Systems toxicology of complex wood combustion aerosol reveals gaseous carbonyl compounds as critical constituents.

Epidemiological studies identified air pollution as one of the prime causes for human morbidity and mortality, due to harmful effects mainly on the cardiovascular and respiratory systems. Damage to the lung leads to several severe diseases such as fibrosis, chronic obstructive pulmonary disease and cancer. Noxious environmental aerosols are comprised of a gas and particulate phase representing highly complex chemical mixtures composed of myriads of compounds.

Agglomeration State of Titanium-Dioxide (TiO) Nanomaterials Influences the Dose Deposition and Cytotoxic Responses in Human Bronchial Epithelial Cells at the Air-Liquid Interface.

Extensive production and use of nanomaterials (NMs), such as titanium dioxide (TiO), raises concern regarding their potential adverse effects to humans. While considerable efforts have been made to assess the safety of TiO NMs using in vitro and in vivo studies, results obtained to date are unreliable, possibly due to the dynamic agglomeration behavior of TiO NMs. Moreover, agglomerates are of prime importance in occupational exposure scenarios, but their toxicological relevance remains poorly understood.

Air-Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects.

Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays.

A novel TEM grid sampler for airborne particles to measure the cell culture surface dose.

The applied surface dose is a key parameter for the measurement of toxic effects of airborne particles by air liquid interface exposure of human lung cells. Besides online measurement of the deposited particle mass by quartz crystal microbalance frequently other dose metrics such as particle size distribution, surface and agglomeration state are required. These particle properties and their spatial distribution can be determined by digital processing of micrographs obtained by transmission electron microscopy (TEM).

Characterization of Nanoparticle Batch-To-Batch Variability.

A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs.

Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions: Different Effects of Heavy Fuel Oil and Refined Diesel Fuel.

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO.

Toxicity of wood smoke particles in human A549 lung epithelial cells: the role of PAHs, soot and zinc.

Indoor air pollution is associated with increased morbidity and mortality. Specifically, the health impact of emissions from domestic burning of biomass and coal is most relevant and is estimated to contribute to over 4 million premature deaths per year worldwide. Wood is the main fuel source for biomass combustion and the shift towards renewable energy sources will further increase emissions from wood combustion even in developed countries.

Particulate matter from both heavy fuel oil and diesel fuel shipping emissions show strong biological effects on human lung cells at realistic and comparable in vitro exposure conditions.

Background: Ship engine emissions are important with regard to lung and cardiovascular diseases especially in coastal regions worldwide. Known cellular responses to combustion particles include oxidative stress and inflammatory signalling.

Objectives: To provide a molecular link between the chemical and physical characteristics of ship emission particles and the cellular responses they elicit and to identify potentially harmful fractions in shipping emission aerosols.

[The flexibility of family medicine].

We are a European academic group of family doctors and we propose a definition of flexibility in family medicine. A review of the literature shows that flexibility and complexity are emerging concepts in the field of family practice. The outcomes of a workshop at the WONCA-Europe congress in 2014 are discussed.

Silica nanoparticles are less toxic to human lung cells when deposited at the air-liquid interface compared to conventional submerged exposure.

Background: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air-liquid interface.

High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy.

Background: Takotsubo cardiomyopathy is an acute heart failure syndrome characterized by myocardial hypocontractility from the mid left ventricle to the apex. It is precipitated by extreme stress and can be triggered by intravenous catecholamine administration, particularly epinephrine. Despite its grave presentation, Takotsubo cardiomyopathy is rapidly reversible, with generally good prognosis.

Plasticity of surface structures and β(2)-adrenergic receptor localization in failing ventricular cardiomyocytes during recovery from heart failure.

Background: Cardiomyocyte surface morphology and T-tubular structure are significantly disrupted in chronic heart failure, with important functional sequelae, including redistribution of sarcolemmal β(2)-adrenergic receptors (β(2)AR) and localized secondary messenger signaling. Plasticity of these changes in the reverse remodeled failing ventricle is unknown. We used AAV9.

Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages.

In cell culture studies, foetal calf serum (FCS) comprising numerous different proteins is added, which might coat the surface of engineered nanomaterials (ENMs) and thus could profoundly alter their biological activities. In this study, a panel of industrially most relevant metal oxide nanoparticles (NPs) was screened for toxic effects in A549 lung epithelial cells and RAW264.7 macrophages in the presence and absence of FCS.

