Pregnane X Receptor (PXR), a master regulator of drug metabolism and inflammation, is abundantly expressed in the gastrointestinal tract. Baicalein and its O-glucuronide baicalin are potent anti-inflammatory and anti-cancer herbal flavonoids that undergo a complex cycle of interconversion in the liver and gut. We sought to investigate the role these flavonoids play in inhibiting gut inflammation by an axis involving PXR and other potential factors. The consequences of PXR regulation and activation by the herbal flavonoids, baicalein and baicalin were evaluated in vitro in human colon carcinoma cells and in vivo using wild-type, Pxr-null, and humanized (hPXR) PXR mice. Baicalein, but not its glucuronidated metabolite baicalin, activates PXR in a Cdx2-dependent manner in vitro, in human colon carcinoma LS174T cells, and in the murine colon in vivo. While both flavonoids abrogate dextran sodium sulfate (DSS)-mediated colon inflammation in vivo, oral delivery of a potent bacterial β-glucuronidase inhibitor eliminates baicalin’s effect on gastrointestinal inflammation by preventing the microbial conversion of baicalin to baicalien. Finally, reduction of gastrointestinal inflammation requires the binding of Cdx2 to a specific proximal site on the PXR promoter. Pharmacological targeting of intestinal PXR using natural metabolically labile ligands could serve as effective and potent therapeutics for gut inflammation that avert systemic drug interactions.

Despite a randomized controlled trial showing clear safety concerns with the Wingspan intracranial stent system, the device remains on the market. Ari J Gartenberg and colleagues argue that the exemption system used to obtain its market approval in the US is not adequate for high risk devices

Nitrogen quaternization in the analgesic nefopam [( f )-3,4,5,Btetrahydre9methyl-l-phenyl-lH-2,5,-benzoxaze cine hydrochloride] by either N-trideuteriomethylation or N-oxidation affords reaction product diastereomeric mixtures differing in N-configuration. The axial to equatorial N-CH, product ratios were found to be ca. 3:2 (N-trideuteriomethylation) and approximately equimolar (ca. 48 : 52, N-oxidation). Both diastereomeric N-oxides have boat-(flattened chair) conformations of the octagonal ring in which the phenyl group is exo-oriented. The quaternary ammonium salts showed considerable line broadening in the 'H NMR spectrum owing to rapid conformational equilibration. The same boat-(flattened chair) conformation is clearly the preponderant contributor to the timeaveraged structure of nefopam methiodide in CD,CI, solution, similar to the case for the equatorial N-methyl isomer of the parent hydrochloride salt. Conformational assignments were based on the vicinal coupling constants in the --OCH,CH,N-fragment and on the finding of an NOE intensity enhancement for the benzhydrylic-H on irradiation of the equatorially oriented 4 C H .

Histologic findings of GC infiltration and bone regeneration qualifiers did not correlate with demographics or with exposure to ERT. Most specimens unexpectedly showed good regenerative responses to osteonecrosis despite heavy GC infiltration.

The title complex, dicarbonyl-3κ2 C-(μ3-3,6-dimethyl-3,6-diaza­octane-1,8-dithiol­ato-1:2:3κ7 S:S,N,N′,S′:S,S′)(μ2-3,6-di­methyl-3,6-diaza­octane-1,8-dithiol­ato-1:2κ5 S,N,N′,S′:S)-1,2-diiron(II)-3-nickel(0) [Fe2Ni(C8H18N2S2)2(CO)2], is the second example showing M(μ-SR)2Ni0(CO)2 coordination (M = any metal atom). Both FeII ions are five-coordinated in distorted trigonal–bipyramidal geometries by two N atoms and three S atoms. The Ni atom is four-coordinated in a distorted tetra­hedral geometry by two S atoms and two carbonyl ligands. One of the 3,6-dimethyl-3,6-diaza­octane-1,8-dithiol­ate ligands is disordered, the major component having a refined occupancy of 0.873 (2). The Fe⋯Fe distance is 3.0945 (3)Å and the Ni⋯Fe distance is 2.8505 (3) Å.