Biomedical subjects

W Kreyling

Publications and source records attributed to W Kreyling.

10 recordsLinked to original sources

PubMed2004

Translocation of inhaled ultrafine particles to the brain.

Ultrafine particles (UFP, particles <100 nm) are ubiquitous in ambient urban and indoor air from multiple sources and may contribute to adverse respiratory and cardiovascular effects of particulate matter (PM). Depending on their particle size, inhaled UFP are efficiently deposited in nasal, tracheobronchial, and alveolar regions due to diffusion. Our previous rat studies have shown that UFP can translocate to interstitial sites in the respiratory tract as well as to extrapulmonary organs such as liver within 4 to 24 h postexposure. There were also indications that the olfactory bulb of the brain was targeted. Our objective in this follow-up study, therefore, was to determine whether translocation of inhaled ultrafine solid particles to regions of the brain takes place, hypothesizing that UFP depositing on the olfactory mucosa of the nasal region will translocate along the olfactory nerve into the olfactory bulb. This should result in significant increases in that region on the days following the exposure as opposed to other areas of the central nervous system (CNS). We generated ultrafine elemental (13)C particles (CMD = 36 nm; GSD = 1.66) from [(13)C] graphite rods by electric spark discharge in an argon atmosphere at a concentration of 160 microg/m(3). Rats were exposed for 6 h, and lungs, cerebrum, cerebellum and olfactory bulbs were removed 1, 3, 5, and 7 days after exposure. (13)C concentrations were determined by isotope ratio mass spectroscopy and compared to background (13)C levels of sham-exposed controls (day 0). The background corrected pulmonary (13)C added as ultrafine (13)C particles on day 1 postexposure was 1.34 microg/lung. Lung (13)C concentration decreased from 1.39 microg/g (day 1) to 0.59 microg/g by 7 days postexposure. There was a significant and persistent increase in added (13)C in the olfactory bulb of 0.35 microg/g on day 1, which increased to 0.43 microg/g by day 7. Day 1 (13)C concentrations of cerebrum and cerebellum were also significantly increased but the increase was inconsistent, significant only on one additional day of the postexposure period, possibly reflecting translocation across the blood-brain barrier in certain brain regions. The increases in olfactory bulbs are consistent with earlier studies in nonhuman primates and rodents that demonstrated that intranasally instilled solid UFP translocate along axons of the olfactory nerve into the CNS. We conclude from our study that the CNS can be targeted by airborne solid ultrafine particles and that the most likely mechanism is from deposits on the olfactory mucosa of the nasopharyngeal region of the respiratory tract and subsequent translocation via the olfactory nerve. Depending on particle size, >50% of inhaled UFP can be depositing in the nasopharyngeal region during nasal breathing. Preliminary estimates from the present results show that approximately 20% of the UFP deposited on the olfactory mucosa of the rat can be translocated to the olfactory bulb. Such neuronal translocation constitutes an additional not generally recognized clearance pathway for inhaled solid UFP, whose significance for humans, however, still needs to be established. It could provide a portal of entry into the CNS for solid UFP, circumventing the tight blood-brain barrier. Whether this translocation of inhaled UFP can cause CNS effects needs to be determined in future studies.

Air Pollutants↗

PubMed2004

Nanotoxicology.

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Humans↗

PubMed2003

Effects of fine and ultrafine particles on cardiorespiratory symptoms in elderly subjects with coronary heart disease: the ULTRA study.

The ULTRA Study, a study investigating the association between fine and ultrafine particulate air pollution and cardiorespiratory health, was conducted during the winter of 1998-1999 in Amsterdam, the Netherlands; Erfurt, Germany; and Helsinki, Finland. At each study center, a panel of elderly subjects with coronary heart disease recorded cardiac and respiratory symptoms in a diary. Exposure to ambient air pollution was characterized by measuring daily mass concentrations of particles smaller than 10 micro m (PM(10)) and 2.5 micro m (PM(2.5)), number concentrations of ultrafine particles (NC(0.01-0.1)), and gases. Odds ratios for the relation of symptoms to air pollution, adjusted for time trend, respiratory infections, and meteorologic variables, were mostly homogeneous across the centers. No association was found between air pollution and chest pain. A 10- micro g/m(3) increase in PM(2.5) was positively associated with the incidence of shortness of breath (odds ratio (OR) = 1.12, 95% confidence interval (CI): 1.02, 1.24) and with avoidance of activities (OR = 1.09, 95% CI: 0.97, 1.22). NC(0.01-0.1) was only associated with the prevalence of avoidance of activities (OR = 1.10, 95% CI: 1.01, 1.19). In conclusion, PM(2.5) was associated with some cardiac symptoms in three panels of elderly subjects. PM(2.5 )was more strongly related to cardiorespiratory symptoms than ultrafine particles were.

