in rodents, their application in non-rodent species remains underexplored. This study evaluated the feasibility and reliability of the VAB system in two Göttingen Minipigs, comparing its performance with the conventional vena cava cranialis puncture. Pharmacokinetic assessments and clinical pathology analyses revealed consistent results across both techniques, demonstrating the VAB system's ability to generate reproducible, high-quality data. Additionally, its durability and ease of use highlight its potential as a practical and ethical alternative to both traditional venipunctures and VAPs in pharmacokinetic and long-term studies in minipigs. These findings support the integration of the VAB system in toxicological and pharmacokinetic research, particularly in studies requiring repeated blood collection or chronic intravenous dosing.

Laboratory animal welfare has received increasing attention in recent years as housing protocols move toward favoring environments that allow natural behaviors. Within this study, the effects of housing male and female Sprague Dawley rats in standard cages versus taller cages with an upper shelf were investigated. To determine differences in behavior and physiology based upon cage type, home-cage assessment of ultrasonic vocalizations and analysis of fecal corticosterone metabolites, as well as various behavioral tests, were performed. Rats in shelved cages produced significantly less 50 kHz calls, demonstrated better working memory in the spontaneous alternation task and had higher concentrations of fecal corticosterone metabolites. No differences were observed in the open field, elevated plus maze or light-dark box. While no significant treatment differences were found in the ultrasonic vocalization playback paradigm, results confirmed previous evidence of approach behavior upon 50 kHz call playback. The observed differences in behavior and physiology as a consequence of housing conditions inevitably have implications for experimental reproducibility as comparing studies across laboratories may be difficult if different housing parameters are utilized. The results of this study can also be used in guiding future animal welfare protocols given that certain cage modifications such as increased vertical space and/or the presence of a shelf might improve welfare. Investigation of additional parameters and strains of rodents will enhance our understanding of optimal laboratory animal housing conditions.

The 3Rs strongly shape the practice of laboratory animal use, as well as related policies worldwide. This success should not obscure the fact that implementing the 3Rs comes with challenges. A major problem is that it is fundamentally unclear under which conditions the 3Rs may be considered fulfilled in specific contexts. We argue that this lack of clarity is largely a result of the fact that the normative nature of the 3Rs has so far been disregarded. Hence, this paper seeks to answer the following research question: how is the normative nature of the 3Rs to be understood, and how can this understanding transparently guide their implementation? Based on a distinction between different types of norms, we show that the 3Rs, which have been called 'principles' since their origin, are indeed to be understood as principles in a substantive (norm-theoretical) sense. That is, they are norms that command the highest possible realization of their content. This understanding of the normative nature of the 3Rs has a significant effect on their implementation in practical contexts. As we will argue, it turns the orthodox idea of implementation strategies upside down. Building on this theoretical claim, we propose an ethics tool designed to help applicants, review committee members and authorities to apply the 3Rs transparently and, above all, in accordance with a reflected understanding of the relevant EU Directive's intention (Directive 2010/63/EU) and of the work of Russell and Burch, the pioneers of this milestone in the promotion of animal welfare in research.

Good education and training for scientists undertaking animal experiments is important for providing understanding of key issues in experimental design (ED) and for alleviating continuing concerns about the conduct of animal and in vitro research studies. We present here outputs from the FELASA Experimental Design Working Group, set up to consider the current provision of ED teaching and how it might be improved and harmonised across the laboratory animal science community. It is hoped that these outputs will provide practical help to ED teachers who wish to enhance the effectiveness of their teaching; they include• A list of learning outcomes (LOs) that should be achieved by learners, principally aimed at early career researchers;• An example of an (adaptable) template of how these LOs could be addressed in 16 h (12 h tuition plus breaks), ideally as a 2-day workshop. If circumstances make 12 h tuition impossible to achieve, key LOs for a shorter course are identified;• Guidance and recommendations for running ED courses, including some ideas for achieving effective learning, the ideal skill set for tutors, some teaching scenarios, and the amount of statistics to have in a basic experimental design course;• A glossary of relevant terms (in supplemental material);• A description of how the 2-day course format ran on two trial occasions, with results of informal assessment of participants as well as their feedback, both immediate and a year afterwards, indicating it was effective;• A programme for a potential 2-day, training-the-trainers style, workshop, describing its key elements and the results of trialling this with a range of ED tutors.

Cervical dislocation (CD) is a widely used method worldwide for humanely killing adult laboratory mice in accordance with national legislation, such as the Animals (Scientific Procedures) Act 1986 in the UK. However, concerns have been raised regarding the limitations and potential risks associated with CD, including a reported failure rate of up to 20% and the risk of injury to the thoracic or lumbar spine region. To address these concerns, we have adopted a CD method that avoids the use of tension on the tail or any additional tools. In this study, we detail our process of validation through self-reporting and direct observation leading up to present our implementation of computerised tomography and three-dimensional imaging software to evaluate the effectiveness and efficiency of this tail-force free CD method. Our findings reveal a 100% success rate in achieving accurate cervical dislocation without causing damage to other vertebrae, thereby providing an improved and more reliable approach to humane killing for both male and female adult laboratory mice.

