Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Syrian hamsters were exposed to the aerosol of a 5% solution of papain in the presence of cysteine and ethylenediamine-tetraacetic acid. Pulmonary emphysema in hamsters was observed after exposure to papain for two to three hours. There was no change with time in the severity of emphysema from the second through the fourth weeks after exposure to papain. Pathogenesis of pulmonary emphysema was discussed in relation to proteolysis of glycosaminoglycan-protein complex.
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PMID:Experimental pulmonary emphysema in Syrian hamsters. 82 20

By intratracheal injection of the protease papain to experimental animals parenchymal changes in the lung can be induced, that resemble human emphysema. Papain (dosage 26 to 112 mg, 1 to 4 injections) was given intratracheally to 8 bastard dogs (weighing from 12.5 to 20 kg) during light general anesthesia. Pulmonary function was assessed in weekly intervals and related to morphologic changes in the lung. Static compliance of the lung and FRC measured during respiratory arrest were increased after papain, bronchial resistance, measured while artifically ventilated at constant pressure was also increased. Changes of static lung compliance and FRC were seen after the first administration of papain, but further increased with time of observation and after multiple doses of papain. Increase of resistance was not found before 5 weeks. At quiet breathing resistance was not increased at all. No significant changes were found of arterial pO2 and pCO2, pH, standard and actual bicarbonate, diffusion capacity for O2, tidal volume, minute ventilation and ventilatory rate. Morphological findings confirmed the changes described by others. Pulmonary function appears to be pathological at a time when morphology still seems to be normal. The question is discussed to what extent the model of experimental emphysema induced by proteolytic enzymes can contribute to the understanding of human pulmonary emphysema. Lung function in the course of experimental emphysema is compared with function in different clinical types of emphysema.
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PMID:[Pulmonary emphysema. Changes in the pulmonary function of experimentally induced emphysema]. 84 85

Rats were exposed to an aerosol of 10% papain for 8 h found in pilot studies to produce marked emphysema. One week after exposure some animals were forced to exercise in a motor-driven activity wheel 2 h daily for 4 wk, while others remained at rest. Another group of rats which served as the control were exposed to saline under the same conditions and divided into exercise and rest groups. Elastic recoil pressure (Pst) of lung was measured from static deflation pressure-volume curves with air and saline. Pst measured in air-filled lungs was not significantly different between the emphysema-rest and emphysema-exercise groups. When inflated with saline the Pst was significantly reduced in the emphysema-exercise compared to the emphysema-rest group at high and mid (100, 80, 60%) lung volumes. Pst in air- and saline-filled lungs was not significantly different between the control-rest and control-exercise groups. We therefore conclude that mechanical stress resulting from physical exercise decreased Pst of lung tissue in emphysematous rats.
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PMID:Exercise stress and enzyme-induced emphysema. 96 1

Distribution of transpulmonary pressure (Ptp) at FRC, during spontaneous breathing, and during inflation of the relaxed respiratory system was studied in the supine, lateral and head-up postures after papain had been injected intratracheally into dogs. Functional and morphological changes of the lung resembling those of panlobular emphysema occurred in papain-treated dogs. In all postures the relationship between lung height and Ptp at FRC was steeper and shifted to the left of that obtaining for normal dogs. During artifical inflation changes of Ptp were larger in the dependent than in the upper lung and the vertical gradient of Ptp eventually disappeared, as observed in normal dogs. During spontaneous breathing changes of Ptp were uniform in the horizontal postures, but larger over the upper regions in the head-up posture; whereas they are uniform in all postures in normal dogs. From local Ptp values and lung P-V curve, distribution of specific lung volumes at FRC and ventilation during spontaneous breathing were assessed for both normal and papain-treated head-up dogs: the results agreed with those obtained using radioactive gases in normal and in elderly man or emphysematous subjects with no apparently localized lesions.
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PMID:Effect of papain-induced emphysema on the distrubtion of pleural surface pressure. 96 99

The possibility that human alpha1-antitrypsin could effectively prevent development of emphysematous lesions produced in hamsters 7 days after exposure to aerosolized papain (3% for 3 hours) was investigated. Pretreatment with intratracheal human alpha1-antitrypsin prevented the appearance of these lesions in a dose-dependent manner. On the other hand, systemic administration of large doses of human alpha1-antitrypsin failed to prevent papain-induced pulmonary lesions, despite a significant increase in serum trypsin inhibitory capacity. These results suggest that intra-alveolar rather than serum concentrations of human alpha1-antitrypsin are critical for preventing the development of pulmonary emphysema in this animal model. It is interesting that although the mechanism by which human alpha1-antitrypsin prevented the papain-induced lesions is unknown, intratracheally administered human alpha1-antitrypsin similarly prevented the development of pulmonary emphysematous lesions induced by 0.1 mg of porcine pancreatic elastase given intratracheally.
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PMID:Effect of human alpha-antitrypsin in papain-induced emphysema in the hamster. 108 1