Regulation of the arachidonic acid mobilization in macrophages by combustion-derived particles.

Background: Acute exposure to elevated levels of environmental particulate matter (PM) is associated with increasing morbidity and mortality rates. These adverse health effects, e.g.

Neuroprotection and Functional Recovery Associated with Decreased Microglial Activation Following Selective Activation of mGluR2/3 Receptors in a Rodent Model of Parkinson's Disease.

Clinical trials have demonstrated positive proof of efficacy of dual metabotropic glutamate receptor 2/3 (mGluR2/3) agonists in both anxiety and schizophrenia. Importantly, evidence suggests that these drugs may also be neuroprotective against glutamate excitotoxicity, implicated in the pathogenesis of Parkinson's disease (PD). However, whether this neuroprotection also translates into functional recovery is unclear.

Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation.

The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins), and the functional implications of their localization have been unclear. We combined nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy techniques and found that, in cardiomyocytes from healthy adult rats and mice, spatially confined beta2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional beta1ARs are distributed across the entire cell surface.

Simultaneous removal of mercury, PCDD/F, and fine particles from flue gas.

A multifunctional scrubber (MFS) has been developed to reduce the complexity of flue gas cleaning plants. The MFS integrates an oxidizing scrubber equipped with a dioxin-absorbing tower packing material and a space charge electrostatic precipitator. All these processes have been previously developed at Forschungszentrum Karlsruhe.

The response of a co-culture lung model to fine and ultrafine particles of incinerator fly ash at the air-liquid interface.

Elevated concentrations of particulate matter in the environmental atmosphere constitute a potential risk to human health. In vitro cell-based assays are therefore necessary to evaluate the toxicological potential of inhaled particulate emissions. In this study, the exposure of a co-culture cell model at the air-liquid interface was used to evaluate the dose-dependent biological effects of a test aerosol.

Formation of nanoparticles in flames; measurement by particle mass spectrometry and numerical simulation.

The size distributions of nanoparticles in flames are measured using a novel particle mass spectrometer (PMS), which is developed for the size range between 0.3 and 50 nm and for number concentrations between 10(9) and 10(13). Using this instrument the particles are sampled without prior dilution from the flame into a molecular beam.

Electron-beam treatment of aromatic hydrocarbons that can be air-stripped from contaminated groundwater. 2. Gas-phase studies.

The electron-beam (EB) degradation of volatile aromatics (benzene, toluene, ethylbenzene, xylenes: BTEX) in groundwater strip gas, which in the present work has been modeled by the introduction of the desired aromatic(s) to a stream of air or another gas, such as oxygen, is initiated essentially by the addition of *OH radicals to the aromatic ring, giving rise to hydroxycyclohexadienyl radicals, which form the corresponding peroxyl radicals upon addition of oxygen. As studied in some detail with benzene as a BTEX representative, various reactions of these lead to numerous oxidation products in a cascade of reactions, including the decomposition of products under the prevailing conditions of high turnover of the initial aromatic. Importantly, hydroxycyclohexadienylperoxyl radical formation is partly reversible, and the reactions of the hydroxycyclohexadienyl radicals, which thus have a significant presence in these systems, must therefore also be taken into consideration.

In vitro effects of incinerator fly ash on pulmonary macrophages and epithelial cells.

Fly ash from a municipal waste incinerator was used as a model for atmospheric particles in order to identify parameters relevant for the induction of adverse health effects. The aim of this study was to compare the biological effects of the total incinerator fly ash (IFA), the soluble and the insoluble fraction with the effects of quartz by in vitro toxicity studies. The previously sized fly ash (< 20 microns) was characterized by elemental composition and particle size distribution.

Adsorption of PCDD/F on MWI fly ash.

The removal of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) from waste incinerator off-gas is a costly task, because a considerable part of the PCDD/F may exist in the gas phase (often 50-100% around 200 degrees C). The volatile fraction passes the particle filter and the subsequent gas cleaning equipment, so that an additional unit is needed to remove the gaseous PCDD/F from the flue gas. Moreover, dioxins and furans can accumulate in some parts of the equipment in a way that they can act as a latent source.