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Biomedical subjects

M O Amdur

Publications and source records attributed to M O Amdur.

At least 37 records · Page 2Linked to original sources
PubMed1985

Kinetics of respiratory tract absorption and plasma clearance of horseradish peroxidase in guinea pigs.

Horseradish peroxidase (HRP) absorption across the wall of the upper airway, monitored by the amount detected in the blood, is used to measure epithelial damage by toxins. Full details of kinetics of absorption and blood clearance have not been reported previously. We measured the kinetics under the experimental conditions used in testing toxins. HRP was administered to guinea pigs either by intraarterial injection of a 7.5 microgram bolus (plasma clearance) or by intratracheal instillation of 1 mg (respiratory tract absorption). Plasma concentrations were monitored for 60 min. Plasma concentrations of HRP rose linearly with time after intratracheal instillation, reaching 236 +/- 51 ng/ml (mean +/- SE) at 60 min after instillation. HRP was cleared from the plasma rapidly after bolus injection. The elimination coefficient, k2, determined from the biphasic log normal plot, was 0.322 min-1. These data were used to estimate the kinetics of absorption across the respiratory epithelium. A single 3-hr exposure to an atmosphere containing 2.5 mg/m3 of submicrometer zinc oxide particles increased plasma concentration of HRP after intratracheal deposition (407 +/- 63 ng/ml at 60 min) and had no effect on plasma clearance (k2 = 0.342 min-1). Therefore plasma concentrations of HRP measured after intratracheal deposition can be used as a sensitive indicator to evaluate the effects of inhalation of a test atmosphere on epithelial permeability, if plasma clearance kinetics are not altered by the exposure.

Absorption↗
PubMed1985

Lung injury in guinea pigs caused by multiple exposures to submicron zinc oxide mixed with sulfur dioxide in a humidified furnace.

Sulfur dioxide, water vapor, and ultrafine particles rich in oxides of zinc and other surface-deposited trace elements are important products of coal combustion. In order to study the toxicity of zinc oxide generated under conditions simulating combustion, guinea pigs were exposed in a nose-only apparatus for 3 h on 6 consecutive days to 6 mg/m3 of submicron zinc oxide particles (count median diameter of 0.05 micron, sigma g 2.0), which were generated in a humid furnace and mixed with 1 ppm sulfur dioxide. The exposures caused increases in lung weight and [3H] thymidine labeling index of terminal bronchiolar cell nuclei and inflammation of the proximal portion of the alveolar duct. The lung weights and labeling index had returned to normal and inflammatory changes had nearly resolved by 72 h after the last exposure. Total lung capacity, vital capacity, functional residual volume, alveolar volume, and diffusing capacity for carbon monoxide were decreased following exposure and had not returned to normal by 72 h after the last exposure. Large airways were not affected by the repeated exposures, as indicated by normal morphology of trachea and bronchi, unchanged secretory cell concentration, and unaltered epithelial permeability to horseradish peroxidase. These results are essentially identical to changes we reported in guinea pigs exposed to zinc oxide alone, suggesting that surface-deposited sulfur compounds, which are important determinants of the response to a single exposure to these ultrafine particles, become less important as exposure progresses.

Animals↗
PubMed1984

Ozone-induced airway hyperreactivity in the guinea pig.

The predominant airway site and mechanism underlying ozone (O3)-induced respiratory hyperresponsiveness was examined in anesthetized guinea pigs and in vitro tissue preparations. Animals exposed to 1.0 or 1.2 ppm O3 (1 h) demonstrated an enhanced airway response to subcutaneous histamine compared with air-exposed animals. The anatomic site of hyperresponsiveness most likely did not involve the parenchyma, since quasi-static deflationary pulmonary compliance was decreased to a similar extent by histamine in air- and O3-preexposed animals. In contrast, the conducting airways were probably involved as changes in pulmonary resistance elicited by subcutaneous histamine were greater in O3- than in air-exposed animals. Neither atropine nor vagotomy abolished this enhanced responsiveness induced by O3. Although vagal interruption did not alter responsiveness, O3-exposed animals demonstrated greater respiratory responses to efferent electrical stimulation of the vagi than air-exposed animals. This suggests the site of hyperresponsiveness may be located distal to the site of efferent stimulation, possibly in the smooth muscle itself or in its microenvironment.

