Laboratory Animals最新文献

Researchers often need to justify their choice of sample size, particularly in fields such as animal and clinical research, where there are obvious ethical concerns about relying on too many or too few study subjects. The common approach is still to depend on statistical power calculations, typically carried out using simple formulas and default values. Over-reliance on power, however, not only carries the baggage of statistical hypothesis tests that have been criticized for decades, but also blocks an opportunity to strengthen the research in the design phase by learning about challenges in interpretation before the study is carried out. We recommend constructing a 'quantitative backdrop' in the planning stage of a study, which means explicitly connecting ranges of possible research outcomes to their expected real-life implications. Such a backdrop can facilitate a priori considerations of how potential results, for example represented by intervals, will ultimately be interpreted. It can also serve, in principle, to help select single values of interest for use in traditional power analyses, or, better, inform sample size investigations based on the goal of achieving an interval width narrow enough to distinguish values deemed practically or clinically important from those not representing practically meaningful effects. The latter bases calculations on a desired precision, rather than desired power. Sample size justification should not be seen as an automatic math exercise with a right answer, but as a nuanced a priori investigation of measurement, design, analysis and interpretation challenges. Construction of the quantitative backdrop provides a tangible starting place for such an investigative process.

Animals used in science and education should be used by competent laboratory animal science (LAS) staff, both for reasons of reproducibility and to safeguard animal welfare. In this article, we propose entrustable professional activities (EPAs) as a structure to support and assess development of competence and valid entrustment decisions of persons working with laboratory animals in practice following, or in combination with, basic training. We propose the creation of a consensus framework and provide concepts that would encourage harmonisation in competence-based development. We anticipate that these will ensure that supervisors, trainers and competence assessors can more reliably establish the operator's competence in procedures on animals which are used in scientific research or education professionally.

The streptozotocin (STZ)-induced hyperglycaemic rat model is widely used in diabetes research, particularly for investigating diabetic retinopathy; however, animal welfare concerns are often underreported. This study evaluated welfare outcomes in two commonly used rat lines, Brown Norway (BN/Crl) and Sprague Dawley (RjHan:SD). Data were collected from a series of diabetic retinopathy studies, in which a total of 183 BN/Crl and 76 RjHan:SD male rats received 40-65 mg/kg STZ via intraperitoneal injection and were monitored for 5-12 weeks. Welfare parameters, including body weight development and urologic complications (notably paraphimosis), were recorded and compared. Both lines achieved hyperglycaemia (≥16 mmol/l) within three weeks. However, BN/Crl rats exhibited a high incidence (82.5%) and severity of paraphimosis, along with marked weight loss, resulting in 13.7% of the animals reaching humane endpoint criteria for euthanasia. Weight loss positively correlated with STZ doses, with the highest dose (65 mg/kg) leading to 17.2% humane endpoint rate. In contrast, RjHan:SD rats exhibited significantly fewer urologic complications and maintained better weight gain, with none reaching humane endpoint. Our findings suggest that, while BN/Crl rats may offer advantages for ocular research owing to their pigmented eyes, their susceptibility to severe welfare issues raises concerns regarding their routine use. Furthermore, standardised supportive treatments, such as insulin supplementation, are worth considering for the model. This study highlights that careful selection of model animals, disease induction protocols and supportive treatments can optimise research outcomes and avoid loss of experimental animals, while adhering to the 3Rs.

Swine are a common neurobehavioral model. Visual event related potentials (VERPs) are an electroencephalogram (EEG) technique that assesses visual processing and can inform brain function and sensory changes after trauma or disease. We hypothesized that piglet visual EEG processing for 2D conspecific (CS) images would produce more cortical activity than a simple white square stimulus. We measured VERPs in healthy piglets presented with a 2D CS piglet image (N = 5) and compared these results with animals presented with a simple white square (WS, N = 5). EEG waveforms were input into a source localization model of the brain to estimate cortical activity. N1 and P2 amplitudes and latencies and current density were extracted for each animal. Visual processing of CS produced longer N1 and P2 latencies than WS in the visual processing regions, suggesting that pigs may require longer processing times for more detailed images. Contrary to our hypothesis, CS had lower P2 amplitudes (frontal and left temporal) and current density (right temporal and occipital), which suggests that CS requires less processing power. Magnitudes may be related to the brightness of the stimuli presented (a feature that was not controlled for) with WS having on average a higher lux (112) than CS (98). Regardless, latency differences between CS and WS demonstrate that visual processing is sensitive to subtle stimulus features which can inform future studies on pig behavior and attention. Finally, these data serve as a healthy reference to compare VERPs in experimental cohorts subject to brain injury or other neurological diseases affecting visual processing.

In this study we aimed to determine the optimal epidural dose and concentration of diphenhydramine (DPH) for prolonged analgesia while preserving motor function, comparing its effects with lidocaine. A single-blind, randomized-controlled trial was conducted with 32 healthy rabbits assigned to two experiments (2.5 ± 0.5 kg). Experiment 1 (n = 25) assessed optimal DPH doses (4, 8, 12, 18, 24 mg kg^-1), while Experiment 2 (n = 15) compared DPH concentrations (5%, 10%, 15%, 20%) at 12 mg kg^-1. Antinociceptive effects were measured using pinprick tests on the perineal and digital areas, and motor blockade was evaluated using a modified 4-point grading system for limb paralysis. The results showed that epidural administration of 10% DPH at 12 mg kg^-1 provided profound analgesia, with hindlimb analgesia lasting 201 ± 2.5 min and motor blockade persisting for 157.2 ± 3.4 min. In contrast, 5% DPH resulted in 96 ± 15 min of analgesia and 5.2 ± 2.2 min of motor block. Lidocaine failed to provide effective digital analgesia. No significant difference was observed between 10% and 15% DPH in analgesic and motor effects. The motor blockade duration was consistently shorter than the antinociceptive effect. DPH demonstrated superior potency, and a prolonged, sensory-selective epidural block compared with lidocaine, minimizing motor blockade and the risk of akinesia-like analgesia. DPH (preferably >5%) offered effective and safe analgesia, making it a promising option for hindlimb analgesia in rabbits, reducing animal suffering and providing better outcomes than lidocaine.

The aim of this experimental, descriptive study was to evaluate feasibility, safety and side effects of alfaxalone and midazolam by intranasal instillation for anaesthesia induction in rabbits. We included 26, healthy, female New Zealand White Rabbits undergoing general anaesthesia in context of a study to test different coatings for stifle joint endoprosthesis. Midazolam (0.1 mg/kg) and alfaxalone 3 mg/kg (group 1) or 4 mg/kg (group 2) were mixed and administered intranasally. The number of sneezes, swallows and evasive attempts were recorded. Time to lateral recumbency, presence of salivation, nystagmus, induction and intubation qualities were scored. If intubation was not possible, a top-up of 1 mg/kg alfaxalone was administered intranasally. If still not sufficient, anaesthesia was induced by mask-insufflation of isoflurane. Data were analysed using IBM SPSS Statistics 30.0.0.0 and non-parametric data compared using either a Mann-Whitney test or a chi-square test. Overall, 10 animals assigned to group 1 and 16 animals to group 2 were included in the study. In 24/26 rabbits (92.3%) no significant complications were noted. One rabbit showed 20 s of apnoea after induction and one rabbit died during induction. Top-up dosages of alfaxalone were necessary in three cases and in two of these three, isoflurane administration was also required to complete anaesthetic induction. The median time to lateral recumbency was 32.5 s in group 1 and 15 s in group 2. By intranasal application of midazolam with alfaxalone at both dosages, the anaesthetic state was induced shortly after application.

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.