Intimal hyperplasia (IH) is a vessel wall remodeling process responsible of early failure after vascular surgery or endovascular interventions. An ex vivo perfusion was used to study human venous segments regarding functional, histomorphological, immunohistochemical and molecular alterations after 7 (group 1, n = 6) and 14 days (group 2, n = 6) of ex vivo perfusion. All vessel segments showed preserved smooth muscle function before and after perfusion. Histomorphometry revealed IH development which was more pronounced after 14 days rather than 7 days (p < 0.05). Expression of CD34, factor VIII, alpha-actin and MIB-1 was demonstrated in all segments from both groups indicating that muscular and endothelial integrity was preserved after ex vivo perfusion of up to 14 days. PAI-1 mRNA expression was significantly increased after perfusion (p < 0.05), suggesting that the endothelial fibrinolytic function may be modulated in this ex vivo perfusion model of human saphenous veins.

Actins↗

PubMedDate not supplied

MDR hamster cells exhibiting multiple altered gene expression: effects of dexniguldipine-HCl (B859-35), cyclosporin A and buthionine sulfoximine.

An actinomycin D selected, multidrug-resistant (MDR) hamster CHO subline showed strong expression of the P-glycoprotein and sorcin genes together with several other alterations such as a: (i) reduced growth rate, (ii) lowered topoisomerase II, (iii) lowered glutathione-S-transferase-P gene expression, and (iv) the emergence of a 15.5 kDa protein. Besides high resistances to adriamycin, actinomycin D, and vincristine, we observed a lowered sensitivity towards bleomycin, a rather hydrophilic drug usually not involved in P-glycoprotein associated MDR. Moreover, the MDR subline showed a pronounced collateral (enhanced) sensitivity towards the sterically pure dihydropyridine anticancer drug dexniguldipine-HCl (B859-35) preventing its characterization for MDR modulation here. At a non-cytotoxic dose (10 microM) the immunosuppressive cyclic peptide cyclosporin A completely abolished the resistance to vincristine, partially reversed the resistance to teniposide and strongly enhanced the sensitivity towards bleomycin, while not influencing the drug sensitivities of the parental cell line. Buthionine sulfoximine (BSO), an agent depleting cellular glutathione levels, distinctly increased the sensitivity towards teniposide at nontoxic doses (50 microM) exclusively in the MDR subline, while it did not alter vincristine or bleomycin cytotoxicity.

Adenine Phosphoribosyltransferase↗