The Complex Solid-State Landscape of Sodium Diatrizoate Hydrates.

Pharmaceutical sodium salts are prone to incorporate water into their crystal structures. The model compound diatrizoic acid monosodium salt, an X-ray contrast agent, has been investigated in depth towards its interaction with water in the solid state. Five hydrates with water content ranging from 0.3 to 8 molar equivalents of water show a high degree of interconvertibility, stoichiometric and non-stoichiometric behaviour, and potential of amorphisation during release of water. A DMSO/water mixed solvate further highlights the high attraction of this salt to incorporate water. All incorporated solvent coordinates to the sodium cation and can further interact and stabilise the respective crystal forms by hydrogen bonding. DTS thus highlights the importance of an in-depth investigation of sodium salts used pharmaceutically to guarantee dose uniformity and stability of final formulation.

New fluorescent bile acids: synthesis, chemical characterization, and disastereoselective uptake by Caco-2 cells of 3-deoxy 3-NBD-amino deoxycholic and ursodeoxycholic acid.

Deoxycholic acid (DCA), a secondary bile acid (BA), and ursodeoxycholic acid (UDCA), a tertiary BA, cause opposing effects in vivo and in cell suspensions. Fluorescent analogues of DCA and UDCA could help investigate important questions about their cellular interactions and distribution. We have prepared a set of isomeric 3α- and 3ß-amino analogues of UDCA and DCA and derivatised these with the discrete fluorophore, 4-nitrobenzo-2-oxa-1,3-diazol (NBD), forming the corresponding four fluorescent adducts. These absorb in the range 465-470 nm and fluoresce at approx. 535 nm. In order to determine the ability of the new fluorescent bile acids to mimic the parents, their uptake was studied using monolayers of Caco-2 cells, which are known to express multiple proteins of the organic anion-transporting peptide (OATP) subfamily of transporters. Cellular uptake was monitored over time at 4 and 37°C to distinguish between passive and active transport. All four BA analogues were taken up but in a strikingly stereo- and structure-specific manner, suggesting highly discriminatory interactions with transporter protein(s). The α-analogues of DCA and to a lesser extent UDCA were actively transported, whereas the ß-analogues were not. The active transport process was saturable, with Michaelis-Menten constants for 3α-NBD DCA (5) being K(m)=42.27±12.98 µM and V(max)=2.8 ± 0.4 nmol/(mg protein*min) and for 3α-NBD UDCA (3) K(m)=28.20 ± 7.45 µM and V(max)=1.8 ± 0.2 nmol/(mg protein*min). These fluorescent bile acids are promising agents for investigating questions of bile acid biology and for detection of bile acids and related organic anion transport processes.

Intake of repeatedly heated palm oil causes elevation in blood pressure with impaired vasorelaxation in rats.

Oxidization of dietary cooking oil increases the risk of cardiovascular diseases such as hypertension by increasing the formation oxidative oxygen radicals. The aim of study was to investigate the effects of repeatedly heated palm oil on blood pressure, plasma nitrites, and vascular reactivity. Nitrites were measured, as an indirect marker for nitric oxide production. Male Sprague-Dawley rats were divided into four groups: control group fed with basal diet and other three groups fortified with 15% weight/weight fresh palm oil (FPO), palm oil heated five times (5HPO) or palm oil heated ten times (10HPO) for 24 weeks. The oil was heated to 180 degrees C for 10 min. Blood pressure was measured at baseline and at intervals of four weeks for 24 weeks using non-invasive tail-cuff method. Following 24 weeks, the rats were sacrificed and thoracic aortas were dissected for measurement of vascular reactivity. Blood pressure was elevated significantly (p < 0.05) in 5HPO and 10HPO groups, with the 10HPO group showing higher values. Aortic rings from animals fed with heated oil showed diminished relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Acetylcholine and sodium nitroprusside cause endothelium-dependent and endothelium-independent relaxation, respectively. Relaxation responses remained unaltered in the FPO group, with the attenuated contractile response to phenylephrine, compared to control group. FPO increased plasma nitrites by 28%, whereas 5HPO and 10HPO reduced them by 25% and 33%, respectively. Intake of repeatedly heated palm oil causes an increase in blood pressure, which may be accounted for by the attenuated endothelium-dependent vasorelaxant response.