Influence of birth weight, sex, age and adiposity on central leptin and insulin sensitivity in young growing sheep, as indicated by changes in voluntary food intake

Non peer reviewedPublisher PD

Growth, body composition and metabolism at neonatal and adolescent life stages in low birth weight offspring

Non peer reviewedPublisher PD

Central and peripheral insulin resistance in a large animal model of obesity

Non peer reviewedPublisher PD

An Investigation of the Role of Thymidine Phosphorylase in the Activation of 5-Fluorouracil in Colon Tumour Cell Lines

Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and was originally isolated from platelets as the sole moiety with endothelial cell mitogenic activity. TP activity is increased in a number of tumour types compared with adjacent normal tissues including colon, stomach and breast cancer. TP has a role in tumour angiogenesis and increased activity in tumours confers a more aggressive tumour phenotype. TP also has a role in the activation of the fluoropyrimidine 5-fluorouracil (5-FU) to 5-fluorodeoxyuridine (5FdUrd). Intratumoural expression of TP is heterogeneous and may explain why only a proportion of patients respond to therapy with 5-FU. Modulation of 5-FU with interferon-alpha (IFN-alpha) increases the cytotoxicity of 5-FU in colon cancer cell lines. This is thought to occur through an increase in the activity of TP leading to greater formation of 5'-fluorodeoxyuridine monophosphate (FdUMP) and increased inhibition of thymidylate synthase (TS). HT-29 colon adenocarcinoma cell lines were transfected with TP cDNA and a novel TP activity assay demonstrated a 5-fold increase in TP activity in HT-29(TP) cells compared with the parental cells and the vector alone transfected controls, HT-29(V). 5-FU cytotoxicity was increased 1.6-fold in HT-29(TP) cells compared with HT-29(V) cells (p0.1, Students' t-test). Transfection alone without TP cDNA increased the resistance of HT-29 cells to 5-FU. The apparent increase in 5-FU cytotoxicity in HT-29(TP) cells was not enhanced by Leucovorin (LCV) or Deoxyinosine and cytotoxicity was not significantly reversed by exogenous thymidine, although a small increase in 5-FU IC50 was observed in the controls. Inhibition of TS by FdUMP was observed in these cells; however it does not appear to be the critical mechanism of action of 5-FU. The data from this thesis suggest that an increase in the activity of TP alone (5-fold) is not sufficient to significantly increase 5-FU cytotoxicity. Confirmation was obtained when TP activity and 5-FU cytotoxicity were measured in a number of cell lines from several tumour types. TP activity alone did not determine the sensitivity of the cell lines to 5-FU. Despite disappointing results with respect to 5-FU, a greater and more significant effect may be observed with 5-FU pro-drugs such as 5-dFUrd and Tegafur, which require activation by TP. The application of TP as a candidate gene for gene-directed/fluoropyrimidine pro-drug therapy is therefore promising as a means of improving the current lack of effective treatment for colon cancer and requires further investigation

How men and women learn about sex: multi-generational perspectives on insufficient preparedness and prevailing gender norms in Scotland

Attitudes towards sexual health and relationships are learned from a young age, and there is an ongoing need for innovative and comprehensive approaches to sex education that keep pace with rapidly changing contexts of people’s lives. We used thematic analysis of data from two qualitative studies in Scotland to explore learning contexts from a multi-generational perspective, as well as the influence of different socio-cultural factors on provision, access to and experience of sex education. The importance, but inadequacy, of school as a source of learning, was a persistent theme over time. Participants’ strategies to address perceived gaps in knowledge included experience, conversations, vicarious and online learning. Gender and age differences emerged, with younger participants more likely to go online for information, and prevailing gender norms shaping attitudes and behaviours across both study groups. Participants who identified as gay, lesbian or bisexual described feeling particularly unprepared for sex and relationships due to the narrow, heteronormative content received. Although schools continue to be a common source of information, it appears that they fail to equip young people for their post-school sexual life-course. We recommend the mandatory provision of comprehensive, positive, inclusive and skills-based learning to improve people’s chances of forming and building healthy, positive relationships across the lifespan

The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells

AbstractFlavonoids may be a principal contributor to the cancer preventative activity of fruit- and vegetable-rich diets and there is interest in their use as dietary supplements. However, there is potential conflict between the cytoprotective and cytotoxic activities of flavonoids, and their efficacy as anti-cancer agents is unresolved. Here, the integrity and survival of HL-60 promyelocytic leukaemia cells following short-term (90 min) exposure to the dietary abundant flavonoid kaempferol (1–100 μM) is reported. Supplementation initially decreased reactive oxygen levels but, paradoxically, a dose-dependent increase in single-strand DNA breakage occurred. However, there was no increase in oxidised DNA purines or membrane damage. Following a 24-h recovery period in non-kaempferol supplemented media, DNA single-strand breakage had declined and kaempferol exposed and control cultures possessed similar reactive oxygen levels. A reduction in 3H-thymidine incorporation occurred with ≥10 μM kaempferol. One hundred micromolar kaempefrol increased the proportion of cells in G2-M phase, the proportion of cells with a sub-G1 DNA content and enhanced ‘active’ caspase-3 expression but only induced a loss of mitochondrial membrane potential within a minority of cells. The relevance of induced DNA damage within a non-overtly oxidatively stressed environment to the disease preventative and therapeutic use of kaempferol is discussed

Gender Inequalities and Childbearing: A Qualitative study of Two Maternity Units in Nepal

The role and status of women in South Asian countries like Nepal are widely recognised to be lower than that of men. This gender inequality can be found throughout all levels of society. Our study is about the influence of gender on pregnancy and childbirth, which are very much in the female domain in South Asia, both at home and in health facilities. A mixed-method, qualitative research study was undertaken in two birthing facilities in Kathmandu Valley to examine barriers to women accessing these services from the perspective of hospital staff. Thematic analysis identified seven subthemes related to gender, namely: (1) support from family, autonomy & decision making; (2) women’s workload; (3) finances; (4) women wanting female doctor; (5) consent; (6) delivery room; and (7) preference for male offspring. Overall, gender-based roles negatively impacted many stages of the mother’s childbirth journey. Some staff recognised gender roles as a barrier to women accessing services but did not recognize themselves or their practices as a potential barrier. Gender issues identified at both birthing facilities generally reflect those of Nepali society as a whole. Raising awareness among maternity-care workers about gender issues and what they can do about it in personal interaction and how they reflect can on it would be the first step to improving the experiences of women of childbearing age

Breads Fortified with Freeze-Dried Vegetables : Quality and Nutritional Attributes. Part 1: Breads Containing Oil as an Ingredient

Acknowledgments: Funds for the study were provided by the Scottish Government’s Rural and Environment Science and Analytical Services Division and conducted as part of the Scottish Government Strategic Research programme (Diet and Health Theme of the Food Land & People Programme). The authors are grateful to Phillip Morrice, Vivian Buchan and Donna Henderson for helping with the nutritional analysis of the breads. The authors declare no conflicts of interest.Peer reviewedPublisher PD

Breads Fortified with Freeze-Dried Vegetables : Quality and Nutritional Attributes. Part II: Breads Not Containing Oil as an Ingredient

Acknowledgments: Funds for the study were provided by the Scottish Government's Rural and Environment Science and Analytical Services Division and conducted as part of the Scottish Government Strategic Research programme (Diet and Health Theme of the Food Land & People Programme). The authors are grateful to Phillip Morrice, Vivian Buchan, and Donna Henderson for helping with the nutritional analysis of the breads. The authors declare no conflicts of interest.Peer reviewedPublisher PD