Secondary Organic Aerosol Formation from Aromatic Alkene Ozonolysis: Influence of the Precursor Structure on Yield, Chemical Composition, and Mechanism.

The influence of the precursor chemical structure on secondary organic aerosol (SOA) formation was investigated through the study of the ozonolysis of two anthropogenic aromatic alkenes: 2-methylstyrene and indene. Experiments were carried out in three different simulation chambers: ICARE 7300L FEP Teflon chamber (ICARE, Orléans, France), EUPHORE FEP Teflon chamber (CEAM, Valencia, Spain), and CESAM evacuable stainless steel chamber (LISA, Créteil, France). For both precursors, SOA yield and growth were studied on a large range of initial concentrations (from ∼60 ppbv to 1.9 ppmv) and the chemical composition of both gaseous and particulate phases was investigated at a molecular level. Gas phase was described using FTIR spectroscopy and online gas chromatography coupled to mass spectrometry, and particulate chemical composition was analyzed (i) online by thermo-desorption coupled to chemical ionization mass spectrometry and (ii) offline by supercritical fluid extraction coupled to gas chromatography and mass spectrometry. The results obtained from a large set of experiments performed in three different chambers and using several complementary analytical techniques were in very good agreement. SOA yield was up to 10 times higher for indene ozonolysis than for 2-methylstyrene ozonolysis at the same reaction advancement. For 2-methylstyrene ozonolysis, formaldehyde and o-tolualdehyde were the two main gaseous phase products while o-toluic acid was the most abundant among six products detected within the particulate phase. For indene ozonolysis, traces of formic and phthalic acids as well as 11 species were detected in the gaseous phase and 11 other products were quantified in the particulate phase, where phthaldialdehyde was the main product. On the basis of the identified products, reaction mechanisms were proposed that highlight specific pathways due to the precursor chemical structure. These mechanisms were finally compared and discussed regarding SOA formation. In the case of 2-methylstyrene ozonolysis, ozone adds mainly on the external and monosubstituted double bond, yielding only one C8- and monofunctionalized Criegee intermediate and hence more volatile products as well as lower SOA mass than indene ozonolysis in similar experimental conditions. In the case of indene, ozone adds mainly on the five-carbon-ring and disubstituted C═C double bond, leading to the formation of two C9- and bifunctionalized Criegee intermediates, which then evolve via different pathways including the hydroperoxide channel and form highly condensable first-generation products.

Organic aerosol molecular composition and gas-particle partitioning coefficients at a Mediterranean site (Corsica).

Molecular speciation of atmospheric organic matter was investigated during a short summer field campaign performed in a citrus fruit field in northern Corsica (June 2011). Aimed at assessing the performance on the field of newly developed analytical protocols, this work focuses on the molecular composition of both gas and particulate phases and provides an insight into partitioning behavior of the semi-volatile oxygenated fraction. Limonene ozonolysis tracers were specifically searched for, according to gas chromatography-mass spectrometry (GC-MS) data previously recorded for smog chamber experiments. A screening of other oxygenated species present in the field atmosphere was also performed. About sixty polar molecules were positively or tentatively identified in gas and/or particle phases. These molecules comprise a wide range of branched and linear, mono and di-carbonyls (C3-C7), mono and di-carboxylic acids (C3-C18), and compounds bearing up to three functionalities. Among these compounds, some can be specifically attributed to limonene oxidation and others can be related to α- or ß-pinene oxidation. This provides an original snapshot of the organic matter composition at a Mediterranean site in summer. Furthermore, for compounds identified and quantified in both gaseous and particulate phases, an experimental gas/particle partitioning coefficient was determined. Several volatile products, which are not expected in the particulate phase assuming thermodynamic equilibrium, were nonetheless present in significant concentrations. Hypotheses are proposed to explain these observations, such as the possible aerosol viscosity that could hinder the theoretical equilibrium to be rapidly reached.

Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model.

