Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms

Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters

Using the dendritic polymer PAMAM to form gold nanoparticles in the protein cage thermosome

The chaperonin thermosome (THS) is a protein cage that lacks binding sites for metal ions and inorganic nanoparticles. However, when poly(amidoamine) (PAMAM) is encapsulated into THS, gold nanoparticles (AuNP) can be prepared in the THS. The polymer binds HAuCl4. Subsequent reduction yields nanoparticles with narrow size distribution in the protein-polymer conjugate

Biological effects in lung cells In vitro of exhaust aerosols from a gasoline passenger car with and without particle filter

Exhaust aerosol from gasoline passenger cars is a complex mixture of a particulate fraction as well as volatile compounds. In contrary to the observed adverse effects of diesel exhaust particles the gasoline exhaust has, however, received little attention so far. The aim of this study was to perform a comparison of exhaust composition and biological responses from freshly produced non-filtered exhaust as well as from exhaust filtered with a noncoated gasoline particle filter (GPF). A 3D model of the human epithelial airway barrier was exposed to the exhaust directly at the air-liquid interface and different effects such as cytotoxicity, antioxidative response, pro- inflammation, and activation of the aryl hydrocarbon receptor (AhR) were studied. In addition, genotoxicity was assessed using the Ames test. By an online analysis of the exhaust, it has been shown that the GPF efficiently filters the particle count in both the cold and warm phase when the new European driving cycle (NEDC) was applied. The lung cell tests revealed that the use of the GPF increased the antioxidative glutathionine (GSH) response as well as the pro-inflammatory potential, i.e., IL-8, expression, indicating increased cell stimulation by the volatile compounds alone. The removal of the particulate fraction, however, decreased significantly the AhR activation in comparison to unfiltered exhaust, and the exhaust genotoxicity was reduced as tested by the Ames test. In conclusion, GPF exhaust did not completely reduce the adverse effects of gasoline exhaust in the in vitro test and further experiments with a coated GPF are needed in the future

Quantitatives Potenzial zur Verwertung von Molke in Lebensmitteln in der Schweiz

Aus der Käseherstellung ergeben sich in der Schweiz jährlich 1 300 000 t Molke. 24 % davon werden bereits für Lebensmittelzwecke genutzt, 31 % zu höherwertigen Futtermitteln verarbeitet und noch 45 % direkt an Schweine verfüttert. Eine stärkere Verwendung der Molke in Lebensmitteln ist wünschenswert, wird jedoch durch das dezentrale und damit transportintensive Anfallen vergleichsweise kleiner Molkenmengen erschwert. Je nach Käseherstellungsprozess sind die Molken zudem heterogen zusammensetzt, was verarbeitungstechnische Schwierigkeiten mit sich bringt und die Herstellung von Molkenproteinpulvern mit immer gleichen Eigenschaften erschwert. Dieses Problem könnte durch die Gewinnung «idealer» Molken umgangen werden, dies würde aber Prozessanpassungen bei der Käseherstellung erfordern, zudem ist die ökonomische Relevanz zu prüfen. Bei der Abschätzung der Umweltbelastung zeigt sich, dass diese positv oder negativ ausfallen kann, abhängig vom Ausmass der Proteinkonzentrierung beziehungsweise des Laktoseentzugs. Insgesamt liegen nur wenige Kenntnisse darüber vor, welche Assoziationen der Begriff Molke beim Konsumenten hervorruft und wie eine geeignete Strategie aussehen könnte, um die verzehrte Molkenproteinmenge zu erhöhen

Novel Agonist Bioisosteres and Common Structure-Activity Relationships for The Orphan G Protein-Coupled Receptor GPR139

GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and Parkinson’s disease. The two aromatic amino acids (L)-Trp and (L)-Phe have been proposed as putative endogenous agonists, and three structurally related benzohydrazide, glycine benzamide, and benzotriazine surrogate agonist series have been published. Herein, we assayed 158 new analogues selected from a pharmacophore model, and identified 12 new GPR139 agonists, containing previously untested bioisosteres. Furthermore, we present the first combined structure-activity relationships, and a refined pharmacophore model to serve as a rationale for future ligand identification and optimization

Assessment of lung cell toxicity of various gasoline engine exhausts using a versatile in vitro exposure system

Adverse effect studies of gasoline exhaust are scarce, even though gasoline direct injection (GDI) vehicles can emit a high number of particles. The aim of this study was to conduct an in vitro hazard assessment of different GDI exhausts using two different cell culture models mimicking the human airway. In addition to gasoline particle filters (GPF), the effects of two lubrication oils with low and high ash content were assessed, since it is known that oils are important contributors to exhaust emissions. Complete exhausts from two gasoline driven cars (GDI1 and GDI2) were applied for 6 h (acute exposure) to a multi-cellular human lung model (16HBE14o-cell line, macrophages, and dendritic cells) and a primary human airway model (MucilAir™). GDI1 vehicle was driven unfiltered and filtered with an uncoated and a coated GPF. GDI2 vehicle was driven under four settings with different fuels: normal unleaded gasoline, 2% high and low ash oil in gasoline, and 2% high ash oil in gasoline with a GPF. GDI1 unfiltered was also used for a repeated exposure (3 times 6 h) to assess possible adverse effects. After 6 h exposure, no genes or proteins for oxidative stress or pro- inflammation were upregulated compared to the filtered air control in both cell systems, neither in GDI1 with GPFs nor in GDI2 with the different fuels. However, the repeated exposure led to a significant increase in HMOX1 and TNFa gene expression in the multi-cellular model, showing the responsiveness of the system towards gasoline engine exhaust upon prolonged exposure. The reduction of particles by GPFs is significant and no adverse effects were observed in vitro during a short-term exposure. On the other hand, more data comparing different lubrication oils and their possible adverse effects are needed. Future experiments also should, as shown here, focus on repeated exposures

