Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos particle toxicity involve two facets for each particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable elongated mineral particles.

The design of plants or unit operations requires the knowledge of data for multicomponent systems. An approach is presented for the regression of binary interaction parameters required for the calculation of activity coefficients. Binary vapor pressure data are used to correlate these parameters for calculation of vapour/liquid equilibrium data. The advantage of the approach is the fact that only easily measured vapor pressure data are required. The procedure is demonstrated by means of two binary mixtures. Parameter regression, prediction of vapour/liquid equilibrium data as well as their experimental verification are demonstrated.

Greater risk of adverse effects from particulate matter (PM) has been noted in susceptible subpopulations, such as children. However, the physicochemical components responsible for these biological effects are not understood. As critical constituents of PM, transition metals were postulated to be involved in a number of pathological processes of the respiratory system through free radical-medicated damage. The purpose of this study was to examine whether oxidative injury in the lungs of neonatal rats could be induced by repeated short-term exposure to iron (Fe) and soot particles. Sprague Dawley rats 10 d of age were exposed by inhalation to two different concentrations of ultrafine iron particles (30 or 100 µg/m3) in combination with soot particles adjusted to maintain a total particle concentration of 250 µg/m3. Exposure at 10 d and again at 23 d of age was for 6 h/d for 3 d. Oxidative stress was observed at both Fe concentrations in the form of significant elevations in glutathione disulfide (GSSG) and GSSG/glutathione (GSH) ratio and a reduction in ferric/reducing antioxidant power in bronchoalveolar lavage. A significant decrease in cell viability associated with significant increases in lactate dehydrogenase (LDH) activity, interleukin-1-beta (IL-1β), and ferritin expression was noted following exposure to particles containing the highest Fe concentration. Iron from these particles was shown to be bioavailable in an in vitro assay using the physiologically relevant chelator, citrate. Data indicate that combined Fe and soot particle exposure induces oxidative injury, cytotoxicity and pro-inflammatory responses in the lungs of neonatal rats.

AbstractVorgestellt wird ein Verfahren, das aus wenigen Dampfdruckkurven binärer Gemische bei verschiedenen Zusammensetzungen die Wechselwirkungsparameter für die Berechnung von Aktivitätskoeffizienten zugänglich macht und so die Vorhersage von Dampf/Flüssig‐Gleichgewichten ermöglicht. Der Vorteil dieses Verfahrens liegt in der experimentell einfachen Zugänglichkeit von Dampfdruckdaten. Eine Demonstration dieses Verfahrens erfolgt anhand zweier binärer Gemische, für die aus Dampfdruckdaten die entsprechenden Dampf/Flüssig‐Gleichgewichte vorhergesagt und mit experimentell ermittelten Daten verglichen werden.

Background: Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually[1]. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells.Results: A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation.Conclusion: Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.

This paper highlights the influence of a refined microstructure on the wear behaviour of cermets by comparing TiC‐Ni based, VPS‐sprayed microcrystalline and nanocrystalline cermet coatings. The coatings are subjected to two‐body and three‐body abrasive wear at different loads. Fracture behaviour as well as mass loss and surface quality after the wear tests are evaluated. Although at low wear loads, the refined microstructure leads to a higher mass loss, at high loads the wear resistance of the nanocrystalline coating is superior. This behaviour is strongly related to a significantly higher toughness of the nanocrystalline coating. Independent of the wear load, the nanocrystalline microstructure leads to less surface roughness after wear.

Protein Arginine Methyltransferases (PRMTs) catalyze the addition of one or two methyl groups to the guanidino nitrogens of arginine side chains. Although this chemical modification may appear subtle, recent evidence has demonstrated complex levels of regulation and farreaching effects caused by protein arginine methylation. The current study shows that the global pattern of protein arginine methylation in A549 human lung epithelial cells undergoes dramatic changes during asbestos-induced apoptosis. Changes in mRNA expression and protein expression of the various PRMT isoforms are evident. Most notably, PRMT 1 shows a redistribution between cytosolic and nuclear compartments and PRMT6 is only detectable in these cells after asbestos treatment.

