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Circulation. 2002;105:411-414
doi: 10.1161/hc0402.104118
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(Circulation. 2002;105:411.)
© 2002 American Heart Association, Inc.


Brief Rapid Communications

Passage of Inhaled Particles Into the Blood Circulation in Humans

A. Nemmar, DVM, PhD; P.H.M. Hoet, PhD; B. Vanquickenborne, MD; D. Dinsdale, PhD; M. Thomeer, MD; M.F. Hoylaerts, PhD; H. Vanbilloen, PhD; L. Mortelmans, MD, PhD; B. Nemery, MD, PhD

From the Laboratory of Pneumology (Lung Toxicology) (A.N., P.H.M.H., M.T., B.N.), Nuclear Medicine (B.V., H.V., L.M.), and Center for Molecular and Vascular Biology (M.F.H.), Katholieke Universiteit Leuven, Leuven, Belgium; and the MRC Toxicology Unit (D.D.), Leicester, UK.

Correspondence to Prof B. Nemery, K.U.Leuven, Laboratorium voor Pneumologie (Longtoxicologie), Herestraat 49, B-3000 Leuven, Belgium. E-mail ben.nemery{at}med.kuleuven.ac.be


*    Abstract
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Background Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated.

Methods and Results To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine 99mTechnetium-labeled carbon particles (<100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized 99mTc, ie, pertechnetate, there was also a species corresponding to particle-bound 99mTc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body.

Conclusions We conclude that inhaled 99mTc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.


Key Words: air pollution • particles • translocation • blood • lung


*    Introduction
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Epidemiological studies have shown that peaks of air pollution by particulate matter with a diameter of <10 µm (PM10) are associated with increased morbidity and mortality, not only from respiratory causes but mainly from cardiovascular diseases.15 Recently, it has been shown that exposure to particulate air pollution for as little as 2 hours increased the occurrence of myocardial.6 The mechanisms responsible for the cardiovascular effects are not well-elucidated.7 The main current hypothesis is that the particles produce pulmonary inflammation with a systemic release of cytokines, which may influence cardiovascular endpoints.8 It has also been proposed that pollutants may cause (reflex) alterations in cardiac autonomic function thus causing changes in heart rate variability and increasing the risk of sudden cardiac death.9

An alternative hypothesis, which has not been much investigated so far, is that the smallest particles translocate from the lungs into the circulation and thus influence cardiovascular endpoints more directly. Ultrafine particles, ie, particles with diameter <=0.1 µm, represent a substantial component, in terms of particle numbers, in PM10, although they represent a relatively small fraction of the total mass.10 Ultrafine particles have also a much larger surface area, and hence, more toxic potential.11,12 Recently, we have shown, in hamster, that a substantial fraction of intratracheally instilled ultrafine particles (radiolabeled denatured albumin with diameter <100 nm) rapidly diffuses from the lungs into the systemic circulation.13 Others have recently described a systemic distribution of inhaled ultrafine silver particles in rats.14

Therefore, we wanted to verify whether this also occurs in humans inhaling ultrafine particles. No human data are available on this issue. We utilized a technique, commonly used in diagnostic nuclear medicine for measuring the distribution of ventilation,15 based on the inhalation of an aerosol of technetium-99m labeled carbon particles (Technegas).


*    Methods
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This study has been approved by our institution’s ethical committee for experimentation in human subjects.

Technegas consists on an aerosol suspension of 99mTc-labeled, ultrafine carbon particles produced in an atmosphere of high-purity argon. It was considered that 100% of the inhaled particles in Technegas were labeled with 99mTc and that the aerosol did not contain pertechnetate (TcO4-).16 The size of the individualized particles was of the order of 5 to 10 nm, as we confirmed by electron microscopy of particles collected with a thermophoretic precipitator. However, particle aggregates were also seen. Inhalation of these particles enabled static and dynamic images in multiple projections to be acquired.17

