Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 ± 18.5, 37.6 ± 14.6, 34.8 ± 14.6, and 35.4 ± 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 ± 26.8, 48.0 ± 26.9, 48.1 ± 25.7, and 45.7 ± 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.FAPES

Effects of non-linearities on magnetic field generation

Magnetic fields are present on all scales in the Universe. While we understand the processes which amplify the fields fairly well, we do not have a "natural" mechanism to generate the small initial seed fields. By using fully relativistic cosmological perturbation theory and going beyond the usual confines of linear theory we show analytically how magnetic fields are generated. This is the first analytical calculation of the magnetic field at second order, using gauge-invariant cosmological perturbation theory, and including all the source terms. To this end, we have rederived the full set of governing equations independently. Our results suggest that magnetic fields of the order of $10^{-30}$ G can be generated (although this depends on the small scale cut-off of the integral), which is largely in agreement with previous results that relied upon numerical calculations. These fields are likely too small to act as the primordial seed fields for dynamo mechanisms.Comment: 21 pages; v2: minor changes, added references; v3: version accepted for publication in JCA

Cosmological evolution of general scalar fields in a brane-world cosmology

We study the cosmology of a general scalar field and barotropic fluid during the early stage of a brane-world where the Friedmann constraint is dominated by the square of the energy density. Assuming both the scalar field and fluid are confined to the brane, we find a range of behaviour depending on the form of the potential. Generalising an approach developed for a standard Friedmann cosmology, in \cite{delaMacorra:1999ff}, we show that the potential dependence $V(\phi)$ can be described through a parameter $\lambda \equiv -\sqrt{2} m_5^{3/2} V'/(\sqrt{H}V)$, where $m_5$ is the 5-dimensional Planck mass, $H$ is the Hubble parameter and $V' \equiv \frac{dV}{d\phi}$. For the case where $\lambda$ asymptotes to zero, we show that the solution exhibits stable inflationary behaviour. On the other hand if it approaches a finite constant, then $V(\phi) \propto \frac{1}{\phi^2}$. For $\lambda \to \infty$ asymptotically, we find examples where it does so both with and without oscillating. In the latter case, the barotropic fluid dominates the scalar filed asymptotically. Finally we point out an interesting duality which leads to identical evolution equations in the high energy $\rho^2$ dominated regime and the low energy $\rho$ dominated regime.Comment: 10 pages, 3 figure

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival