Particle and Fibre Toxicology, a new journal to meet a real need

This Editorial is to announce Particle and Fibre Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. The field of particle and fibre toxicology has a long and famous history stretching from Agricola and Paracelsus in the 15th and 16th century to the challenges of the 21st century-nanoparticles, nanotubes and particulate matter (PM10) to name just three. Throughout this time there has been no single journal dedicated to the toxicology of particles and fibres and this is finally corrected by the launch of Particle and Fibre Toxicology. The rationale for Particle and Fibre Toxicology rests on this need for a single multi-disciplinary journal that can cover all research relevant to particle and fibre toxicology, from Hygiene studies, through particle generation and characterisation, to animal, cell and human toxicology studies, dosimetry and modelling. The editorial also deals with the philosophy and practicalities of Open Access publishing, the journal's peer-review policy and conflict-of-interest. Particle and Fibre Toxicology is aimed at bringing together multi-disciplinary research findings towards a better understanding of how particles and fibres adversely affect the lungs and the body generally. We hope that the launch of the new journal will aid in the advance of this important discipline to the greater benefit of occupational and public health and invite scientists working in this key discipline to submit their research

The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles

In vitro studies with particles are a major staple of particle toxicology, generally used to investigate mechanisms and better understand the molecular events underlying cellular effects. However, there is ethical and financial pressure in nanotoxicology, the new sub-specialty of particle toxicology, to avoid using animals. Therefore an increasing amount of studies are being published using in vitro approaches and such studies require careful interpretation. We point out here that 3 different conventional pathogenic particle types, PM10, asbestos and quartz, which cause diverse pathological effects, have been reported to cause very similar oxidative stress effects in cells in culture. We discuss the likely explanation and implications of this apparent paradox, and its relevance for testing in nanotoxicology

ROS-mediated TNF-α and MIP-2 gene expression in alveolar macrophages exposed to pine dust

BACKGROUND: Respiratory symptoms, impaired lung function, and asthma have been reported in workers exposed to wood dust in a number of epidemiological studies. The underlying pathomechanisms, however, are not well understood. Here, we studied the effects of dust from pine (PD) and heat-treated pine (HPD) on the release of reactive oxygen species (ROS) and inflammatory mediators in rat alveolar macrophages. METHODS: Tumour necrosis factor-alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2) protein release, TNF-α and MIP-2 mRNA expression, and generation of ROS were studied as end points after treatment of rat alveolar macrophages with PD or HPD. In a separate series of experiments, the antioxidants glutathione and N-acetyl-L-cysteine were included in combination with wood dust. To determine the endogenous oxidative and antioxidant capacity of wood dusts, electron spin resonance (ESR) spectroscopy was used. RESULTS: After 4 h incubation, both PD and HPD elicited a significantly (p < 0.05) increased mRNA expression of TNF-α and MIP-2 as well as a concentration-dependent release of TNF-α and MIP-2 protein. Interestingly, PD induced a significantly higher TNF-α and MIP-2 production than HPD. Moreover, a significantly increased ROS production was observed in alveolar macrophages exposed to both PD and HPD. In the presence of the antioxidants glutathione and N-acetyl-L-cysteine, the PD- and HPD-induced release of ROS, TNF-α, and MIP-2 was significantly reduced. Finally, electron spin resonance analyses demonstrated a higher endogenous antioxidant capacity of HPD compared to PD. Endotoxin was not present in either dust sample. CONCLUSION: These results indicate that pine dust is able to induce expression of TNF-α and MIP-2 in rat alveolar macrophages by a mechanism that is, at least in part, mediated by ROS

Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

<p>Abstract</p> <p>Background</p> <p>A symposium on the mechanisms of action of inhaled airborne particulate matter (PM), pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental Protection Agency (EPA) Conference Center in Research Triangle Park, North Carolina. The meeting was the eighth in a series of transatlantic conferences first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit (1979), that have fostered long-standing collaborations between researchers in the fields of mineralogy, cell and molecular biology, pathology, toxicology, and environmental/occupational health.</p> <p>Results</p> <p>The goal of this meeting, which was largely supported by a conference grant from the NHLBI, was to assemble a group of clinical and basic research scientists who presented and discussed new data on the mechanistic effects of inhaled particulates on the onset and development of morbidity and mortality in the lung and cardiovascular system. Another outcome of the meeting was the elucidation of a number of host susceptibility factors implicated in adverse health effects associated with inhaled pathogenic particulates.</p> <p>Conclusion</p> <p>New models and data presented supported the paradigm that both genetic and environmental (and occupational) factors affect disease outcomes from inhaled particulates as well as cardiopulmonary responses. These future studies are encouraged to allow the design of appropriate strategies for prevention and treatment of particulate-associated morbidity and mortality, especially in susceptible populations.</p