We studied 5 healthy, male nonsmoking volunteers (24 to 47 years, mean age 32.8 years). They inhaled, according to a standard procedure,18 approximately 100 MBq of Technegas in 3 to 5 breaths via a mouthpiece. Immediately after the Technegas inhalation, body images were acquired as follows: static acquisition (1 to 3 minutes) of lungs and thyroid followed by dynamic acquisition (5 to 45 minutes) of the abdomen, including liver, stomach, and bladder, and then successive images of the whole body (50 to 60 minutes). Blood samples were collected (via a venous catheter) at 1, 5, 10, 20, 30, 45, and 60 minutes after Technegas inhalation, and their radioactivity was measured in a gamma counter. At each time point, thin layer chromatography (TLC) was done on a droplet of blood using silica impregnated glass fiber ITLC-SG strips (Gelman Sciences) with NaCl 0.9% as the mobile phase. The chromatograms were cut into 1-cm lengths and their radioactivity measured with a gamma counter (1480W12ARD, Wallac) with a correction for background radiation. TLC was also done on a urine sample at 60 minutes.


*    Results
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Figure 1a illustrates the time course of the radioactivity in blood expressed as counts per minute (CPM) per gram of blood. The radioactivity was detected in blood already after 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. At all time points, TLC of blood (Figure 1b) showed a peak of radioactivity at the application point and another peak that moved with the solvent front. In urine, there was mainly the latter peak. For comparison, we also present the results of TLC after the direct addition of Technegas particles (collected on a filter, at the mouth) or 99mTc-pertechnetate (TcO4-) to blood, showing that the bound radioactivity stays at the origin while the free pertechnetate moves with the solvent front. We also show a TLC of blood at 1 and 60 minutes after the instillation of 200 µL of free 99mTc-pertechnetate (3.7 MBq) in hamsters (n=3), showing a single peak of radioactivity at the solvent front.



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Figure 1. A, Radioactivity in blood at intervals after Technegas inhalation (mean±SEM, n=5). B, distribution of radioactivity after thin layer chromatography (TLC). The y-axis represents percent of total CPM (counts per minute) measured on the TLC paper; x-axis, distance (in cm) on the chromatogram. In blood (unframed graphs), TLC showed the presence of 2 99mTc-label species: one species moved with the solvent front and corresponds to oxidized 99mTc, ie, pertechnetate (TcO4-), and the other species stayed at the application point and corresponds to particle-bound 99mTc. The framed graphs correspond to the TLC profiles after the direct addition of 99mTc-carbon particles or 99mTcO4- to blood, showing that the bound radioactivity stays at the origin while the free technetate moves with the solvent front. The TLC in urine at 60 minutes and in blood at 1 and 60 minutes after the intratracheal (i.t.) administration of 200 µL of 99mTc-pertechnetate in hamsters showed one peak that moved with the solvent front.

The radioactivity recorded over the liver and bladder was expressed as a percentage of the initial lung radioactivity. In liver, the radioactivity remained stable at around 8%, while in the bladder it increased with time (Figure 2).



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Figure 2. Time-activity curve over liver and bladder expressed as percent of initial lung radioactivity. Insert, Whole body gamma camera image of 1 representative volunteer recorded at 60 minutes. The radioactivity over the organs is expressed as counts per minute (CPM) per pixel within each region of interest (ROI). The values recorded over the stomach were not included because this radioactivity may also come partly from swallowing of particles deposited in the mouth.


*    Discussion
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*Discussion
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This study was designed to investigate a plausible mechanistic explanation for the consistent but puzzling epidemiological observations that particulate air pollution is associated with cardiovascular effects.36 Our working hypothesis, which is different but not opposed to more traditional ones,8,9 is that ultrafine particles may pass into the circulation and thus exert direct effects on the heart and vessels.

The type of aerosol used in our study is probably relevant urban air pollutant aerosols. Particles with diameters ranging from 0.02 µm to more than 100 µm are measurable in the air of cities.11,19 Ultrafine particles (smaller than 100 nm) are often emitted from combustion and other high-temperature processes in the form of fractal-like aggregates composed of solid nanoparticles. The primary particle size of atmospheric aggregates ranges from 6 to 100 nm. This broad polydispersity has been related to the fact that atmospheric aggregates come from a variety of sources with different primary particle sizes.20 In addition, Shi et al21 found that the primary particles in diesel aggregates range from 10 to 40 nm. The size of the individualized particles used in our study (5 to 10 nm), as well as the aggregates that were also seen by electron microscopy is therefore relevant to atmospheric ultrafine particles.

