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Biomedical subjects

J A Raub

Publications and source records attributed to J A Raub.

10 recordsLinked to original sources
PubMed1987

Evaluating the toxicity of urban patterns of oxidant gases. II. Effects in mice from chronic exposure to nitrogen dioxide.

The study reported herein evaluates the influence of a chronic exposure to an urban pattern of NO2 (continuous baseline exposure of 0.2 ppm, on which were superimposed two 1-h spikes of 0.8 ppm NO2, 5 d/wk) as compared to the baseline exposure to determine the contribution of the spikes to toxicity. Mice were exposed for up to 52 wk with interim examinations. Multivariate analysis of variance revealed a statistically significant treatment effect on infectivity (p = 0.05) and pulmonary function (p = 0.03) parameters. Infectivity mortality of mice in the spiked exposure regimen was significantly greater than that in either the NO2-background-exposed mice or in control mice. Four of the pulmonary function variables exhibited the greatest differences among the treatment groups: end expiratory volume, vital capacity, respiratory-system compliance, and multiple-breath nitrogen washout. Results from the pulmonary-function analyses indicate that the spiked exposures to 0.8 ppm NO2 may have induced a subtle lesion. The chronic study results indicate that the presence of spikes of NO2 is contributing significantly to effects on antibacterial lung defenses and pulmonary function of mice.

Administration, Inhalation↗
PubMed1985

Inhalation studies of Mt. St. Helens volcanic ash in animals. II. Lung function, biochemistry, and histology.

Rats were exposed by inhalation to 9.4 mg/m3 size-fractionated volcanic ash for 5 days (2 hr/day) and examined for changes in pulmonary function and histology for periods of up to 1 year. Fine-mode volcanic ash, SO2, and a combination of ash and SO2 produced no observable effects in normal rats and rats with elastase-induced emphysema. However, there was a mild irritant response to SO2 which was not influenced by the volcanic ash. Rats injected intratracheally with fine-mode volcanic ash or saline showed no evidence of pulmonary alterations after 6 months. Those injected with coarse-mode volcanic ash showed minor pulmonary functional changes, histologically detectable alveolitis, and small increases in lung weight. In contrast, quartz-injected rats showed large alterations in pulmonary function, lung weight, hydroxyproline levels, and large areas of lung consolidation and fibrosis.

Animals↗
PubMed1984

Functional and biochemical indicators of pneumoconiosis in mice: comparison with rats.

Mice were injected intratracheally with silica or Mt. St. Helens volcanic ash (0.2 mg/g body weight) and examined 6 mo later for changes in pulmonary function, histology, and hydroxyproline content. Results were compared with a similar study using rats. Mice injected with volcanic ash showed significant changes only in wet lung weights. Those injected with silica showed an approximate doubling of lung wet weight and dry weight and hydroxyproline content. Larger increases in lung weight were seen if lymph nodes were left attached. Lung compliance, total lung capacity, and the shape of the pressure-volume curve of the lung were changed as much as 22% in the silica-treated mice. A mild degree of fibrosis with no dense lung consolidation was noted microscopically in silica-treated mice. In contrast, silica-treated rats showed dense lung consolidation, threefold to fivefold increases in both wet and dry lung weights and hydroxyproline content, and up to 40% reductions in pulmonary function measurements. It is concluded that Swiss albino mice develop a milder degree of fibrosis than similarly treated Sprague-Dawley rats and that both biochemical and functional indicators are effective in detecting pneumoconiosis in these species.

Animals↗
PubMed1984

Pulmonary function testing in small laboratory mammals.

The lung is the primary organ likely to be exposed by inhalation studies and, therefore, measurement of changes in lung function are of particular interest to the pulmonary physiologist and toxicologist. Tests of pulmonary function have been developed which can be used with small animals to measure spirometry (lung volumes), mechanics, distribution of ventilation, gas exchange or control of ventilation. These tests were designed on the basis of similar tests which are used in humans to diagnose and manage patients with lung disease. A major difference is that many of the measurements are performed in anesthetized animals, while human pulmonary function is usually measured in awake cooperating individuals. In addition, the measurement of respiratory events in small animals requires sensitive and rapidly responding equipment, because signals may be small and events can occur quickly. In general, the measurements described provide information on the change in normal lung function which results primarily from structural changes. These tests of pulmonary function can be repetitively and routinely accomplished and the results appear to be highly reproducible. Although some are quite sophisticated, many can be undertaken with relatively inexpensive equipment and provide useful information for toxicological testing.

Anesthesia↗
PubMed1983

Pulmonary function in normal and elastase-treated hamsters exposed to a complex mixture of olefin-ozone-sulfur dioxide reaction products.