Acid-Base Equilibrium↗
PubMed1983

Effect of mixing conditions on irritant potency of zinc oxide and sulfur dioxide.

Measurement of mechanics of respiration in guinea pigs was used to assess the irritant potency of zinc oxide and sulfur dioxide mixed under different conditions of temperature and humidity. Concentrations were 1-2 mg/m3 zinc oxide and 1 ppm sulfur dioxide. Dry conditions of mixing (Chamber RH 30%) either at 24 degrees C in the exposure chamber or at 480 degrees C in a dry furnace gave a biological response which could be completely accounted for by responses to zinc oxide and/or sulfur dioxide alone. Chemical examination of the aerosols did not indicate the formation of particulate sulfur species. Zinc oxide and sulfur dioxide mixed dry at 480 degrees C and fed into the exposure chamber at 80% RH reacted to produce an irritant aerosol as evidenced by a rapid increase to levels 29% above control; reversal was rapid when exposure ended. Chemical studies indicated the presence of sulfite on these aerosols. Addition of water vapor to the furnace during mixing at 480 degrees C produced a different irritant aerosol. The resistance rose slowly to 19% above control values and remained elevated during the post-exposure hour. Chemical studies indicated the presence of sulfate, sulfite, and adsorbed sulfur trioxide on these aerosols.

Aerosols↗
PubMed1982

Respiratory response of guinea pigs to zinc oxide fume.

Guinea pigs were exposed for 1 hr to submicrometer zinc oxide fume at a concentration of approximately 1 mg/m3. Measurement of pulmonary mechanics was used to assess the response. The exposure produced a slight decrease in compliance which was statistically significant. The compliance showed a further decrease 1 hr post-exposure. In a second group of animals observed for two hours after exposure a progressive decrease in compliance was observed between the first and second post-exposure hours. No changes were observed in resistance, tidal volume, frequency, or minute volume.

Aerosols↗
PubMed1980

Effect of ozone on respiratory response of guinea pigs to histamine.

The effect of preexposure to ozone on the respiratory response to histamine was studied. The Amdur-Mead technique was used to measure respiratory mechanics in Charles River Hartley guinea pigs. Groups of animals were exposed for 1 h to filtered control air or ozone. Control measurements were made 1 1/2 h after exposure, followed by sc injection of 0.125 mg/kg histamine dihydrochloride. Respiratory measurements were continued at 2-min intervals for 16 min, at which time resistance and compliance had returned to control values. The 2-h interval between exposure and injection and the 0.125 mg/kg histamine were the optimum time interval and dose, respectively, as determined by appropriate time-response and dose-response studies. Although control values did not differ between air-exposed and ozone-exposed animals, animals preexposed to 0.1, 0.2, 0.4, and 0.8 ppm ozone had increases in resistance of 111, 110, 93, and 97% after histamine administration, compared to the air-exposed animals, which had increases of 86, 86, 67, and 46%, respectively. Whereas the only significant difference in resistance between air and ozone animals was at the 0.8-ppm level (p less than 0.05), significant differences in compliance changes were found at all levels of ozone exposure. Ozone animals had compliance decreases of 40, 45, 46, and 46% after histamine injection, while their respective air controls decreased 24, 24, 27, and 31%. Exposures to ozone of 0.2 ppm for 4 h and 0.4 ppm for 2 h provided doses equal to that of 0.8 ppm for 1 h, yet no significant dose-time relationship was found. Lingering sensitivity to pharmacologically active agents is a subtle but important manifestation of ozone toxicity.

Airway Resistance↗
PubMed1979

Respiratory response of guinea pigs to oil mists.