Technegas is different from Pertechnegas, which is also used in nuclear medicine (for measuring lung permeability).22 Pertechnegas is produced in an atmosphere of argon and oxygen, thus allowing the technetium to become oxidized to the hydrosoluble pertechnetate (TcO4-), the kinetics of which have been studied.23 In contrast, Technegas is generated in a pure argon atmosphere, and therefore, the aerosol only consists of 99mTc-labeled particles without any appreciable TcO4-. We verified this to be the case by TLC of the material collected on a filter at the mouth. However, after deposition of 99mTc-labeled particles in the body, some TcO4- is produced. Thus, a species behaving as TcO4- was found by TLC in blood and in urine (Figure 1b), as well as in saliva (not shown), and the intense radioactivity detected over the thyroid, salivary glands, and stomach (Figure 2) is essentially due to the well-known accumulation of TcO4- in these organs.24 In the stomach, besides TcO4- from saliva and gastric secretion, some radioactivity also came from swallowed particles that had deposited in the mouth or been cleared from the trachea via the mucociliary escalator.

However, 3 lines of evidence indicate that the radioactivity that we measured in blood consists, at least partly, of particle-bound radioactivity, ie, radioactivity associated with carbon particles having passed the air-blood barrier, rather than free radioactivity. Firstly, TLC of all blood samples showed, in addition to radioactivity having moved with the solvent front and corresponding to oxidized 99mTc, ie, pertechnetate (TcO4-), a substantial proportion of radioactivity that stayed at the application point and corresponded to particle-bound 99mTc. Such a profile was similar to that obtained after spiking blood with 99mTc-carbon particles collected from the Technegas generator. In contrast, there was only one peak at the solvent front after adding 99mTc-pertechnetate to blood or in blood collected after the intratracheal administration of 99mTc-pertechnetate to hamsters. This excludes the possibility that the noneluting radioactivity was due to free technetium having become bound to plasma proteins. Secondly, the TLC of urine showed only one peak at the solvent front, and this is in agreement with an elimination of free 99mTc-pertechnetate via the urine.24 Finally, the presence of radioactivity in the liver is compatible with an accumulation of particles by Kupffer cells, as is known to occur with colloidal particles.25,26 Because of the rapidity of the accumulation of radioactivity in liver, we think it is unlikely that the liver radioactivity came from the stomach. Admittedly, the above reasoning only provides indirect arguments that radioactivity outside the lungs corresponded to particles, and we would have liked to have more direct evidence. However, we were unable to detect the carbon particles in ultrathin sections of blood by electron microscopy, most probably because of their low electron density. Nevertheless, despite this limitation, we are confident that our findings provide plausible evidence for particle translocation from the lung into the blood and then its distribution to the organs. This conclusion is supported by recent studies in animals.13,14 The exact mechanism for this translocation remains to be established, but its rapidity makes it unlikely that phagocytosis by macrophages and/or endocytosis by epithelial and endothelial cells are (solely) responsible for particle-translocation to the blood. There are experimental data suggesting the existence of (functional) pores in the alveolar-blood barrier,27 and this is supported by the fact that "pneumoproteins" may be found in the blood.28

We conclude that inhaled ultrafine 99mTc-carbon particles, which are very similar to (the ultrafine fraction of) actual pollutant particles, diffuse rapidly into the systemic circulation, and this should be considered relevant for the cardiovascular morbidity and mortality related to ambient particle pollution.


*    Acknowledgments
 
This work was supported by the funds of K.U.Leuven (F/00/058). We are very grateful to K. Stessel (Nuclear Medicine, K.U.Leuven) for his excellent technical assistance.

Received November 14, 2001; revision received December 11, 2001; accepted December 19, 2001.


