Estimation of inhaled ultrafine particle surface area dose for urban environments

There is considerable scientific interest in personal exposure to ultrafine particles. Owing to their small size, these particles are able to penetrate deep into the lungs, where they may cause adverse respiratory, pulmonary and cardiovascular health effects. This article presents Bayesian hierarchical models for estimating and comparing inhaled particle surface area in the lung.

Inhaled particle surface area dose: Stationary vs personal monitoring

The aim of this paper is to determine the suitability of solely stationary measurements for exposure assessment and management applications. For this purpose, quantified inhaled particle surface area (IPSA) doses using both stationary and personal particle exposure monitors were evaluated and compared.

Particles induce apical plasma membrane enlargement in epithelial lung cell line depending on particle surface area dose

Background Airborne particles entering the respiratory tract may interact with the apical plasma membrane (APM) of epithelial cells and enter them. Differences in the entering mechanisms of fine (between 0.1 μm and 2.5 μm) and ultrafine ( ≤ 0.1 μm) particles may be associated with different effects on the APM. Therefore, we studied particle-induced changes in APM surface area in relation to applied and intracellular particle size, surface and number. Methods Human pulmonary epithelial cells (A549 cell line) were incubated with various concentrations of different sized fluorescent polystyrene spheres without surface charge (∅ fine – 1.062 μm, ultrafine – 0.041 μm) by submersed exposure for 24 h. APM surface area of A549 cells was estimated by design-based stereology and transmission electron microscopy. Intracellular particles were visualized and quantified by confocal laser scanning microscopy. Results Particle exposure induced an increase in APM surface area compared to negative control (p < 0.01) at the same surface area concentration of fine and ultrafine particles a finding not observed at low particle concentrations. Ultrafine particle entering was less pronounced than fine particle entering into epithelial cells, however, at the same particle surface area dose, the number of intracellular ultrafine particles was higher than that of fine particles. The number of intracellular particles showed a stronger increase for fine than for ultrafine particles at rising particle concentrations. Conclusion This study demonstrates a particle-induced enlargement of the APM surface area of a pulmonary epithelial cell line, depending on particle surface area dose. Particle uptake by epithelial cells does not seem to be responsible for this effect. We propose that direct interactions between particle surface area and cell membrane cause the enlargement of the APM.

Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

Uncertainty budget in the measurement of typical airborne number, surface area and mass particle distributions

The effects of particulate matter on environment and public health have been widely studied in recent years. A number of studies in the medical field have tried to identify the specific effect on human health of particulate exposure, but agreement amongst these studies on the relative importance of the particles’ size and its origin with respect to health effects is still lacking. Nevertheless, air quality standards are moving, as the epidemiological attention, towards greater focus on the smaller particles. Current air quality standards only regulate the mass of particulate matter less than 10 μm in aerodynamic diameter (PM10) and less than 2.5 μm (PM2.5). The most reliable method used in measuring Total Suspended Particles (TSP), PM10, PM2.5 and PM1 is the gravimetric method since it directly measures PM concentration, guaranteeing an effective traceability to international standards. This technique however, neglects the possibility to correlate short term intra-day variations of atmospheric parameters that can influence ambient particle concentration and size distribution (emission strengths of particle sources, temperature, relative humidity, wind direction and speed and mixing height) as well as human activity patterns that may also vary over time periods considerably shorter than 24 hours. A continuous method to measure the number size distribution and total number concentration in the range 0.014 – 20 μm is the tandem system constituted by a Scanning Mobility Particle Sizer (SMPS) and an Aerodynamic Particle Sizer (APS). In this paper, an uncertainty budget model of the measurement of airborne particle number, surface area and mass size distributions is proposed and applied for several typical aerosol size distributions. The estimation of such an uncertainty budget presents several difficulties due to i) the complexity of the measurement chain, ii) the fact that SMPS and APS can properly guarantee the traceability to the International System of Measurements only in terms of number concentration. In fact, the surface area and mass concentration must be estimated on the basis of separately determined average density and particle morphology. Keywords: SMPS-APS tandem system, gravimetric reference method, uncertainty budget, ultrafine particles.

Exposure to particle number, surface area and PM concentrations in pizzerias

The aim of this work was to quantify exposure to particles emitted by wood-fired ovens in pizzerias. Overall, 15 microenvironments were chosen and analyzed in a 14-month experimental campaign. Particle number concentration and distribution were measured simultaneously using a Condensation Particle Counter (CPC), a Scanning Mobility Particle Sizer (SMPS), an Aerodynamic Particle Sizer (APS). The surface area and mass distributions and concentrations, as well as the estimation of lung deposition surface area and PM1 were evaluated using the SMPS-APS system with dosimetric models, by taking into account the presence of aggregates on the basis of the Idealized Aggregate (IA) theory. The fraction of inhaled particles deposited in the respiratory system and different fractions of particulate matter were also measured by means of a Nanoparticle Surface Area Monitor (NSAM) and a photometer (DustTrak DRX), respectively. In this way, supplementary data were obtained during the monitoring of trends inside the pizzerias. We found that surface area and PM1 particle concentrations in pizzerias can be very high, especially when compared to other critical microenvironments, such as the transport hubs. During pizza cooking under normal ventilation conditions, concentrations were found up to 74, 70 and 23 times higher than background levels for number, surface area and PM1, respectively. A key parameter is the oven shape factor, defined as the ratio between the size of the face opening in respect

