Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) inhibits in vivo platelet aggregation induced in mice by intravenous injection of cells derived from an experimental tumor, the Lewis lung carcinoma. Such a protective effect of ditazole could not be observed when the number of circulating platelets dropped slowly following intramuscular implantation and spontaneous dissemination of the same cancer cells. These results support previous observations suggesting a different mechanism for the thrombocytopenia observed after intravenous and intramuscular injection of cancer cells. Tail transection bleeding time of normal mice is significantly prolonged by ditazole, a finding at variance with that reported in rats.

Animals↗

PubMedDate not supplied

DMSO-induced changes in the procoagulant and fibrinolytic activity of B16 melanoma cells: influence on lung colony formation.

In this study DMSO (dimethylsulphoxide) was used as a tool to test the significance of in vitro modifications of procoagulant and fibrinolytic activity of tumor cells for their in vivo metastatic ability. B16 melanoma cells were chosen as the experimental model. After four days' treatment DMSO increased both the procoagulant and fibrinolytic (plasminogen activator) activity of B16 melanoma cells in a dose-related manner. DMSO treated cells showed significantly greater lung colonizing ability than untreated cells. Our results indicate that DMSO treatment in vitro can modulate procoagulant and fibrinolytic activity and the metastatic ability of B16 melanoma cells; however a direct causal relationship between these in vitro and in vivo effects remains to be established.

Animals↗

PubMedDate not supplied

The effect of synthetic malaria pigment (beta-haematin) on adhesion molecule expression and interleukin-6 production by human endothelial cells.

The effects of synthetic malaria pigment (beta-haematin, BH) on the expression of the intercellular adhesion molecule 1 (ICAM-1) and platelet endothelial cell adhesion molecule 1 (PECAM-1) and the production of interleukin-6 (IL-6) by human microvascular endothelial cells were measured using flow cytometry analysis and immunoenzymatic assay. BH alone did not affect basal levels of ICAM-1, PECAM-1 or IL-6. When added to cell cultures before or with, but not after, lipopolysaccharide or tumour necrosis factor alpha, BH at 1-100 micrograms/mL induced a dose-dependent inhibition of ICAM-1 and PECAM-1 expression and IL-6 production. Cell viability and human leucocyte antigen A,B,C expression remained unaffected. Similar, though more variable, results were obtained using human umbilical vein endothelial cells. These results suggested that accumulation of pigment within endothelial cells following repeated malaria infection reduces local inflammation and parasite sequestration through inhibition of either cytokine production or parasitized erythrocyte receptors on endothelial cells.

Animals↗

PubMedDate not supplied

Oxidized LDLs influence thrombotic response and cyclooxygenase 2.

Oxidative modification of low-density lipoproteins (LDLs) plays a key role in the development of atherosclerosis and the onset of coronary artery disease. LDL oxidation alters the antithrombotic balance of human endothelial cells inducing surface tissue factor (TF) pathway activity, which results in enhanced fibrin deposition. Fibrinolysis, which is strictly regulated by plasminogen activator inhibitor-1 (PAL-1) and tissue-type plasminogen activator (tPA). Is also dysregulated by LDL oxidation with a net increase in the inhibitory rate. Oxidized LDLs (oxLDLs) also affect many aspects of macrophage function linked to the inflammatory response of these cells, In particular, oxLDLs downregulate inducible cyclooxigenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide. This observation may support the hypothesis that, within atheromata, the transformation macrophages into foam cells results in the attenuation of the inflammatory response, thus contributing to the progression of athrogenesis. Among lipid constituents of oxLDLs, Ox-PAPC, a mixture of oxidized arachidonic acid-containing phospholipids, prevents Cox-2 expression, suggesting that it could be considered responsible for the biological activity of oxLDLs.

Arteriosclerosis↗