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*References
 
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T. S. Nawrot, A. Nemmar, and B. Nemery
Update in Environmental and Occupational Medicine 2006
Am. J. Respir. Crit. Care Med., April 15, 2007; 175(8): 758 - 762.
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StrokeHome page
J. Kettunen, T. Lanki, P. Tiittanen, P. P. Aalto, T. Koskentalo, M. Kulmala, V. Salomaa, and J. Pekkanen
Associations of Fine and Ultrafine Particulate Air Pollution With Stroke Mortality in an Area of Low Air Pollution Levels
Stroke, March 1, 2007; 38(3): 918 - 922.
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Toxicol PatholHome page
A. Shimada, N. Kawamura, M. Okajima, T. Kaewamatawong, H. Inoue, and T. Morita
Translocation Pathway of the Intratracheally Instilled Ultrafine Particles from the Lung into the Blood Circulation in the Mouse
Toxicol Pathol, December 1, 2006; 34(7): 949 - 957.
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Hum Exp ToxicolHome page
M R Ray, S Mukherjee, S Roychoudhury, P Bhattacharya, M Banerjee, S Siddique, S Chakraborty, and T Lahiri
Platelet activation, upregulation of CD11b/CD18 expression on leukocytes and increase in circulating leukocyte-platelet aggregates in Indian women chronically exposed to biomass smoke
Human and Experimental Toxicology, November 1, 2006; 25(11): 627 - 635.
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Eur Heart JHome page
A. Maitre, V. Bonneterre, L. Huillard, P. Sabatier, and R. de Gaudemaris
Impact of urban atmospheric pollution on coronary disease
Eur. Heart J., October 1, 2006; 27(19): 2275 - 2284.
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Int J EpidemiolHome page
A. Zeka, J. R Sullivan, P. S Vokonas, D. Sparrow, and J. Schwartz
Inflammatory markers and particulate air pollution: characterizing the pathway to disease
Int. J. Epidemiol., October 1, 2006; 35(5): 1347 - 1354.
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Circ. Res.Home page
A. Bhatnagar
Environmental Cardiology: Studying Mechanistic Links Between Pollution and Heart Disease
Circ. Res., September 29, 2006; 99(7): 692 - 705.
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Eur Respir JHome page
P. Wiebert, A. Sanchez-Crespo, J. Seitz, R. Falk, K. Philipson, W. G. Kreyling, W. Moller, K. Sommerer, S. Larsson, and M. Svartengren
Negligible clearance of ultrafine particles retained in healthy and affected human lungs
Eur. Respir. J., August 1, 2006; 28(2): 286 - 290.
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Toxicol SciHome page
K. Donaldson, R. Aitken, L. Tran, V. Stone, R. Duffin, G. Forrest, and A. Alexander
Carbon Nanotubes: A Review of Their Properties in Relation to Pulmonary Toxicology and Workplace Safety
Toxicol. Sci., July 1, 2006; 92(1): 5 - 22.
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Am. J. Physiol. Cell Physiol.Home page
H. Yamawaki and N. Iwai
Cytotoxicity of water-soluble fullerene in vascular endothelial cells
Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1495 - C1502.
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Toxicol SciHome page
P. Borm, F. C. Klaessig, T. D. Landry, B. Moudgil, J. Pauluhn, K. Thomas, R. Trottier, and S. Wood
Research Strategies for Safety Evaluation of Nanomaterials, Part V: Role of Dissolution in Biological Fate and Effects of Nanoscale Particles
Toxicol. Sci., March 1, 2006; 90(1): 23 - 32.
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Am. J. Respir. Crit. Care Med.Home page
N. L. Mills, N. Amin, S. D. Robinson, A. Anand, J. Davies, D. Patel, J. M. de la Fuente, F. R. Cassee, N. A. Boon, W. MacNee, et al.
Do Inhaled Carbon Nanoparticles Translocate Directly into the Circulation in Humans?
Am. J. Respir. Crit. Care Med., February 15, 2006; 173(4): 426 - 431.
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ScienceHome page
A. Nel, T. Xia, L. Madler, and N. Li
Toxic Potential of Materials at the Nanolevel
Science, February 3, 2006; 311(5761): 622 - 627.
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HeartHome page
H C Routledge, S Manney, R M Harrison, J G Ayres, and J N Townend
Effect of inhaled sulphur dioxide and carbon particles on heart rate variability and markers of inflammation and coagulation in human subjects
Heart, February 1, 2006; 92(2): 220 - 227.