Exposure of human lung epithelial (A549) cells to asbestos fibers causes apoptosis, which is largely attributed to release of iron and generation of reactive oxygen species (ROS) within the cells. To mimic the highly oxidative environment generated by asbestos exposure in the absence of the actual fibers, we used two chemicals; buthione sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis and ferric ammonium citrate (FAC), a source of iron. Here, we report that exposure of A549 cells to crocidolite asbestos led to a significant time-dependent inactivation of signaling proteins, i.e. Akt and all mitogen-activated protein kinases (MAPKs) (p38, ERK1/2 and SAPK/JNK), and subsequently to apoptosis. Unlike crocidolite treatment, the use of BSO and FAC, independently or combined, did not change the phosphorylation status of proteins, nor did it induce apoptosis. Taken together, our results presented herein point to the possibility that crocidolite-induced apoptosis of human lung epithelial cells is not a mere consequence of generation of oxidants but also requires inactivation of major cell growth and differentiation pathways.

The innovative technology of metal injection moulding could be successfully applied to the titanium alloy TiAl6Nb7. For this reactive material the complex processing steps such as feedstock fabrication, injection moulding, debinding and sintering were optimised in the frame of the development of a bone screw implant.

Crocidolite, containing 27% iron by weight, is the most carcinogenic form of asbestos. Crocidolite fibers are endocytized by alpha(v)beta(5) integrin receptors in rabbit pleural mesothelial cells. We show here that crocidolite fibers are endocytized in human lung epithelial (A549) cells and in primary small airway epithelial (SAEC) cells. Presence of the integrin alpha(v)beta(5) blocking antibody, P1F6, significantly reduced the uptake of crocidolite fibers in A549 cells. Thus, the integrin alpha(v)beta(5) receptor is involved in endocytosis, of crocidolite fibers in A549 cells as well.Previously, it has been observed that asbestos fibers lead to changes in the intracellular redox environment, i.e. a marked decrease in intracellular glutathione concentrations and an increase in the extracellular glutathione in A549 cells. In addition, the decrease in intracellular glutathione was found to be largely independent of iron present on the surface of the fiber. A549 cells were treated with crocidolite in the presence of endocytosis inhibitor cytochalasin D. Our data indicate that, upon preventing endocytosis, we were able to reverse the decrease in total intracellular glutathione. The decrease in total intracellular glutathione could also be prevented in the presence of the monoclonal antibody P1F6. Thus, we observed that endocytosis of crocidolite fibers via integrin alpha(v)beta(5) receptor is linked to the marked decrease in total intracellular glutathione in A549 cells. (c) 2005 Elsevier Inc. All rights reserved.

Although primary particle emissions of ash from coal-fired power plants are well controlled, coal fly ash (CFA) can still remain a significant fraction of the overall particle exposure for some plant workers and highly impacted communities. The effect of CFA on pulmonary and systemic inflammation and injury was measured in male Sprague-Dawley rats exposed to filtered air or CFA for 4 h/day for 3 days. The average concentration of CFA particulate matter less than 2.5 microm (PM(2.5)) was 1400 microg/m(3), of which 600 microg/m(3) was PM(1). Animals were examined 18 and 36 h postexposure. Chemical analysis of CFA detected silicon, calcium, aluminum, and iron as major components. Total number of neutrophils in bronchoalveolar lavage fluid (BALF) following exposure to CFA was significantly increased along with significantly elevated blood neutrophils. Exposure to CFA caused slight increases in macrophage inflammatory protein-2, and marked increases in transferrin in BALF. Interleukin-1beta and total antioxidant potential in lung tissues were also increased in rats exposed to CFA. Histological examination of lung tissue demonstrated focal alveolar septal thickening and increased cellularity in select alveoli immediately beyond terminal bronchioles. These responses are consistent with the ability of CFA to induce mild neutrophilic inflammation in the lung and blood following short-term exposure at levels that could be occupationally relevant. However, when comparing the effects of CFA with those of concentrated ambient particles, CFA does not appear to have greater potency to cause pulmonary alterations. This study furthers our understanding of possible mechanisms by which specific sources of particulate air pollution affect human health.

