In vitro and in vivo glucuronidation of 24,25-dihydroxyvitamin D3.

Glucuronidation of 24,25-dihydroxyvitamin D3 has been investigated in in vitro and in vivo experiments. Three positional isomers of 24,25-dihydroxyvitamin D3 monoglucuronide were synthesized from 24,25-dihydroxyprovitamin D3 derivatives with Koenigs-Knorr reaction and used as standard samples. In the presence of the rat liver microsomal fraction and uridine-5'-diphosphoglucuronic acid, 24,25-dihydroxyvitamin D3 gave 3- and 24-glucuronides as the main products in almost equal amounts, but only a small amount of the corresponding 25-glucuronide was obtained. 24,25-Dihydroxyvitamin D3 monoglucuronide was deconjugated with rat intestine homogenate, which indicated the entero-hepatic circulation of 24,25-dihydroxyvitamin D3. After the administration of 24,25-dihydroxyvitamin D3 to rats, its 3- and 24-glucuronides were identified from the bile as inferred from the in vitro experiment. However, the in vivo glucuronidation occurred at the 24-position in preference to the 3-position, and the corresponding 25-glucuronide was not detected. These glucuronides were identified in comparison with standard samples based on their chromatographic behavior during high-performance liquid chromatography and data obtained from liquid chromatography-electrospray ionization-mass spectrometry, which was helpful in identifying these compounds.

The validity of radiographic estimation of total lung capacity in patients with respiratory disease.

STUDY OBJECTIVE: To evaluate the validity of a state-of-the-art computerized planimetry technique for estimation of total lung capacity (TLC) from chest radiographs, when applied to patients with clinical lung disease receiving routine chest radiographs. DESIGN: Retrospective clinical survey. SETTING: An occupational medicine diagnostic clinic. PATIENTS: A convenience sample of 40 subjects with asbestos-related lung disease, 5 patients with nonasbestos-related restrictive defects, 15 subjects with occupational asthma, and 10 subjects with irritant tracheobronchitis. RESULTS: Estimation of TLC using state-of-the-art computerized algorithms demonstrated limited agreement with conventional measures of TLC when applied to patients with occupational lung disease receiving routine chest radiographs. The most pronounced differences occurred in patients with asbestos-related lung disease and restrictive defects, where the radiographic method of measurement significantly overestimated helium dilution TLC by 986 mL (r=0.73, p<0.001) and 1,135 mL (r=0.82, p<0.05), respectively. Good inspiratory effort was associated with significantly increased radiographic TLC relative to helium dilution TLC; however, radiographic features did not fully account for the observed differences between radiographic and helium dilution techniques. CONCLUSIONS: Our findings suggest that this planimetric technique should not be used as a substitute for conventional measures of TLC in clinic populations receiving routine radiographs. The large diagnostic group specific mean differences observed between radiographic and conventional measures of TLC also suggest that this method is of limited utility in clinical evaluation of occupational lung disease.

The effects of albuterol on sulfur dioxide-induced bronchoconstriction in allergic adolescents.

Ten allergic subjects with exercise-induced bronchospasm were studied to determine whether albuterol could prevent sulfur dioxide (SO2)-induced bronchoconstriction. Albuterol or placebo (180 micrograms) were administered by metered-dose inhaler 20 minutes before a 10-minute exposure to SO2 or clean air during moderate exercise on a treadmill at an exercise level that by itself did not produce exercise-induced bronchospasm. Pulmonary functions (FEV1 and total respiratory resistance [RT]) were measured before the drug, after the drug, and after exposure to SO2 or clean air. Albuterol treatment produced significant bronchodilation and also prevented SO2-induced bronchoconstriction. Following SO2 inhalation after placebo, FEV1 decreased 15% (p less than 0.02) and RT increased 50% (p less than 0.03). Following SO2 inhalation after albuterol treatment, neither FEV1 or RT changed significantly. We conclude that albuterol, a beta 2-agonist, inhibits SO2-induced bronchoconstriction. This result suggests that the adrenergic nervous system or mast cell degranulation are involved in SO2-induced bronchoconstriction.

