104,022 research outputs found

    Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

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    The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH

    Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

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    &lt;p&gt;Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH. Dfen mediates PAH via a serotonergic mechanism and we have shown serotonin to up-regulate expression of CYP1B1 in human pulmonary artery smooth muscle cells (PASMCs). Thus here we assess the role of CYP1B1 in the development of Dfen-induced PAH.&lt;/p&gt; &lt;p&gt;Methods and results: Dfen (5 mg kg−1 day−1 PO for 28 days) increased right ventricular pressure and pulmonary vascular remodelling in female mice only. Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1−/− mice. In line with this, Dfen up-regulated expression of CYP1B1 in PASMCs from PAH patients (PAH-PASMCs) and Dfen-mediated proliferation of PAH-PASMCs was ablated by pharmacological inhibition of CYP1B1. Dfen increased expression of tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin) in PAH-PASMCs and both Dfen-induced proliferation and Dfen-induced up-regulation of CYP1B1 were ablated by inhibition of Tph1. 17ÎČ-Oestradiol increased expression of both Tph1 and CYP1B1 in PAH-PASMCs, and Dfen and 17ÎČ-oestradiol had synergistic effects on proliferation of PAH-PASMCs. Finally, ovariectomy protected against Dfen-induced PAH in female mice.&lt;/p&gt; &lt;p&gt;Conclusion: CYP1B1 is critical in the development of Dfen-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro. CYP1B1 may provide a novel therapeutic target for PAH.&lt;/p&gt

    On the viability of the PAH model as an explanation of the unidentified infrared emission features

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    Polycyclic aromatic hydrocarbon (PAH) molecules are widely considered as the preferred candidate for the carrier of the unidentified infrared emission bands observed in the interstellar medium and circumstellar envelopes. In this paper we report the result of fitting a variety of non-PAH spectra (silicates, hydrogenated amorphous carbon, coal and even artificial spectra) using the theoretical infrared spectra of PAHs from the NASA Ames PAH IR Spectroscopic Database. We show that these non-PAH spectra can be well fitted by PAH mixtures. This suggest that a general match between astronomical spectra and those of PAH mixtures does not necessarily provide definitive support for the PAH hypothesis.Comment: 19 pages, 9 figures, accepted for publication in Ap

    Pulmonary arterial hypertension: the burden of disease and impact on quality of life.

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    Pulmonary arterial hypertension (PAH) is a debilitating disease that pervades all aspects of a patients daily life. It is also increasingly acknowledged that the burden of PAH extends to older patients and carers. Until recently, the adverse effect of disease symptoms on the physical, emotional and social factors governing patient health-related quality of life (HRQoL) remained largely unrecognised. With a shift in therapeutic objectives to longer term improvements and HRQoL benefits, clinical trials now frequently include HRQoL measures as study end-points. Most HRQoL instruments used in patients with PAH are generic or non-disease-specific questionnaires and therefore may not accurately capture PAH disease burden. New PAH-specific HRQoL instruments currently undergoing validation include emPHasis-10 and Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Using various HRQoL measures, pharmacological therapies have been shown to improve HRQoL in patients with PAH. Patients also derive HRQoL benefits from nonpharmacological strategies, which include the emotional support provided by multidisciplinary care and support groups that is fundamental to patient wellbeing. Looking to the future, validated PAH-specific HRQoL instruments together with dedicated guidelines and procedures are essential to support the translation of HRQoL scores to the clinic, thus enabling a holistic treatment approach to the management of patients with PAH

    Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor ÎČ in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension.

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    Pulmonary arterial hypertension (PAH) can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc). Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor ÎČ (SCGF ÎČ) is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg). MIF and SCGF ÎČ levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF ÎČ in patients with idiopathic PAH (P=0.03 and P=0.004) and with PAH secondary to SSc (P=0.018 and P=0.023) compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA) class (P=0.03). We can hypothesize that MIF and SCGF ÎČ are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease

    Extended Red Emission and the evolution of carbonaceaous nanograins in NGC 7023

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    Extended Red Emission (ERE) was recently attributed to the photo-luminescence of either doubly ionized Polycyclic Aromatic Hydrocarbons (PAH++^{++}), or charged PAH dimers. We analysed the visible and mid-infrared (mid-IR) dust emission in the North-West and South photo-dissociation regions of the reflection nebula NGC 7023.Using a blind signal separation method, we extracted the map of ERE from images obtained with the Hubble Space Telescope, and at the Canada France Hawaii Telescope. We compared the extracted ERE image to the distribution maps of the mid-IR emission of Very Small Grains (VSGs), neutral and ionized PAHs (PAH0^0 and PAH+^+) obtained with the Spitzer Space Telescope and the Infrared Space Observatory. ERE is dominant in transition regions where VSGs are being photo-evaporated to form free PAH molecules, and is not observed in regions dominated by PAH+^+. Its carrier makes a minor contribution to the mid-IR emission spectrum. These results suggest that the ERE carrier is a transition species formed during the destruction of VSGs. Singly ionized PAH dimers appear as good candidates but PAH++^{++} molecules seem to be excluded.Comment: Accepted for publication in A&

    PAHs in protoplanetary disks: emission and X-ray destruction

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    We study the PAH emission from protoplanetary disks. First, we discuss the dependence of the PAH band ratios on the hardness of the absorbed photons and the temperature of the stars. We show that the photon energy together with a varying degree of the PAH hydrogenation accounts for most of the observed PAH band ratios without the need to change the ionization degree of the molecules. We present an accurate treatment of stochastic heated grains in a vectorized three dimensional Monte Carlo dust radiative transfer code. The program is verified against results using ray tracing techniques. Disk models are presented for T Tauri and Herbig Ae stars. Particular attention is given to the photo-dissociation of the molecules. We consider beside PAH destruction also the survival of the molecules by vertical mixing within the disk. By applying typical X-ray luminosities the model accounts for the low PAH detection probability observed in T Tauri and the high PAH detection statistics found in Herbig Ae disks. Spherical halos above the disks are considered. We show that halos reduce the observed PAH band-to-continuum ratios when observed at high inclination. Finally, mid-IR images of disks around Herbig Ae disks are presented. We show that they are easier to resolve when PAH emission dominate.Comment: Accepted for publication in A&A. 10 pages, 7 figures, 2 tabl

    Mapping PAH sizes in NGC 7023 with SOFIA

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    NGC 7023 is a well-studied reflection nebula, which shows strong emission from polycyclic aromatic hydrocarbon (PAH) molecules in the form of aromatic infrared bands (AIBs). The spectral variations of the AIBs in this region are connected to the chemical evolution of the PAH molecules which, in turn, depends on the local physical conditions. We use the capabilities of SOFIA to observe a 3.2' x 3.4' region of NGC 7023 at wavelengths that we observe with high spatial resolution (2.7") at 3.3 and 11.2 um. We compare the SOFIA images with existing images of the PAH emission at 8.0 um (Spitzer), emission from evaporating very small grains (eVSG) extracted from Spitzer-IRS spectral cubes, the ERE (HST and CFHT), and H_2 (2.12 um). We create maps of the 11.2/3.3 um ratio to probe the morphology of the PAH size distribution and the 8.0/11.2 um ratio to probe the PAH ionization. We make use of an emission model and of vibrational spectra from the NASA Ames PAHdb to translate the 11.2/3.3 um ratio to PAH sizes. The 11.2/3.3 um map shows the smallest PAH concentrate on the PDR surface (H_2 and extended red emission) in the NW and South PDR. We estimated that PAHs in the NW PDR bear, on average, a number of carbon atoms (N_c) of ~70 in the PDR cavity and ~50 at the PDR surface. In the entire nebula, the results reveal a factor of 2 variation in the size of the PAH. We relate these size variations to several models for the evolution of the PAH families when they traverse from the molecular cloud to the PDR. The PAH size map enables us to follow the photochemical evolution of PAHs in NGC 7023. Small PAHs result from the photo-evaporation of VSGs as they reach the PDR surface. Inside the PDR cavity, the PAH abundance drops as the smallest PAH are broken down. The average PAH size increases in the cavity where only the largest species survive or are converted into C_60 by photochemical processing.Comment: accepted for publication in A&
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