Magnesium based Metal Matrix Composites (MMCs) reinforced by a combination of short Al2O3-fibres and SiC-particles are promising construction materials due to the low density and thermal expansion, high creep and wear resistance. Such a material is the hybrid reinforced magnesium alloy AE42, which is produced by the melt infiltration of fibre-particle preforms in the squeeze casting process. Many problems arise by machining these preforms with common machining tools because of the high wear resistance caused by the ceramic reinforcement. Solutions are only expensive tools with cutting edges made of polycrystalline diamonds or CVD-diamond coatings. This work is focussed on the application of abrasive water jet cutting for machining these wear resistant MMCs. Cutting tests were performed at MMC-specimens with thickness of 2-25 mm. Experimental results are presented which clearly indicate the high potential and efficiency of the abrasive water jet for machining MMCs.

This study demonstrates the potential of high-energy milling to use nanostructured cermet powders for thermal spraying utilizing a TiC–Ni-based composite as model material. The microstructure of coatings processed by VPS and HVOF spraying of nanostructured composite powders is characterized and compared to the initial microstructure of the feedstock. Thus, the effect of different microstructures, which can be produced by high-energy milling, on the microstructural evolution during spraying is evaluated. Results show that partial dissolution and reprecipitation of hard phase material as well coarsening of the binder phase crystallite size occur during the spraying process. However, a homogeneously dispersed hard phase distribution similar to that of the nanostructured precursor powder with hard phase sizes in the range of 100 nm is formed. Additionally, hard phase particles bigger than of 300 nm are retained during spraying. First results concerning hardness and wear resistance of respective coatings are shown and discussed.

German researchers demonstrate that careful handling of titanium alloy powders is the key to a manufacturing system for sophisticated medical implants. In doing so they point up the versatility of metal injection moulding and its ability to stem some spiralling health service costs…

A novel design for a dry-aerosol generator that efficiently produces a well-dispersed dust suspension using small quantities of a PM2.5-enriched powder sample is described. The motivation to develop a highly efficient dry-aerosol particle generator was to facilitate collaborative projects that combine in vitro cell culture experiments and multiday inhalation exposures using a single batch of well-characterized particles. Premixing of the test particles with larger diameter glass beads permits delivery of aerosol concentrations from 100–1000 μ g/m3 to an exposure chamber using only milligram quantities of the test powder per hour. Examination of exposure chamber filter samples by scanning electron microscopy showed well-dispersed particles of the test powder free of glass spheres or fragments. Data are presented from experiments using coal fly ash as the test powder to illustrate the system performance.

Das Metallpulverspritzgießen (Metal Injection Moulding: MIM) ist eine junge Urformtechnologie, die sich hervorragend für die Herstellung von kleinen, geometrisch komplexen Bauteilen aus Metall‐Legierungspulver eignet. Diese innovative Fertigungstechnologie wurde für die MIM‐technische Herstellung einer komplexen Knochenschraube aus Metallpulver der biokompatiblen Titan‐Legierung Ti Al6 Nb7 genutzt. In dieser Arbeit werden die MIM‐technischen Rahmenbedingungen zur Herstellung der Schraube vorgestellt, sowie die Ergebnisse aus mechanischen und chemischen Bauteilprüfungen diskutiert, die dieses komplexe Spritzgussteil für ein hoch belastetes Implantat qualifizieren.

In the present study, the wear behaviour of nanocrystalline coatings of the composition (Ti,Mo)(C,N)–45 vol. % NiCo, prepared by vacuum plasma spraying (VPS) and high-velocity oxy-fuel (HVOF) spraying of high-energy-milled powder, is characterized and compared to microcrystalline coatings of the same composition. Two-body abrasive wear tests, as well as scratch tests, are applied to produce wear traces on the surfaces of the nano- and microcrystalline coatings. While nanocrystalline HVOF coatings are weaker than their microcrystalline counterparts, nanocrystalline VPS coatings show superior wear resistance. The worn surface morphologies are investigated with optical microscopy, scanning electron microscopy and atomic force microscopy. The wear mechanisms and failure of nano- and microcrystalline coatings are distinctly different and are discussed in detail.