Nanoparticles-A Thoracic Toxicology Perspective

A substantial literature demonstrates that the main ultrafine particles found in ambient urban air are combustion-derived nanoparticles (CDNP) which originate from a number of sources and pose a hazard to the lungs. For CDNP, three properties appear important-surface area, organics and metals. All of these can generate free radicals and so induce oxidative stress and inflammation. Inflammation is a process involved in the diseases exhibited by the individuals susceptible to the effects of PM-development and exacerbations of airways disease and cardiovascular disease. It is therefore possible to implicate CDNP in the common adverse effects of increased PM. The adverse effects of increases in PM on the cardiovascular system are well-documented in the epidemiological literature and, as argued above, these effects are likely to be driven by the combustion-derived NP. The epidemiological findings can be explained in a number of hypotheses regarding the action of NP:-1) Inflammation in the lungs caused by NP causes atheromatous plaque development and destabilization; 2) The inflammation in the lungs causes alteration in the clotting status or fibrinolytic balance favouring thrombogenesis; 3) The NP themselves or metals/organics released by the particles enter the circulation and have direct effects on the endothelium, plaques, the clotting system or the autonomic nervous system/ heart rhythm. Environmental nanoparticles are accidentally produced but they provide a toxicological model for a new class of purposely 'engineered' NP arising from the nanotechnology industry, whose effects are much less understood. Bridging our toxicological knowledge between the environmental nanoparticles and the new engineered nanoparticles is a considerable challenge

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

Characteristics and health implications of fine and coarse particulates at roadside, urban background and rural sites in UK

Recent studies have pointed to evidence that fine particles in the air could be significant contributors to respiratory and cardiovascular diseases and mortality. Epidemiologists looking at the health effects of particulate pollution need more information from various receptor locations to improve the understanding of this problem. Detailed information on temporal, spatial and size distributions of particulate pollution in urban areas also is important for air quality modellers as well as being an aid to decision and policy makers of local authorities. This paper presents a detailed analysis of temporal and seasonal variation of PM10 and PM2.5 levels at one urban roadside, one urban background and one rural monitoring location. Levels of PM10, PM2.5 and coarse fraction of particulates are compared. In addition, particulate levels are compared with NO2 and CO concentrations. The study concludes that PM10 and PM2.5 are closely related at urban locations. Diurnal variation in PM2.5/PM10 ratio shows the influence of vehicular emission and movement on size distribution. This ratio is higher in winter than in summer indicating a build-up or longer residence time of finer particulates or washout due to wet weather in winter. In the second part of this study, a disease burden analysis is carried out based on the dose-response relationships recommended by the UK Committee on the Medical Effects of Air Pollution. The disease burden analysis indicates that if Marylebone Road levels of PM10 were prevalent all over London, it will result in around 2.5% increase in death rates due to all causes. Whereas, if Bloomsbury levels were prevalent in London, which is more likely to occur as this is more representative of the urban background environment to which people in London are likely to be exposed, the corresponding increase would be around 1.7%. Considering this, in London, at Bloomsbury levels 973 deaths and 1515 Respiratory Hospital Admissions (RHA) are attributable to PM10 while 2140 RHA are attributable to NO2. After deducting the disease burden due to background levels at Rochester, PM10 emission caused by anthropogenic activities in London equate to 273 additional deaths and 410 additional RHA while NO2 account for additional 1205 incidences of RHA

Includes a Commentary by the Institute’s Health Review Committee HEALTH

in 1980, is an independent and unbiased source of information on the health effects of motor vehicle emissions. HEI studies all major pollutants, including regulated pollutants (such as carbon monoxide, ozone, nitrogen dioxide, and particulate matter) and unregulated pollutants (such as diesel engine exhaust, methanol, and aldehydes). To date, HEI has supported more than 200 projects at institutions in North America and Europe and has published over 130 research reports. Typically, HEI receives half its funds from the US Environmental Protection Agency and half from 28 manufacturers and marketers of motor vehicles and engines in the United States. Occasionally, funds from other public and private organizations either support special projects or provide resources for a portion of an HEI study. Regardless of funding sources, HEI exercises complete autonomy in setting its research priorities and in reaching its conclusions. An independent Board of Directors governs HEI. The Institute’s Health Research and Health Review Committees serve complementary scientific purposes and draw distinguished scientists as members. The results of HEI-funded studies are made available as Research Reports, which contain both the Investigators’ Report and the Review Committee’s evaluation of the work’s scientific quality and regulatory relevance