22 research outputs found
Applying refinement to the use of mice and rats in rheumatoid arthritis research
Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat âmodelsâ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research
Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging
We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTXePC) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3Luc) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with TaxolÂź, sustained PTXePC therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTXePC implant system, which could potentially translate into successful clinical outcomes
Determining overweight and underweight with a new weightâforâheight index in captive groupâhoused macaques
Housing primates in naturalistic groups provides social benefits relative to solitary housing. However, food intake may vary across individuals, possibly resulting in overweight and underweight individuals. Information on relative adiposity (the amount of fat tissue relative to body weight) is needed to monitor overweight and underweight of groupâhoused individuals. However, the upper and lower relative adiposity boundaries are currently only known for macaques living solitarily in small cages. We determined the best measure of relative adiposity and explored the boundaries of overweight and underweight to investigate their incidence in groupâhoused adult male and female rhesus macaques and longâtailed macaques living in spacious enclosures at the Biomedical Primate Research Centre (BPRC), the Netherlands. During yearly health checks different relative adiposity measures were obtained. For longâtailed macaques, comparable data on founder and wild animals were also available. Weightâforâheight indices (WHI) with height to the power of 3.0 (WHI3.0) for rhesus macaques and 2.7 (WHI2.7) for longâtailed macaques were optimally independent of height and were highly correlated with other relative adiposity measures. The boundary for overweight was similar in groupâhoused and solitaryâhoused macaques. A lower boundary for underweight, based on 2% body fat similar to wild primates, gave a better estimate for underweight in groupâhoused macaques. We propose that for captive groupâhoused rhesus macaques relative adiposity should range between 42 and 67 (WHI3.0) and for longâtailed macaques between 39 and 62 (WHI2.7). The majority of groupâhoused macaques in this facility have a normal relative adiposity, a considerable proportion (17â23%) is overweight, and a few (0â3%) are underweight