Chronic hypoxia up-regulates expression of adenosine A1 receptors in DDT1-MF2 cells.

As the first step to understand how chronic hypoxia might regulate smooth muscle function in health and disease, we have employed an established immortalised cell model of smooth muscle, DDT1-MF2 cells, to address the hypothesis that adenosine A1 receptor density is modulated by O2 availability. Maximal specific binding (Bmax) of the selective adenosine A1 receptor antagonist, [3H]-DPCPX, to cell membranes increased 3.5-fold from 0.48 +/- 0.02 pmol/mg to 1.7 +/- 0.5 pmol/mg protein after 16 hr of hypoxia and this effect was not accompanied by any statistically significant changes in either binding affinity (0.84 +/- 0.2 nM vs. 1.2 +/- 0.3 nM) or Hill coefficient (1.1 +/- 0.1 vs. 0.99 +/- 0.03). Hypoxia-evoked increases in membrane receptor density were paralleled in intact DDT1-MF2 cells. In addition, the increase in [3H]-DPCPX binding to intact cells was inhibited by co-incubation during hypoxia with the translational inhibitor cycloheximide, the transcriptional blocker actinomycin D and the NFkappaB inhibitor sulphasalazine. Together, these data show that adenosine A1 receptor density is modulated, at least in part, by O2-dependent activation of the transcription factor NFkappaB and adds to the list of processes dynamically regulated by ambient oxygen availability. Since hypoxia is an initiating factor in acute renal failure, similar changes in transcription may account for up-regulation of adenosine A1 receptors noted previously in the renal vasculature of rats with acute renal failure.

Alternative learning environments: what do they contribute to professional development of medical students?

Special study modules provide opportunities for students to develop lifelong learning skills and develop areas of interest. The GMC also recommends opportunities to study topics not included in the core medical curriculum. This paper reports the evaluation of modules based within alternative learning environments developed to provide students with experiences outside traditional medical, scientific or academic cultures. The attachment was highly rated as contributing to professional development, provided novel learning experiences, and was stimulating for both students and supervisors. All students achieved new skills that they felt were pertinent to their personal development. Assessment was by standardized pro forma, including generic transferable skills and module specific outcomes. Whilst overall assessment grades were comparable to similar course components, unease amongst both students and supervisors was expressed reflecting anxieties in the diversity of workloads and assessment. Attempts to standardize assessment across the diversity of modules did not reduce anxieties and potentially detracted from the learning experiences.