No abstract

Ricinoleic acid, oleic acid, dioctyl sodium sulphosuccinate, deoxycholic acid, sennoside A + B and mannitol reduced or reversed water flux from lumen to blood in rat colon in situ. Stearinic acid was without any effect. Ricinoleic acid, oleic acid, dioctyl sodium sulphosuccinate, deoxycholic acid and sennoside A + B stimulated release of PGE‐like material into the colonic lumen whereas the osmotic laxative mannitol and stearinic acid did not. Inhibition of PGE biosynthesis by pretreatment of the rats with indomethacin significantly reduced (but did not abolish) the effect of ricinoleic, oleic and deoxycholic acids on net water flux and PGE release. Indomethacin reduced the effect of dioctyl sodium sulphosuccinate and of sennoside A + B on PGE release but not their effect on the net water flux. The effect of mannitol was not influenced by indomethacin. The amount of PGE release in experiments with ricinoleic acid, oleic acid, stearinic acid and dioctyl sodium sulphosuccinate (with and without indomethacin) showed a good correlation (r = 0·99) with the change in net water flux. Deoxycholic acid, sennoside A + B and mannitol did not show this correlation. It is assumed that the action of non‐osmotic laxatives is partially mediated by PGE, although other mechanisms also seem to be involved in their mode of action.

1 We investigated the contracting actions of the isoprostanes (isoPs), 8-iso-prostaglandin (PG) F 2a and 8-iso-PGE 2 , in comparison to the eects of the thromboxane (TX) A 2 -mimetic U 46619 and the traditional prostaglandin PGE 2 in the isolated rat aorta, isolated rat gastric fundus and the isolated guinea-pig ileum. 2 U 46619 and 8-iso-PGF 2a caused contractions in the rat aorta and rat gastric fundus in a concentration-dependent manner, whereas these agonists showed no eects in the guinea-pig ileum. However, 8-iso-PGE 2 and PGE 2 caused contractions in all isolated organs used. 3 The prostanoid TP-receptor antagonist SQ 29,548 (10 nM) signi®cantly antagonized vasoconstrictions induced by the agonists used in the rat aorta. SQ 29,548 at a ®nal concentration of 3 mM, but not at lower concentrations, signi®cantly inhibited contractions induced by U 46619, 8-iso-PGF 2a and 8-iso-PGE 2 in the rat fundus. Responses to PGE 2 were unchanged. The prostanoid EP 1 -receptor antagonist SC 51089 (3 mM) signi®cantly inhibited contractions induced by 8-iso-PGE 2 and PGE 2 in the rat fundus and in the guinea-pig ileum. SC 51089 had no eect on responses to any of the agonists tested. 4 Our results show that 8-iso-PGE 2 , in contrast to 8-iso-PGF 2a , can also cause contractions by activation of the EP 1 -receptors in the rat gastric fundus and the guinea-pig ileum. The ®ndings of the present study do not support the existence of a unique isoP-receptor in the tissues used.

Hydroxymethylfurfural (HMF), a well-known heterocyclic Maillard reaction product, has often been studied for its potential toxic, mutagenic, and carcinogenic effects. Recent clinical studies, however, have strongly suggested that HMF might have exciting antitumor potential. We report on the development and validation of a bioanalytical assay for HMF that could be suitable as a basis for pharmacokinetic models in cancer patients. Two strategies were tested, i.e., direct and indirect methodologies. A direct isocratic LC determination at 283 nm was designed. Two indirect attempts involved derivatization coupled to HPLC-UV. It was possible to resolve the stereoisomers of the HMF derivative, and factors influencing their equilibrium ratio are discussed. HMF was extracted from the biomatrix by solid-phase extraction using different cartridges. A comparative study was made of the implemented methods as well as the extraction protocols. Both indirect assays proved to be more sensitive and were used to assess HMF quantitatively in human plasma. However, the newly introduced derivatization conditions led to the highest sensitivity with a LOD (S/N ratio = 3) of at least 2 pmol analyte on column. The assay selectivity was satisfactory in pre- and post-dose real samples. The mean recoveries of the assays were 79% and 89%, with acceptable accuracies and reproducibilities. Figure Schematic representation of hydroxymethylfurfural (HMF) in human plasma.

This study demonstrates that increased post-operative release of fNA and fA as well as of cNA and cA correlates with high post-operative serum levels of troponins in cardiac risk patients undergoing non-cardiac surgery.