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Toxicol SciHome page
J. S. Tsuji, A. D. Maynard, P. C. Howard, J. T. James, C.-w. Lam, D. B. Warheit, and A. B. Santamaria
Research Strategies for Safety Evaluation of Nanomaterials, Part IV: Risk Assessment of Nanoparticles
Toxicol. Sci., January 1, 2006; 89(1): 42 - 50.
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Am. J. Respir. Crit. Care Med.Home page
F. Forastiere, M. Stafoggia, S. Picciotto, T. Bellander, D. D'Ippoliti, T. Lanki, S. von Klot, F. Nyberg, P. Paatero, A. Peters, et al.
A Case-Crossover Analysis of Out-of-Hospital Coronary Deaths and Air Pollution in Rome, Italy
Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1549 - 1555.
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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
H. M. Kipen and D. L. Laskin
Smaller is not always better: nanotechnology yields nanotoxicology
Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L696 - L697.
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Occup. Environ. Med.Home page
R-S Koskela, P Mutanen, J-A Sorsa, and M Klockars
Respiratory disease and cardiovascular morbidity
Occup. Environ. Med., September 1, 2005; 62(9): 650 - 655.
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Toxicol SciHome page
D. H. R. F. Rivero, S. R. C. Soares, G. Lorenzi-Filho, M. Saiki, J. J. Godleski, L. Antonangelo, M. Dolhnikoff, and P. H. N. Saldiva
Acute Cardiopulmonary Alterations Induced by Fine Particulate Matter of Sao Paulo, Brazil
Toxicol. Sci., June 1, 2005; 85(2): 898 - 905.
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Am. J. Respir. Crit. Care Med.Home page
W. S. Beckett, D. F. Chalupa, A. Pauly-Brown, D. M. Speers, J. C. Stewart, M. W. Frampton, M. J. Utell, L.-S. Huang, C. Cox, W. Zareba, et al.
Comparing Inhaled Ultrafine versus Fine Zinc Oxide Particles in Healthy Adults: A Human Inhalation Study
Am. J. Respir. Crit. Care Med., May 15, 2005; 171(10): 1129 - 1135.
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Am. J. Respir. Crit. Care Med.Home page
A. Nemmar, B. Nemery, P. H. M. Hoet, N. Van Rooijen, and M. F. Hoylaerts
Silica Particles Enhance Peripheral Thrombosis: Key Role of Lung Macrophage-Neutrophil Cross-Talk
Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 872 - 879.
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Occup. Environ. Med.Home page
P S Gilmour, E R Morrison, M A Vickers, I Ford, C A Ludlam, M Greaves, K Donaldson, and W MacNee
The procoagulant potential of environmental particles (PM10)
Occup. Environ. Med., March 1, 2005; 62(3): 164 - 171.
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StrokeHome page
R. Maheswaran, R. P. Haining, P. Brindley, J. Law, T. Pearson, P. R. Fryers, S. Wise, and M. J. Campbell
Outdoor Air Pollution and Stroke in Sheffield, United Kingdom: A Small-Area Level Geographical Study
Stroke, February 1, 2005; 36(2): 239 - 243.
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Journal of the Geological SocietyHome page
T. MORENO, W. GIBBONS, T. JONES, and R. RICHARDS
Geochemical and size variations in inhalable UK airborne particles: the limitations of mass measurements
Journal of the Geological Society, December 1, 2004; 161(6): 899 - 902.
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QJMHome page
J.E. Sharman, J.R. Cockcroft, and J.S. Coombes
Cardiovascular implications of exposure to traffic air pollution during exercise
QJM, October 1, 2004; 97(10): 637 - 643.
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CirculationHome page
A. Nemmar, P. H.M. Hoet, J. Vermylen, B. Nemery, and M. F. Hoylaerts
Pharmacological Stabilization of Mast Cells Abrogates Late Thrombotic Events Induced by Diesel Exhaust Particles in Hamsters
Circulation, September 21, 2004; 110(12): 1670 - 1677.
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J. Immunol.Home page
N. Li, J. Alam, M. I. Venkatesan, A. Eiguren-Fernandez, D. Schmitz, E. Di Stefano, N. Slaughter, E. Killeen, X. Wang, A. Huang, et al.
Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals
J. Immunol., September 1, 2004; 173(5): 3467 - 3481.
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CirculationHome page
R. D. Brook, B. Franklin, W. Cascio, Y. Hong, G. Howard, M. Lipsett, R. Luepker, M. Mittleman, J. Samet, S. C. Smith Jr, et al.
Air Pollution and Cardiovascular Disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association