Hazard Identification of Exhausts from Gasoline-Ethanol Fuel Blends Using a Multi-Cellular Human Lung Model

Ethanol can be produced from biomass and as such is renewable, unlike petroleum-based fuel. Almost all gasoline cars can drive with fuel containing 10% ethanol (E10), flex-fuel cars can even use 85% ethanol (E85). Brazil and the USA already include 10–27% ethanol in their standard fuel by law. Most health effect studies on car emissions are however performed with diesel exhausts, and only few data exists for other fuels. In this work we investigated possible toxic effects of exhaust aerosols from ethanol-gasoline blends using a multi-cellular model of the human lung. A flex-fuel passenger car was driven on a chassis dynamometer and fueled with E10, E85, or pure gasoline (E0). Exhausts obtained from a steady state cycle were directly applied for 6 h at a dilution of 1:10 onto a multi-cellular human lung model mimicking the bronchial compartment composed of human bronchial cells (16HBE14o-), supplemented with human monocyte-derived dendritic cells and monocyte-derived macrophages, cultured at the air-liquid interface. Biological endpoints were assessed after 6 h post incubation and included cytotoxicity, pro-inflammation, oxidative stress, and DNA damage. Filtered air was applied to control cells in parallel to the different exhausts; for comparison an exposure to diesel exhaust was also included in the study. No differences were measured for the volatile compounds, i.e. CO, NOx, and T.HC for the different ethanol supplemented exhausts. Average particle number were 6×102 #/cm3 (E0), 1×105 #/cm3 (E10), 3×103 #/cm3 (E85), and 2.8×106 #/cm3 (diesel). In ethanol-gasoline exposure conditions no cytotoxicity and no morphological changes were observed in the lung cell cultures, in addition no oxidative stress - as analyzed with the glutathione assay - was measured. Gene expression analysis also shows no induction in any of the tested genes, including mRNA levels of genes related to oxidative stress and pro-inflammation, as well as indoleamine 2,3-dioxygenase 1 (IDO-1), transcription factor NFE2-related factor 2 (NFE2L2), and NAD(P)H dehydrogenase [quinone] 1 (NQO1). Finally, no DNA damage was observed with the OxyDNA assay. On the other hand, cell death, oxidative stress, as well as an increase in pro-inflammatory cytokines was observed for cells exposed to diesel exhaust, confirming the results of other studies and the applicability of our exposure system. In conclusion, the tested exhausts from a flex-fuel gasoline vehicle using different ethanol-gasoline blends did not induce adverse cell responses in this acute exposure. So far ethanol-gasoline blends can promptly be used, though further studies, e.g. chronic and in vivo studies, are needed

Molke - auf den Teller statt in den Trog

Das Interesse an einer besseren Verwertung der Molke ist weltweit stark gestiegen - aufgrund des steigenden Bewusstseins für einen nachhal­tigen Umgang mit Lebensmitteln, der neuen technologischen Möglichkeiten der Membran­trenntechnik und des ökonomischen Potenzi­als. Internationale Konzerne arbeiten intensiv daran, Molke nicht nur in Lebensmittel zu integrieren, sondern die funktionellen Eigenschaf­ten von Molkefraktionen gezielt zu nutzen oder zu verändern. Produkte sind bereits auf dem Markt. Wie stellt sich die Situation in der Schweiz dar und wie gross ist das Verwertungs­potenzial von Molke in der menschlichen Ernährung

Impact of herbage proportion, animal breed, lactation stage and season on the fatty acid and protein composition of milk

Impact of herbage proportion, breed, average days in lactation (ADiL), and season on bulk milk composition of 12 dairy farms were investigated over a year using a mixed effect model approach. A 10%-points higher proportion of herbage led to higher contents of omega 3 (n-3) fatty acids (FAs), conjugated linoleic acids (CLA), vaccenic acid, and branched chain FAs (+0.08, +0.08, +0.19, +0.05 g 100 g−1 fat, respectively). Breed influenced n-3 FAs and CLA (+0.31, +0.17 g 100 g−1 fat, respectively), κ-casein, lipoprotein lipase, β-lactoglobulin, total whey protein, fatty acid synthase, and glycoprotein-2, resulting in +0.96, −0.019, −0.83, −1.12, +0.009, and +0.01 g 100 g−1 measured proteins, respectively, in Brown Swiss milk. ADiL influenced lactoferrin and crude protein; season affected all FAs and proteins examined. The identification of these quantitative relationships allow predictions that provide new insights for the production, processing and commercialisation of grassland-based dairy products