Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease.

Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media.

Magnetogenesis under physiological conditions with probes that report on (bio-)chemical stimuli.

Switched on: A molecular concept allows the generation of magnetism in an aqueous sample under the influence of a freshly added (bio-)chemical analyte. The analyte (a chemical reagent or enzyme) triggers the conversion of the probe, a diamagnetic chelate compound, into a paramagnetic compound (see scheme). The two probes prepared are easily accessible iron(II) chelates, and are operative at physiological conditions and/or in serum.

Awakening of a ferrous complex's electronic spin in an aqueous solution induced by a chemical stimulus.

A low-spin, macrocyclic iron(II) complex in an aqueous solution responds to the addition of a chemical reactant (dithionite) by transformation into a high-spin complex, detectable by measurement of the longitudinal relaxation time (T(1)) of surrounding water hydrogen nuclear spins. The initial compound does not modify T(1) of pure water at concentrations as high as 4 mM. The response is pH-dependent, and the complex is robust at a variety of conditions.

An electroneutral macrocyclic iron(II) complex that enhances MRI contrast in vivo.

The first example of a macrocyclic ferrous complex, where two tetrazolyl pendent arms compensate the charge of the metal center, is synthesized and examined for its capacity to enhance MRI contrast in vitro and in vivo in the mouse.

Colorectal cancer screening with the addition of flexible sigmoidoscopy to guaiac-based faecal occult blood testing: a French population-based controlled study (Wintzenheim trial).

Objective: To assess the feasibility, participation and neoplasia yield of adding a flexible sigmoidoscopy (FS) once in a lifetime to a colorectal cancer screening programme with guaiac-based faecal occult blood test (gFOBT).

Methods: A total of 4771 average risk residents aged 50-74 of a canton of the Haut-Rhin, a French administrative area, were invited every other year to participate in an organised screening programme with gFOBT. Of them, those aged 55-64 (1824 people) were, in addition, invited once by mail to visit their general practitioner (GP) for a screening with FS performed by a gastroenterologist.