RESUMO
OBJECTIVE: Drug eluting stents have recently been associated with the increased risk of adverse thrombogenic events and/or late luminal loss, which is highly associated with incomplete re-endothelialization. The increased risks behoove the design of alternative delivery modalities and/or drugs that do not compromise the re-endotheliaization process. The objective of the present study is to elucidate the biological mechanism(s) by which non-stent-based delivery modalities for the anti-proliferative lipid metabolite, C(6)-ceramide, could lead to a reduction in arterial injury after angioplasty. RESULTS: Immunohistochemical studies in rabbit and porcine models suggest that C(6)-ceramide-coated balloon catheters limit arterial stenosis without inhibiting endothelial wound healing responses. Specifically, C(6)-ceramide-coated balloon catheters reduce internal elastica injury with a corresponding reduction in medial fracture length in a 28-day porcine coronary artery stretch model. In addition, C(6)-ceramide decreases the formation of the fibrin matrix to possibly augment the subsequent wound healing response. We hypothesized that differential metabolism of exogenous ceramide by coronary endothelial and smooth muscle cells could explain the apparent discrepancy between the anti-proliferative actions of ceramide and the pro-wound healing responses of ceramide. Human coronary artery endothelial cells (HCAEC), in contrast to human coronary artery smooth muscle cells (HCASMC), preferentially express ceramide kinase and form ceramide-1-phosphate, which promotes endothelial cell survival. CONCLUSION: Differential metabolism of ceramide between HCASMC and HCAEC offers a mechanism by which ceramide preferentially limits smooth muscle cell growth, in the presence of active wound healing. The combinatorial ability of ceramide to limit vascular smooth muscle proliferation and promote re-endothelialization, offers the potential for C(6)-ceramide-coated catheters to serve as adjuncts to stent-based modalities or as a stand-alone treatment.
Assuntos
Humanos , Lactente , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Abdome Agudo/etiologiaAssuntos
Humanos , Lactente , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Abdome Agudo/etiologiaRESUMO
From September 1977, 11 general practitioners took part in a survey of 12 months' duration in which they recorded morbidity at every doctor-patient encounter. 35,143 patients made 53,094 encounters and a total of 62,932 problems were identified. The most common reason for going to the doctor was for examination with no disease detected. Acute upper respiratory tract infections, hypertension and pregnancy were the 3 most common specific problems with which the doctors dealt. The results demonstrated some features of general practice such as the abundance of the common diseases, the need to be alert to the infrequent occurrence of wide range major disease, pre-symptomatic screening of the healthy "at risk" patient and the problems of the ill-defined conditions. Comparisons with other surveys show some similarities in general practice morbidity, but also important differences that can be related to prevailing local conditions (AU)