To investigate the effect of a papain-induced emphysema-like condition on pulmonary absorption of drugs, rats were exposed to either papain aerosol or distilled water aerosol (control) intermittently for 2 wk, and rates of drug absorption from damaged and control lungs were compared. To measure absorption rates, 0.1 ml of drug solution (0.1-10 mM) was administered through a tracheal cannula to anesthetized animals, and after various times lungs were assayed for unabsorbed compound. In absorption experiments with the lipoid-insoluble compounds, mannitol, p-aminohippuric acid, and procaine amide ethobromide, all three drugs were absorbed from the lungs about twice as rapidly in papain-treated rats as in control. In contrast, procaine amide, a relatively lipoid-soluble drug, was absorbed at the same rate in both control and papain-treated animals. The results suggest that papain-induced lung damage increases the porosity of the pulmonary epithelium.
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PMID:Effect of papain-induced emphysema on permeability of rat lung to drugs. 116 92

Papain is a proteolytic enzyme widely used by biochemists. In experiments on animals papain has been shown to cause emphysema either when they inhaled a single small dose or after intratracheal inhalation. Four food technologists were occupationally exposed to heavy concentrations of papain dust in air. Subjects 1 and 2 developed an immediate acute asthmatic reaction, and symptoms of obstructive airways disease persisted for some months while each remained in the same working area, presumably exposed to small gradually diminishing amounts of residual papain dust. Tests of respiratory function were carried out on all four subjects 1 1/2 years later and showed in subjects 1 and 3 minimal abnormality of bronchial reactivity and of ventilation distribution. Review of the literature reveals only two reports of asthma resulting from papain inhalation, although its antigenic and skin sensitizing qualities have been known and described for many years. It seems remarkable that a substance such as papain, shown to be a potent cause of lung damage in experimental animals, should have produced so little evidence of abnormality in our subjects after considerable exposure. Follow-up ventilatory function tests may cast further light on this but we postulate that the asthmatic response may be biologically protective and those lacking this reaction could later develop emphysema as a long-term outcome.
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PMID:Occupational asthma after inhalation of dust of the proteolytic enzyme, papain. 120 Dec 57

The study was carried out on an experimental papain induced model of pulmonary emphysema. The authors assessed the cell populations sampled with lavage. Special emphasis was directed on alveolar macrophages and neutrophils. Extent of emphysema was analysed morphometrically. The authors demonstrated an influx of neutrophils 24 hours after papain was introduced intratracheally. This was followed by a swift decrease of the number of sampled neutrophils. Seven days latter the neutrophil count returned to normal. A significant increase of alveolar macrophages was seen on the seventh day. The increased macrophage count correlated with the extent of the pulmonary emphysema destruction.
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PMID:[Free alveolar cells in experimental pulmonary emphysema. I. Statistical analysis of cellular composition and lung morphometry]. 149 4

Current theories of pathogenesis suggest that pulmonary emphysema develops in humans because of progressive loss or derangement of lung elastin through a process mediated by elastolytic enzymes released by inflammatory cells. Neutrophils are considered primary etiologic factors because these cells produce and release two potent serine proteinases that cause emphysema when instilled into the lungs of animals. It has been suggested that alveolar macrophages also contribute to the development of emphysema through production of several enzymes with elastolytic activity, including the lysosomal cysteine proteinases cathepsin B and cathepsin L, but this has not been verified experimentally. In the current study, we instilled 115 micrograms of active cathepsin B into the lungs of hamsters three times at 48-h intervals. After 6 wk microscopic evaluation revealed that lung sections of five of seven animals given cathepsin B contained focal areas of enlarged and distorted alveoli, in the absence of fibrosis, which were similar to changes seen in the lungs of animals given papain intratracheally. Morphometrically, mean linear intercept (micron) values were significantly higher (p less than 0.025) in animals given cathepsin B (204.4 +/- 20.8) as compared with control animals (173.2 +/- 7.8), and internal surface area (sqcm) values were significantly lower (935 +/- 120 versus 1,083 +/- 56 in control animals), thereby confirming that airspace enlargement had developed after instillation of the enzyme. Lung volumes (ml) and compliance (ml/cm H2O) were not significantly higher in animals given cathepsin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of emphysema in hamsters by intratracheal instillation of cathepsin B. 154 48

Patients with cardiopulmonary insufficiency undergoing laparoscopic surgery with carbon dioxide (CO2) pneumoperitoneum may retain CO2 resulting in clinically significant respiratory acidosis. A canine model of pulmonary emphysema induced by papain inhalation was utilized to evaluate the respiratory effects of both CO2 and helium pneumoperitoneum. Prior to papain inhalation and 5 and 8 weeks after initial treatment under general anesthesia, mechanical ventilation was adjusted to maintain the end-tidal CO2 (ETCO2) at 40 mm Hg during baseline and pneumoperitoneum physiologic monitoring periods. Utilizing an analysis of variance, hemodynamic and respiratory physiologic parameters were compared. In this canine model, all dogs demonstrated consistent hypercarbia during CO2 pneumoperitoneum prior to papain treatments, but CO2 retention was significantly increased in the emphysematous state. The occurrence of hypercarbia during CO2 pneumoperitoneum may be underestimated by ETCO2 monitoring as was revealed by an increased PaCO2 (arterial carbon dioxide pressure)-ETCO2 gradient with an increasing time interval between papain exposure and period of physiologic monitoring. Irrespective of the pulmonary condition of the dog, helium pneumoperitoneum did not produce any hypercarbic or acidic changes when compared with the concomitant baseline period of dogs prior to the induction of pneumoperitoneum, thus suggesting that helium pneumoperitoneum may be a reasonable alternative in patients at risk for CO2 retention.
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PMID:Hypercarbia during carbon dioxide pneumoperitoneum. 173 68


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