Search Results (6)

Blood sampling often requires restraint that negatively affects animal welfare. This case study evaluated three methods for jugular vein blood sampling (V-bench, sling, and clicker training) with the overall aim of assessing the negative impact on animal welfare and providing a general recommendation on the use of methods. First, the effects of simulated blood sampling in V-bench and sling on behaviour, heart rate, and saliva cortisol concentrations 15 min after sampling were assessed. The sling (which had the least negative effects) was re-evaluated after one week of habituation to assess a possible positive effect. Clicker training was evaluated using behavioural observations only. The heart rate was significantly higher in animals placed in the V-bench compared to the sling (p < 0.05), but no significant differences were found in the saliva cortisol concentrations. Habituation to the sling resulted in a further reduction in heart rate compared to the V-bench (p < 0.01). When trained to voluntarily cooperate, three out of six minipigs allowed blood sampling from the jugular vein without restraint. We are convinced that all six minipigs would have succeeded if the training environment had been optimised. In conclusion, clicker training results in blood sampling with no negative behaviours displayed such as struggling or squealing/screaming. When restraint is unavoidable, the sling is preferable compared to the V-bench. Full article

Background: The biosafety of gene therapy products remains a major challenge to their introduction into the clinic. In particular, the problem of immunogenicity of viral vectors is the focus of attention. Large animals such as pigs, whose anatomical and physiological characteristics are similar to those of humans, have an advantage in testing vector systems. Methods: We performed a comprehensive in vitro and in vivo study to evaluate the biosafety of a chimeric adenoviral vector carrying a green fluorescent protein gene (Ad5/35F-GFP) in a mini-pig model. Results: Transcriptome and secretome analyses of mini-pig leucocytes transduced with Ad5/35F-GFP revealed changes restraining pro-inflammatory processes and cytokine production. No adverse effects were revealed through the clinical, instrumental, laboratory, and histological examinations conducted within a week after the direct or autologous leucocyte-mediated administration of Ad5/35F-GFP to mini-pigs. The decrease in cytokine levels in the blood of experimental animals is also consistent with the in vitro data and confirms the immune tolerance of mini-pigs to Ad5/35F-GFP. Conclusions: Here, we show the safety of Ad5/35F in a mini-pig model and provide evidence that Ad5/35F is a promising vector for gene therapy. These results advance our understanding of vector–host interactions and offer a solid foundation for the clinical application of this vector. Full article

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril’s effects on the GI following TBI (⁶⁰Co 1.79 or 1.80 Gy, 0.42–0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI. Full article

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package. These refinements benefit the welfare of fish, mice, rats, rabbits, dogs, minipigs, and non-human primates (NHPs) whilst maintaining or improving data quality within general toxicology, metabolism, and other studies and can also bring efficiencies to processes that benefit study costs and timings. Examples are shared which cover the following topics: social housing of dogs and NHPs, surgical refinements in the rat bile duct cannulation model for collection of data for metabolism studies, whether fasting is really required prior to clinical pathology sampling, and the use of microsampling for toxicokinetics. Full article

Biomedical research seeks to generate experimental results for translation to clinical settings. In order to improve the transition from bench to bedside, researchers must draw justifiable conclusions based on data from an appropriate model. Animal testing, as a prerequisite to human clinical exposure, is performed in a range of species, from laboratory mice to larger animals (such as dogs or non-human primates). Minipigs appear to be the animal of choice for studying bone surgery around intraoral dental implants. Dog models, well-known in the field of dental implant research, tend now to be used for studies conducted under compromised oral conditions (biofilm). Regarding small animal models, research studies mostly use rodents, with interest in rabbit models declining. Mouse models remain a reference for genetic studies. On the other hand, over the last decade, scientific advances and government guidelines have led to the replacement, reduction, and refinement of the use of all animal models in dental implant research. In new development strategies, some in vivo experiments are being progressively replaced by in vitro or biomaterial approaches. In this review, we summarize the key information on the animal models currently available for dental implant research and highlight (i) the pros and cons of each type, (ii) new levels of decisional procedures regarding study objectives, and (iii) the outlook for animal research, discussing possible non-animal options. Full article

The present review aims to summarize the main features of mammary gland anatomy, and the physiology of lactation and colostrum/milk in the most commonly used animal species for regulatory toxicity. The final goal is the selection of a preferred animal species to be enrolled in studies investigating the potential transfer of drugs and exogenous molecules through milk, within the Innovative Medicines Initiative (IMI) funded project ConcePTION. Reference data regarding humans were also collected and analyzed in order to highlight critical similarities and differences with the studied species. Additional practical considerations were also taken into account, such as ethical consideration regarding the chosen species which affects the group size, financial implications and technical feasibility of lactation trials (e.g., ease of sampling, volume of sampling, husbandry requirements and scientific recognition). In conclusion, the present analysis of the literature confirms the complexity of the decisional process behind the choice of an animal model for in vivo trials. For some of the evaluated species, data were either poor or missing, highlighting the necessity to generate more physiological background studies for species that are routinely used in laboratory settings. Overall, when taking into consideration ethical factors, feasible group size, milk volume and ease of milk collection, and physiological similarities with humans, minipigs seem to represent the most appropriate choice. Full article