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Biomedical subjects

E M Postlethwait

Publications and source records attributed to E M Postlethwait.

29 records · Page 2Linked to original sources
PubMed1989

Effect of altered dose rate on NO2 uptake and transformation in isolated lungs.

While the pulmonary toxicity of NO2 is clearly established, the mechanism by which it is removed from inspired air is poorly understood. Uptake is most likely dependent on chemical reaction since, despite limited per se gaseous NO2 aqueous solubility, uptake proceeds rapidly without ready saturation. We utilized an isolated perfused rat lung model to characterize the effect of dose rate on uptake and transformation. Dose rate was varied via alterations in inspired concentration, tidal volume, and ventilation frequency. Dose equaled the total amount inhaled, uptake the amount removed from inspired air, and transformation the amount of NO2- that accumulated in the perfusate. We found a linear proportionality between both inspired concentration (4-20 ppm) and minute ventilation (45-130 ml/min) and uptake. Fractional uptakes (65%) were similar for all groups. Regression of combined concentration and minute ventilation data yielded a linear relationship between total inspired dose (25-330 micrograms NO2) and both uptake (r2 = 0.99) and transformation (r2 = 0.98). Testing of the functional descriptions resulted in measured uptakes and transformation that fell within a few percentage points of those predicted. We conclude that in acutely exposed isolated lungs (1) NO2 uptake is dependent on total inhaled dose rather than on the variables which serve to affect dose rate, (2) transformation is related to both total inspired dose and uptake, and (3) uptake is more accurately described using a regression equation rather than by use of fractional uptakes.

Animals↗
PubMed1988

Effects of culture conditions on susceptibility of alveolar epithelial cell monolayers to NO2.

The effects of nitrogen dioxide (NO2) exposure on primary cultured monolayers of rat type II pneumocytes were investigated as a function of the isolation and culture conditions. Monolayers were cultured in Eagle's minimum essential medium (MEM) and in MEM supplemented with Ham's F-12; in some experiments, the initial cell suspension was also replated after 3 h. Both supplementation of the basal medium and replating increased the sensitivity of the monolayers to NO2, as measured by reduction in dome formation of plastic dishes 24 h post-exposure. These findings suggest that comparisons of in vitro toxicologic observations may be complicated by the effects of specific experimental conditions.

Animals↗
PubMed1987

Effects of exposure to NO2 on dome formation in alveolar epithelial cell monolayers.

Primary cultured monolayers of rat Type II pneumocytes were used to investigate the effects of NO2 on alveolar epithelial barrier properties. Such monlayers form fluid-filled domes which are thought to result from active solute transport from medium to substratum, with water following passively. Using dome formation as a transport marker, 5-day-old cultures were directly exposed to 30 ppm NO2 in 5% CO2/air at 25 degrees C by cyclically tilting culture plates from side to side such that both halves of the monolayer were exposed during each cycle. Exposures consisted of 10 cycles of 4 min each (2 min per side), for a cell exposure time of 20 min. Control plates were simultaneously exposed to 5% CO2/air under identical conditions. Twenty-four hours after exposure, NO2-exposed monolayers exhibited significant decreases in dome density and individual dome volume as compared to controls. By 48 hr postexposure, differences between NO2-exposed and control values were less but remained significant. Control monolayers were essentially unaffected by exposure to 5% CO2/air. These results show that short-term sublethal exposures to NO2 produce a decrease in dome formation in Type II alveolar epithelial cell monolayers. This finding is most likely due to a decrease in the active transepithelial sodium transport rate and/or an increase in the permeability of cell membranes or tight junctions.

Animals↗
PubMed1987

Effects of nitrogen dioxide on alveolar epithelial barrier properties.

This study analyzed the effects of nitrogen dioxide (NO2) on alveolar epithelial permeability and transport properties. Primary cultured monolayers of rat Type II pneumocytes, cultured on both nonporous and porous surfaces, were used as models of isolated alveolar epithelium for in vitro exposure to nitrogen dioxide. The effects of nitrogen dioxide exposure for monolayers cultured on nonporous substrata were monitored by observing the changes in the net volume of fluid under the monolayer; for cells cultured on porous substrata, alterations in tissue bioelectric properties were noted. As a first step, primary cultured monolayers of rat Type II pneumocytes plated on nonporous plastic Petri dishes were used to investigate the effects of nitrogen dioxide on alveolar epithelial barrier properties. Such monolayers form fluid filled domes that are thought to result from active solute transport from medium to substratum, with water following passively. We used dome formation as a transport marker. Five-day-old cultures were directly exposed to 30 ppm NO2 in 5 percent CO2 in air at 25 degrees C, by cyclically tilting culture plates from side to side, so that both halves of the monolayer were exposed during each cycle. Exposures consisted of 10 cycles of four minutes each (two minutes per side), for a cell exposure time of 20 minutes. Control plates were simultaneously exposed to 5 percent CO2 in air under identical conditions. One day after the exposure, nitrogen dioxide-exposed monolayers exhibited significant decreases in dome density and individual dome volume, compared to the controls. By 48 hours post-exposure, differences between nitrogen dioxide-exposed and control monolayers were less, but remained significant. These results showed that short-term sublethal exposures to nitrogen dioxide produce a decrease in dome formation in Type II alveolar epithelial cell monolayers. This finding is most likely due to a decrease in the active transepithelial sodium transport rate, or an increase in the permeability of cell membranes or tight junctions, or both. Addition of vitamin E-containing liposomes to the culture media 24 hours pre-exposure did not affect the nitrogen dioxide-induced decrease in dome formation, indicating that under these circumstances no protective effect was provided by the antioxidant.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

In vivo and in vitro release of cyanide from neurotoxic aminonitriles.