An elastase-induced emphysema model was utilized to determine if hamsters with preexisting lung disease were more susceptible to lung damage from air pollutant exposure. Male golden hamsters, divided into two treatment groups, were given a single intratracheal injection of either 6 units of porcine pancreatic elastase (EMP) or buffer (CNT). After a 4-week recovery period, equal numbers of each group were exposed 23 hr/day X 28 day to filtered air (AIR) or to the complex by-products from a dark phase reaction mixture of trans-2-butene, ozone, and sulfur dioxide (MIX). Lung function measurements on the elastase-treated groups showed changes consistent with mild emphysema. There were no significant differences in lung volumes or lung compliance between the AIR- and MIX-exposed animals. However, the nitrogen washout slope decreased (P less than 0.05), and the diffusing capacity for carbon monoxide increased (P less than 0.05) in both the CNT and EMP hamsters exposed to the MIX. The change in diffusing capacity was greater (P less than 0.05) in normal hamsters than in hamsters with emphysema, and it is hypothesized that animals with impaired lung function had a decreased ability to respond to a pulmonary insult from the mix.

Air Pollutants↗
PubMed1983

Can animal pulmonary function testing provide data for regulatory decision making?

The process of setting health standards requires rigorous, scientifically sound data that relate to man's interaction with his environment. Tests of pulmonary function are especially useful, since they may permit some direct comparisons between animals and man. The development of tests to measure pulmonary function in small animals has been important, and research into the health effects of air pollution may be greatly strengthened with the use of data from such measurements.

Air Pollutants↗
PubMed1983

Effects of prenatal nitrofen exposure on postnatal lung function in the rat.

The herbicide Nitrofen was administered by gavage to pregnant F-344 rats during Days 10 through 13 of gestation. Postnatal lung function was measured in male progeny at 3 and 6 weeks of age. There were no differences in body weight or wet and dry lung weights between control and Nitrofen-exposed rats in either age group. Nitrofen produced no observable effects on lung function at 3 weeks of age. However, by 6 weeks of age the Nitrofen-exposed animals had significant decreases in tidal volume (p less than 0.01), vital capacity (p less than 0.01), total lung capacity (p less than 0.05), and quasi-static lung compliance (p less than 0.01). There was also a mild ventilation inhomogeneity, as indicated by significant increases in the nitrogen washout slope (p less than 0.01) and the moment ratio (p less than 0.05). Histopathology of lung, liver, kidney, and testes was not significantly altered by Nitrofen exposure. These data suggest that prenatal Nitrofen exposure may have an effect on postnatal lung maturation in the rat and could potentially be useful as a model of pulmonary hypoplasia.

Aging↗
PubMed1982

Morphologic changes in the lung during the lifespan of Fischer 344 rats.

Pulmonary structure and function were quantitatively investigated over the lifespan of the Fischer 344 rat by morphometric and physiologic techniques. Male animals 1 week, 6 weeks, 5 months, 14 months, and 26 months of age and female animals 5 months, 14 months, and 26 months of age were studied. All alveolar tissue compartments demonstrated significant increases in volume, surface area, and cell number during the first 5 months of life. From 5 to 26 months of age, remodelling in the epithelial and interstitial compartments continued to take place while the endothelial compartment remained relatively unchanged. In the epithelial compartment the ratio of type II cells to type I cells lining the alveolar surface decreased as age increased. In the interstitial compartment the volume of the noncellular components of the interstitium increased by 39% in males and by 89% in females from 5 to 26 months of age. Physiologic measurements of lung volumes in males at 6 weeks, 14 months, and 26 months demonstrated progressive increases in vital capacity (VC) and total lung capacity (TLC). Morphometric pulmonary-diffusion capacity (DLO2) increased in males from 1 week to 5 months of age and remained relatively unchanged from 5 to 26 months of age in both sexes.

Aging↗
PubMed1982

Dose response of elastase-induced emphysema in hamsters.

Elastase-induced emphysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. Single intratracheal injections of 6, 12, or 24 units of porcine pancreatic elastase produced dose-related changes in pulmonary function after 4 wk when compared with sham-injected control animals. Boyle's law end-expiratory volume and residual volume, measured by gas dilution, increased (p less than 0.05) at 12 and 24 units, respectively, whereas vital capacity, determined plethysmographically, and total lung capacity wee increased (p less than 0.05) at all 3 elastase doses. Respiratory system compliance, calculated by a nonlinear least squares regression fit of the deflation pressure-volume curve, increased (p less than 0.05) at 24 units only. The multiple-breath nitrogen washout slope (N2 slope) and the single-breath diffusing capacity for carbon monoxide (DLCO) decreased (p less than 0.05) at all 3 doses of elastase. Both histologic and physiologic evaluation showed dose-related pulmonary impairment. It appears, therefore, that as little as 6 units of elastase produces mild emphysema in hamsters, which is detectable by pulmonary function testing. Of these tests, the DLCO and N2 slope were the most effective in detecting the degree of impairment.

Animals↗