OBJECTIVE Sirolimus-eluting stent therapy has achieved considerable success in overcoming coronary artery restenosis. However, there remain a large number of patients presenting with restenosis after the treatment, and the source of its persistence remains unclarified. Although recent evidence supports the contribution of vascular stem/progenitor cells in restenosis formation, their functional ...

OBJECTIVES Avoidance of calcineurin inhibitor-associated nephrotoxicity has recently gained focus. To assess the impact of the conversion to sirolimus, we performed a retrospective audit on renal transplant patients switched to sirolimus at the Inkosi Albert Luthuli Central Hospital (South Africa) from 2003 until June 2007. MATERIALS AND METHODS Medical records of transplant recipients were a...

BACKGROUND Neointimal hyperplasia is the major cause of in-stent restenosis (ISR). The sirolimus-eluting stent (SES) has emerged as a promising therapy to prevent ISR; however, the exact mechanism by which locally delivered sirolimus, an immunosuppressive agent, prevents ISR remains unknown. Recent evidence suggests that circulating progenitor cells may contribute to neointimal formation. MET...

BACKGROUND We investigated the pattern of late luminal loss after sirolimus-eluting or bare stent implantation. METHODS AND RESULTS The study population comprised 238 patients treated with sirolimus-eluting stents and 526 patients treated with conventional stents. The distribution of late loss of sirolimus stents was largely skewed to the right and differed from the distribution for bare sten...

Cyclosporine A (CsA) and tacrolimus have been associated with an increased risk for diabetes after transplantation, whereas sirolimus is deemed to be devoid of any effect on glucose metabolism. This study was performed to investigate the effect of the withdrawal of calcineurin inhibitors and the switch to sirolimus on peripheral insulin resistance and pancreatic beta cell response. Twenty-six p...

OBJECTIVE To investigate whether mammalian target of rapamycin complex 1 (mTORC1) inhibitors could reduce seizure frequency in children with tuberous sclerosis complex (TSC). METHODS Due to slow inclusion rate, target inclusion of 30 children was not reached. Twenty-three children with TSC and intractable epilepsy (age 1.8-10.9 years) were randomly assigned (1:1) to open-label, add-on sirolim...

BACKGROUND We initiated a randomized controlled clinical trial to assess the effect of sirolimus on disease progression in patients affected by autosomal dominant polycystic kidney disease (ADPKD). Here we report the preliminary safety results of the first 6 months of treatment. METHOD A total of 25 patients were randomized to sirolimus 2 mg/day and 25 patients to no treatment except standard...

BACKGROUND Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of neointimal hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up. METHODS AND RESULTS Fifte...

BACKGROUND Fast post-implantation stent endothelialization is desirable for theoretically reducing the possibility of stent thrombosis. OBJECTIVE To evaluate the extent of sirolimus-eluting stent strut endothelialization (delivered from the luminal and abluminal aspects or abluminal aspect only) in the iliac arteries of rabbits. METHODS The iliac arteries of 10 rabbits were implanted with f...

Sirolimus (rapamycin) has a macrolide structure and is under clinical investigation as an immunosuppressant after organ transplantation. An HPLC/mass spectrometry assay to quantify sirolimus in blood was developed. 28-O-Acetyl sirolimus was used as internal standard. Blood samples were extracted with C18 columns. The extracts were injected into an HPLC system and isocratically eluted with metha...