Technical note : a technique for measuring the surface area of articular cartilage in acetabular fractures

The aim of this study was to develop a reliable technique for measuring the area of a curved surface from an axial computed tomography (CT) scan and to apply this clinically in the measurement of articular cartilage surface area in acetabular fractures. The method used was a triangulation algorithm. In order to determine the accuracy of the technique, areas of hemispheres of known size were measured to give the percentage error in area measurement. Seven such hemispheres were machined into a Perspex block and their area measured geometrically, and also from CT scans by means of the triangulation algorithm. Scans of 1, 2 and 4 mm slice thickness and separation were used. The error varied with slice thickness and hemisphere diameter. It was shown that the 2 mm slice thickness provides the most accurate area measurement, while 1 mm cuts overestimate and 4 mm cuts underestimate the area. For a hemisphere diameter of 5 cm, which is of similar size to the acetabulum, the error was -11.2% for 4 mm cuts, +4.2% for 2 mm cuts and + 5.1% for 1 mm cuts. As expected, area measurement was more accurate for larger hemispheres. This method can be applied clinically to quantify acetabular fractures by measuring the percentage area of intact articular cartilage. In the case of both column fractures, the percentage area of secondary congruence can be determined. This technique of quantifying acetabular fractures has a potential clinical application as a prognostic factor and an indication for surgery in the long term.

A comparison of submicrometer particle dose between Australian and Italian people

Alveolar and tracheobronchial-deposited submicrometer particle number and surface area data received by different age groups in Australia are shown. Activity patterns were combined with microenvironmental data through a Monte-Carlo method. Particle number distributions for the most significant microenvironments were obtained from our measurement survey data and people activity pattern data from the Australian Human Activity Pattern Survey were used. Daily alveolar particle number (surface area) dose received by all age groups was equal to 3.0×1010 particles (4.5×102 mm2), varying slightly between males and females. In contrast to gender, the lifestyle was found to significantly affect the daily dose, with highest depositions characterizing adults. The main contribution was due to indoor microenvironments. Finally a comparison between Italian and Australian people in terms of received particle dose was reported; it shows that different cooking styles can affect dose levels: higher doses were received by Italians, mainly due to their particular cooking activity.

Individual dose and exposure of Italian children to ultrafine particles

Time-activity patterns and the airborne pollutant concentrations encountered by children each day are an important determinant of individual exposure to airborne particles. This is demonstrated in this work by using hand-held devices to measure the real-time individual exposure of more than 100 children aged 8-11 years to particle number concentrations and average particle diameter, as well as alveolar and tracheobronchial deposited surface area concentration. A GPS-logger and activity diaries were also used to give explanation to the measurement results. Children were divided in three sample groups: two groups comprised of urban schools (school time from 8:30 am to 1:30 pm) with lunch and dinner at home, and the third group of a rural school with only dinner at home. The mean individual exposure to particle number concentration was found to differ between the three groups, ranging from 6.2×104 part. cm-3 for children attending one urban school to 1.6×104 part. cm-3 for the rural school. The corresponding daily alveolar deposited surface area dose varied from about 1.7×103 mm2 for urban schools to 6.0×102 mm2 for the rural school. For all of the children monitored, the lowest particle number concentrations are found during sleeping time and the highest were found during eating time. With regard to alveolar deposited surface area dose, a child's home was the major contributor (about 70%), with school contributing about 17% for urban schools and 27% for the rural school. An important contribution arises from the cooking/eating time spent at home, which accounted for approximately 20% of overall exposure, corresponding to more than 200 mm2. These activities represent the highest dose received per time unit, with very high values also encountered by children with a fireplace at home, as well as those that spend considerable time stuck in traffic jams.

Health effects of daily airborne particle dose in children : direct association between personal dose and respiratory health effects

Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35×103 mm2. The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child’s activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles.

The effect of hydroxyl groups and surface area of hematite derived from annealing goethite for phosphate removal

Synthetic goethite and thermally treated goethite at different temperatures were used to remove phosphate from sewage. The effect of annealing temperature on phosphate removal over time was investigated. X-ray diffraction(XRD), transmission electron microscopy (TEM), N2 adsorption and desorption (BET), and infrared emission spectrum (FT-IES) were utilized to characterize the phase, morphology, specific surface area, pore distribution, and the surface groups of samples. The results show that annealed products of goethite at temperatures over 250 °C are hematite with the similar morphology as the original goethite with different hydroxyl groups and surface area. Increasing temperature causes the decrease in hydroxyl groups, consequential increase in surface area at first and then experiences a decrease (14.8–110.4–12.6 m2/g) and the subsequent formation of nanoscale pores. The variation rate of hydroxyl groups and surface area based on FT-IES and BET, respectively, are used to evaluate the effect of annealing temperature on phosphate removal. By using all of the characterization techniques, it is concluded that the changes of phosphate removal basically result from the total variation rate between hydroxyl groups and surface area.