Circulation, June 1, 2004; 109(21): 2655 - 2671.
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Am J EpidemiolHome page
D. Liao, Y. Duan, E. A. Whitsel, Z.-j. Zheng, G. Heiss, V. M. Chinchilli, and H.-M. Lin
Association of Higher Levels of Ambient Criteria Pollutants with Impaired Cardiac Autonomic Control: A Population-based Study
Am. J. Epidemiol., April 15, 2004; 159(8): 768 - 777.
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CirculationHome page
A. Khandoga, A. Stampfl, S. Takenaka, H. Schulz, R. Radykewicz, W. Kreyling, and F. Krombach
Ultrafine Particles Exert Prothrombotic but Not Inflammatory Effects on the Hepatic Microcirculation in Healthy Mice In Vivo
Circulation, March 16, 2004; 109(10): 1320 - 1325.
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Am. J. Physiol. Heart Circ. Physiol.Home page
A. Bhatnagar
Cardiovascular pathophysiology of environmental pollutants
Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H479 - H485.
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CirculationHome page
R. L. Johnson Jr
Relative Effects of Air Pollution on Lungs and Heart
Circulation, January 6, 2004; 109(1): 5 - 7.
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HeartHome page
H C Routledge, J G Ayres, and J N Townend
Why cardiologists should be interested in air pollution
Heart, December 1, 2003; 89(12): 1383 - 1388.
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Am. J. Respir. Crit. Care Med.Home page
A. Nemmar, B. Nemery, P. H. M. Hoet, J. Vermylen, and M. F. Hoylaerts
Pulmonary Inflammation and Thrombogenicity Caused by Diesel Particles in Hamsters: Role of Histamine
Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1366 - 1372.
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Toxicol PatholHome page
L. Calderon-Garciduenas, R. R. Maronpot, R. Torres-Jardon, C. Henriquez-Roldan, R. Schoonhoven, H. Acuna-Ayala, A. Villarreal-Calderon, J. Nakamura, R. Fernando, W. Reed, et al.
DNA Damage in Nasal and Brain Tissues of Canines Exposed to Air Pollutants Is Associated with Evidence of Chronic Brain Inflammation and Neurodegeneration
Toxicol Pathol, August 1, 2003; 31(5): 524 - 538.
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CirculationHome page
A. Nemmar, P. H.M. Hoet, D. Dinsdale, J. Vermylen, M. F. Hoylaerts, and B. Nemery
Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis
Circulation, March 4, 2003; 107(8): 1202 - 1208.
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Hum ReprodHome page
B.E. Lee, E.H. Ha, H.S. Park, Y.J. Kim, Y.C. Hong, H. Kim, and J.T. Lee
Exposure to air pollution during different gestational phases contributes to risks of low birth weight
Hum. Reprod., March 1, 2003; 18(3): 638 - 643.
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CirculationHome page
W. M. Burch, A. Nemmar, P.H.M. Hoet, M. Thomeer, B. Nemery, B. Vanquickenborne, H. Vanbilloen, L. Mortelmans, M.F. Hoylaerts, A. Verbruggen, et al.
Passage of Inhaled Particles Into the Blood Circulation in Humans * Response
Circulation, November 12, 2002; 106 (20): e141 - e142.
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Am. J. Respir. Crit. Care Med.Home page
J. S. Brown, K. L. Zeman, and W. D. Bennett
Ultrafine Particle Deposition and Clearance in the Healthy and Obstructed Lung
Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1240 - 1247.
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Am. J. Respir. Crit. Care Med.Home page
A. Nemmar, M. F. Hoylaerts, P. H. M. Hoet, D. Dinsdale, T. Smith, H. Xu, J. Vermylen, and B. Nemery
Ultrafine Particles Affect Experimental Thrombosis in an In Vivo Hamster Model
Am. J. Respir. Crit. Care Med., October 1, 2002; 166(7): 998 - 1004.
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CirculationHome page
R. L. Verrier, M. A. Mittleman, and P. H. Stone
Air Pollution: An Insidious and Pervasive Component of Cardiac Risk
Circulation, August 20, 2002; 106(8): 890 - 892.
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Am. J. Respir. Crit. Care Med.Home page
W. D. Bennett, A. Nemmar, H. Vanbilloen, M. F. Hoylaerts, P. H. M. Hoet, A. Verbruggen, and B. Nemery
Rapid translocation of nanoparticles from the lung to the bloodstream?
Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1671 - 1672.
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