The hormone relaxin has been shown to cause coronary vasodilation and to prevent ischemia/reperfusion-induced cardiac injury in rodents. This study provides evidence that relaxin, used as an adjunctive drug to coronary reperfusion, reduces the functional, biochemical, and histopathological signs of myocardial injury in an in vivo swine model of heart ischemia/reperfusion, currently used to test cardiotropic drugs for myocardial infarction. Human recombinant relaxin, given at reperfusion at doses of 1.25, 2.5, and 5 microg/kg b.wt. after a 30-min ischemia, caused a dose-related reduction of key markers of myocardial damage (serum myoglobin, CK-MB, troponin T) and cardiomyocyte apoptosis (caspase 3, TUNEL assay), as well as of cardiomyocyte contractile dysfunction (myofibril hypercontraction). Compared with the controls, relaxin also increased the uptake of the viability tracer 201Thallium and improved ventricular performance (cardiac index). Relaxin likely acts by reducing oxygen free radical-induced myocardial injury (malondialdehyde, tissue calcium overload) and inflammatory leukocyte recruitment (myeloperoxidase). The present findings show that human relaxin, given as a drug to counteract reperfusion-induced cardiac injury, affords a clear-cut protection to the heart of swine with induced myocardial infarction. The findings also provide background to future clinical trials with relaxin as adjunctive therapy to catheter-based coronary angioplasty in patients with acute myocardial infarction.

Relaxin inhibits lipopolysaccharide-induced adhesion of neutrophils to coronary endothelial cells by a nitric oxide-mediated mechanism.

Neutrophil margination within blood vessels is an early finding during myocardial ischemia and can result in myocardial tissue injury. This phenomenon depends on the endothelial expression of adhesion molecules, which allow leukocyte extravasation. The hormone relaxin (RLX) was found to protect against experimental myocardial injury and to reduce neutrophil extravasation into the inflamed tissues. This study addresses the role of RLX in down-regulating endothelial adhesiveness to neutrophils and the possible involvement of NO, an anti-adhesive molecule, in the mechanism of action of RLX. Lipopolysaccharide (LPS)-primed rat coronary endothelial RCE) cells and neutrophils were co-cultured and their adhesion was quantified in the absence and presence of RLX, alone or together with the NO-synthase inhibitor L-NMMA. Inactivated RLX was used as control for specificity of the RLX effect. A 24-h incubation of LPS-primed RCE cells with RLX (60 and 600 ng/ml) caused a significant reduction of adherent neutrophils and of endothelial expression of the adhesion molecules P-selectin and VCAM-1 protein and mRNA, evaluated by immunohistochemistry, Western blot, and RT-PCR. These effects of RLX were blunted by L-NMMA and were not reproduced by inactivated RLX. These findings suggest that RLX has anti-inflammatory properties that could be of benefit in ischemic heart disease.

Effects of relaxin on vascular smooth muscle and endothelial cells in normotensive and hypertensive rats.

We tested the effects of relaxin on [Ca2+]i response to angiotensin II in smooth muscle (vSMC) and endothelial cells isolated from hypertensive (SHR) and normotensive (WKY) rats. Relaxin markedly reduced the [Ca2+]i response of vSMCs from WKY, but not from SHR rats. Western blots showed that cGMP-dependent protein kinase G was reduced in vSMCs from SHR as compared with WKY rats. Relaxin also blunted the [Ca2+]i response in endothelial cells from WKY, but not from SHR rats. However, in endothelial cells from SHR and WKY rats, protein kinase G was nearly unexpressed, thus accounting for an alternative pathway of the intracellular response to nitric oxide and relaxin. Hence, vSMCs and endothelial cells in SHR rats show a deficiency response to nitric oxide that may render them insensitive to relaxin.

Relaxin favors the morphofunctional integration between skeletal myoblasts and adult cardiomyocytes in coculture.

We have investigated the interaction between mouse skeletal myoblasts and rat cardiomyocytes in coculture and the influence of relaxin. Connexin43 expression, Lucifer yellow microinjection, Ca2+ propagation, and electrophysiological analysis have shown that myoblasts and cardiomyocytes are coupled by functional gap junctions. Cardiomyocytes and relaxin upregulated connexin43 expression and gap junctional communication in myoblasts. Relaxin also increased transjunctional current between myoblasts and between myoblasts and cardiomyocytes. In conclusion, relaxin potentiates the intercellular coupling, upregulating the transcellular exchange of regulatory molecules between myoblasts and cardiomyocytes, including Ca2+. This could favor the transdifferentiation of myoblasts toward a cardiac phenotype.

Relaxin restores altered ileal spontaneous contractions in dystrophic (mdx) mice.

