Metabolism of methyl mercury (203Hg) compounds in man.
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Biomedical subjects
Publications and source records attributed to R Falk.
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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.
Large lung retentions (up to 50%) of particles < or = 4 microns inhaled with a bolus technique at a penetration depth less than dead space have been reported to occur after 24 h. This retention may be due to retarded clearance of particles deposited in the airways of the tracheobronchial tract; an alternative explanation could be that particles are deposited in the alveolar region. The purpose of the present study was to confirm the occurrence of retained fractions and to study the influence of a cholinergic drug, which is assumed to give a more central particle deposition, on these retentions in human lungs after shallow aerosol bolus inhalation. Twelve healthy subjects inhaled, with a bolus technique, monodisperse Teflon particles (2.4 microns geometric diameter, 3.5 microns aerodynamic diameter), labeled with 111In. The volumetric lung depth of the inspired bolus was around 60 mL and flow rate was about 300 mL/s. Six subjects inhaled the test particles after a provocation with a cholinergic aerosol, which induced a threefold increase in airway resistance. The other six subjects inhaled a cholinergic aerosol after inhalation of the test particles or inhaled no cholinergic aerosol at all. Radioactivity in the body was measured after 0.5, 24, 48, and 72 h with a whole-body scanner with three 127 x 101-mm Nal detectors. The investigation confirmed results obtained earlier by a group in Frankfurt claiming that great retentions occur after 24 h. The retentions tended to be lower in the group receiving a bronchoconstricting drug before the bolus inhalations. There was a significant lung clearance of particles between 24 and 72 h, in contrast to the findings in earlier studies in healthy subjects and asthmatics who inhaled Teflon particles in large volumes. On the other hand, the clearance agreed well with the clearance in healthy subjects with extensive deposition of Teflon particles in the small ciliated airways, obtained by means of an extremely low inhalation flow rate. The results suggest that a considerable fraction of the particles in the bolus inhalation have been deposited in small ciliated airways in which the mucociliary transport is less efficient or in the alveolar region.
Ten healthy males inhaled monodisperse Teflon particles (geometric diameter 3.6 microns, aerodynamic diameter 5.3 microns) labeled with 195Au (half-life 183 days). The leakage of 195Au from the particles in vitro in water was less than 0.2% per year. Retention over the thorax was followed for about 900 days using two separate detector systems. One system consisted of four Ge detectors placed close to the front of the chest over the upper and lower regions of the lungs. The other system consisted of three NaI crystals placed in a ring around the thorax at some distance from the chest wall. Activities of 195Au in feces (24- or 48-h samples) could be measured as long as activities in the thorax could be measured. For the period 7-250 days, the half-times were similar for the two detectors, on the average 740 days for the NaI detectors and 680 days for the Ge detectors. The average half-times estimated from measurements from about 250 days to about 900 days were 1750 days with the NaI detectors and 880 days with the Ge detectors. Clearance curves constructed from measurements from feces agreed very well with clearance measured with the NaI detectors. The excretion via feces was well described by a power function with days after exposure as base. This total clearance from the thoracic region was slower than in earlier studies. No activity could be measured in the urine. The measurements with the two detector systems show that a translocation within the thoracic region occurred. This might be explained by transportation of particles from the lung parenchyma to the regional lymph nodes. The accumulation of particles in the regional lymph nodes was tentatively calculated on the basis of that assumption.