Improvement of vascular endothelial function using the oral endothelin receptor antagonist Bosentan in patients with systemic sclerosis

Objective. Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients. Methods. A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel. Results. FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 13% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged. Conclusion. Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted

Red Wine Acutely Induces Favorable Effects on Wave Reflections and Central Pressures in Coronary Artery Disease Patients

Forest overstory composition influences both light and nutrient availability in the mixed boreal forest. The influence of stand composition on understory cover and biomass was investigated on two soil types (clay and till deposits). Four forest composition types were considered in this study: aspen (Populus tremuloides Michx.), paper birch (Betula papyrifera Marsh.), jack pine (Pinus banksiana Lamb.) and a mixture of balsam-fir (Abies balsamea (L.) Mill.) and white spruce (Picea glauca (Moench) Voss). The cover of all understory species was recorded while the biomass of two important and ubiquitous species was measured: mountain maple (Acer spicatum Lam.) of the shrub layer and large-leaved aster (Aster macrophyllus L.) of the herb layer. Soil analyses were conducted to evaluate the influence of overstory composition on understory biomass through its influences on soil characteristics. Analyses of variance showed a significant effect of forest canopy type on mountain maple biomass, understory cover and shrub cover but not on herb cover and large-leaved aster biomass. Path analysis was performed to explore the relationships between canopy type, nutrient availability and understory biomass. Contrary to what was expected, the variation in plant biomass associated with forest composition was weakly related to soil nutrient availability and more strongly related to stand structural attributes

Paclitaxel chemotherapy and vascular toxicity as assessed by flow-mediated and nitrate-mediated vasodilatation

Background: Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. Methods: We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-alpha and IL-6 before and after chemotherapy. Results: Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p = 0.005) and NMD (p = 0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p = 0.045), whereas NMD was not affected (p = 0.421). Although TNF-alpha and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy. Conclusion: Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markers. (C) 2010 Elsevier Inc. All rights reserved

Paclitaxel chemotherapy and vascular toxicity as assessed by flow-mediated and nitrate-mediated vasodilatation

Background: Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. Methods: We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-alpha and IL-6 before and after chemotherapy. Results: Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p = 0.005) and NMD (p = 0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p = 0.045), whereas NMD was not affected (p = 0.421). Although TNF-alpha and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy. Conclusion: Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markers. (C) 2010 Elsevier Inc. All rights reserved