The effects of sulfur oxides on nasal and lung function in adolescents with extrinsic asthma.

Ten adolescent subjects with extrinsic asthma were exposed during intermittent exercise to filtered air, 0.5 ppm of sulfur dioxide (SO2), or 100 micrograms/m3 of sulfuric acid (H2SO4) on 5 separate days. The purpose of the study was to compare changes in nasal power (the work of nose breathing) with pulmonary functional changes depending on the route of inhalation of the sulfur oxide pollutants, oral inhalation through a rubber mouthpiece or oronasal inhalation via a face mask. Nasal power was measured with a modified skin diving mask equipped with two differential pressure transducers. Statistically significant changes in total respiratory resistance, FEV1, and maximum flow calculated at 50% and 75% vital capacity were observed after all exposures to SO2 and H2SO4. The magnitude of change in FEV1 and maximum flow calculated at 50% vital capacity was higher after oral compared to oronasal inhalation of SO2. The nasal work of breathing increased 32% after SO2 exposure by mouthpiece and 30% after SO2 exposure via face mask (p less than 0.05). The nasal power changes after the H2SO4 exposures were not different from the sham exposures. We conclude that oronasal inhalation of 0.5 ppm of SO2 produces a significant increase in the nasal work of breathing and that the route of exposure reduces but does not eliminate the lower airway reactions observed on oral exposure.

Acute effects of 0.12 ppm ozone or 0.12 ppm nitrogen dioxide on pulmonary function in healthy and asthmatic adolescents.

Adolescent asthmatic subjects have been shown to be much more sensitive than healthy adolescents to the inhaled effects of sulfur dioxide. To test whether similar adolescent asthmatics are more sensitive to other common ambient air pollutants, 10 healthy and 10 asthmatic adolescent subjects were exposed for 60 min to filtered air, 0.12 ppm ozone (O3), and 0.12 ppm nitrogen dioxide (NO2) on separate days at rest. The following pulmonary functional values were measured before, at 30 min, and after 60 min of exposure: peak flow, total pulmonary resistance (RT), thoracic gas volume at functional residual capacity (FRC), maximal flow at 50 and 75% of expired vital capacity (Vmax50 and Vmax75), and forced expiratory volume in one second (FEV1). Following 60 min of exposure at rest to low concentrations of O3 or NO2, there were no consistent significant functional changes in either healthy or asthmatic adolescent subjects. There also were no measurable differences between the 2 groups.

The effects of inhaled sulfuric acid on pulmonary function in adolescent asthmatics.

Ten adolescent subjects with extrinsic asthma and exercise-induced bronchospasm were studied. The subjects were exposed for 30 min at rest followed by 10 min during moderate exercise on a treadmill to either 100 micrograms/m3 sodium chloride (NaCl) or 100 micrograms/m3 sulfuric acid (H2SO4) droplet aerosols. All exposures were at approximately 75% relative humidity and 22 degrees C. Pulmonary functional measurements were recorded before, during, and after exposure while the subject was seated in a body plethysmograph. Exposure to the NaCl aerosol during exercise produced a small (12%) but significant drop in maximal expiratory flow (Vmax75) (p less than 0.05). However, exposure to the H2SO4 aerosol produced larger reductions in Vmax75 (29%; p less than 0.01) and also significant changes in 3 other parameters of pulmonary function: Vmax50, FEV1, and total respiratory resistance (RT). The changes were similar to those reported for exposure to 0.5 ppm of sulfur dioxide in a similar group of adolescents with extrinsic asthma. Our results are the first report of reversible pulmonary functional changes after H2SO4 exposure in a group of adolescent asthmatic subjects.

A comparison of the pulmonary effects of 0.5 ppm versus 1.0 ppm sulfur dioxide plus sodium chloride droplets in asthmatic adolescents.

