The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through removal of damaged or old materials as well as coordinate skeletal muscle repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation to impact resident and infiltrating skeletal muscle immune cells has not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Male C57BL/6 mice were given a physiologically translatable dose (35 mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (\u3e5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophages were reduced with 5FU treatment while total M2-like CD206+CD11c- macrophages were unchanged. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes. Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in association with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest. Together our results highlight that skeletal muscle is sensitive to 5FU’s off-target effects which disrupts both circulating and skeletal muscle immune cells

"I just gotta have my own space!": The role of space and audience in recreational choices made by adolescent girls in Western Australia

Adolescent girls are not as fit as adolescent boys. Although many adolescent girls pursue physically active lifestyles, others choose more passive options. This dissertation explores how perceptions towards recreational spaces may contribute to these differences. In the spirit of feminist research, girls and their perceptions were the focus of the study. After a brief exploratory stage, 276 15-year old schoolgirls were surveyed regarding their attitudes towards a range of potential recreational spaces in the school, community and their homes. A year later, a subset of these girls was interviewed about three specific spaces: public swimming pools, basketball courts and bedrooms. Four focus groups were followed by individual interviews with 16 of the girls. Emergent factors that affected girls’ recreational choices in each of the spaces were drawn out and analysed. Conceptual frameworks that shed light on the relationships between these factors are provided. My thesis is that participation in recreational activity is not spontaneous for many adolescent girls. Prior to participation, a girl appears to assess how a potential audience in a particular space at any one time might react to her physical appearance, athletic competence or behaviour. She weighs this up against other factors such as the potential of the activity to satisfy her desire for fun, inclusion, relaxation, exercise or sense of control. This may inhibit her active participation in some public spaces and make the generally passive site of the bedroom an attractive option. The study contributes to an understanding of the factors that affect an adolescent girl’s recreational participation. This understanding should be of use to recreation programmers, facility providers, educational authorities and parents in their efforts to increase girls’ levels of participation in healthful physical activity