Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapamycin (RAPA) is a strong immunosuppressant with a chemical structure similar to that of FK506, although it acts by a mechanism different from both FK506 and cyclosporin A. The effect of RAPA on T cell development in mice was investigated in this study. RAPA caused significant thymic atrophy. The major histological change in the RAPA-treated thymus was thinning of the cortex. No other apparent damage in the cortex or medulla was observed. Consistent with these histological findings, in vivo thymocyte cycling was blocked by RAPA before the S phase, and the ex vivo and in vitro proliferation of the thymocytes was also strongly repressed by the drug. According to electron microscopy and DNA fragmentation assays, RAPA did not induce apoptosis. These results indicate that the repressed thymocyte proliferation is a major mechanism causing RAPA-induced thymic atrophy. Further, RAPA had no effect on thymocyte apoptosis induced by anti-CD3 or ionomycin, and the drug did not interfere with deletion of CD4+8+ thymocytes or peripheral V beta 6+ T cells induced by anti-CD3 or Mls-1a, respectively. These data suggest that RAPA does not hamper the negative selection. There was a relative increase in the CD3- fraction of the de novo developing CD4 and CD8 double-positive (DP) thymocytes in the RAPA-treated mice. Moreover, there were relative increases of the CD3-fractions of the CD4 or CD8 single-positive (SP) cells in both the thymi and periphery. The generation of the CD3-SP under the influence of RAPA could be used as a useful model for further study of the function and signal transduction of these CD3-defective SP cells.
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PMID:The effect of rapamycin on T cell development in mice. 812 38

Percutaneous transluminal coronary angioplasty (PTCA) has become the main method of coronary revascularization. However, despite technical advancement, restenosis with incidence rate of 30 to 50% remains a major limitation to the long-term success of PTCA. The introduction of stents has significantly improved capability of interventional cardiology in treatment and prevention of restenosis. Recent experimental studies in animals, clinical studies in humans and multi-center randomized clinical trials with Sirolimus-eluting stents, have demonstrated a significant reduction in vasculoproliferative response with no intimal tissue growth. Moreover, no significant adverse clinical events have been reported at long-term follow-up and first studies that explored the potential of this technology for the treatment of in-stent restenosis demonstrated safety and efficacy. Although the first clinical experiences with drug-eluting stents have produced stunning results, there are a number of theoretical limitations to these devices, including: 1) limitations of drug loading capacity and 2) ability to control drug elution that could result in unfavorable pharmacokinetics. There are also questions about the durability of the polymer coatings (deformation under mechanical stress, gaps between metal and arterial wall, etc). The thickness of some coatings makes them unsuitable for very small vessels. Finally most biodegradable coatings are prone to chronic inflammation. Since only a polymer-coated bare metal stent remains following the drug's release, the potential for long term polymer biocompatibility problems remains a concern. The potential for some drugs to produce radiation-like effects such as "black holes", malapposed and naked struts and wall thinning are potentially the dark side of this technology and may contribute to late thrombosis, aneurysms or delayed restenosis. Long term clinical follow-up is necessary to assess the long term safety of this technology. There is a legitimate question as to whether drug-eluting stents will produce similar results across all patient subsets encountered in "real-life" interventional practice (e.g. long lesions, small diameter vessels, vein grafts, chronic total occlusions, bifurcated and ostial lesions). Cost-benefit issues also need to be addressed, especially because multivessel stenting and multistent usage is likely to increase.
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PMID:Update on sirolimus drug-eluting stents. 1496 95