Hmm - sounds like there could well be some issues
What I think I will do is continue to use my current Python 2.6 + Eclipse VM for Calibre work, but build the Python 2.5+IronPython VM as a background activity to experiment with.
I will report back with any positive findings.
I will also keep my eyes open for other attempts to integrate standard Python into Visual Studio. This used to be available in the VS2003 days, but appears to have dropped by the wayside (I think due to licensing/GPL isssues).