Proliferative Activity and Cholesterol Ester Metabolism in Primary Culture of Human Pterygium Fibroblasts

Purpose: There is now increasing evidence that pterygium is a tumor-like tissue, and that cell growth, as well as DNA replication, is closely linked to cholesterol ester metabolism. Therefore, in the present study, primary cultures of human pterygium fibroblasts in vitro were utilized to investigate a possible correlation between cell growth and cholesterol ester metabolism in pterygial formation. Methods: Primary cultures of pterygium and normal conjunctiva fibroblasts were obtained from patients classified above grade 3 using micro-dissection surgery and from healthy donors, respectively. Expression of p53 and Ki-67 oncogenes was evaluated by immunostaining techniques. Growth kinetic studies were evaluated by growth curve, and 3H-thymidine incorporation. Cholesterol esterification was evaluated by 14C- oleate incorporated into cholesterol esters. Results: Pterygium fibroblasts revealed an increased expression of P53 and Ki-67 compared to normal cells. In addition they grow at faster rate than normal cells. In pterygium fibroblasts, cholesterol esterification increased as cells progressed from resting to proliferating phase. These results provide evidence that cholesterol esterification “per se” may be a limiting factor in determining pterygium cell cycle progression. These conclusions are consistent with the fact that, when fibroblasts are treated with potent inhibitors of cell growth such as pioglitazone and everolimus, the reduction of DNA synthesis caused by the drugs is accompanied by an extensive decrease of cholesterol esterification. Conclusions: This study indicates that pterygium has an altered metabolism of cholesterol esters, and thus that cholesterol esterification could be a potential pharmacological target for prevention and treatment of pterygium

Use of Marginal Donors for Liver Transplantation: A Single-Center Experience Within the Eurotransplant Patient-Driven Allocation System

Background: Due to the organ shortage, marginal donors are increasingly used in liver transplantation (OLT). These grafts may be safely used in less critical recipients but, the real influence of extended donor criteria (EDC) remains uncertain when graft-recipient matching is not applied. Our study analyzed the impact of EDC on initial graft function within the Eurotransplant patient-driven allocation system. Patients and methods: We reviewed 70 OLT performed between 2004 and 2006. The impact of the following EDC were analyzed: age > 60; intensive care unit (ICU) stay > 4 days; peak serum Na+ > 160 mEq/L; body mass index (BMI) > 30; cardiac arrest with cardiopulmonary resuscitation, and high doses of vasopressors. Early graft function, as defined according to peak transaminase level and spontaneous prothrombin time within the first 5 posttransplant days, was compared between the donors with none or one criterion (group A = 39) and those with >1 criterion (group B = 31). Results: The most frequent EDC were high vasopressor use, ICU stay > 4 days and BMI > 30, were present in respectively 44%, 27%, and 16% of the donors. No EDC were present in 13 donors, one in 26, three in eight, and four in three. Demographics and origin and severity of the liver disease were similar in both groups. We failed to observe significant differences in initial graft function. Conclusion: The presence of EDC did not significantly affect early graft function in a population where donor and recipient were not matched. While this observation must be confirmed in a multicenter analysis, it tends to support the use of marginal liver grafts, even in patient-driven allocation systems. © 2007 Elsevier Inc. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe