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1رسالة جامعية
المؤلفون: Nardone, Anthony
الوصف: The incubation of murine leukaemic L1210 cells in vitro for 4 hours (hr) with 10uM nitrogen mustard (HN2), a bifunctional alkylating agent, inhibited the influx of the potassium congener, 88rubidium+ ( 86Rb+) by the selective inhibition of the Na+-K+-CI- cotransporter. The aim of this project was to investigate the importance of this lesion in HN2-induced cytotoxicity. 86Rb+ uptake in human erythrocytes was inhibited by high concentrations of HN2 (2mM) and occurred in two phases. In the first hour both the Na+/K+ ATPase pump and the Na+-K+-CI- cotransporter were equally inhibited but after 2 hrs exposure to 2mM HN2, the Na+ -K+ -CI- cotransporter was significantly more inhibited than the Na+/K+ ATPase pump. In contrast, both potassium transport systems were equally inhibited in L1210 cells incubated for 10 minutes with 1mM HN2. The selective inhibition of the Na+-K+-CI- cotransporter, after a 3 hrs exposure to 10uM HN2, was not absolved by coincubation with 5ug/ml cycloheximide (CHX), an inhibitor of protein synthesis. Incubation of L1210 cells with concentrations of diuretics which completely inhibited Na+-K+-CI- cotransport did not enhance the cytotoxicity of either HN2 or its monofunctional analogue 2-chloroethyldimethylamine (Me-HN1). The incubation of L1210 cells with a twice strength Rosewell Park Memorial Institute 1640 media did not enhance the toxicity of HN2. An L1210 cell line (L1210FR) was prepared which was able to grow in toxic concentrations of furosemide and exhibited a similiar sensitivity to HN2 as parental L1210 cells. Treatment of L1210 cells with 10uM HN2 resulted in a decrease in cell volume which was concurrent with the inhibition of the Na+-K+-CI- cotransporter. This was not observed in L1210 cells treated with either 1 or O.SuM HN2. Thus, possible differences in the cell death, in terms of necrosis and apoptosis, induced by the different concentrations of HN2 was investigated. The cell cycle of L1210 cells appeared to be blocked non-specifically by 10uM HN2 and in S and G2/M by either 1 or 0.5uM HN2. There were no significant changes in the cytosolic calcium concentrations of L1210 cells for up to 48 hrs after exposure to the three concentrations of HN2. No protection against th_ toxic effects of HN2 was observed in L1210 cells incubated with 5ug/ml CHX for up to 6 hrs. Incubation for 12 or 18 hrs with a non-toxic concentration (5mM) of L-Azetidine-2- carboxylic acid (ACA) enhanced the toxicity of low concentrations (< 0.5uM) of HN2.
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2رسالة جامعية
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3رسالة جامعية
المؤلفون: Desai, M.
المساهمون: Gilson, R., Mercey, D., Burns, F., Nardone, A.
مصطلحات موضوعية: 610
الوصف: Reminders have been successfully used in healthcare to improve reattendance rates but evidence for their effectiveness in sexual health remains unknown. A programme of studies explored the effectiveness of, and drivers and barriers to active recall reminders in increasing reattendance/re-testing rates for HIV/STIs among men who have sex with men (MSM), underpinned by the Theory of Planned Behaviour. The systematic literature review suggested efficacy of reminders in increasing reattendance/re-testing rates for HIV/STIs, but was unable to determine which modality of reminder was most effective. In a service evaluation, text SMS reminders were offered to MSM who reported unprotected anal sex in the past three months. The evaluation was unable to demonstrate an increase in reattendance rates; however concurrent health promotion may have counfounded the results. To explore preferred type and frequency of reminder, and attitudes to HIV/STI testing and reminders, 406 MSM attending a sexual health clinic were surveyed. Preferring SMS reminders, liking being reminded to check health status, not being concerned about the confidentiality of reminders and preferring to have a reminder to test were associated with intention to reattend in multivariable analysis, but not with documented reattendance. Concern about potential stigma of being sent a reminder was associated with reduced intention to reattend. Contextual factors influencing these attitudes to testing and reminders were explored in 16 interviews. Drivers for testing included easy access to testing facilities and the influence of peers or a regular male partner. Conversely, barriers included conflict with being in a trusting relationship, difficulty of accessing tests, fear/embarrassment and concerns about wasting resources. Key themes in responding to reminders included convenience and confidentiality of the reminder, control over receipt and response to the reminder, and reminder persistence. These findings will inform HIV testing recall policies and provides further support for preference for SMS reminders.
