The development of infections is one of the main complications in orthopaedics, especially in the presence of implants for the osteosynthesis of compound fractures and joint prosthesis. Indeed, foreign materials and implants act as substrates for the adhesion and proliferation of bacterial strains able to produce biofilm, causing peri-implant osteomyelitis. The eradication of biofilm remains a great challenge for the host immune system, as well as for medical and surgical approaches, thus imposing the need for new prophylactic and/or therapeutic strategies in which animal models have an essential role. In vivo orthopaedic models have mainly been used to study the pathogenesis of infections, biofilm behaviour and the efficacy of antimicrobial strategies, to select diagnostic techniques and test the efficacy of novel materials or surface modifications to impede both the establishment of bone infections and the associated septic loosening of implants. Among several models of osteomyelitis and implant-related infections described in small rodents and large animals, the rabbit has been widely used as a reliable and reproducible model of orthopaedic infections. This review examines the relevance of rabbits for the development of clinically representative models by analysing the pros and cons of the different approaches published in the literature. This analysis will aid in increasing our knowledge concerning orthopaedic infections by using this species. This review will be a tool for researchers who need to approach pre-clinical studies in the field of bone infection and have to identify the most appropriate animal model to verify their scientific hypothesis.

Brain structures differ in the magnitude of age-related neuron loss with the cerebellum being more affected. An underlying cause could be an age-related decline in mitochondrial bioenergetics. Successful aging of mitochondria reflects a balanced turnover of proteins involved in mitochondrial biogenesis and mitophagy. Thus, an imbalance in mitochondrial turnover can contribute to the diminution of cellular function seen during aging. Mitochondrial biogenesis and mitophagy are mediated by a set of proteins including MFN1, MFN2, OPA1, DRP1, FIS1 as well as DMN1l and DNM1, all of which are required for mitochondrial fission. Using N15 labeling, we report that the turnover rates for DMN1l and FIS1 go in opposite directions in the cerebellum of 22-month-old C57BL6j mice as compared to 3-month-old mice. Previous studies have reported decreased turnover rates for the mitochondrial respiratory complexes of aged rodents. In contrast, we found increased turnover rates for mitochondrial proteins of the oxidative phosphorylation chain in the aged mice as compared to young mice. Furthermore, the turnover rate of the components that are most affected by aging –complex III components (ubiquinol cytochrome C oxidoreductase) and complex IV components (cytochrome C oxidase)– was significantly increased in the senescent cerebellum. However, the turnover rates of proteins involved in mitophagy (i.e., the proteasomal and lysosomal degradation of damaged mitochondria) were not significantly altered with age. Overall, our results suggest that an age-related imbalance in the turnover rates of proteins involved in mitochondrial biogenesis and mitophagy (DMN1l, FIS1) in conjunction with an age-related imbalance in the turnover rates of proteins of the complexes III and IV of the electron transfer chain, might impair cerebellar mitochondrial bioenergetics in old mice.

Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-inwater emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

Periodontal disease is that condition resulting in the destruction of periodontal tissues, bone resorption, and tooth loss, the etiology of which is linked to immunological and microbiological factors. The aim of this study was to evaluate the potential trigger of periodontal disease in a rat model using bacterial species incriminated in the pathology of human periodontitis and to establish their optimal concentrations capable of reproducing the disease, with the idea of subsequently developing innovative treatments for the condition. In this study, we included 15 male Wistar rats, aged 20 weeks, which we divided into three groups. In each group, we applied ligatures with gingival retraction wire on the maxillary incisors. The ligature and the gingival sac were contaminated by oral gavage with a mixture of fresh cultures of Aggregatibacter actinomycetemcomitans (A.a), Fusobacterium nucleatum (F.n) and Streptococcus oralis (S.o) in concentrations of 108, 109, and 1010 CFU/mL each for 5 days a week for 4 weeks. During the clinical monitoring period of 28 days, overlapped with the period of oral contamination, we followed the expression of clinical signs specific to periodontitis. We also monitored the evolution of body weight and took weekly samples from the oral cavity for the microbiological identification of the tested bacteria and blood samples for hematological examination. At the end of the study, the animals were euthanized, and the ligated incisors were taken for histopathological analysis. The characteristic symptomatology of periodontal disease was expressed from the first week of the study and was maintained until the end, and we were able to identify the bacteria during each examination. Hematologically, the number of neutrophils decreased dramatically (p < 0.0001) in the case of the 109 group, unlike the other groups, as did the number of lymphocytes. Histopathologically, we identified neutrophilic infiltrate in all groups, as well as the presence of coccobacilli, periodontal tissue hyperplasia, and periodontal lysis. In the 109 group, we also observed pulpal tissue with necrotic bone fragments and pyogranulomatous inflammatory reaction. By corroborating the data, we can conclude that for the development of periodontal disease using A.a, F.n, and S.o, a concentration of 109 or 1010 CFU/mL is required, which must necessarily contaminate a ligature thread applied to the level of the rat’s dental pack.