Cyanide release from neurotoxic aminonitriles was measured following in vitro incubation with both microsomes and liver slices. Investigation of cyanide released as urinary thiocyanate following ip aminonitrile administration to rats was also measured. The yield of cyanide in the in vivo study, as measured by the mole percent of administered dose, was greatest from dimethylaminonitrile (DMAA), followed by trimethylaminopropionitrile (TMAPN), dimethylaminopropionitrile (DMAPN), 3,3'-iminodipropionitrile (IDPN), dimethylaminobutyronitrile (DMABN), and monomethylaminopropionitrile (MMAPN). Urinary excretion of thiocyanate accounted for 48.9% of the administered DMAA, 11.6% of TMAPN, 8.0% of DMAPN, 6.8% of IDPN, 3.1% of DMABN, and 1.8% of MMAPN. Incubation of aminonitriles and related compounds with microsomes or liver slices from rats yielded measurable quantities of cyanide from all the compounds tested except for DMABN, TMABN, and succiononitrile. Quantitative evaluation of the yield of formaldehyde by demethylation following microsomal incubation was also determined. The signs of acute toxicity in rats after ip administration of KCN were similar only to those in rats administered DMAA.

Aminopropionitrile↗
PubMed1984

A comparison of biochemical effects of nitrogen dioxide, ozone, and their combination in mouse lung.

Swiss Webster mice were exposed to either 4.8 ppm (9024 microgram/m3) nitrogen dioxide (NO2), 0.45 ppm (882 microgram/m3) ozone (O3), or their combination intermittently (8 hr daily) for 7 days, and the effects were studied in the lung by a series of physical and biochemical parameters, including lung weight, DNA and protein contents, oxygen consumption, sulfhydryl metabolism, and activities of NADPH generating enzymes. The results show that exposure to NO2 caused relatively smaller changes than O3, and that the effect of each gas alone under the conditions of exposure was not significant for most of the parameters tested. However, when the two gases were combined, the exposure caused changes that were greater and significant. Statistical analysis of the data shows that the effects of combined exposure were more than additive, i.e., they might be synergistic. The observations suggest that intermittent exposure to NO2 or O3 alone at the concentration used may not cause significant alterations in lung metabolism, but when the two gases are combined the alterations may become significant.

Animals↗
PubMed1981

Fate of inhaled nitrogen dioxide in isolated perfused rat lung.

The fate of inhaled NO2 was studied with isolated perfused rat lungs. The isolated lungs were exposed to 5 ppm NO2 for 90 min at a ventilation rate of 34 ml/min. The NO2 exposure had no adverse effects on the lungs as judged from their weights, glucose uptake, or lactate production compared to control lungs. Isolated lungs absorbed 36% of ventilated NO2, which was detected in perfusate and lung tissue as NO2- but not NO3-. The NO2- concentration in perfusate increased linearly with time, and after 90 min of ventilation with NO2 and perfusion with erythrocyte-free medium the NO2- accumulation was 6.36 +/- 0.39 micrograms. If perfusate contained 10% erythrocytes, the ventilated NO2 product was mostly NO3- in perfusate but NO2- in lung tissue. Protein solutions absorbed NO2 more effectively than simple salt solutions, but they all yielded mainly NO2- unless erythrocytes were present, when the product was mostly NO3-. The results indicate that absorbed NO2 in the lung is converted predominantly to NO2-, but after its diffusion into the vascular space it is oxidized to NO3- by interactions with erythrocytes.

Absorption↗
PubMedDate not supplied

Age-dependent pulmonary response of rats to ozone exposure.

The influence of age on O3 effects in the lung was studied in 8 groups of Sprague-Dawley rats: 7, 12, and 18 d of age (neonatal); 24, 30, and 45 d of age (infant); and 60 and 90 d of age (adult). Lung weight, total lung protein and DNA contents, and a series of marker enzyme activities in lung tissue were determined. After exposure of rats from each group to 0.8 ppm (1568 microgram/m3) O3 continuously for 3 d, a biphasic effect was noted. The biochemical parameters, expressed per lung, in O3-exposed rats relative to their corresponding controls decreased in the 7- and 12-d-old groups, increased or remained unchanged in the 18-d-old group, and increased in the 24- to 90-d-old groups. However, the increases were much greater for 60- to 90-d-old rats than for 24- to 30-d-old rats. The increase in lung biochemical parameters is thought to occur in response to lung injury and subsequent repair processes, and greater increases in the lungs of older rats suggest that they are more responsive to O3 exposure than younger rats. The decrease in lung biochemical parameters and increased mortality in 7- and 24-d-old neonatal rats suggest that they are more susceptible to O3 stress than infant and adult rats.

Aging↗
PubMedDate not supplied

Comparison of pulmonary biochemical effects of low-level ozone exposure on mice and rats.

The biochemical effects of a 5-d continuous exposure to 0.45 ppm (882 microgram/m3) O3, were studied in the lungs of 2-mo-old male, specific-pathogen-free mice (Swiss Webster) and three strains of rats (Long-Evans, Wistar, and Sprague-Dawley). The results, expressed per lung, indicated a general increase in lung weight, DNA and protein contents, oxygen consumption, sulfhydryl metabolism, and the activities of several NADP+-reducing enzymes for all exposed animals relative to their controls. When the increases in the two species (mice versus three strains of rats) were compared, the mice showed significantly higher increases than the rats in several parameters. The responses among the three strains of rats were variable, but the differences were not significant. These observations suggest that Swiss Webster mice may offer a more sensitive animal model than rats for studying the pulmonary effects of a given low-level O3 exposure.

Animals↗