Aged↗

PubMed2001

PM25 measurements in ambient aerosol: comparison between Harvard impactor (HI) and the tapered element oscillating microbalance (TEOM) system.

A comparison, based on the regression of 32 daily mean PM25 aerosol loadings determined by a tapered element oscillating microbalance (TEOM) and by a Harvard impactor (HI), is reported for the ambient aerosol of Erfurt (Germany). The PM2.5 concentrations measured by the TEOM were systematically lower then those obtained by the HI. The ratio of the means TEOM/HI was 0.74 and the regression equation is TEOM = 0.69 x HI + 0.071. This result is consistent with reports elsewhere suggesting that semi-volatile aerosol material is lost from the heated sample filter on the TEOM. To verify this assertion, a heating system was developed for the HI which was able to keep the HI sample filter at 50+/-1 degrees C. After the implementation of this heating system, no systematically differences were observed between the TEOM and the heated HI system. The ratio of means was 1.06 and the regression equation TEOM = 1.10 x HI - 0.668. Because the measured levels of ammonium nitrate were very low in Erfurt, we concluded that other compounds like semi-volatile organics were responsible for the loss of particulate material at 50 degrees C.

Aerosols↗

PubMed1996

Aerosol production and aerosol droplet size distribution during mechanical ventilation (IPPV) with a new ultrasonic nebulizer.

Administration of drugs via the airway is increasingly practiced in ICU- and surgical patients. For this purpose, aerosols may be produced by either jet nebulization or ultrasonic droplet generation. In mechanically ventilated patients, aerosol delivery is often insufficient. The influence of the ventilatory pattern on nebulizer efficacy is poorly understood. In the present in vitro study we determined the efficacy of a new ultrasonic nebulizer in delivering aerosolized epoprostenol using defined ventilator settings. We determined aerosol delivery rates, the aerosol droplet size distribution and the impact of the connection tubing on drug delivery, applying adult and infant ventilation patterns. Aerosol production rates ranged from 0.28 to 0.57 ml per minute. Using an adult ventilator setting volume controlled ventilation (CMV) led to a higher aerosol production rate than pressure controlled ventilation (PCV) at identical tidal volumes and mean airway pressures (0.57 ml/min,CMV vs 0.39 ml/min, PCV). With an infant ventilator setting, nebulizer rates were lower than those found for the adult ventilator setting, but did not differ substantially between CMV and PCV mode (0.29 ml/min, CMV vs 0.28 ml/min, PCV). Aerosol delivery rates distal to the endotracheal tube changed according to aerosol production rates (adult mode: 0.18 ml/min, CMV vs 0.10 ml/min, PCV; infant mode: 0.03 ml/min, both CMV and PCV). In the infant ventilation mode, a higher percentage of the aerosol was trapped in the catheter mount as compared to the adult ventilation mode. Mass median droplet diameters for each of the four ventilator settings were almost identical (4.63 to 5.09 micron) and smaller than indicated in the product specifications (8 micron). Delivery rates and sizes of droplets delivered by the new ultrasonic nebulizer SUN 345(R) agree well with previously reported data from comparable settings using diverse nebulizer devices.

Adult↗

PubMed1994

In vivo evaluation of chemical biopersistence of nonfibrous inorganic particles.

