Recombinant activated factor VII decreases bleeding without increasing arterial thrombosis in rabbits

PURPOSE: To compare the effects of recombinant activated factor VII (rFVIIa) and platelet-rich plasma (PRP) in an experimental model of bleeding and arterial thrombosis. METHODS: The Folts model was used in 60 rabbits. After anesthesia, the carotid artery was exposed and a 75% stenosis was induced. A compression injury of the artery triggered a series of cyclic flow reductions (CFRs). After counting baseline CFRs, animals were assigned randomly to one of four groups (n = 15 in each): control, PRP, rFVIIa and placebo. Control animals received 10 mL.kg(-1) of saline while 10 mL.kg(-1) of a hydroxyethyl starch solution (200,000/6%/0.5) were infused in the three other groups. CFRs were measured again, followed by treatment with PRP, rFVIIa or placebo and by a final measurement of CFRs. At the end of each observation period, an ear immersion bleeding time (BT) was measured and a blood sample was drawn for the evaluation of hematological variables. Microvascular bleeding was evaluated at the end of the experiment in grams of blood shed from liver and spleen sections. Results are presented as median (range). RESULTS: rFVIIa shortened the BT and decreased microvascular bleeding as compared with placebo [60 (35-100) sec vs 110 (50-140) sec, P = 0.0019 and 9 (4-24) g vs 17 (5-28) g, P = 0.002, respectively]. rFVIIa did not increase CFRs [3(0-9) vs |(0-5), P = 0.11]. CONCLUSION: rFVIIa led to a decrease in BT and microvascular bleeding but did not significantly affect arterial thrombosis in rabbits.     

Estrogen receptor alpha as a key target of organochlorines to promote angiogenesis

Epidemiological studies report that exposure to pesticides like chlordecone and lindane increases risk of cancer. They may act as endocrine disruptors via the activation of estrogen receptor α (ERα). Carcinogenesis involved angiogenesis and no available data regarding these organochlorines have been reported. The present study aimed at investigating the effects of lindane and chlordecone on cellular processes leading to angiogenesis through an involvement of ERα. Angiogenesis has been analyzed both in vitro, on human endothelial cells, and in vivo by quantifying neovascularization with the use of ECMgel^? plug in mice. Both pesticides increased endothelial cell proliferation, migration and MMP2 activity. These toxics potentiated cell adhesion by enhancing FAK phosphorylation and stress fibers. The two organochlorines increased nitric oxide production via an enhancement of eNOS activity without modification of oxidative stress. Evidence has been provided that the two toxins increased in vivo neovascularization. Most interestingly, all the above processes were either partially or completely prevented after silencing of ERα. Altogether, these data highlight that organochlorines modulate cellular angiogenic processes through activation of ERα. This study further reinforces the harmful effects of these pesticides in carcinogenesis, particularly in the modulation of angiogenesis, a critical step in tumor promotion, through ERα.