Respiratory function was measured in guinea pigs exposed for one hour to submicrometer oil mists. Five oils were used: medicinal grade mineral oil, laboratory grade paraffin oil, light lubricating oil, unused motor oil and used motor oil. The last three oils were also studied after having been reacted with sulfur dioxide. No alterations were produced by exposure to any of the oils at concentrations of 10 or 40 mg/m3. At concentrations above 200 mg/m3 both the reacted and unreacted light lubricating oil caused a decrease in compliance which remained throughout the post-exposure period. Although the average flow-resistance of the group was increased by the unreacted unused motor oil and by the reacted used motor oil, the variation in response was too great to make this response statistically significant. The fact that reaction of the oils with sulfur dioxide did not increase irritant action indicates that the reaction products with sulfur dioxide are not acutely irritant.

Aerosols↗
PubMed1979

Effect of oil mists on the irritancy of sulfur dioxide. I. Mineral oils and light lubricating oil.

The increase in pulmonary flow resistance in unanesthetized guinea pigs was used to assess the effect of sub-micrometer oil aerosols on the response to sulfur dioxide. At a concentration of about 10 mg/m3 neither a medicinal grade mineral oil nor a light lubricating oil altered the response when given simultaneously with 1 or 10 ppm sulfur dioxide. The naphthenic medicinal oil at 100 mg/m3 failed to protect against 50 ppm sulfur dioxide when administerd simultaneously. A 30-minute pre-exposure, however, conferred complete protection. A paraffinic laboratory grade mineral oil conferred protection when given simultaneously but was less effective when the pre-exposure protocol was used.

Aerosols↗
PubMed1979

Effect of oil mists on the irritancy of sulfur dioxide. II. Motor oil.

This study examines the effect of sub-micrometer aerosols of motor oil on the irritant potency of sulfur dioxide. The increase in pulmonary flow resistance in guinea pigs was used as the bioassay of irritant response. When administered simultaneously, both unused and used motor oil protected against the irritant response to sulfur dioxide. This protective effect was lost when the oils had been previously reacted with sulfur dioxide. The additives used in the motor oil provided an equivalent protection when dissolved in a mineral oil which alone did not protect. Pre-exposure to motor oil did not provide protection. Sulfur dioxide and motor oil given together as a pre-exposure provided protection against further exposure to sulfur dioxide.

Aerosols↗
PubMed1978

Respiratory response of guinea pigs to ozone alone and with sulfur dioxide.

This study was designed to utilize our guinea pig bioassay method for irritant response to address the question of whether or not ozone and sulfur dioxide appeared to react to form sulfuric acid in the respiratory tract. Animals were exposed to 0.2, 0.4, and 0.8 ppm of each gas alone and to the combination at concentrations of 0.4 and 0.8 ppm. In these experiments sulfur dioxide alone produced no statistically significant alterations in respiration. All concentrations of ozone produced an increase in respiratory frequency. At the two higher concentrations the increase in frequency was accompanied by a decrease in compliance. The response to the combinations was the same as the response to those levels of ozone alone. No sulfuric acid was detected in the chamber atmosphere. The biological data suggest that none was formed in the lung.

Animals↗
PubMed1978

Respiratory response to iodine vapor alone and with sodium chloride aerosol.

Respiratory function measurements in guinea pigs were used to evaluate the irritant response to 1-h exposures to iodine vapor and the effect of 10 mg/m(3) submicrometer sodium chloride aerosol on this response. Iodine alone at 0.5 ppm produced no detectable response. Concentrations of 3-4 ppm increased resistance and decreased frequency and minute volume. The response appeared to be upper respiratory. At 7 ppm there was also a decrease in compliance, suggesting pulmonary effects. The response was potentiated by the sodium chloride aerosol. Increased resistance and decreased compliance and frequency were observed at 0.4 ppm. The changes at concentrations of 1-2 ppm were greater when the aerosol was present and included a decrease in compliance. The comparative effects of the sodium chloride aerosol on iodine, sulfur dioxide, and formaldehyde are discussed.

Aerosols↗