Circulating endothelial progenitor cells are inversely correlated with in-stent restenosis in patients with non-ST-segment elevation acute coronary syndromes treated with EPC-capture stents (JACK-EPC trial).

AIM: Aim of the study was to evaluate the association between circulating endothelial progenitor cells (EPCs) and angiographic outcomes after implantation of GenousTM stent in patients with non-ST-segment elevation acute coronary syndromes (ACS) (NSTE-ACS) undergoing urgent percutaneous coronary intervention (PCI). METHODS: Sixty patients treated with EPC-capture stent (N.=30) or bare metal stents (BMS) (N.=30) receiving 80 mg atorvastatin and dual antiplatelet therapy (DAT) for 12 months. Restenosis was assessed after 6 months by quantitative coronary angiography (QCA) and major acute coronary events (MACE) evaluated after 6 and 12 months. INCLUSION CRITERIA: de novo lesion >70% in native vessel, diameter 2.5-4 mm, lesion length <30 mm. EXCLUSION CRITERIA: diabetes, previous revascularization, significant left main stenosis, chronic total occlusions (CTO) and multivessel disease. RESULTS: Majority of patients in EPC-capture stent and BMS groups presented with NSTEMI (73.3% and 70%, respectively). Mean stent length was 20.1±8 and 19.9±10 mm, diameter 3±0.97 and 3.1±0.88 mm in respective groups. The binary restenosis was significantly lower in GenousTM (13 vs. 26.6%, P=0.04). Risk of MACE after 6 and 12 months were comparable in both groups. There was no stent thrombosis. Numbers of circulating EPCs were significantly approximately 2-fold higher during the ACS than after 6 months. Mobilization of EPCs during acute ischemia was significantly lower in patients who developed restenosis after 6 months (3 vs. 4.5 cells/µL, P=0.002) and it was negatively correlated with late-loss after 6 months (R=-0.42; P<0.03). CONCLUSION: Use of GenousTM stents in NSTE-ACS is associated with lower restenosis rate than BMS at 6 months. There was no ST through 1 year. The number of circulating EPCs is inversely correlated with in-stent late loss (LL).

Binding of 3H-metronidazole in olfactory, respiratory and alimentary epithelia in rats.

Whole-body autoradiography of 3H-metronidazole in rats showed retention of bound metabolites in the epithelia lining the olfactory part of the nose, the tongue, the gingiva, the palate, the pharynx, the oesophagus and the forestomach. In vitro microautoradiography in O2- and N2-atmosphere with some of these tissues indicated reductive formation of bound metabolites in specific cells of the epithelia. Studies with subcellular fractions of the nasal olfactory mucosa showed formation of DNA- and protein-bound metronidazole metabolites. A lower bioactivating capacity was found in experiments with the liver. The bioactivation was dependent on N2-atmosphere, and presence of the P450-inhibitor metyrapone or GSH in the incubation media depressed the protein-binding of metronidazole both in the nasal olfactory mucosa and the liver. These data indicate that the bioactivation is partly P450-dependent and GSH may play an important role in scavaging the bioactivated drug. The epithelial cells with a capacity to bioactivate metronidazole may be potential targets for negative effects of the drug. Whole-body autoradiography also showed a strong binding of radioactivity in the contents of caecum and colon. This can be considered to be due to reductive bioactivation of metronidazole by the intestinal microorganisms and reflects the principal site of action of the drug.