The effects of inhaled sulfur dioxide (SO2) on pulmonary function in nine adolescent subjects with extrinsic asthma were studied. The exposure modes, inhaled via a mouthpiece, were (1) 1 mg/m3 sodium chloride solution droplet aerosol (NaCl); (2) 0.5 ppm SO2 + NaCl; or (3) 1.0 ppm SO2 + NaCl. All exposures were at greater than or equal to 75% relative humidity and approximately 22 degrees C. The following pulmonary functional measurements, with the subject seated in a body plethysmograph, were recorded: total respiratory resistance (RT), functional residual capacity (FRC), maximal flow at 50% and 75% expired vital capacity (Vmax50 and Vmax75), and forced expiratory volume in one second (FEV1). Following 10 min of exposure to either SO2 mode during moderate exercise on a treadmill, statistically significant changes in all pulmonary functional measurements except FRC were seen. There were no statistically significant changes following 10 min of exposure during moderate exercise to the NaCl droplet aerosol alone. Since the average pulmonary changes following exposure to 0.5 ppm SO2 mixture during moderate exercise ranged from 8 to 47%, we conclude that this dose of SO2 is above the response threshold for these subjects. To explore the effects of nasal (or oronasal) inhalation on the SO2-induced pulmonary functional changes, 7 of the 9 subjects inhaled 0.5 ppm SO2 + NaCl via a face mask with no nose clips. The average percentage changes in pulmonary functional values seen after exposure via face mask were similar to those seen after exposure via mouthpiece. However, the changes seen after exposure via face mask were not as consistent as following inhalation via mouthpiece and not statistically different from baseline. We conclude that oral, and to a lesser degree oronasal, inhalation of 0.5 ppm of SO2 elicits SO2-induced changes in pulmonary function in these subjects.

Bronchoconstrictor responses to sulfur dioxide or sulfur dioxide plus sodium chloride droplets in allergic, nonasthmatic adolescent.

Eight atopic adolescent subjects without diagnosis of clinical asthma but with signs of hyperactive airways were studied. The subjects were exposed for 30 min at rest followed by 10 min during moderate exercise on a treadmill to the following: (1) filtered air, (2) 1 mg/m3 NaCl droplet aerosol, (3) 1 ppm SO2 and NaCl droplet aerosol, or (4) 1 ppm SO2. All exposures were at 75% relative humidity and 22 degrees C. Exposures to either SO2 mode produced statistically significant changes in pulmonary function, whereas sham exposures to air on NaCl did not. These results are similar to those seen earlier in a group of extrinsic asthmatic adolescent subjects and are three to 22 times greater than changes we saw in a group of normal adolescent subjects. The changes seen after inhalation of SO2 were not statistically different from those seen after inhalation of SO2 and NaCl droplet aerosol. Our results indicate that inhalation of 1 ppm SO2 by a group of atopic adolescents can produce exercise-induced bronchospasm at a level of exercise that has no effect by itself.

Effects of inhaled sulfur dioxide (SO2) on pulmonary function in healthy adolescents: exposure to SO2 alone or SO2 + sodium chloride droplet aerosol during rest and exercise.

Recently we reported statistically significant changes in pulmonary functional measurements in asthmatic adolescents exposed at rest or during exercise. To demonstrate whether those results were due to the subjects' adolescence, or more likely, to their diagnosis of asthma, we repeated identical exposures in healthy adolescents. The changes after exposure to sulfur dioxide (SO2); however the changes were only slightly greater than those seen after sham exposure. After exposure at rest to 1.0 ppm SO2 + 1 mg/m3 sodium chloride (NaCl) droplet aerosol, the healthy adolescents showed small (3%) but statistically significant reductions in forced expiratory volume in one second (FEV1.0). No significant changes were seen following exposure to NaCl of SO2 alone at rest. Exposure to the SO2 modes during moderate exercise produced greater changes. Following exposure to either the SO2 + NaCl mixture or 1.0 ppm of SO2 alone, the reductions in FEV1.0 were slightly greater (6%) and prolonged compared with those seen at rest. Significant decreases also were seen in Vmax50 and Vmax75. A small decrease (4%) in FEV1.0 was seen following exposure to NaCl alone during exercise, but the change was not statistically significant. The changes seen in the healthy adolescents were slight compared to those seen in the asthmatic adolescents previously exposed (changes of 23-67%). We conclude that asthmatic adolescents are much more sensitive to the effects of inhaled SO2 than are healthy adolescents.