Exposure to diesel exhaust induces changes in EEG in human volunteers

Background: Ambient particulate matter and nanoparticles have been shown to translocate to the brain, and potentially influence the central nervous system. No data are available whether this may lead to functional changes in the brain. Methods: We exposed 10 human volunteers to dilute diesel exhaust (DE, 300 μg/m3) as a model for ambient PM exposure and filtered air for one hour using a double blind randomized crossover design. Brain activity was monitored during and for one hour following each exposure using quantitative electroencephalography (QEEG) at 8 different sites on the scalp. The frequency spectrum of the EEG signals was used to calculate the median power frequency (MPF) and specific frequency bands of the QEEG. Results: Our data demonstrate a significant increase in MPF in response to DE in the frontal cortex within 30 min into exposure. The increase in MPF is primarily caused by an increase in fast wave activity (β2) and continues to rise during the 1 hour post-exposure interval. Conclusion: This study is the first to show a functional effect of DE exposure in the human brain, indicating a general cortical stress response. Further studies are required to determine whether this effect is mediated by the nanoparticles in DE and to define the precise pathways involved

The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung

BACKGROUND: Translocation of ultrafine particles (UFP) into the blood that returns from the lungs to the heart has been forwarded as a mechanism for particle-induced cardiovascular effects. The objective of this study was to evaluate the role of the endothelial barrier in the translocation of inhaled UFP from the lung into circulation. METHODS: The isolated perfused rat lung (IPRL) was used under negative pressure ventilation, and radioactive iridium particles (18 nm, CMD, (192)Ir-UFP) were inhaled during 60 minutes to achieve a lung burden of 100 – 200 μg. Particle inhalation was done under following treatments: i) control perfusion, ii) histamine (1 μM in perfusate, iii) luminal histamine instillation (1 mM), and iv) luminal instillation of H(2)O(2). Particle translocation to the perfusate was assessed by the radioactivity of (192)Ir isotope. Lung permeability by the use of Tc(99m)-labeled diethylene triamine pentaacetic acid (DTPA). In addition to light microscopic morphological evaluation of fixed lungs, alkaline phosphatase (AKP) and angiotensin converting enzyme (ACE) in perfusate were measured to assess epithelial and endothelial integrity. RESULTS: Particle distribution in the lung was homogenous and similar to in vivo conditions. No translocation of Ir particles at negative pressure inhalation was detected in control IPL, but lungs pretreated with histamine (1 μM) in the perfusate or with luminal H(2)O(2 )(0.5 mM) showed small amounts of radioactivity (2–3 % dose) in the single pass perfusate starting at 60 min of perfusion. Although the kinetics of particle translocation were different from permeability for (99m)Tc-DTPA, the pretreatments (H(2)O(2), vascular histamine) caused similar changes in the translocation of particles and soluble mediator. Increased translocation through epithelium and endothelium with a lag time of one hour occurred in the absence of epithelial and endothelial damage. CONCLUSION: Permeability of the lung barrier to UFP or nanoparticles is controlled both at the epithelial and endothelial level. Conditions that affect this barrier function such as inflammation may affect translocation of NP

First Magnetic Resonance Imaging-Guided Aortic Stenting and Cava Filter Placement Using a Polyetheretherketone-Based Magnetic Resonance Imaging-Compatible Guidewire in Swine: Proof of Concept

The purpose of this study was to demonstrate feasibility of percutaneous transluminal aortic stenting and cava filter placement under magnetic resonance imaging (MRI) guidance exclusively using a polyetheretherketone (PEEK)-based MRI-compatible guidewire. Percutaneous transluminal aortic stenting and cava filter placement were performed in 3 domestic swine. Procedures were performed under MRI-guidance in an open-bore 1.5-T scanner. The applied 0.035-inch guidewire has a PEEK core reinforced by fibres, floppy tip, hydrophilic coating, and paramagnetic markings for passive visualization. Through an 11F sheath, the guidewire was advanced into the abdominal (swine 1) or thoracic aorta (swine 2), and the stents were deployed. The guidewire was advanced into the inferior vena cava (swine 3), and the cava filter was deployed. Postmortem autopsy was performed. Procedural success, guidewire visibility, pushability, and stent support were qualitatively assessed by consensus. Procedure times were documented. Guidewire guidance into the abdominal and thoracic aortas and the inferior vena cava was successful. Stent deployments were successful in the abdominal (swine 1) and thoracic (swine 2) segments of the descending aorta. Cava filter positioning and deployment was successful. Autopsy documented good stent and filter positioning. Guidewire visibility through applied markers was rated acceptable for aortic stenting and good for venous filter placement. Steerability, pushability, and device support were good. The PEEK-based guidewire allows either percutaneous MRI-guided aortic stenting in the thoracic and abdominal segments of the descending aorta and filter placement in the inferior vena cava with acceptable to good device visibility and offers good steerability, pushability, and device suppor