Comparison with the structure of cyclosporin A shows distinct stereochemical differences between the two molecules. It is suggested that didemnin B and cyclosporin A are unlikely to have a common receptor binding site.

The present study shows that acute aspirin-induced damage to the gastric mucosa can be reduced by chemically associating ASA with PC. The mechanism of mucosal protection provided by this compound is not related to any alteration in the ability of ASA to inhibit mucosal COX activity. We believe this protection is attributable to the maintenance of the defensive hydrophobic barrier of the gastric mucosa.

Background: Treatment and prevention of non‐steroidal anti‐inflammatory drug‐induced gastropathy involve the concurrent use of antisecretory drugs. Recently, we have shown that the ability of these drugs to increase the intragastric pH to values pKa of NSAIDs compromises their therapeutic activity. In the present study, we evaluated the potential of omeprazole to interfere with the bioavailability of aspirin administered to rats either alone or complexed with the zwitterionic phospholipid, dipalmitoylphosphatidylcholine (DPPC). Methods: Aspirin or aspirin/DPPC was administered intragastrically to rats pre‐dosed with either saline or omeprazole. Concentrations of aspirin and salicylic acid in the blood and the gastric mucosa were assessed by HPLC and the 6‐keto‐PGF1α gastric mucosal concentration by radioimmunoassay. Results: Gastric absorption of aspirin and its relative bioavailability were reduced by an antisecretory dose of omeprazole; its inhibitory effect on gastric prostaglandin synthesis was consequently attenuated. However, these effects could be partly overcome if aspirin was administered as a complex with DPPC. Conclusions: These observations suggest that: (i) DPPC increases the lipid solubility and gastric permeability of NSAIDs; and (ii) neutralization of the gastric pH results in a shift of aspirin absorption toward the intestine where it could be degraded to salicylic acid.

We determined the expression of isoforms of prostaglandin H synthase (PGHS) and thromboxane A synthase (TXAS) in a human megakaryocyte cell line (MEG-01. The basal levels of full-length TXAS mRNA and the 60 kDa TXAS protein were high when compared to those of PGHS-1 and PGHS-2 in uninduced cells. Despite a high TXAS level, uninduced MEG-01 cells synthesized only a small amount of thromboxane A2 (TXA2) due to limited PGHS-1 or PGHS-2 expressions. Following PMA induction there was little change in TXAS. PGHS-2 mRNA was significantly increased at only 3 h of PMA treatment and the level declined rapidly, whereas PGHS-1 mRNA and protein levels were concordantly stimulated. Induction of PGHS-1 reached plateau on day 3 of PMA treatment. Analysis of arachidonate metabolism in cells induced by PMA for 3 and 5 days showed a high level of PGH2 synthesis which exceeded the TXAS capacity for TXA2 synthesis. Only traces of PGHS-2 mRNA and alternate-spliced TXAS mRNA were detected in human platelets. We conclude that TXAS and PGHS are differentially expressed in MEG-01 during PMA-induced differentiation.

A new method is described for the synthesis of soluble poly(1-methoxy-4-(2-ethylhexyloxy)-p-phenylenevinylene) (MEH−PPV) using N,N-dimethylformamide (DMF) as the solvent. Based on a modification of the traditional Gilch method, the polymerization of α,α‘-dibromo-2-methoxy-5-(2-ethylhexyloxy)xylene was conducted in DMF under a variety of experimental conditions. The resultant MEH−PPVs were characterized and compared to those prepared using analogous syntheses in tetrahydrofuran (THF). Characterization techniques included 1H NMR spectroscopy, UV−vis spectroscopy, and gel permeation chromatography (GPC). Although the molecular weights of the polymers prepared in DMF were routinely lower than those prepared in THF, the polydispersities were as low as (and in most cases lower than) those obtained using THF. Significantly, the use of DMF in polymerizations conducted at 100 °C led to no gelation of the polymer, which circumvented the need for any controlled addition of monomer during the reaction. Moreover, control over the polymer molecular weights in DMF could be achieved using chosen aliquots of the molecular weight modifier 4-(tert-butyl)benzyl bromide and/or by controlling the concentration of the reactants.