Chronic venous insufficiency is associated with elevated level of circulating microparticles.

BACKGROUND: Chronic venous insufficiency (CVI) results when the veins in the legs no longer pump blood back to the heart effectively. Microparticles (MPs) are small membrane vesicles released by several circulating and vascular cells upon activation or apoptosis. OBJECTIVES: The purpose of this study was to assess the subpopulations of circulating endothelial (EMPs) and platelet microparticles (PMPs) in CVI, and to disclose their contribution in mediating dysfunction of human peripheral venules. PATIENTS AND METHODS: Human peripheral venules were explanted during leg surgery on patients with CVI and on control subjects (C); concurrently, blood samples were collected and circulating MPs isolated. The techniques used were: flow cytometry, fluorescence and electron microscopy, myograph technique and western-blotting technique. RESULTS: The results showed that compared with controls, patients with CVI had: (i) a marked elevation of circulating EMPs and PMPs; (ii) a structural modification of the venous wall consisting of activation of endothelial and smooth muscle cells, an abundance of intermediary filaments and synthesis of hyperplasic-multilayered basal lamina; (iii) a significantly altered reactivity of the venous wall, closely associated with EMPs and PMPs adherence; (iv) altered contractile response to noradrenaline, acetylcholine, 5-hydroxytryptamine and KCl, and an impeded relaxation in response to sodium nitroprusside; and (iv) a substantially increased protein expression of tissue factor (TF) and of P-Selectin both in the venular vascular wall and on the surface of EMPs and PMPs. CONCLUSIONS: The findings indicate that CVI is accompanied by an enhanced release of EMPs and PMPs that contribute to altered dysfunctional response of the venous wall.

The priming effect of human interferon-alpha is mediated by protein kinase C.

Human embryo fibroblasts (HEF) were primed when treated with a synthetic diacylglycerol, OAG, or the phorbol esters TPA or DBP. These primed HEF produce more interferon-beta (IFN-beta) in response to poly(rI).poly(rC), or poly(rA).poly(rU), added 1 h or 18 h later. These priming agents are activators of protein kinase C (PKC). A PKC inhibitor, H-7, blocked their priming effects and also those of human IFN-alpha. Two phorbol esters, 4PDD and 4P, that did not activate PKC did not prime HEF cells. Pretreatment of HEF cells for 1 h or 18 h with TPA or DBP reduced their susceptibility to infection with vesicular stomatitis virus (VSV); this effect was blocked by treatment with H-7. In contrast, the antiviral effects of IFN-alpha were not blocked by H-7, or by previous down-regulation of PKC by prolonged treatment of HEF cells with TPA. These results show that in HEF cells treated with IFN-alpha PKC plays a role in the processes that prime for IFN production, but not in those which establish the antiviral state.

[The antiproliferative effects associated with vincristine and human interferons in experimental in vitro systems]. / Effets antiprolifératifs associés du vincristine et des interférons humains dans des systèmes expérimentaux in vitro.

Cytotoxic potential of suboptimal doses of vincristine associated with human interferon was studied in two cell lines of tumoral origin, as compared to the action of or gamma type interferon preparations. Results show that the vincristine cytotoxic effect may be synergistically augmented in both culture types by simultaneous interferon administration.

[Gamma interferon induced in human leukocytes by phytohemagglutinin: its production and biological characteristics]. / Inteféron gamma induit dans des leucocytes humains par la phytohémagglutinine: production et carcatéristiques biologiques.

Human gamma type interferon (IFN) preparations were obtained through phytohemagglutinin stimulation of leukocytes from the peripheral blood. Biological value of these preparations varied between 160 u and 800 u/ml, depending on leukocyte incubation medium, culture system and inductor conservation. The rising of the antiviral activity through association between gamma (3 u) and alpha (27 u) interferons was revealed by the virus quantity reduction (in this case the vesicular stomatitis virus was used) during a 24-hour multiplication cycle. The protection ensured by the mixture of the two types of interferon was about ten times higher than the additive effect of the two preparations. Study of the antiproliferative activity of a gamma interferon preparation was conducted on two human cell lines of tumoral origin (T-10 from a glioblastoma, and HEp-2) and revealed the difficulties to quantify precisely this property of the crude gamma interferon preparations.

[Gamma (or immune) interferon]. / L'interféron gamma (ou immun).

Research on interferon progressed very much during the last years, especially studies on the gamma type of interferon. Historical data about the research conducted on the gamma interferon, its inductors, its physical, chemical and biological properties, the methods of preparation and purification, as well as the perspective of therapeutical utilisation of this type of interferon, in spite of some reversible side effects, are presented and discussed.

[Anti-proliferative and antiviral effects of human alpha-interferon on tumor cells]. / Effets antiprolifératif et antiviral de l'interféron humain du type alpha sur des cellules tumorales.

Antiproliferative and antiviral activities of a type alpha human leukocytic interferon on several heteroploidic cell lines: HeLa, HEp-2, and T-10, a cell line of malignant origin (glioblastoma) were investigated, as compared to subcultures of human embryo fibroblasts. The tumor cell multiplication rate decreased proportionally to the amount of interferon in the culture medium. The highest interferon concentration used in our experiments (1,000 mu/ml) induced a decrease of the normal cell multiplication rate (human embryo fibroblasts). The same amount of interferon had a cytotoxic effect against the T-10 cells, but this phenomenon is reversible if the interferon is excluded after 24 h from the culture medium. There was no quantitative relation between the magnitude of the antiviral and of the cytotoxic effects of the type alpha human interferon on the tested cellular substrates.