Distinct patterns of circulating endothelial cells in pulmonary hypertension.

The respective abundance of circulating endothelial cells and endothelial progenitor cells may reflect the balance between vascular injury and repair. As pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can share features of pulmonary remodelling, we postulated that the two disorders might be associated with different types of pulmonary endothelial dysfunction. We studied 25 consecutive patients undergoing cardiac catheterisation for suspected pulmonary hypertension. Nine patients had PAH, nine had CTEPH, and seven had normal pulmonary arterial pressure and served as controls. Circulating endothelial cells were isolated with CD146-coated beads. CD34(+)CD133(+) cell and endothelial progenitor cell numbers were respectively determined by flow cytometry and cell culture, in peripheral vein and pulmonary artery blood. Plasma levels of soluble vascular endothelial growth factor (VEGF), soluble E-selectin and soluble vascular cell adhesion molecule (sVCAM) were measured by ELISA. No difference in progenitor counts or VEGF levels was found across the three groups. Compared to controls, circulating endothelial cell numbers were significantly increased in PAH but not in CTEPH, in keeping with the elevated soluble E-selectin and sVCAM levels found in PAH alone. In conclusion, PAH, in contrast to CTEPH, is associated with markers of vascular injury (circulating endothelial cells, soluble E-selectin and sVCAM) but not with markers of remodelling (endothelial progenitor cells, CD34(+)CD133(+) cells and VEGF).

Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-kappaB and endothelin-1.

Pulmonary hypertension is rare in chronic respiratory diseases but has a strong impact on the prognosis and is partly underlined by factors other than hypoxaemia. The aim of the present study was to assess the potential role of endothelin-1 (ET-1) and nuclear factor (NF)-kappaB vasoconstrictive pathways in pulmonary hypertension. The effects of ET-1 receptors blockers (BQ 123 and 788) and of genistein were assessed on response to acetylcholine of pulmonary vascular rings from cystic fibrosis (CF) lung transplant recipients (n = 23). NF-kappaB and ET-1 receptor expression was immunodetected in pulmonary arteries and quantitated using Western blotting. ET-1 vascular content was quantitated using ELISA. In total, 14 out of 23 subjects exhibited strongly impaired pulmonary vasodilation (p<0.01 versus nine out of 23 subjects with a normal response) associated with an activation of ET-1 receptors A and NF-kappaB pathways. Genistein restored vasodilation in subjects with an abnormal response. Pulmonary vascular dysfunction is frequent in end-stage CF, involving the NF-kappaB pathway and that of ET-1 through ET-1 receptor A (ETAR). These data leave a conceptual place for ETAR blockers and isoflavones in the management of the devastating vascular complication of chronic obstructive respiratory diseases such as CF.

Tiered environmental risk assessment of methyltins from heat stabilizers in rigid PVC in Sweden.

The methyltins, methyltin 2-ethylhexyl mercaptoacetate and methyltin-2-mercaptoethyloleate sulfide, are used as heat stabilizers in rigid PVC. The degradation products monomethyltintrichloride (MMTTC) and dimethyltindichloride (DMTDC) may leach from the PVC, and enter the environment. A risk assessment was executed for the use of these products in Sweden, with the double aim to (a) assess the potential environmental risks, and (b) explore the possibilities of a tiered risk assessment. An initial assessment was executed with EUSES 1.0. The initial assessment showed no significant environmental risks on a regional scale. On a local scale however, emissions from a sewage treatment plant to the surface water pose a potential risk for the near proximity. In a second tier, this critical exposure route was studied in more detail; an improved exposure scenario was drawn up; and an additional sorption experiment was performed. This refinement resulted in much lower predicted environmental concentrations (<

Emission, fate and effects of soluble silicates (waterglass) in the aquatic environment.

Soluble silicates, commercially known as waterglass, are among the largest volume synthetic chemicals in the world. Silicon from waterglass is rapidly transformed to the biologically active orthosilicic acid (referred to as dissolved silicate). This paper aims to assess the impact of waterglass on the aquatic environment in Western Europe. The emission to surface waters from the four most relevant application areas, household detergents, pulp and paper production, water and wastewater treatment, and soil stabilization, is estimated to be ca. 88-121 kton of SiO2 per year. This is a small fraction (<2%) of the estimated total amount of dissolved silicate transported by rivers to the oceans. Locally, increases in dissolved silicate concentration will decrease the ratios of N:Si and P:Si, which could influence phytoplankton species composition and favor the growth of diatoms over other groups of algae. Significant adverse effects in aquatic ecosystems are not expected.