104,022 research outputs found
Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.
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
<p>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.</p>
<p>Methods and results: Dfen (5 mg kgâ1 dayâ1 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 CYP1B1â/â 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.</p>
<p>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.</p>
On the viability of the PAH model as an explanation of the unidentified infrared emission features
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.
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.
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
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 (PAH 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
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
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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