Experimental lung research
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Sequential exposures to inhaled environmental pollutants may result in injuries/responses not predicted by evaluating exposures to an individual toxicant. This may indicate that the lung is damaged or primed by earlier events, so exposure to a nontoxic dose of an environmental pollutant may be sufficient to trigger adverse responses. The present study was designed to test the hypothesis that stimulating lung epithelial damage or inflammatory cell activation followed by a second stimulus leads to responses not seen after individual exposures in the postnatal lung. ⋯ These results demonstrate that preexposure to LPS, which primarily activates inflammatory cell recruitment, can cause sensitization to a secondary stimulus. However, preexposure to ozone, which primarily damages the epithelium, inhibited proinflammatory responses. Thus it was concluded that sequential exposures to ozone and LPS resulted in responses not predicted by evaluating individual exposures during postnatal lung development.
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Review
A/J mouse as a model for lung tumorigenesis caused by tobacco smoke: strengths and weaknesses.
Strain A/J mice have successfully been used to develop an animal model for tobacco smoke carcinogenesis. In 18 individual studies, reported by 4 different laboratories, a significant increase in lung tumor multiplicities following exposure from 50 to 170mg/m3 of total suspended tobacco smoke particulates was found in 15 studies (83 %) and a significant increase in lung tumor incidence in 10 studies (56%). ⋯ From a toxicological standpoint, this indicates that cigarette smoke is a weak animal carcinogen. Although the assay allowed one to detect substantial chemopreventive activity of a mixture of myo-inositol and dexamethasone, it was less successful in showing efficacy for several other agents.
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Comparative Study
Progressive, severe lung injury secondary to the interaction of insults in gastric aspiration.
This study examines lung injury and inflammation over 24 hours following intratracheal instillation of hydrochloric acid (acid), small nonacidic gastric particles (SNAP), or combined acid and small particles (CASP) in adult rats. The severity and duration of injury was significantly greater for CASP compared to acid or SNAP based on PaO2/FiO2, bronchoalveolar lavage (BAL) albumin, and BAL cell numbers. The inflammatory response associated with aspiration injury from CASP was distinct in several respects. ⋯ Additional cytokine cluster analyses indicated that levels of MCP-1 and CINC-1 in BAL from all injured animals were strongly correlated with inflammatory neutrophil numbers at 6 and 24 hours post aspiration, and that IL-10 levels in BAL were strongly correlated with inflammatory cell numbers at 24 hours. Preliminary blocking experiments showed that administration of anti-IL-10 antibody increased the albumin permeability index at 6 hours in SNAP and CASP animals, but anti-MCP-1 antibody did not affect the severity of injury. The results of this study support the possibility that different forms of aspiration are associated with identifiable cytokine profiles, and that specific cytokines, including IL-10 and MCP-1, may have utility as diagnostic or prognostic markers in clinical applications.
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Comparative Study
Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats.
A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). ⋯ Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus, while inhalation treatment caused greater levels of the drug in lung tissue in comparison to that of injection-treated animals, treatment with ATRA by either route of administration did not cause a reversal of lung tissue damage in this model of elastase-induced emphysema.
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To test the effect of transition from sustained hypoxia to normoxia on production of reactive oxygen species (ROS) in lungs, the authors measured hydrogen peroxide (H(2)O(2)) output in the expired air of rats breathing hypoxic, normoxic, and hyperoxic gas mixtures at the end of exposure to 72 hours of hypoxia. Twenty-one male Wistar rats (200 to 280 g) were randomly assigned to 1 of 3 groups. First two groups (experimental) were kept for 3 days in normobaric hypoxic chamber (F(1)O(2) 0.1), rats of the third group (controls) breathed air. ⋯ Transition from hypoxia to normoxia resulted in an increase in the H(2)O(2) production (SH-A 421+/-24 pmol/h, and SH-H-A 366+/-19 pmol/h). Following transition from air breathing to hyperoxia did not affect the H(2)O(2) production (SH-A-O(2) 373+/-25 pmol/h). The results showed that sustained hypoxia and transition from sustained hypoxia to normoxia increased H(2)O(2) formation in the lungs.