As commissioned by the Federation of European Laboratory Animal Science Associations, these working group recommendations define the requirements to achieve the humane killing of fish, compare methods of killing, recommend methods of killing depending on context, and detail protocols leading to good practice. With a review of current practices in a fish laboratory and available literature to guide the recommendations, the concept of ideal euthanasia is discussed, and the dilemma of a prompt but stressful death versus a slow but stress-free experience is introduced. Noticeably, the context of fish killing varies widely whether to satisfy European Directive requirements, efficacy for species and/or developmental stages, scientific needs, health and safety, or animal welfare. Examples in the recommendations are based on the most common laboratory fish species, such as zebrafish Danio rerio, and the most commonly used methods of killing, such as overdose of anaesthesia, hypothermic shock, electrical stunning, and concussion - percussive blow to the head. Practical applications of completion of death, refinements, and protocols for good practice are proposed for all developmental stages and depending on the potential fate of the carcass as a scientific sample.

To provide an alternative to oral gavage for per os treatments in laboratory mice, we have recently developed and introduced the micropipette-guided drug administration (MDA) method. This procedure is based on the presentation of a palatable solution consisting of sweetened condensed milk diluted with water, encouraging voluntary consumption of the vehicle and drug formulations. In this study, we compared the MDA method in male and female C57BL/6N and BALB/c mice, two inbred strains widely used in basic and preclinical research. Administering a diluted condensed milk solution daily over a period of 30 days, we observed that male C57BL/6N mice reached the fully voluntary drinking stage within five days or less, requiring the least amount of time to drink from the micropipette. Compared with males, female C57BL/6N mice showed increased consumption times during the initial administration period, yet they all managed to reach a fully voluntary stage within seven days or less. By contrast, BALB/c mice in general, and female BALB/c mice in particular, consistently required more time to consume the diluted condensed milk solution, whether administered voluntarily (no restraint) or semi-voluntarily (with mild tail restraint). Notably, a substantial portion of BALB/c mice (12.5% of males and 62.5% of females) failed to achieve fully voluntary consumption by MDA, despite their ability and willingness to drink the condensed milk solution when using a mild tail restraint. Taken together, the present study identified significant strain and sex differences in the MDA method as applied to laboratory mice.

Inflammatory bowel diseases (IBDs) are a major health burden, and incidence as well as prevalence have increased over the last decades. Colitis animal models are used to explore the underlying pathogenesis of and therapeutic options for IBD. Since the reporting of specific aspects of colitis studies using mice has been criticized in the past, we performed a scoping review based on the PRISMA guidelines to assess putative improvements in the quality of reporting. A defined search for dextran sulfate sodium (DSS) murine colitis models was performed in three literature databases (PubMed, PubMed Central®, and Embase) for two time periods: 2007/2008 and 2017. Data were extracted from 122 articles published in 2007/2008 and 236 publications from 2017. We checked the articles for the reporting of details of the colitis model (DSS properties, manufacturer, concentration, duration of application, mouse strain, sex, source), measures to reduce allocation, performance and detection bias (randomization and blinding), and information on clinical assessment, refinements, and humane endpoints. Our results showed that there was significant improvement over time in the scores for refinement and, based on this, also the completeness score. However, the other aspects were poorly reported, suggesting that this research field may need to adopt reporting guidelines such as ARRIVE, the Gold Standard Publication Checklist, or the colitis methods checklist when writing and reviewing publications.

Oral gavage is a widely used method to infect mice with Cryptosporidium parvum (CP), the most common animal model of infection. Cryptosporidium spp. are worldwide distributed, gastrointestinal parasites that mainly cause diarrhea in humans and neonatal ruminants. CP is transmitted via the fecal-oral route, usually through contaminated water. In rodent models of Cryptosporidium infection, oral gavage is used as the route of infection. This method, while effective, induces a generalized stress response and requires specific skills and experience. Our aim was to replace oral gavage by a refined method using a mixture palatable to mice, where oocysts could be mixed in. A peanut butter gelatin mix (PBG) containing CP oocysts was developed and used for voluntary oral infection of mice. We were able to confirm CP infections in young interferon-gamma knock out mice by detecting oocyst shedding in feces, demonstrating that the PBG method successfully produced infections similar to those obtain through oral gavage, and could be used for other pathogens or as a method to deliver experimental therapeutics or other substances.

Murine aggression has profound implications on animal welfare and husbandry. This report examines how three distinct combinations of environmental enrichment - wheel, igloo and tunnel; wheel, igloo, and tunnel with nesting; and tunnel with nesting - affect aggressive behaviour in CD-1 male mice. We found that combining wheel/igloo/tunnel enrichment with nesting or replacing the wheel/igloo with two tunnels while maintaining the nesting enrichment reduced aggression. These findings not only suggest how enrichment can improve the welfare of aggressive male mice but also emphasise the need for further research to determine the optimal combination of enrichment.