We studied the effects of relaxin on ileal contractility in normal and dystrophic (mdx) mice. Ileal preparations from male normal and mdx mice showed spontaneous myogenic contractions whose amplitude was significantly higher in the latter ones. Relaxin added to the bath medium together with l-arginine depressed the amplitude of the spontaneous contractions in the mdx mice to a level similar to that of the normal mice. The nitric oxide synthase (NOS) inhibitor L-N(G)-nitroarginine reverted this effect. In mdx mice pretreated for 18 hours with relaxin, spontaneous motility was greatly reduced in amplitude, resembling that of the normal mice. Concurrently, iNOS expression in the muscle coat was markedly increased. Therefore, in mdx mice, relaxin can restore an ileal motility pattern similar to that of the normal mice by upregulating endogenous NO biosynthesis.

A new device for formaldehyde and total aldehydes real-time monitoring.

A new sensitive technique for the quantification of formaldehyde (HCHO) and total aldehydes has been developed in order to monitor these compounds, which are known to be involved in air quality issues and to have health impacts. Our approach is based on a colorimetric method where aldehydes are initially stripped from the air into a scrubbing solution by means of a turning coil sampler tube and then derivatised with 3-methylbenzothiazolinone-2-hydrazone in acid media (pH = -0.5). Hence, colourless aldehydes are transformed into blue dyes that are detected by UV-visible spectroscopy at 630 nm. Liquid core waveguide LCW Teflon® AF-2400 tube was used as innovative optical cells providing a HCHO detection limit of 4 pptv for 100 cm optical path with a time resolution of 15 min. This instrument showed good correlation with commonly used techniques for aldehydes analysis such as DNPH derivatisation chromatographic techniques with off-line and on-line samplers, and DOAS techniques (with deviation below 6%) for both indoor and outdoor conditions. This instrument is associated with simplicity and low cost, which is a prerequisite for indoor monitoring.

Multi-tool formaldehyde measurement in simulated and real atmospheres for indoor air survey and concentration change monitoring.

Formaldehyde is of particular health concern since it is carcinogenic for human and ubiquitous in indoor air where people spend most of their time. Therefore, it is important to have suitable methods and techniques to measure its content in indoor air. In the present work, four different techniques have been tested in the INERIS exposure chamber and in indoor environments in comparison to a standard active method: passive sampling method based on the reaction of 2,4-dinitrophenylhydrazine with formaldehyde, two on-line continuous monitoring systems based on fluorescence and UV measurements and a portable commercialised analyser based on electrochemical titration. Two formaldehyde concentrations, about 10 and 25 µg m(-3) were generated in an exposure chamber under controlled conditions of temperature, relative humidity, and wind speed to simulate real conditions and assess potential influence on passive sampling and continuous systems response. Influence of sampling periods on passive sampling has also been evaluated. The real atmosphere experiments have been performed in four different indoor environments: an office, a furniture shop, a shopping mall, and residential dwellings in which several potential formaldehyde sources linked to household activities have been tested. The analytical and sampling problems associated with each measurement method have been identified and discussed. An overall agreement between each technique has been observed and continuous analyzers allowed for formaldehyde concentrations change monitoring and secondary formation of that pollutant observation.

Morphofunctional integration between skeletal myoblasts and adult cardiomyocytes in coculture is favored by direct cell-cell contacts and relaxin treatment.

The success of cellular cardiomyoplasty, a novel therapy for the repair of postischemic myocardium, depends on the anatomical integration of the engrafted cells with the resident cardiomyocytes. Our aim was to investigate the interaction between undifferentiated mouse skeletal myoblasts (C2C12 cells) and adult rat ventricular cardiomyocytes in an in vitro coculture model. Connexin43 (Cx43) expression, Lucifer yellow microinjection, Ca2+ transient propagation, and electrophysiological analysis demonstrated that myoblasts and cardiomyocytes were coupled by functional gap junctions. We also showed that cardiomyocytes upregulated gap junctional communication and expression of Cx43 in myoblasts. This effect required direct cell-to-cell contact between the two cell types and was potentiated by treatment with relaxin, a cardiotropic hormone with potential effects on cardiac development. Analysis of the gating properties of gap junctions by dual cell patch clamping showed that the copresence of cardiomyocytes in the cultures significantly increased the transjunctional current and conductance between myoblasts. Relaxin enhanced this effect in both the myoblast-myoblast and myoblast-cardiomyocyte cell pairs, likely acting not only on gap junction formation but also on the electrical properties of the preexisting channels. Our findings suggest that myoblasts and cardiomyocytes interact actively through gap junctions and that relaxin potentiates the intercellular coupling. A potential role for gap junctional communication in favoring the intercellular exchange of regulatory molecules, including Ca2+, in the modulation of myoblast differentiation is discussed.