NSAM-derived total surface area vs. SMPS-derived "mobility equivalent" surface area for different environmentally relevant aerosols

The surface area of inhaled particles deposited in the alveolar region, as reported by the TSI nanoparticle surface area monitor (NSAM), was compared with the corresponding value estimated by a TSI scanning mobility particle sizer (SMPS) for a range of environmentally relevant aerosols, including petrol emissions, ETS, laser printer emissions, cooking emissions and ambient aerosols. The SMPS values were based on a mobility size distribution assuming spherical particles using the appropriate size-dependent alveolar-deposition factors provided by the ICRP. In most cases, the two instruments showed good linear agreement. With petrol emissions and ETS, the linearity extended to over 103 μm2 cm-3. With printer emissions, there was good linearity up to about 300 μm2 cm-3 while the NSAM increasingly overestimated the surface area at higher concentrations. The presence of a nucleation event in ambient air caused the NSAM to over-estimate the surface area by a factor of 2. We summarize these results and conclude that the maximum number concentration up to which the NSAM is accurate clearly depends on the type of aerosol being sampled and provide guidance for the use of the instrument.

Nanoporous Pt with High Surface Area by Reaction-Limited Aggregation of Nanoparticles

Nanoporous structures with high active surface areas are critical for a variety of applications. Here, we present a general templateless strategy to produce such porous structures by controlled aggregation of nanostructured subunits and apply the principles for synthesizing nanoporous Pt for electrocatalytic oxidation of methanol. The nature of the aggregate produced is controlled by tuning the electrostatic interaction between surfactant-free nanoparticles in the solution phase. When the repulsive force between the particles is very large, the particles are stabilized in the solution while instantaneous aggregation leading to fractal-like structures results when the repulsive force is very low. Controlling the repulsive interaction to an optimum, intermediate value results in the formation of compact structures with very large surface areas. In the case of Pt, nanoporous clusters with an extremely high specific surface area (39 m(2)/g) and high activity for methanol oxidation have been produced. Preliminary investigations indicate that the method is general and can be easily extended to produce nanoporous structures of many inorganic materials.

On the relationship of thermodynamic parameters with the buried surface area in protein-ligand complex formation

Prediction of thermodynamic parameters of protein-protein and antigen-antibody complex formation from high resolution structural parameters has recently received much attention, since an understanding of the contributions of different fundamental processes like hydrophobic interactions, hydrogen bonding, salt bridge formation, solvent reorganization etc. to the overall thermodynamic parameters and their relations with the structural parameters would lead to rational drug design. Using the results of the dissolution of hydrocarbons and other model compounds the changes in heat capacity (DeltaCp), enthalpy (DeltaH) and entropy (DeltaS) have been empirically correlated with the polar and apolar surface areas buried during the process of protein folding/unfolding and protein-ligand complex formation. In this regard, the polar and apolar surfaces removed from the solvent in a protein-ligand complex have been calculated from the experimentally observed values of changes in heat capacity (DeltaCp) and enthalpy (DeltaH) for protein-ligand complexes for which accurate thermodynamic and high resolution structural data are available, and the results have been compared with the x-ray crystallographic observations. Analyses of the available results show poor correlation between the thermodynamic and structural parameters. Probable reasons for this discrepancy are mostly related with the reorganization of water accompanying the reaction which is indeed proven by the analyses of the energetics of the binding of the wheat germ agglutinin to oligosaccharides.

Aromatic, microporous polymer networks with high surface area generated in Friedel-Crafts-type polycondensations

A series of novel, microporous polymer networks (MPNs) have been generated in a simple, acid catalysed Friedel-Crafts-type self-condensation of A(2)B(2)- and A(2)B(4)-type fluorenone monomers. Two A2B4-type monomers with 2,7-bis(N, N-diphenylamino) A or 2,7-bis [4-(N, N-diphenylamino) phenyl] D substitution of the fluorenone cores lead to MPNs with high S(BET) surface areas of up to 1400 m(2) g(-1). Two MPNs made of binary monomer mixtures showed the highest Brunauer-Emmett-Teller (BET) surface areas S(BET) of our series (SBET of up to 1800 m(2) g(-1)) after washing the powdery samples with supercritical carbon dioxide. Total pore volumes of up to 1.6 cm(3) g(-1) have been detected. It is observed that the substitution pattern of the monomers is strongly influencing the resulting physicochemical properties of the microporous polymer networks (MPNs).