The lung's response to deposited particles may depend upon the physical-chemical properties of the particles, the amount initially deposited, and the persistence of the particles. Clearance involves mucociliary transport as well as the action of phagocytic cells in nonciliated regions of the lung. Depending on the animal species studied, particle type, and particle load, inorganic materials are ingested by macrophages on alveolar surfaces with half-times of 0.6 to 7 hr. Particle-laden macrophages may migrate to airways, but we believe that an important mechanism of clearance is the dissolution of particles within alveolar macrophages and the subsequent translocation of dissolved materials to the blood. Particle dissolution in situ has long been recognized but was often thought to be carried out extracellularly in the alveolar lining layer, airway mucus, or interstitial fluid. However, many particles such as cobalt oxide or iron oxide which dissolve very little in simulated lung fluid, are solubilized more rapidly within alveolar macrophages. Clearance of particles from the lungs can be followed by a number of techniques, both invasive and noninvasive. The approaches vary in expense and resolution, and can be directed toward quantifying mechanical removal of particles versus their intracellular dissolution. Noninvasive methods permit repeated measurements of particle retention in the lungs of the same animal or human and thus allow replications and serial measurements. Greater precision with respect to the sites of retention and redistribution is achieved with quantitative morphometric methods that utilize fixation followed by physically dividing the respiratory tract into individual pieces.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

PubMed1992

Phagolysosomal pH and dissolution of cobalt oxide particles by alveolar macrophages.

We studied phagolysosomal pH in rabbit alveolar macrophages (AM) incubated with 0-15 microM chloroquine. There was a dose-related increase in pH with chloroquine concentration. Electron microscopy showed that chloroquine increased lysosomal size. In a second experiment we studied dissolution of radiolabeled cobalt oxide particles by rabbit AM, phagolysosomal pH, and lysosomal size. The cells were incubated for 2 days with 0, 2.5, and 10 microM chloroquine. Size and pH increased with chloroquine concentration. Dissolution of cobalt particles by the AM did not clearly change with pH. In a third experiment, dissolution of cobalt oxide particles in 0.1 M acetate buffer in saline with pH 4.0, 5.0, and 6.0 was studied. At the same pH, dissolution in acetate buffer was faster than in the AM, and the dissolution appeared to decrease faster with increasing pH than in the AM. A simple model for dissolution of a particle in a phagolysosome was proposed. This model predicts the types of differences in dissolution between AM and buffered saline.

Animals↗

PubMed1985

Total and regional lung retention of monodisperse cobalt compound aerosols after a single inhalation.

After a single short term inhalation of monodisperse cobalt compound aerosols with preselected physical and chemical parameters the long term retention in beagle dogs is determined measuring their radioactive Co-57 label by a gamma camera. Additionally the major clearance pathways are estimated by excretion analyses. The biological variability of the lung retention is small but it depends clearly on the physiochemical properties of the inhaled aerosol particles. The predominant clearance mechanism in the lung is a moderate dissolution process depending on the specific surface area of the particles. So cobalt oxide particles with an adjustable solubility in the lung can be used for studies of distinct dissolution processes in the lung. Using a gamma camera the dynamics of particle accumulation in the tracheobronchial lymph nodes and the subsequent clearance are analysed on single dogs.

Aerosols↗

PubMedDate not supplied

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility.

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular (RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng.kg(-1).min(-1)) and, consecutively, ILO (60 ng.kg(-1).min(-1)) for 20 min each. We measured pulmonary artery pressure (PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E(es)). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E(es) was enhanced during all doses tested, which reached statistical significance during EPO(25 ng) and ILO, but not during EPO(50 ng). PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function.

Administration, Inhalation↗

PubMedDate not supplied

Phagolysosomal morphology and dissolution of cobalt oxide particles by human and rabbit alveolar macrophages.

The effect of phagolysosomal size on dissolution of cobalt oxide particles was evaluated in two different macrophage systems: alveolar macrophages (AM) of human smokers with phagolysosomes enlarged by ingested cigarette smoke products, and rabbit AM incubated in vitro with sucrose, which causes swelling of the phagolysosomes by osmosis. Human AM from smokers and nonsmokers were studied in vitro. There was no significant difference in particle dissolution between AM obtained from smokers and nonsmokers, although there was a clear difference in the morphological appearance of AM, including significantly larger phagolysosomes in smokers. Rabbit AM were incubated for 24 or 72 h with or without 80 mM sucrose in the medium. The sucrose-treated cells had 3-4 times larger phagolysosomes than untreated cells, with no major change in phagolysosomal pH. The increased size of the phagolysosomes did not affect the ability of the AM to dissolve cobalt oxide particles. Furthermore, rabbit AM showed the same ability as human AM to dissolve the cobalt oxide particles, in spite of the fact that they had markedly smaller phagolysosomes. Another difference between human and rabbit AM was that phagolysosomes in human AMs increased in size with time in culture, while rabbit AM phagolysosomes decreased in size.

Adult↗